Global 240/720 Before you start - 1 Table of Contents 1 BEFORE YOU START .................................................................................................................................5 1.1.1 ............................................................................................................ .... 5 What’s new in this release ................................................................................................................ 1.1.2 Using this manual ............................................................................................................................. 5 1.1.3 Where to start ................................................................ ............................................................................................................................... ................................................................... .... 5 1.1.4 Conventions used in this manual ...................................................................................................... 5 1.2 PRIMARY SAFETY PRECAUTIONS ................................................................................................................ .................................................................................................................... .... 6 1.2.1 Safe use of the system ...................................................................................................................... 6 1.2.2 Installation environment precautions ............................................................................................. ............................................................. ................................ 10 1.2.3 System labels and displays ........................................................ .............................................................................................................. ...................................................... 10 1.3 2 SYSTEM OVERVIEW ............................................................................................................................... 11 11 2.1 HOW THE GLOBAL ANALYSES SAMPLES ...................................................................................................... ........................................................... ........................................... 11 2.1.1 Summary of the process ............................................................ .................................................................................................................. ...................................................... 11 2.1.2 Computer automation .................................................................................................................... 12 2.1.3 Sample identification ...................................................................................................................... 12 2.1.4 Sample and reagent transfer .......................................................................................................... 13 2.1.5 Sample and reagents reagent s mixing ................................................................ ........................................................................................................... ........................................... 13 2.1.6 Measurement by photometry ......................................................................................................... 13 2.1.7 Washing and drying ........................................................................................................................ ........................................................................................ ................................ 13 2.1.8 Calculating results ......................................................................................................................... .......................................................... ................................................................. .. 13 2.1.9 Colorimetric reaction ...................................................................................................................... 13 2.1.10 Determination of the secondary wavelength ............................................................................. 14 2.1.11 Importance of the reagent blank ................................................................ ................................................................................................ ................................ 14 2.1.12 Kinetics reactions ........................................................................................................... ........................................................................................................................ ............. 14 2.2 UNDERSTANDING THE SYSTEM HARDWARE ........................................................ ................................................................................................... ........................................... 15 2.2.1 Power-On switch ..................................................................................................... ............................................................................................................................. ........................ 15 2.2.2 Voltage selector .............................................................................................................................. 15 2.2.3 Power inlet and fuses ...................................................................................................................... 16 2.2.4 Serial port RS 232 23 2 ........................................................... .......................................................................................................................... ................................................................. .. 16 2.2.5 Samples and reagents tray ............................................................................................................. 16 2.2.6 Reagents and samples arm ....................................................... ............................................................................................................. ...................................................... 16 2.2.7 2.2.8 Photometer unit .............................................................................................................................. ................................................................................................................. ............. 16 Washing and drying unit ................................................................................................................. ........................................................... ...................................................... 17 2.2.9 Sample and reagent syringe ........................................................................................................... 17 2.2.10 Housing of reaction cuvettes ...................................................................................................... 17 2.2.11 Refrigeration unit ....................................................................................................................... 17 2.2.12 External fluids connectors .......................................................................................................... 18 2.2.13 Barcode reader (optional) .......................................................................................................... 18 2.2.14 ISE unit (Global 720) ................................................................................................................... 18 2.2.15 ISE pumps group g roup ....................................................................................................................... ........................................................ ................................................................. .. 18 2.3 GRAPHICAL USER INTERFACE (GUI) ............................................................................................................. ....................................................... ...................................................... 19 2.4 MAIN SCREEN OVERVIEW ........................................................................................................................ ......................................................... ................................................................. .. 19 2.4.1 3 BPC BIOSED GUARANTEE ............................................................................................................. .......................................................................................................................... ............. 10 Warning messages ......................................................... ........................................................................................................................ ................................................................. .. 21 2.5 SPECIFICATIONS ....................................................................................................................................... 22 2.6 ACCESSORIES SUPPLIED WITH THE ANALYZER ................................................................................................ 24 INSTALLATION ....................................................................................................................................... 25 BPC BIOSED srl - User's Manual Rev.1 En. 2 Global 240/720 3.1 HOW TO INSTALL THE ANALYZER ................................................................................................................ 25 3.1.1 Unpacking ....................................................................................................................................... 25 3.1.2 Selecting a suitable location ........................................................................................................... 26 3.1.3 Installation environment e nvironment ................................................................................................................. ........................................................... ...................................................... 27 3.1.4 Electrical requirements ................................................................................................................... 27 3.2 4 Before you start - 1 PREPARATION OF THE INSTRUMENT ............................................................................................................ 27 3.2.1 Fluid connections ............................................................................................................................ 28 3.2.2 Connection to the electrical outlet .................................................................................................. ....................................................... ........................................... 28 3.2.3 Connecting the computer................................................................................................................ 29 3.2.4 Software installation ..................................................................................................................... ....................................................................................................................... .. 29 3.3 SWITCHING ON THE GLOBAL ....................................................................................................................... ................................................................. ...................................................... 30 3.4 HOW RESTORE THE METHODS FROM THE ARCHIVE .......................................................................................... 31 CONFIGURING TESTS ............................................................................................................................. 33 4.1 POSITIONING OF TESTS IN THE GRID.............................................................................................................. ........................................................ ...................................................... 33 4.2 ADDING A NEW TEST................................................................................................................................. 34 4.2.1 Entering Specific Test Parameters .................................................................................................. 34 4.2.2 Programming calculated tests ........................................................................................................ 37 4.2.3 Edit or delete a method .................................................................................................................. 38 4.2.4 Loading of reagents ........................................................................................................................ 38 4.2.5 Setting normal ranges ..................................................................................................................... ............................................................... ...................................................... 38 4.2.6 Creating a new profile. .................................................................................................................... .............................................................. ...................................................... 39 4.3 CALIBRATION PROCESS ............................................................................................................................ ............................................................. ................................................................. .. 39 4.3.1 Reconstitution of multi calibrator and control sera ........................................................................ 40 4.3.2 Entry of concentration values of the multi-calibrator ........................................................ ..................................................................... ............. 40 4.3.3 Entry of minimum and maximum values of control sera .............................................................. ................................................................ .. 41 4.3.4 Selection of the tests t ests to be calibrated ............................................................. ............................................................................................. ................................ 42 4.3.5 Loading of calibrators and control sera on the samples tray ........................................................ .......................................................... .. 44 4.3.6 Check of the reagents volume ......................................................................................................... .............................................................. ........................................... 45 4.3.7 Starting the calibration process ...................................................................................................... ........................................................... ........................................... 46 4.3.8 Validation of calibration data ......................................................................................................... 46 4.3.9 Chemical reactions in clinical chemistry ......................................................................................... 49 4.4 5 QUALITY CONTROL ...................................................................................................................... ........................................................ ........................................................................... ............. 51 PERFORMING ANALYSIS ........................................................................................................................ 54 5.1 HOW TO ACCEPT NEW PATIENTS ................................................................................................................ .......................................................... ...................................................... 54 5.1.1 Entry of new patients and start of the process ............................................................................... 55 5.1.2 Performing an emergency stop ............................................................ ....................................................................................................... ........................................... 55 5.1.3 Performing a planned stop ............................................................................................................. 55 5.1.4 Reagent and sample addition addit ion ......................................................................................................... .............................................................. ........................................... 55 5.1.5 Archiving or removal of patients ..................................................................................................... .......................................................... ........................................... 56 5.1.6 How to use the archive of the patients ........................................................................................... 57 5.1.7 Checking Results ............................................................................................................................. 59 5.1.8 Results with flags ............................................................................................................................ 61 5.2 5.2.1 REPEAT TESTING ...................................................................................................................................... 61 Automatic repetition ................................................................. ....................................................................................................................... ...................................................... 61 5.3 INCOMPATIBILITY BETWEEN TESTS............................................................................................................... ......................................................... ...................................................... 62 5.4 SETTINGS OF THE GLOBAL ......................................................................................................................... 62 5.5 PRINTING DATA ....................................................................................................................................... 64 BPC BIOSED srl - User's Manual Rev.1 En. 3 Global 240/720 5.5.1 Patient report ................................................................................................................................ ................................................................. ................................................................. .. 64 5.5.2 Laboratory Heading ........................................................................................................................ 65 5.6 6 BARCODE READER ....................................................................................................................... ......................................................... ........................................................................... ............. 67 MAINTENANCE ...................................................................................................................................... 68 6.1 SCHEDULED PREVENTIVE MAINTENANCE ...................................................................................................... 68 6.1.1 Washing of Cuvettes ....................................................................................................................... ............................................................................ ........................................... 69 6.1.2 How replace the photometer lamp ................................................................................................. 69 6.1.3 How replace the t he cuvettes ................................................................................................................ .......................................................... ...................................................... 70 6.1.4 How to replace the needle and the cleaner .................................................................................... 70 6.2 MECHANICAL ALIGNMENTS AND CONTROLS.................................................................................................. ....................................................... ........................................... 71 6.2.1 Centering of the needles ................................................................................................................. 72 6.2.2 Rise from sample............................................................................................................................. 72 6.2.3 Descent on sample and check of level sensor ................................................................................. 72 6.2.4 Check of the volume dispensed ....................................................................................................... 73 6.2.5 Check of the reaction cuvettes ........................................................................................................ 73 6.2.6 Check of the photometric reading .................................................................................................. 74 6.3 7 Before you start - 1 TROUBLESHOOTING ..................................................................................................................... .................................................................................................................................. ............. 76 6.3.1 Some tips ............................................................................................................................ .............................................................. ........................................................................... ............. 76 6.3.2 Troubleshooting the problem ......................................................................................................... 77 6.3.3 Alert messages .............................................................................................................................. ............................................................... ................................................................. .. 79 6.3.4 Runtime error .................................................................................................................................. ..................................................................................................................... ............. 81 ISE (ION SELECTIVE ELECTRODES) .......................................................................................................... 82 7.1 OVERVIEW ...................................................................................................................... ........................................................ ...................................................................................... ........................ 82 7.2 ELECTRODES.................................................................................................................... ...................................................... ...................................................................................... ........................ 82 7.3 FLUID MANAGEMENT ............................................................................................................................... 83 7.4 MECHANICAL FEATURES ............................................................................................................................ ............................................................................................................... ............. 84 7.5 INSTALLATION OF ISE ............................................................... .............................................................................................................................. ................................................................. .. 85 7.5.1 Components of ISE system .............................................................................................................. 85 7.5.2 Reagent pack .................................................................................................................................. 87 7.5.3 Installation of reagent pack ............................................................................................................ 88 7.5.4 Start-up of ISE system ..................................................................................................................... 88 7.5.5 Performance verification ................................................................................................................ 90 7.5.6 System integration notes ................................................................................................................ 92 7.6 MAINTENANCE SCHEDULED........................................................................................................................ 93 7.6.1 Washing electrodes with cleaning solution .................................................................................... 93 7.6.2 Cleaning of sample inlet inle t port ............................................................... .......................................................................................................... ........................................... 94 7.6.3 Replacement of electrodes.............................................................................................................. ........................................................ ...................................................... 94 7.6.4 Shutdown procedure: preparing the ISE module for storage .......................................................... ........................................................ .. 96 7.6.5 ISE module re-activation ................................................................................................................. 96 7.6.6 Pump tube replacement.................................................................................................................. ............................................................ ...................................................... 96 7.6.7 Alignment of the probe on the ISE entry port ................................................................................. .............................................. ................................... 97 7.7 TROUBLESHOOTING ..................................................................................................................... .................................................................................................................................. ............. 97 7.7.1 Fluid delivery ................................................................................................................................... 98 7.7.2 ISE error messages .......................................................................................................................... 98 7.7.3 Troubleshooting guide .................................................................................................................... 99 7.7.4 Flag list .................................................................................................................... ...................................................... .................................................................................... ...................... 101 7.8 ISE THEORY .......................................................................................................................................... 101 BPC BIOSED srl - User's Manual Rev.1 En. 4 Global 240/720 Before you start - 1 1 Before you start Thank you for choosing the BPC Biosed GLOBAL automated chemistry system. The intended use of this automated system is the photometric and potentiometric determination of analytes in samples, in combination with appropriate reagents, calibrators, quality control materials and other accessories. This system is for in-vitro diagnostic use only. To ensure optimal performance and prevent system failure, you should always operate the system in accordance with the procedures outlined. 1.1.1 What’s new in this release This release of the user manual has been prepared in accordance to the software release 5.0 or higher. 1.1.2 Using this manual This manual explains in a step-by-step way how to understand and use the system effectively. It is also a maintenance and troubleshooting manual and is intended as the primary source of reference for all GLOBAL users. This includes all medical laboratory personnel who might have to use any part of the system or might have to prepare samples to be processed by the system. It is assumed that the user has a knowledge of analytical chemistry processes and specialist knowledge of sample analysis. This manual also assumes users have basic PC operating skills and knowledge of a Windows operating system. 1.1.3 Where to start Before operating this system, you should receive training either directly from BPC Biosed or from someoneauthorized who has has already attended a BPC Biosed-approved training training course. While this user manual deals with each system procedure in a step-by-step manner, it does not aim to be a substitute for training. If you have never used an automated chemistry system before or you are only slightly familiar with one of the other BPC Biosed models, it is recommended that you read this user manual thoroughly before operating the system, even if you have completed an BPC Biosed approved instructor-led training course. 1.1.4 Conventions used in this manual This section describes the conventions used in this manual: This symbol alerts the user to the presence of dangerous tensions and not isolated within the instrument, (risk of electric shock). This symbol indicates a caution. Cautions indicate that appropriate care or action must be taken. Failure to do so may result in minor injury, sub-optimal system performance or damage, which may generate hazards. This symbol alerts you the fluids used are biological fluids to be treated with care by wearing adequate protections BPC BIOSED srl - User's Manual Rev.1 En. 5 Before you start - 1 Global 240/720 A software path is a sequence of keys or buttons that should be selected in the software interface in the order indicated. Often the sequence is expressed with the name of the buttons separated by the symbol ">". Normally, unless otherwise specified, the sequence starts at the Main Screen also named Home Screen Explanatory notes List of abbreviations Cal Calibrator COM Communication port Dil Diluent Global Global 240 - 720 GUI Graphical user interface ISE Ion selective electrode LED Light emitting diode LIS Laboratory information system LLD Liquid level detection n/a Not applicable OD Optical density OS Operative system QC Quality control P2P Pin to pin REF Reference SD Standard deviation . 2 P r i m a r y S a f e t y P r e c a u t io io n s You must understand how to use the Global safely before you begin using the system. This chapter provides instructions on: – – – 1.2.1 Safe Use of the System. Installation Environment Precautions. System Labels and Displays. Safe use of the system You should read the following safety precautions carefully before using the system. If the system is not operated according to the following precautions, the manufacturer or provider cannot be liable for any damage or injury that might result. Read all the following safety precautions: – – Preventing Electric Shocks. Preventing Minor and Serious Injury. BPC BIOSED srl - User's Manual Rev.1 En. 6 Global 240/720 – – – – – – – – – – Before you start - 1 Ensuring Optimal Analytical Performance. Treating Waste Liquids. Preventing Infection. Correct Handling of Reagents, Calibrators and Control Sera. Handling Specimens. Electromagnetic Wave and Noise Precautions. Replacing Parts. Setting Analysis Parameters. Planned Maintenance Routines. Performing Important Checks at Analysis. Preventing Electric Shocks – – Never remove surfaces secured by screws, including the top and side covers. If liquid spills or leaks within the system, system, contact contact your local BPC representative immediately. Careless handling of liquids around the system might result in an electric shock. Preventing Minor and Serious Injury Minor Injury is considered any injury that does not require hospitalisation or long term medical care. Serious injury is considered any injury that leaves permanent effects and requires long-term medical care or hospitalisation: – – – – Always operate the system with the main lid down. Do not touch any moving parts of the system while it is in operation. o peration. Do not put your fingers or hands into any holes or openings. When replacing the photometer lamp, turn off the power switch and allow at least five minutes for the lamp to cool down. Touching the lamp before it is cool might result in burning. – Observe the precautions on the system labels and in this user manual. Ensuring Optimal Analytical Performance – – Do not open the lamp lids, the reagent lid, cuvette wheel lid or ISE lid during analysis. Perform system maintenance, parts replacement and inspection routines, as outlined in this user manual (see Chapter Chapter 6, “Maintenance”). “Maintenance”). – Refer to the instructions for use supplied with reagents, calibrators, controls or accessories to be used on the system and follow them carefully. – Ensure appropriate quantities of reagents and wash solutions are present prior to daily operation. BPC BIOSED srl - User's Manual Rev.1 En. 7 Global 240/720 Before you start - 1 Treating Waste Liquids The waste liquids and mixtures might require special treatment before being discarded. This system is designed to discard the concentrated waste liquids (mixtures) and washing waste liquids (washing water) separately. For proper waste disposal, refer to relevant local authority m manuallines. anuallines. Preventing Infection – – To avoid infection, always wear personal protective clothing when handling samples, performing maintenance and coming in contact with waste. If infectious substances come in contact with your skin, flush the area and seek medical advice. – – Wipe off any spilled contaminant immediately from the system. If any of the reagents or samples are accidentally swallowed, seek medical advice. Correct Handling of Reagents, Calibrators and Control Sera – Strictly follow any safety instructions supplied with reagents, calibrators and control sera Refer to the reagent manufacturer for any questions concerning the safe handling of any material to be used on this system. – Prepare reagents in accordance with the manufacturer’s instructions for use, paying particular attention to any reconstitution, r econstitution, mixing and pre-treatment instructions. – Store reagents correctly, prior to placing them on-board the system. Refer to the manufacturer’s instructions. Pay particolar attention to the temperature requirements and light protection, where appropriate. – During the stay of reagents on board, to reduce evaporation and thus preserve the stability of the reagent, is recommended the use of pierced caps. – If reagents are removed from the system for later use, particular care should be taken to ensure they are protected from contamination. A clean cap should be applied and careful inspection should be undertaken prior to re-use. Handling Specimens – The quality of the sample placed on the BPC Biosed system is of paramount importance and all efforts should be made to ensure it is of the highest quality. Numerous pre-analytical variables exist and these should be accounted for before interpretation of the final result. – Typical samples used on the BPC Biosed system include serum, plasma, urine. Other fluids might not be suitable for analysis and care should be taken before analysis. – All samples should be handled as if potentially infectious and protective clothing should be worn at all times. – Serum and plasma samples should be separated from blood cells as soon as possible to reduce the risk of adulteration. Prior to analysis, samples should be free from suspended matter such as fibrin. Any abnormal optical characteristics such as lipemia, icterus or hemolysis should be noted. Results from such samples should be interpreted after consultation with the applicable reagents instructions for use. Care should be taken to BPC BIOSED srl - User's Manual Rev.1 En. 8 Global 240/720 Before you start - 1 ensure that any anticoagulants or collection devices that employ a barrier are compatible with the test reagent being employed. – Urine samples should be collected into appropriate preservatives and any suspended matter removed by centrifugation prior to analysis. – All samples should be protected from evaporation, contamination and, where applicable, light (i.e. for bilirubin determination) prior to analysis. Electromagnetic Wave and Noise Precautions To safeguard the system from electromagnetic waves and noise, adhere to the following manuallines: – – Do not locate this system near equipment that generates estreme levels of noise. Never use, in the immediate vicinity of medical equipments that due to the high electromagnetic fields generated, might be cause of malfunction. Replacing Parts – Calibration of system reagents is required after replacement of key parts such as syringes or probes. – Only use detergents (Wash Solution, Cleaning Solution etc.) of the type specified in this manual to ensure optimum system performance. – Only use BPC Biosed-approved consumables to ensure optimum system performance. Setting Analysis Parameters – To ensure optimum system performance, be sure that the set parameters such as the reagents and samples volume, are in agreement with the product inserts provided with reagents. Planned Maintenance Routines – Have a planned maintenance routine for this system and follow the manuallines contained in Chapter 6, “Maintenance”. If this system is not maintained in accordance with these instructions, then optimum system performance and safe operation cannot be guaranteed. – Have a maintenance routine for the computer software and hardware. This must include frequently backing up data that contains analysis parameters and results history. – The computer hardware should be dedicated to running the system software only. Performing Important Checks at Analysis To ensure the validity of analytical data, operators should pay particolar attention to the following: – – – – – Ensure system maintenance is performed adequately and repeat it if necessary. Check the quality of purified water. Check the calibration for abnormality. Check the quality control data. Check the individual analysis results for flags. BPC BIOSED srl - User's Manual Rev.1 En. 9 Global 240/720 – – – 1.2.2 Before you start - 1 Check the syringes and tubing for leaks. Check the samples for contaminants (dust, fibrin, etc.). Check the quantity of each sample and that no bubbles are present. Installation environment precautions It is important to be aware of installation requirements. See chapter 3 1.2.3 System labels and displays The name of the instrument, power supply voltage, serial number and other information regarding the GLOBAL are shown on a label sticked in the back. 1 .3 BPC Biosed Guarantee BPC Biosed guarantees this automated chemistry system to be free from defects in materials or workmanship under normal use for a period of one year commencing on the day of purchase. In the event that the system should be rendered defective within the guarantee period, it is repaired onsite free of charge. All activities of repair, setup, testing, under warranty and out of warranty are provided by authorized local dealer, trained and officially authorized by BPC Biosed. The BPC Biosed guarantee does not include the following: • • • Defect or damage caused by natural disasters such as fires or floods. Defect or damage caused by carelessness or abuse. Defect or damage resulting from maintenance performed by personnel not approved by the BPC Biosed Service Department. • Defect or damage caused by the use of consumables or fitting replacement parts not recommended by BPC Biosed. • Corrosion caused by exposure to a system environment other than that stated in this manual. • Deterioration of the Optical measurement system resulting from exposure to a system environment other than that stated in this manual, such as exposure to extremely strong corrosive gases like salt or sulphur. • Loss of stored data caused by inadequate or incorrect system maintenance. BPC Biosed shall not be liable for any consequential damages such as loss of profit or business that might arise from the misuse of this system. BPC BIOSED srl - User's Manual Rev.1 En. 10 Global 240/720 System Overview - 2 2 System Overview This chapter aims to provide you with a general understanding of how the system works. It also gives an introductory outline to the key processes, each of which are dealt with in detail in later. It also provides you with a hardware profile of the instrume instrument nt that enables you tto o better understand the the technical composition of the entire system. Here are the topics covered: – How the GLOBAL analyses samples – Understanding the System Hardware – Structure of the graphical user interface (GUI) – Main screen overview – Specifications – Accessories supplied with the analyzer 2 .1 How The GLOB AL Analyses Samples This system carries out automated analysis of serum, plasma, urine samples. It measures sample components and automatically generates results. This section describes the key processes: 2.1.1 Summary of the process The GLOBAL performs analysis as follows: 1. The user places the cups or primary tubes with samples on the tray. tr ay. 2. A robotic arm dispenses Reagent 1 and sample into one of the fifthy cuvettes placed on a rotating carousel BPC BIOSED srl - User's Manual Rev.1 En. 11 Global 240/720 System Overview - 2 3. After a preset time the arm adds the reagent 2 and 3 if provided provi ded to the cuvette and mixes it. 4. Once the incubation time is expired, the cuvette is positioned in front to the photometer. In this way the white light properly filtered that crosses the cuvette may be measured. 5. Between reagent and sample a chemical reaction occurs the magnitude of which is proportional to the concentration concentration of the analyte in the sample. This reaction generates a change in OD which is measured by the analyser. 6. Once the reading phase is completed, the the cuvette is emptied, washed and dried, ready to be reused. 7. To eliminate pollution between the various analytes and reagents, all parts of the instrument in touch are automatically washed and ready for a new process. 2.1.2 Computer automation The whole analysis process is controlled by a computer system linked directly to the analyzer and located beside it as an integral part of the system. The computer system used is a PC which runs a Windows graphical user interface. While this computer can drive the analysis process fully independently, the system is often connected to a network. This allows information to be received from a main computer that stores them in a database and manipulates them in an appropriate way to print the report. The methods parameters must be entered before the system can be used for the first time. These data can also be uploaded from a removable memory device. The computer system allows you to: – Edit Test Parameters. – – – – – – Monitor the analysis process closely. Measure the progress of analysis. Analyse and edit analysis results. Print analysis results. Monitor the QC data Storage and review the patients data in the archive . 2.1.3 Sample identification A test requisition involves a specific programme or set of instructions entered by users and used by the system to specify exactly what parameters to use when testing each sample. It is important, therefore, that the system correctly identifies each sample on the tray to associate it to the request of tests received. A more automated system uses the barcode for sample identification and the association with the tests that are demanded. There are three modes of recognising samples on racks: Sequential mode: The sample barcode is not required in sequential mode. The user places the sampes on the tray in strict numerical order as assigned automatically by the Patient Number counter. The system analyzes the first sample on the tray, using the information entered by the user at the stage of patient acceptance. Immediately after It passes to analyze the second sample, third sa sample mple and so on. Barcode (sample ID): the sample barcode is read on each sample tube and the ID must match with the ID entered by the user at the acceptance acceptance stage. Samples can therefore be BPC BIOSED srl - User's Manual Rev.1 En. 12 Global 240/720 System Overview - 2 positioned randomly and there can be even vacant spaces on the tray. After the recognition, the system links the tests to be run with each ID recognised. Sample data from LIS: Laboratory Information System (LIS) transmits for each patient the ID, name, specie and tests to be run. The user places the tubes on the tray randomly. The system reads the barcode on each sample tube and, for each ID recognised, joins the tests to be run. 2.1.4 Sample and reagent transfer A prefixed volume of reagent is aspirated from a specific container placed in the reagents tray and kept in the teflon tube of the sampling needle. Immediately after a prefixed volume of sample is aspirated from the sample cup or tube but a small gap of air separates the sample from the reagent to prevent the start of the chemical reaction. The sample and reagent aspirated are then injected into one of the 50 reaction cuvettes. If the test requires 2 reagents, at the time set the arm moves on the second second reagent. The prefixed volume volume is aspirated aspirated and then injected into the same same cuvette with R1+sample. Mixing is provided according to the parameters entered. The system uses information entered in the system parameters to determine the volume of reagent and sample to use. The needle is washed internally with distilled water and externally by the cleaner device, after every test. 2.1.5 Sample and reagents mixing After completing the sampling phase, immediately after the injection of the second reagent, the probe dips into the cuvette containing sample and reagents to aspirate a part of the volume and dispens again the content into the cuvette cuvette with the aim to mix the mixture . 2.1.6 Measurement by photometry When a reagent is added to a sample, the resulting chemical reaction causes the mixture to undergo an optical change. Measuring the change in optical density of this mixture allows a result to be calculated. Concentration of the analyte being measured is proportional to the optical change. Optical density is measured by passing a beam of light at a wavelenght preset through the mixture and measuring the amount of absorbance. This value is then used in the calculation of the result. 2.1.7 Washing and drying After that a sample is analysed, the cuvette used is placed below the washing and drying unit. This unit empties the cuvette cuvette of the reaction mixture then replanishes with water and rinses several time. The process ends definitely after that the cuvette is dried. For those tests that are particularly polluting, the software sets the execution of a post-wash with specific cleaning solutions. 2.1.8 Calculating results In clinical chemistry there are two basic classes of chemical reactions: – – 2.1.9 Colorimetric reactions Kinetics reactions Colorimetric reaction Colorimetric reactions are based on the development a coloration,of the intensityin of which, measurable photometrically, is directly proportional to theof concentration the analyte question. The colorimetric reactions can be further differentiate in: BPC BIOSED srl - User's Manual Rev.1 En. 13 Global 240/720 – – – System Overview - 2 End Point Simple Bichromatic Differential End Point are the majority reactions that you have in clinical chemistry. In this type of reaction, after the mixing of the sample with the reagent, expects an interval of time defined during which develops a color of stable intensity that can be measured photometrically. End Point reactions may be further differentiated in End Point Simple, Bichromatic and Differential or with subtraction of the Sample Blank. Bichromatic this type of reactions develops as a simple end-point, but the reading is carried out using two wavelengths. The primary wavelength is specific for the type of staining, while the secondary is used to eliminate any interference from other analytes or caused by the same sample. Differential are End Point reactions simple but, in addition to the traditional reading, it is carried out a reading of the diluted sample to eliminate any interference caused by its own color. 2.1.10 Determination of the secondary wavelength In reactions bichromatic the primary wavelength is appropriate for the color developed by the reaction but the secondary wavelength must be chosen in function of the specific color of the analyte that can eventually interfere with the reading. For example, if the interfering substance is green, it is necessary to perform a reading with a magenta color that has the absorption peak in the green color. 2.1.11 Importance of the reagent blank Because reagents have some intrinsic optical characteristics, the Optical Density of the reagent used must always be calculated before being used for analysis and this data stored by the system. This is achieved during the calibration process when the OD of the reagent is the first parameter to be calculated. The resulting optical density is termed Reagent Blank. The reagent blank is used by the system to compensate for any optical contribution due to the reagent on the final optical density of the reaction. It must be considered, especially for reactions End Point, the initial coloring of the reagent used, as this can affect the final result. To eliminate this drawback, from the absorbance of the reaction is deducted the absorbance of the reagent blank. The check of the reagent blank is also useful to verify the freshness of the reagent in use 2.1.12 Kinetics reactions Kinetic reactions are based on the measurement, in a determinated time, of the change in absorbance that during the reaction can increase or decrease. Are reactions in which it is measured BPC BIOSED srl - User's Manual Rev.1 En. 14 System Overview - 2 Global 240/720 the activity of an analyte, an enzyme normally. In such a case the reaction does not develop a color but it is important quantitate the activity in the time. In a given time frame, is measured the variation of absorbance to dynamically determine the speed of the reaction and therefore the concentration of the enzyme. Within certain limits, the concentration of the enzyme is directly proportional to the speed of the reaction. The kinetics reactions can be further differentiate into: – – Classic Kinetic Two-Point or Initial Rate Classic Kinetics are reactions in which is performed a number of readings in a determinated time frame in order to calculate the gradient of the curve traced by the reaction. This gradient represents the speed of the reaction and consequently the enzyme activity. Two-Point kinetics or also named Initial Rate, is a pseudo kinetics and is the only kinetic reaction whose result is the concentration of the analyte and not the activity of an enzyme. After an incubation time, is performed a reading at the beginning of the reaction and another at the end in a predetermined time interval. 2 .2 U n d e r s t a n d i n g T h e S y s t e m H a r d w a r e This section describes the hardware components of the Global which are visible externally and a few of the main internal assemblies. 2.2.1 Power-On switch Part of the analyzer is powered when the power cord is connected to the power socket. The button shown enables the supply of power to the whole unit and makes start the initialization process of the program. 2.2.2 Voltage selector Select the range of the AC voltage 115/240 50-60 in use. BPC BIOSED srl - User's Manual Rev.1 En. Pull out to access the fuses 15 Global 240/720 2.2.3 System Overview - 2 Power inlet and fuses Use the supplied cable or an equivalent one with the same characteristics. Power to the reagents refrigerator is constantly supplied if the cable is connected to the main power. Two fuses of 4 A each, housed in the power inlet, protect the power supply against overvoltages. If the instrument does not turn on disconnect the cable and pull out the fuses holder. 2.2.4 Serial port RS 232 Connects the Global to the computer through the serial cable P2P supplied. 2.2.5 Samples and reagents tray The outer ring houses 40 small cups or primary tubes for samples in addition to 10 positions for control sera and calibrators. The internal space is divided into 30 slots, each of which houses a container for single or double reagent. 2.2.6 Reagents and samples arm The instrument is equipped with one robotic arm that move two needle horizontally and vertically. The needle first aspires the reagent 1 soon after the sample and dispenses the whole content into the cuvette. If provided, after a predetermined time the needle aspires the reagent 2 and then dispenses the content into the same cuvette. The process of aspiration is achieved by means a syringe syringe of 1000ul, actuated by electric motors, used as pumps for aspirating and dispensing. The mixing is carried out through the re-aspiration and redispensing of a part of the mixture sample-reagent. The needle is washed externally by a washer device and internally by the water sucked and dispensed dispensed by the syringe syringe pump pump then discharged in the well 2.2.7 Photometer unit A halogen lamp is employed as a source of white light. The light beam, crosses 9 optical rotating rotating filters of different wavelenght and is suitably conveyed via an optical fiber through the reaction cuvette. Allows simultaneous readings in the range 340 - 700 nm. BPC BIOSED srl - User's Manual Rev.1 En. 16 Global 240/720 2.2.8 System Overview - 2 Washing and drying unit The assembly is constituted by a group of 3 elements: one double needle, one single needle and a dryer stump. The first double needle empties the reaction cuvette immediately after it has occurred the photometric measurement (needle longer). Right after fills (needle shorter) and empties the cuvettes several times with distilled water. The dryer stump pu pushes shes on the bottom of the cuvette any drops of water attached to the walls. The water collected is sucked away through a vacuum pump which is connected to. At the end of the process each cuvette is well cleaned and dried. 2.2.9 Sample and reagent syringe The Global has one syringe of 1000 ul used as pumps to aspirate the reagent and the sample. The syringe, by means an electro-valve, also sucks distilled water to wash internally the needle and the tube of teflon containing the reagent. 2.2.10 Housing of reaction cuvettes Consists of 50 plastic cuvettes with optical characteristics housed in a plastic ring. The rotational movement of the cuvettes is obtained by a step motor. A resistive element, electronically controlled, stabilizes the temperature of the cuvettes at 37°C. 2.2.11 Refrigeration unit The tray chilled that houses the chemical reagents, keep the temperature approximately 10 degrees below the room temperature even when the system is shut down (it is sufficient to leave the Global connected to the Main Power). The tray has 30 slots which can house single and double reagent containers. BPC BIOSED srl - User's Manual Rev.1 En. 17 Global 240/720 System Overview - 2 2.2.12 External fluids connectors The figgure shows the panel where connect the containers of distilled water and waste. 3 inlets for distilled water, 3 outlets for the waste liquids of which that for biological waste may be collected separately. 3 sockets multipole to connect the level sensors of each container. 2.2.13 Barcode reader (optional) The analyzer can be equipped on request with the barcode reader for samples and reagents. Automatically identifies the reagents within the tray and the tubes with samples. It is particularly useful realize a complete automated syst system em if the analyzer is connected to the LIS through a serial line or LAN. 2.2.14 ISE unit (Global 720) The ISE module, housed inside the instrument, is easily accessible by removing one of the top panels. It contains 4 electrodes plus the reference electrode. Likewise to the refrigeration system is always powered as long as the power cord is plugged in. The electronics inside the module controls the operation of the pumps group and communicates the results of tests to the Interface board of the Global 720. 2.2.15 ISE pumps group The assembly consists of three peristaltic pumps, two of which are for the standard A and B. The third pump positions the liquid in front of the electrodes to achieve the electric measurement to then convey them towards the internal discharge of the reagent package. The pumps are attached to the package by a connecting cable electro-hydrauic and to the ISE module through 3 silicon tubes. BPC BIOSED srl - User's Manual Rev.1 En. 18 System Overview - 2 Global 240/720 2 . 3 G r a p h i c a l U s e r I n t e r fa fa c e G U I ) The management software of the GLOBAL allows a so easy and intuitive use of the available functions such as to reduce the learning time. Each screen offers several options that can be selected directly with the mouse left click. Overview of the work areas. The software interface of the Global 240 is structured as the union of three interlaced programs which operate independently: the interface for the instrument general control (marked with blue background); the one concerning the samples (marked with yellow background) and lastly one regarding the methods (marked with a green background). The three programs, interacting with each other, take the entire management simple, fast and flexible to the point that while performing the tests, you can accept new patients, or print new reports. INSTRUMENT GENERAL SAMPLES METHODS CONTROL 2 .4 M a i n S c r e e n O v e r v i e w Based on the feedback from the end users, the software of the Global has been developed in such a manner that appears to be simple and intuitive. This feature minimizes the learning time and allows to use the analyzer after a very short time. Every screen offers different options which can be selected directly via left-click of the mouse or a touch of your finger. Not casually, the GUI has been conceived expressly to favor the use of a touch screen. Hereinafter you can see the image of the main screen of the program, with the tray of samples and reagents. Soon after follows a description of the buttons and of details most relevant. BPC BIOSED srl - User's Manual Rev.1 En. 19 System Overview - 2 Global 240/720 TITLE BAR, defines the ALERT BAR, displays current screen in operating conditions Same time and addition to the version that require the date set on the of the software intervention of the user Floating Side Bar 40 positions for sample cups or primary tubes Command BAR 10 positions reserved for control sera and calibrators In the main screen are easily identifiable the following elements: – Tray for the reagents and samples. It is composed by a removable external ring that houses 40 samples. Internally there is a removable metal basket with 30 slots refrigerated which preserve the reagents. – – Color legend that distinguishes each element on the t he tray. Reagents on the tray, labeled labeled with their own code, in blue, yellow and red to distinguish R1, R2 and any reagent with insufficient volume. Other colors identify the diluent and the cleaning solution for ISE. – Numbering of the slots from 1 to 60. You can load 30 containers of type C in the positions 130 or 30 double containers of type A-B in positions 1-60. – The position 30 is reserved to the cleaning of the ISE system (if present) while the position 60 to the diluent used for pre and post sample dilution. – The samples tray houses 40 cups or primary tubes. The positions 41-48 are reserved to the control sera C3-C10 and calibrators. The positions 49-50 are reserved respectively to the two control sera C1-C2 run in calibration. – The bar at the top of the screen, besides the name of the analyzer displays the manufacturer and the software release in use. BPC BIOSED srl - User's Manual Rev.1 En. 20 System Overview - 2 Global 240/720 – Just below, a second bar displays the current time and date (computer data) and the "i" button that if clicked, displays information about the softwares released. Furthermore, in the left part of the bar are shown messages that warn the operator about a supervening condition that prevents the proper functioning of the analyzer and therefore requires his intervention. – – At the bottom, is visible vi sible the command bar with the buttons more frequently used. At the far right is visible a floating side bar that if clicked shows a few buttons used less frequently. – Placing the pointer over the circled label of the reagent and left clicking, opens a window that allows the user to enter the the internal volume – Placing the pointer over a sample, it opens a pop-up that displays the ID, patient's name and the tests to be run Position 60 Position 31 2.4.1 Warning messages As already mentioned, during the process of analysis but also when the instrument is in standby, the Global can warn the user by warning messages in case one or more functionalities of the instrument do not allow its regular usage. Some messages appear in the Alert Bar while others are displayed in middle of the screen. The table below shows all the warning messages which can be displayed: Alert Cause Insufficient distilled water the level sensor indicates that the level of distilled water Waste Full! Please Empty is insufficient the level sensor indicates that the waste container is full BPC BIOSED srl - User's Manual Rev.1 En. 21 System Overview - 2 Global 240/720 Insufficient sample Position xx insufficient sample into the position indicated Insufficient reagent R1/R2 xx insufficient reagent into the position indicated Insufficient Diluent D x diluent is insufficient Some volumes are insufficient automatic check of reagents detected one or more volumes insufficient Cover is open! Must be closed c losed the protective cover is open, during operation must be Alert! Cuvette lamp Failure! closed after the photometric check with water all filters measure less than 1 volt Warning! Lamp Values out of Range after the photometric check with water one or more filters show values out the range 4.5-9.5 V Reagent Pack Expired reagents pack of ISE expired (next to the result appears the flag RPE) 2 .5 S pec i fi c ati ons Designed as bench analyzer, the Gloabal needs an external computer connected to a LCD disply and to a Printer. High productivity, reliability, easily of use make this analyzer ideal for medium-large workload. Suitable to be used for special tests or as backup unit. Unlimited STAT function, Quality Control, View of the reaction curves in real time and possibility of "remote control" via Internet for specialistic assistance, are some of the qualities that characterize this instrument. The analyzer has been conceived to perform chemical tests in different applicative fields as tests of clinical chemistry, turbidimetry, electrolytes, specific proteins, therapeutic drugs, drugs of abuse, wine tests. Operating characteristics characteristics Throughput: 240 photometric photometric tests/h (480 tests/h with with ISE) Ise Module: Na+, K+, Cl-, Li+ (optional) Diluter, equipped with 1cc Hamilton syringes Needle with capacitive level sensor 96 methods on board Graphic representation of the reaction curves Remote control via Internet for specialistic support Reagents Tray Tray removable Up to 60 positions for mono-reagent; up to 30 positions for bi-reagent Reagents bottle of 17, 40 and 60 mL Tray refrigerated by Peltier system 24 hours a day even with the analyzer off (about 10°C lower than the room temperature) Recognition of reagents through bar code reader (optional) 10 positions for calibrators and control sera Samples Tray Tray removable sample position: 40 small sample cups or Primary tubes (12/13x100) Recognition of samples through bar code reader (optional) STAT function for managing emergencies BPC BIOSED srl - User's Manual Rev.1 En. 22 Global 240/720 System Overview - 2 Automatic sample pre-dilution and post-dilution, from 1:2 to 1:100 Separate biological outlet Reaction Cuvettes 50 x 6mm optical cuvettes Temperature controlled at 37 ° C + / - 0.1 ° C Volumes of reaction between 220 and 350 microliters Automatic washing and drying of cuvettes Photometer Tungsten halogen lamp as light source (2000 hours span life) Optical range from 0.000 to 3.000 ABS Multi-wavelenght unit with interference filters Simultaneous reading at 10 wave lengths (from 340 to 700 nm) Mono or bi-chromatic reading Reagents Liquid reagents ready to use, equipped with bar codes for positive recognition High stability Pack differentiated for mono and bi-reagent Large number of reagents for regular and special chemistry including turbidimetry, drugs, substances of abuse and enology Technical Specifications Power supply: 110-240 AC Volt Frequency 50/60 Hz, consumption <400 watt Distilled water consumption: less than 3 liters / hour Instrument dimensions: 79W x 58D x 54H cm Instrument weight: 60 kg External devices: computer with serial port and OS Windows, LCD monitor with size 4\3 and minimum resolution of 1280x1024, printer for paper size A4 BPC BIOSED srl - User's Manual Rev.1 En. 23 Global 240/720 System Overview - 2 2 .6 A c c e s s o r i e s S u p p l i e d W i t h T h e A n a l y z e r Containers of reagents type A, B and C Sample caps: Pierced caps: used to reduce the evaporation of the reagent inside the refrigerated tray and allow maximum board stability Containers of water and waste Sensor of level for water, waste and washing solution containers Power cable (european standard) Serial cable RS232-C (P2P connections) USB cable (optional) Reagent pack connection (Global 720 only) BPC BIOSED srl - User's Manual Rev.1 En. 24 Installation- 3 Global 240/720 3 Installation Installation of the GLOBAL should be performed by BPC Biosed-approved engineers only. The information provided in this guide are intended for staff trained and qualified to perform this operation. If you wish to change any aspect of the installation, please contact your local BPC Biosed Representative or seek the help of a BPC Biosed-approved installation engineer. 3 .1 H o w T o I n s t a l l T h e A n a l y z e r Installation of the instrument is a delicate operation that requires compliance with a few simple rules that can affect the proper operation and limit the life of the analyzer over time. 3.1.1 Unpacking The image below shows the packing of the Global. Before unpacking the instrument check the state of the crate and if damaged notify the carrier of any physical damage revealed. 1. Remove all the clips that secure the top and bottom of the wooden crate 2. Remove the top cover and Lift the protective instrument material of containing the the accessories BPC BIOSED srl - User's Manual Rev.1 En. 25 Global 240/720 Installation- 3 3. carefully lift the outer case. 4. lift the instrument and place it on the bench. 5. The analyzer is ready to be installed. Reassemble the packing crate and keep it for future use. 6. Check the presence of all the accessories listed in the packing list. 3.1.2 Selecting a suitable location To ensure proper operation, place the Global in a place that meets the following requirements: The bench must be vibration free and able to support the weight of the instrument, computer, LCD display and printer (Approximately 100 Kg). The space requirements will vary depending on the configuration of the Global and components. In fact the graphical interface of the Global has been conceived for using a LCD display equipped with touch screen. The useful space required for the positioning on a desk of the instrument and other devices is shown in the drawing below: It is recommended to leave the space suggested at the sides and below the unit to allow proper ventilation The environment must be as free as possible from dust, mechanical vibrations, loud noises and electrical interference. Avoid proximity to brush-type motors, flickering fluorescent lights and electrical contacts that regularly open and close. Avoid placing the instrument in direct sunlight or in front of a source of heat or drafts. BPC BIOSED srl - User's Manual Rev.1 En. 26 Global 240/720 3.1.3 Installation- 3 Installation environment For indoors use only Operating temperature 18 °C to 32 °C or (64.4 °F to 89.6 °F) Maximum relative humidity at 70% for temperature up to 32 °C (87.8 °F) 3.1.4 Electrical requirements For proper operation and to obtain reliable results are essential the following electrical requirements: A properly grounded outlet supplying 200-240 V AC or 100-120 V AC, 50 to 60 Hz. Maximum fluctuation of voltage not exceeding 6% of the nominal value The power outlet must be free of interfering electrical noise (less than 0.5V neutral to ground) It is recommended to connect the Global to a dedicated line. In areas where the power network suffers frequent power outages, it is recommended the use of an opportunely sized UPS equipment (1 Kw is recommended) 3 .2 P r e p a r a t i o n O f T h e I n s t r u m e n t As a precaution, to avoid damage during transport, some moving parts of the instrument are locked with screws and carefully shaped material that hinder the mobility. Follow the instructions hereinafter to restore the operating conditions of the instrument – Remove the screws that block the vertical movement of the two arms. – Open slightly the two parts of the cover, pay attention to not force the screw fixing the two parts then facilitate the entry of the cable and tube. BPC BIOSED srl - User's Manual Rev.1 En. 27 Global 240/720 – Installation- 3 Position the cable and the tube in the proper hole then lower the cover up to meet the holes of the screws. – Put in the 4 screws supplied and tighten by an Allen wrench of 2 mm. 3.2.1 – Fluid connections Connect tubes and level sensor (the shortest) of waste to the proper outlets. In case of separate container for biological liquids, connect tube and level sensor to the outlet dedicated (yellow zone). – Connect tubes and level sensor (the longest) of water to the proper inlets. Fill the container with distilled water. 3.2.2 Connection to the electrical outlet Connect the serial port of the Global to the COM port of the computer by the serial cable supplied (The USB cable is provided, if the instrument is equipped with serial-USB adapter) BPC BIOSED srl - User's Manual Rev.1 En. 28 Global 240/720 Installation- 3 To avoid the risk of shock, do not remove the shell of the instrument – The analyzer is shipped with the voltage selector set to 200-240V. Remind to change the setting if the main voltage of your country is 110 AC V. – If the power cable supplied does not conform to local standards, replace it with one having the same characteristics. – if the instrument is equipped with USB port, it is supplied a USB cable for computer connection As soon as the power cord is connected to the power inlet, it is audible the noise produced by the fan of the cooling system regardless from the status of the power switch 3.2.3 Connecting the computer This procedure, assumes that Windows is already installed on the computer and all updates were made. The same applies for the printer and for the touch screen if provided. It is strongly recommended to disable the options to save energy that disable the hard drive after a period of keyboard inactivity. It is also recommended to disable the screen saver. Any computer of the latest generation can be used to control the Global. It is indispensable the presence of at least a serial port to connect the instrument to the computer and a CD reader to install the instrument’s software. The computer must be equipped with two serial ports in case the instrument is connected to a LIS and 3 serial ports if it is also used an external barcode reader for uploading data of the control sera and multi calibrators. All Windows OS, starting from Windows XP, are compatible with the sofware of the analyzer. Connect the serial port of the Global to the COM port of the computer using the serial cable P2P supplied. – – Connect the LCD display, keyboard, mouse and printer to the computer. Connect all the equipments to the power outlet. if you want to use an external barcode reader for loading data of o f the control sera and multi-calibrator, the reader must be connected to the serial COM port 3 of the computer for it to be identified by the Global software 3.2.4 Software installation – – Turn on the external computer and wait for the loading of Windows. Insert the CD with the software of the Global into the CD reader. The CD is self-installing therefore follow the instructions appearing on the monitor otherwise make double click on “setup.exe” BPC BIOSED srl - User's Manual Rev.1 En. 29 Global 240/720 – Installation- 3 For your convenience, create a shortcut on the desktop with the executable file of the program. 3 .3 S w i t c h i n g o n t h e G l o b a l – – Double click on the Global icon then turn on the power switch and confirm with Enter – you can select the automatic COM port (Search) or enter directly which is the computer the screen displays the following picture port connected to the Global (manual selection) – – receipt of mechanical settings stored inside the analyzer reset of all robotic assemblies carried out successfully If during initialization, one or more settings are missing, a red screen listing the settings required The red screen is a warning for the user who is going to use the analyzer. Make reference to the Maintenance chapter to perform the settings required. The Global is shipped with all settings made and stored in a permanent memory of the instrument. – Click the button Continue to set the main screen. BPC BIOSED srl - User's Manual Rev.1 En. 30 Installation- 3 Global 240/720 to complete the installation you must execute the following steps: restore the file with the principal assays stored in the archive. To do this step, perform the procedure described in the next paragraph. load the reagent bottles in the tray, taking care to place them into the correct slot. execute a washing cycle of the cuvettes with the solutions IPO+Extra cleaning. For this step, carry out the procedure How to wash the cuvettes descrbed in the Maintenance chapter. 3 .4 How restore the m ethods from the archive The file Met4500.Arc contains the data of the principal clinical chemistry methods. The restore operation places these methods in the grid making them accessible and usable. How restore the file "met600.arc click Methods/Methods/Archive – – in the left side double click on the – folder "Methods" double click on the folder "met600" – in the field File Name highlight "met600.arc" – click the button "Restore", then confirm – Exit to return to the grid of methods below shown BPC BIOSED srl - User's Manual Rev.1 En. 31 Global 240/720 Installation- 3 After restoring the file "met600.arc" the reagents tray appears as in the figure: BPC BIOSED srl - User's Manual Rev.1 En. 32 Global 240/720 Configuring Tests- 4 4 Configuring Tests This chapter describes all the operations hereinafter listed, required before starting the routine: – positioning of tests in the grid – – – – – – – – adding a new test entering specific test parameters programming calculated test edit or delete a method Loading of reagents setting normal ranges creating a new profile calibration process 4 .1 P os i ti oni ng of tes ts i n the gri d The location of the tests in the grid is not accidental as it determines the order of execution of the tests during the analysis process. Some of the positions assigned are explained by reasons of convenience. In fact, some chemical reagents, despite the action of the automatic washing, significantly affect the chemical reaction of some tests so much that the end result is altered. To limit such a drawback, the reagent pollutant is positioned in the grid after the tests that could be affected. First test processed . If you need to to swap the position of two tests, select the tests and click Arrange Test BPC BIOSED srl - User's Manual Rev.1 En. 33 Global 240/720 Configuring Tests- 4 4 .2 A d d i n g a n e w T e s t To enter a new test, perform the following steps: Main screen> Methods>Methods>New Methods>Methods>New Test The window that opens allows the entry of a maximum of three characters that identify the new test. After confirmation it is displayed the first of the four pages where set the parameters of the new test. 4.2.1 Entering Specific Test Parameters The parameters that characterize each method are collected into 4 pages or screens. Moving between pages is achieved with the arrow buttons, located at the bottom on the command bar. Each page includes a number of parameters some of which are mandatory and others optional. Among the data mandatory, we find the following parameters: number of the tray containing the reagents – – – position of reagents on the tray – – number of washings of the needle after the aspiration of sample and reagent type of chemical reaction volume of sample and reagents BPC BIOSED srl - User's Manual Rev.1 En. 34 Configuring Tests- 4 Global 240/720 – – – Timing of the reaction wavelength used for the photometric reading concentration of the calibrator or factor Once entered the parameters, Exit key automatically saves the data. If one of the mandatory parameters is not introduced, the software alerts the user with a message. The new method is placed in the first free space in the grid. Among optional parameters, some of them should always be introduced, because provide important information on the reliability of the results. While some parameters are always present in each method, there are others whose presence depends by the number of reagents, by the type of reaction selected, by the type of calibration adopted. The following table summarizes the parameters visible in the 4 pages: Parameter 1 e g a P Meaning Code Maximum 3 character that determine the test Method Full name of the test description Tray tray containing the reagents Units Unit of measurement Linearity limit range in which the method is linear Calculated Method It indicates whether a test is i s processed by the machine or comes from a mathematical calculation Min.Reag.Blank Minimum acceptable optical density of the reagent Note Max.Reag.Blank Maximum acceptable optical density of the reagent 2 e g a P Decimal positions Reagent code Code of the reagent pack also present in the barcode Reagent lot Lot of the reagent pack Post Dilutions Ratio of the post-dilution STD Lot Lot of Standard or multicalibrator Description Chemical method Sample Vol. Acceptable range of sample volume (2-100) Water Vol. Volume of water added to the mixture sample-reagent Sample Wash (1-3) N°.of Reag. Multipoint Number of decimal figures Number of sampling needle washing between one test and the next Number of reagents used It indicates if the calibration curve is a straight line passing through the center of the axes (1 point) or is a curve constructed with maximum 6 points BPC BIOSED srl - User's Manual Rev.1 En. 35 Configuring Tests- 4 Global 240/720 Std number (1-8) Reag. 1 Vol. Positioning of the standard / MultiCal on the sample tray (S1S8) Volume of R1 in µl. The total volume including sample, reagents and water must not exceed 350 µl (2-350) Vial R1 Type of reagent container Reag. 1 Pos. Reagent position on the tray STD Conc. Known concentration of Std / MultiCal S3-S8 known concentration of multi-standard Reaction Mode Mode of chemical reaction Reading time Time interval in which the photometric reading will be performed. It begins at the end of the incubation time Only for Kinetic and Initial Rate mode Incubation time Time interval in which the chemical reaction takes place. not provided for ISE mode Time first read 3 e g a P Only for Differential mode Filter 1 Wavelength used for the photometric measurement Filter 2 Second wavelength used for the measurement R2 Add time Time of addition of R2 that occurs during the incubation time provided only with the use of R2 or for Differential mode R3 Add time Time of addition of R3 that occurs during the incubation time provided only with the use of R3 Substrate It is an index of the sample hyperactivity obtained by measuring the OD variation in 1 minute. It monitors the speed of the reaction and alerts the operator of the ne need ed to Provided for Kinetic and Initial Rate mode It indicates whether the reaction curve is ascending or descending not provided for ISE mode OD of the reagent measured in calibration. If activated, the calculation of the result is performed by subtracting the reagent blank not provided for Kinetic and ISE mode Factor (1cm) Theoretical factor provided by the reagent manufacturer or derived from the calibration process not provided for ISE mode Electrode Code Identifies the position of each electrode within the ISE module. Only for ISE mode Model (1-6) 6 mathematical models each of which changes the calibration curve. Choose the one that provides the answer more Only for multipoint calibration re ress on onsi sive ve to to the the ex ecta ectati tion on Percentage value that determines the maximum deviation between the theoretical value of each point and the value Deplection Reaction Direction R.Blank Corr. 4 e g a P if equal to 0, the calculation is against factor Only if Multipoint is 1 Max Variance (1-100) calculated BPC BIOSED srl - User's Manual Rev.1 En. 36 Configuring Tests- 4 Global 240/720 Predilution ratio Pre-dilution of samples and controls. It also acts in the Samples/control calibration phase 4.2.2 Instrument factor Multiplication factor that increases or decreases the result of samples or controls analyzed. It has no effect on the calibration Instrument Values higher or lower than zero are added or subtracted to the result of samples and controls. It has no effect on the intercept Diluent calibration Diluent used for predilution of samples, controls and Type Type of the diluent container Position Position of the diluent on the tray Sample Blank If enabled, it measures the ID of the diluted sample and then subtract it from calculation of the result Vol.Dil. SB Volume of the diluent used for the sample blank Diluent SB Type of diluent used for the sample blank Type Type of the diluent SB container Position Position of the diluent SB on the tray the parameter can be enabled / disabled in the "Info" screen by a password not provided for ISE mode Programming calculated tests It is a method that is not processed regularly but the result of which is the product of a mathematical calculation in which appear the results provided by other tests. For setting follow the same steps used to create a new test after which, type type 1 in the box "Calculated Method". Clicking on the arrow in the command bar, the following screen appears: Entry the number BPC BIOSED srl - User's Manual Rev.1 En. 37 Global 240/720 Configuring Tests- 4 The drop down menu "Type", allows you to select 5 different mathematical expressions where the terms are represented by the tests selected in the grid or by numbers entered by the user. To enter the terms of the expression click inside the rectangle in which you want to set the term then select the test or enter the number in the appropriate rectangle rectangle and press Enter. 4.2.3 Edit or delete a method One method can be modified or deleted on condition that there are no tests loaded into permanent memory. This condition is indicated by the t he number shown by the automatic counter "Patient" visible in the patient acceptance mask. You can not change the characters that identify the method. In this case, the method should be first deleted and then created the ne new w one with the name changed. If you change one sensible data of a method that is already calibrated, the calibration is automatically canceled after the alert message. message. 4.2.4 Loading of reagents The loading of reagents on board is simple but requires care to place the container in the correct slot. Remember that the tray accommodates either bottles of mono-reagent and bottles of bireagent. The graphic interface is a useful tool for the user when carrying out this operation. In fact, the correct graphical representation, in addition to showing where to place the reagent, indicates that the parameters set on the reagent type and container are correct. 4.2.5 Setting normal ranges There are two ways to introduce the normal ranges of the various methods: 1. by clicking the key Refence Range located on the command bar of the method parameters screen 2. by clicking the key Refence Range in the screen Methods Management The substantial difference between the two alternatives is that the second way allows to differentiate the range according to the gender. For the greater completeness here is described the second way. Main screen>Methods>Methods>Reference Range BPC BIOSED srl - User's Manual Rev.1 En. 38 Configuring Tests- 4 Global 240/720 On the screen below, first of all you have to click on the test in the grid after enter the gender and the minimum and maximum reference value. Use the arrows in the command bar if you want to change gender and range. Repeat the process by selecting a test at a time. By clicking "Print Reference Values" you get a printout of the reference ranges based on gender or the selected tests. Exit key automatically saves the setting. 4.2.6 Creating a new profile. Main screen>Methods>Panels screen>Methods>Panels Enter the profile name where indicated in the figure after which select the tests required for that type of pathology. The arrows allow you to move between different profiles. Exit key automatically saves the new profile. Enter the type of profile 4 . 3 C a l i b r a ti ti o n P r o c e s s In a colorimetric method, the concentration of an analyte contained in a substance is determined by comparing the absorption of light with that of a substance named calibrator, containing a known quantity of the same analyte. In other words, the calibration of a method allows to find a correlation factor between a sample substance of known value and an unknown substance that you want to quantify. According the kinetics of the reaction, the correlation can be: – Against one Point. Using a single standard you can establish a correlation factor between Optical Density and concentration of analyte. The correlation must be necessarily direct. This calibration allows you to take into account the decay of the reagents, but does not allow to avoid any instrumental errors. – Against Curve using multiple standards. With the OD readings measured you can draw a correlation curve between optical density and concentration of the analyte.. The correlation BPC BIOSED srl - User's Manual Rev.1 En. 39 Global 240/720 Configuring Tests- 4 may be linear or nonlinear. This type of calibration allows to take into account either the instrumental error and the error due to a possible deterioration of reagent. – Against Factor. It uses a correlation previously defined experimentally by the reagent manufacturer. In this case calibration is only fictitious. Calibration process is an essential pre-requisite that provides the habilitation to run the test. It is assumed that the parameters of the methods are in line with that indicated by the manufacturer of the reagents. The various steps of the calibration process hereinafter explained are the following: Reconstitution of multi calibrator and Controls Entry of concentration values of the multi-calibrator Entry of minimum and maximum values of control sera Selection of the tests to be calibrated Loading of calibrators and control sera on the samples tray Check of the reagents volume Starting the calibration process Validation of calibration data 4.3.1 Reconstitution of multi calibrator and control sera Prepare the calibrator and control sera taking care to dissolve the powders with the exact volume of distilled water. Preparation inaccurate clearly affects the calibrations and therefore the accuracy of results Once reconstituted, it is convenient to divide the multicalibratore and control sera in portions of 500 µl each. If properly stored at the recommended temperature, they may be used in the space of one month. After defrosting should not be refrozen. 4.3.2 Entry of concentration values of the multi-calibrator Main screen>Methods>View/Modify STD BPC BIOSED srl - User's Manual Rev.1 En. 40 Global 240/720 Configuring Tests- 4 in the right side are listed all the tests shown in the grid using only one STD or calibrator concentrations can be entered manually or by using a barcode reader connected to the COM 3 of the computer. The reader reads the QR code that is in the product insert Manual Loading select the test then enter the concentration and the lot of the calibrator. The loaded data are automatically stored magnifying glass shows the position of standard/calibrator on the tray. This data is set in the method's parameters Exit key automatically saves the new data. Automatic Loading – click "BarCode" to access the below screen in the left side appear the concentrations of the calibrators currently in use. On the right will appear the data loaded with barcode reader click "Read QR code" then point the light beam of the reader against the QR code. New data uploaded overwrite those in use 4.3.3 Entry of minimum and maximum values of control sera Main screen> Methods>View/Modify Controls BPC BIOSED srl - User's Manual Rev.1 En. 41 Global 240/720 Configuring Tests- 4 This mask allows the loading of the control sera ranges used by the analyzer. Because you can use 10 different controls, it is essential to associate each test to one or more control sera. in the right side are listed all the tests present in the grid of methods, in the left side are listed 10 controls that can be associated with multiple tests. Also for the control sera, the entry of data can be realized manually or through the bar code reading connected to COM 3 of the computer. This symbol means that the selected test is associated with the selected control serum – select the test then enter minimum and maximum acceptable values of the control serum. Also, enter the name, lot and expiration date. Exit key automatically saves the new data. The procedure for the automatic loading is similar to that used for standard and calibrators. Also in this case the "BarCode" button has the same function as mentioned in the previous paragraph. It makes access to the screen that allows you to upload the data of control sera by reading the QR code present in the product insert. 4.3.4 Selection of the tests to be calibrated To set the tests that you need to calibrate carry out the following steps: Main screen> Methods>Calibration – select the tests to be calibrated in the grid below then cclick lick "Calibrate Selected Tests" BPC BIOSED srl - User's Manual Rev.1 En. 42 Configuring Tests- 4 Global 240/720 The following picture shows the tests selected for calibration with the positions where the calibrators have to be placed on the tray. Also, it is displayed the concentration of each calibrator in addition to the factor of the previous calibration or that one provided by the manufacturer. Concentration of standard or calibrators in Factor of old Control sera position 48 calibrations or entered by run after calibration the user Multipoint calibration with 5 calibrators in Allows modification position 41-45. Position 46 (N) is not used of the factor for the Allows the methods processed change of the against factor concentration BPC BIOSED srl - User's Manual Rev.1 En. 43 Global 240/720 Configuring Tests- 4 Observe the graphical representation of the sample tray after the previous setting: Multipoint calibration with 5 calibrators in position 41-45. Multicalibrator in position 48 Control sera C1-C2 4.3.5 Loading of calibrators and control sera on the samples tray The previous graphic shows the position where you have to place the cups with calibrators and control sera. Whereas that the dead volume of the cup is around 150 ul, it is advisable put a suitable amount of calibrator or control serum Main screen> Start>Select Test>Test to calibrate>Continue A summary with the calibration data set and the work to be run is shown BPC BIOSED srl - User's Manual Rev.1 En. 44 Configuring Tests- 4 Global 240/720 Tests to be calibrated Position, type of bottle and factor currently in use volume of R2 C=Calibration Position, type of bottle and volume of R1 4.3.6 Number of teststo be run for each method: 1 for reagent blank 1 for each calibrator 1 for C1 1 for C2 Check of the reagents volume After the replenishing, you have to update the volume. This operation can occur automatically by the automatic check or by entering manually the volumes. If the automatic control is enabled, from the above screen click "CK Volume" otherwise enter the volumes manually. In the first case the sampling arm moves on the reagent bottles listed in the screen and each time lowers the needle until it detects the presence of the reagent. The volume displayed is immediately updated. The Global checks the volume of reagents which will be used during the calibration process. The graphics updates the volumes on the basis of the new check and if one or more volumes are insufficient, the following message is displayed BPC BIOSED srl - User's Manual Rev.1 En. 45 Configuring Tests- 4 Global 240/720 If ceck and updating of the volume is made manually, with the mause select the test as shown in the previous picture, then click "Enter Volume" Vo lume" and type the new volume. it is not advisable refill the bottles already used with fresh reagent. In fact, the residual reagent might be contaminated and could deteriorate the fresh reagent 4.3.7 Starting the calibration process To kick start the calibration process, press the "Only Calibration" button, after the user confirms that the instrument is ready to start, the following screen is displayed. Test in progress Time required to complete the calibration zeroing cuvette in progress Beep that alerts the user to the end of the process or in the presence of an anomaly that prevents normal operation The screen identifies the beginning of the calibration process. During the process, for each test the software displays the optical density read during the analysis process. When the screen fills up, the data are scrolled down and are no longer visible. To review the calibration data, You need access the screen "Select Calibration". 4.3.8 Validation of calibration data Main screen>Methods>C sc reen>Methods>Calibration alibration In the grid, appear all methods available in the analyzer. The + mark means that the method is calibrated. The reddish color is to mean that one or both results of the control sera processed during the calibration were out of the range. BPC BIOSED srl - User's Manual Rev.1 En. 46 Configuring Tests- 4 Global 240/720 Select the test of which you want to verify the calibration data, then t hen click "View / Modify". The screen below shows the following data: – – – – – OD of the reagent blank OD of standard or calibrator OD of control sera Factor calculated results of control sera OPtical density measured Results in (blue) and out (red) the range Control range In the case of result always underestimated or overestimated, the user has the possibility to make a correction. By changing the intercept or factor, also changes the results of the control sera up to get the best compromise. Clicking on "Details", you enter the screen shown below, where you can observe the reaction curves of the reagent blank, calibrator and control sera. Also, are visible the readings taken every 30 seconds, with all the interference filters. Calibration can be considered valid if for equal reagent, the factor calculated does not differ too much from the previous one and the control sera are within the range indicated in the product insert BPC BIOSED srl - User's Manual Rev.1 En. 47 Global 240/720 Configuring Tests- 4 Terminated the calibration process, the figure below is an example of how the grid of calibration is represented: All tests, for which the calibration process has been successful, are represented with the mark + All tests that during the calibration process have provided results of controls out of range are represented with the mark + but colored in red all the tests with the requirements mentioned above are ready to be processed All tests without mark + even if selected in the acceptance screen, will not be processed BPC BIOSED srl - User's Manual Rev.1 En. 48 Global 240/720 4.3.9 Configuring Tests- 4 Chemical reactions in clinical chemistry Here are some information on the chemical reactions occurring during opera operation tion of the analyzer. In a colorimetric method the concentration of a substance is determinated by reading the relative absorption of light (usually visible) respect to a known concentration of that substance. Calibrate a methods means to define the correlation factor between the optical density of the solution and concentration of the analyte present in it. END POINT The curve shows the trend over time of a colorimetric reaction. The maximum coloring is reached in a predetermined time within which the optical density increases in proportion to staining. Only one lecture at the end of INCUBATION TIME. R1 and the sample are added in the same cycle at time zero; R2 and R3 may be added between the 64th and the 256th second, also concurrently, but only during the incubation time BPC BIOSED srl - User's Manual Rev.1 En. 49 Global 240/720 Configuring Tests- 4 DIFFERENTIAL Two lectures. The firtst one is done on a volume of reagent (R1 + S ), the second one in done on the same volume plus R2. Subtract the Sample Blank when the coloration of the latter may influence the reading. KINETIC - INITIAL RATE Initial Rate: two readings, one at the end of the INCUBATION TIME, the other at the end of the READING TIME. Kinetic: one reading every 16 seconds during the READING TIME. BPC BIOSED srl - User's Manual Rev.1 En. 50 Configuring Tests- 4 Global 240/720 4 .4 Q u a l i t y C o n t r o l There are 10 controls made available by the software. While C1 and C2 can only be processed during calibration, all the others can be selected in the acceptance phase in or order der to keep under control the correct operation of the instrument. Every time a control is processed, the results is stored and remain available for one year. If the same control is processed repeatedly during the same day, each time the result is overwritten. The archived data are presented in both tabular form and graphically (Levey-Jennings Control Chart). The graphic shows the trend of points than the average and the two standard deviations. It also provides the outcome of the comparison of the numeric sequence with the Westgard rules. A similar control can be performed selecting selecting the optical densities of the re reagent agent blank and the factors calculated in calibration. To access the quality control screen follow these steps: Main screen> Methods> Q.C.>select a test>Controls Unless otherwise selected, they are shown all stored results in the last 12 months. m onths. The command bar and the "More" button, allow you to select all 10 available controls. Westgard 12S rule violation The acceptance phase concerns the acquisition of identification data of each individual patient. Data entry is facilitated by the mask made available by the software. Main screen> Patients>Patient Entry BPC BIOSED srl - User's Manual Rev.1 En. 51 Configuring Tests- 4 Global 240/720 The meaning of fields and buttons visible in the mask are summarized in the following table: Field/Button Explanation Increases automatically the count for each patient accepted. 200 is the maximum number of patients which can be entered each time ID Patient identity, this data is mandatory if you are working with the barcode for samples. In such a case in the ID field you have to enter the same code sticked on the sample tube label Dil 1 Samples already prediluted. The software takes into account the dilution factor entered and provides automatically the correct results Patient Name This field is not mandatory Gender it is a mandatory field, may be disactivated in the Mechanical Setup screen (see chapter 5.4) Type The patient may be accepted as standard sample or as STAT sample (sample with higher urgency). It can be a control serum, positioned on the tray after a certain number of patients, in order to keep under constant control the performance of the instrument. The Offline option reserves a position on the tray for a sample that will be available later Birth, Disease These fields are not mandatory, if not necessary may be disabled (refer to par. 5.5.2) Panels Groups of tests selected according to the pathology Tests grid all tests available on board BPC BIOSED srl - User's Manual Rev.1 En. 52 Configuring Tests- 4 Global 240/720 Previous Every time is clicked the counter goes back one step Next Every time is clicked the counter advances one step Command Bar Go to Patient Allows the visualization of data from a selected patient Copy Until Allows the entry of multiple patients in need of the same tests. In that case you can not define the personal data of each patient Pick Test Allows you to select a patient Delete Patients Allows deletion or archiving of all patients accepted Data Transfer Allows reception of patients or the transmission of results from / to a LIS Import Allows importing a CSV file with patients data to be entered BPC BIOSED srl - User's Manual Rev.1 En. 53 Performing Analysis- 5 Global 240/720 5 Performing Analysis 5 .1 H o w T o A c c e p t N e w P a t i e n t s The acceptance mask is composed of text fields and buttons. Some text fields are mandatory while others are optional. The software, through the automatic counter, assigns to each patient a progressive number up to 200 that is the maximum number of patients simultaneously acceptable. The samples tray has 40 positions for small cups and primary tubes 75-100 mm long and 13-12 mm of diameter. The graphics provides 5 trays for a total of 200 samples. The correspondence between counter of patients and sample position on the tray is shown in the following table: Patient counter Tray Position 1 - 40 1 1 - 40 41 - 80 2 1 - 40 81 - 120 3 1 - 40 121 - 160 161 - 200 4 5 1 - 40 1 - 40 If the number of patients is such that the samples are distributed on different trays, initially the software processes all the samples assigned to the tray 1 then it stops to allow the operator to remove the samples already processed and upload those to be run and then restart the routine. Observing the mask in the figure, the essential parameters entered for each patient are the following: – – – – "ID" if the sample primary tube is identified through the barcode "Gender" if the field is activated "Type" of sample if different from that predefined "Dil 1" ratio if sample already pre-diluted The identification of the sample on the tray may be done in different way depending on the level of automation required: – manual system: for each patient, the operator enters the identification data and selects the required tests. To collect the samples you can use only the small cups or only the primary tubes. It is not allowed the use of both on the same tray. – automated system using the built-in barcode: it is indispensable the use of primary tubes with sticky barcode labels. For the user is mandatory introduce the ID number then recognized by the barcode reader once the patient's primary tubes are loaded on the samples tray. tray . – automated system realized realized connecting the Global to the LIS: In such a case the LIS sends the request with patient' data to be processed. The ID transmitted allows the identification of the patient's primary tube placed on the samples tray BPC BIOSED srl - User's Manual Rev.1 En. 54 Global 240/720 5.1.1 – – Performing Analysis- 5 Entry of new patients and start of the process enter the patients through the acceptance mask go back to the main screen where the graphics has been updated. Colour of reagents indicates whether the current volume is sufficient for the number of tests to be ru run n Main screen> Start>Select Test>From Enter Pat.>Continue – The screen shows the list of the tests to be run with the current volume of reagent. If need, replenish the reagents insufficient then click the button CK Volume – To kick start the analysis process, press the "Only Calibration" button, soon after make the checks required and confirm that the instrument is ready to start. The following screen shows the process in progress: 5.1.2 Performing an emergency stop If during the analysis process for any reason you need to stop the process, press the button "Abort". The process is interrupted immediately and the work already done in addition to the one in progress is lost. Only the results already acquired are saved. After washing of the cuvettes the main screen is displayed again. 5.1.3 Performing a planned stop During the analysis process, in case of need it is possible to schedule an intelligent stop indicating which sample will mark the stop. The "Stop on Patient" button allows you to determine the moment of the stop without loose data. The click on "Continue" restart the analysis process. 5.1.4 Reagent and sample addition During the analysis process, if in the alert bar appears the message "insufficient reagent", you can replenish the reagent bottle by the button "Add Reagent". The Global completes the process of the tests already sampled, which which should carry out the photometric photometric reading. At the same time It cancels BPC BIOSED srl - User's Manual Rev.1 En. 55 Global 240/720 Performing Analysis- 5 all the tests to be sampled which however will not be lost but will remain in the list of tests to be run. The screen below is displayed In the left side, in red are listed the missing reagents. After replenishing of the reagent click the button "Add Reagent" then in the window opened enter the name and the volume of the reagent. Exit to return to the previous screen where a simple click on "Continue" makes restart the process. A similar procedure is provided even if one of the samples needs to be refilled. In such a case the screen that opens shows the samples tray with the insufficient sample in red. After refilling and updating of the volume the process restarts clicking the button "Continue". 5.1.5 Archiving or removal of patients The entered patients are stored in a reserved area of the permanent memory of the system. They remain stored with the results of the tests run until the user performs the archiving or decide to delete them. As the maximum number of patients allowed is 200, if the maximum limit is reached the user must archive or delete all data. The "Delete Patients" button is located in the Command Bar of acceptance mask. By clicking the button, the user can choose different solutions as needed. The flow chart below shows all the possible solutions: BPC BIOSED srl - User's Manual Rev.1 En. 56 Performing Analysis- 5 Global 240/720 Delete Patients Do you really No Stop want to delete patients? Yes All patients are Keep unfin. No Store current samples patients in (diff.num...as)? archive r No cleared. The automatic counter is reset r . r r Yes Yes All patients are archived. The Store current automatic counter is reset patients in archive? Yes All patients Already completed are archived. The automatic counter updates the count by assigning new positions to the patients to be completed 5.1.6 How to use the archive of the patients Each archiving of patients generates a file named with the date of the day (DD / MM / YYYY) and by extension the characters ".Arc". Archiving repeated in the same day, produces files with the same name and extension as follows: Arc; a01; a02; a03; .... A0n. From the main screen access to the archive of the patients clicking c licking the buttons "Patients" then "Archive" BPC BIOSED srl - User's Manual Rev.1 En. 57 Performing Analysis- 5 Global 240/720 Here is a brief descriptions of the buttons of the Command bar: Button Move Explanation allows you to store the archive files selected on a removable device Set filter It allows you to research one patient in archive by name or ID Delete File It allows you to delete the selected files from the archive Reports It allows you to print the report of one patient archived Patient List It allows you to view all data of the patients included in the selected file. Patients filed contain the following data: Patient data Tests data – – – – – – – – position of the sample on the tray patient ID patient name gender tests list date and time of the test (included repetition) 1st and 2nd Optical Density (included repetition) result with flags (included repetition) Unlike the patient list, the archived data does not allow you to view the curves and the optical densities BPC BIOSED srl - User's Manual Rev.1 En. 58 Performing Analysis- 5 Global 240/720 5.1.7 Checking Results A sound alerts the operator that all the required tests have been performed. To see the results and evaluate the work done, from the main screen click "Patient" then "Patient List", a picture similar to that below is displayed. The patients are filed according to the number of acceptance. The displayed data are as follows: ID, patient's name and species. The selection of a patient shows up all tests with own results and possible flags. Here is a brief description of the buttons of the Command bar: Button Description Already Run Shows only the patients already run To run Shows only the patients to be run All Shows all patients Switch Results are shown in table form Details It allows the view in detail of the patient's data and photometric readings Print Allows printing of all patients or part of them Only Repeat Patients Display only the data of patients who have been repeated Floating Side Bar With/Without Dilution Test will be repeated with or without dilution Repeat Test Buttons that allow the rerun of a single test or of the tests selected BPC BIOSED srl - User's Manual Rev.1 En. 59 Global 240/720 Performing Analysis- 5 Repeat Buttons that allow the repetition of a single patient or of the patients selected CSV Converts data of the patient list in file CSV All data of a patient, with the measured optical density including the repetitions, you can see this by highlighting the interest test and then clicking the button "Details". One more click on the "Details" button shows all the photometric readings of the test and the curve of the chemical reaction: The consultation of the photometric reading and the graphical plot of the chemical reaction allow the user to figure out any anomalies occurred in the analysis process. BPC BIOSED srl - User's Manual Rev.1 En. 60 Performing Analysis- 5 Global 240/720 5.1.8 Results with flags Sometimes alongside the results are visible the initials of the flag's name. One flag represents a further indication for the user, about the reliability of the result. Sometime it is advisable to repeat the test in order to acquire more certainty. The table shows the flags and their meanings: Flag Meaning Description FT FIT < 0,95 Applies to kinetics and Initial Rate reactions. The photometric readings do not have a linear trend BHI High reagent blank (Abs) It appears close to the Reagent Blank. The measured absorbance is greater than the maximum value set in the Low reagent blank (Abs) BLO It appears close to the Reagent Blank. The measured absorbance is lower than the minimum value set in the ES Substrate depletion Applies to kinetics and Initial Rate reactions. Substrate of the reagent depleted before the first reading FC< Out of calibration curve Close to the calculated value in case of multipoint calibration. Result lower than the lowest calibration point Out of calibration curve FC > Close to the calculated value in case of multipoint calibration. Result higher than the highest calibration point OD Abs ≥ Close to the result. Measured absorbance equal to or greater FL Out od linearity limit than the maximum measurable value Close to the result. HI High value The result is greater than the normal range set LO Low value The result is lower than the normal range set R Re-run Close to the result of a test repeated RD Repeated with dilution Close to the result of a test repeated with dilution VR Wrong direction of the reaction Close to the result. The direction of the actual reaction (ascending / descending) does not coincide with the one set in RPE Reagent pack expired It applies only to Global 7500 (with SE) 5 .2 R e p e a t T e s t i n g When next to a result is displayed a flag that warns of a supervening anomaly, it is advisable to repeat the test for more safety. The repetition can be done automatically or manually according to the setting and the test can be repeated with or without predilutionManual repetition required by the user Opening the floating side menu in the screen "Patient List", you can view all the buttons that allow the re-run of the single test, single patient, patients selected and all patients included in the list. In the same menu there are also two buttons that sets the repetition with or without sample predilution. 5.2.1 Automatic repetition To activate the automatic re-run of single tests see the the par. 5.4 that describes the settings available. The automatic repetition of a test takes place when next to the result appears one or more of the following flags: ES, FC>, OD, FL. BPC BIOSED srl - User's Manual Rev.1 En. 61 Global 240/720 Performing Analysis- 5 5 . 3 I n c o m p a t i b i lili t y B e t w e e n T e s t s During the daily routine, the alternation of different methods, using different chemical reagents, generates incompatibilities between tests that heavily influence the result. The contamination takes place in the reaction cuvettes because the automatic washing is not able to eliminate completely the interference but even the sampling needle may be a source of contamination. Incompatibility is manifested when you experience any of the following conditions: in the last three samplings, the needle has aspirated a reagent that contaminant reagents in the last 5 cycles of use, it was dispensed a contaminant reagent into the cuvette The solutions adopted to limit the problem are the following: swap the test to be run with that comes next skip the cuvette and process the test incompatible in a cuvette different fr from om that where the pollutant was processed If the incompatibility is considered very pollutant (reddish), in addition to the mentioned options is added the washing of the cuvette and of the needle with a specific washing solution. 5 .4 S e t t i n g s O f T h e G l o b a l To access the screen with the buttons that allow you to set some important functionality of the Global you have to click "Service" in the Main Screen. The access is protected by password because BPC BIOSED srl - User's Manual Rev.1 En. 62 Performing Analysis- 5 Global 240/720 an improper use of the commands available, would damage the proper operation of the instrument. Contact your local BPC representative to get the password. main screen>Service>Set Steps>click red screen The left part of the screen is reserv reserved ed to the mechanical alignments treated in the Maintenance chapter. The upper right side presents a series of buttons that allow the activation of some important features. Lower down there is a box with some buttons that allow the choice of the type of data transmission with the LIS. With regard to the activation modality, a function is activated when the button is colored and marked with the check mark. The following table provides a brief explanation of the various settings and buttons. Setting Barcode Reader Description The function is active if the optional barcode reader is installed in the instrument. The button enables or disables the use of bar codes for the sample tubes and bottles of reagents ISE Module The function is active if the ISE system is installed in the instrument (Global 720) and the reagent pack attached. If the reagent pack is disconnected the button is automatically disabled Level Detector if active, the sampling needle is able to detect the presence of samples and reagents External Speaker activates the audio signal BPC BIOSED srl - User's Manual Rev.1 En. 63 Performing Analysis- 5 Global 240/720 Automatic Volume CK if activated, enables automatic control of the volume of the reagents before starting the process of analysis Types Management Enables the species box in the patient acceptance mask Automatic Repetition if activated, enables the automatic repetition of tests showing results close to the following flags: ES, FC>, OD, FL. Autoprint Report if activated, enables automatic printout of the report, when all the results of one patient are available Command bar Info It makes access to the test counter (read only) Date/time You can set date and time in different formats ISE setup Only active for the Global 720, it makes access to the screen where you can adjust the needle position over the entry port of the ISE; assign the position of the electrodes; enable the run of control sera during calibration Active only if the optional barcode reader is installed. It makes access to the Set reader screen for setting the barcode reader Check vol. It allows you to verify the accuracy of the metered reagent volume from the level sensor. After activation follow the instructions on the screen It allows you to calibrate the metering of the Setup volumes reagent volume. After activation follow the instructions on the screen 5 . 5 P r i n t in in g D a t a Any A4 printer, Windows compatible, is suitable to work with Global. The software allows various types of research and printout of the data acquired. Perform the following steps to access the screen where you can research data and select the model of preferred print. main screen>Patients>Prints 5.5.1 Patient report The report of the patient may be printed automatically or on request of the user. The automated modality requires to be set in advance (see the par. 5.4). Click the button Reports to access the mask that allows to search the patient data by number, by ID or by name. You can also select a group of patients of whom want to print the report. Some options chosen by the user, characterize printing report. In the floating sidebar there are 4 buttons that allow you to choose the most attractive model. Each button is enabled if it is coloured. Here is a brief description of the buttons: No Flag * In the patient's report flags are not printed. Only the report of control sera includes the two flags LO and HI. Flags are printed in all other models available in the report appears next to the test result if outside of the normal range Graphical depiction of the normal test range on a straight line. It indicates the graphic positioning of the result within the range, below or above. The choice of the button Selects the graphic model on the report BPC BIOSED srl - User's Manual Rev.1 En. 64 Global 240/720 5.5.2 Performing Analysis- 5 Laboratory Heading main screen>Patients>Laboratory Heading It makes access to the screen where you can configure the header of the report and change the logo of the laboratory. In the same screen you can also configure the acceptance mask of the patients. The button "Change Logo" allows you to replace the label with the name of the instrument and logo placed in the upper part of the report. The change must be made with a file bitmap (.bmp) with the following characteristics: BPC BIOSED srl - User's Manual Rev.1 En. 65 Global 240/720 file format: bmp (bitmap) size: 1500 x 300 pixel color: max 16.000 Performing Analysis- 5 Here is a sample report: BPC BIOSED srl - User's Manual Rev.1 En. 66 Global 240/720 Performing Analysis- 5 5 .6 B a r c o d e R e a d e r The sample and reagent barcode reader, is able to identify the patient's identity characterized by the bar code label on each primary tube and recognizes the type of reagent placed on the tray. The drawing shows the measurements of the label with the bar code and how it should be applied onto the primary tube. There are various types of barcode, the type used in the laboratory must be set by clicking the buttons "Set Reader" placed in the Mechanical Setup menu. main screen>Service>Set Steps>click red screen>Set Reader In the left side of the screen select the type of code used for the samples identification. In the right part, the number 3 indicates how many characters are used to identify the sample ID (if need you can use a greater number of characters). Within all barcode characters, the tenth character is the first of the three characters which identify the sample ID. The two buttons in the floating menu, enable the automatic recognition of samples and reagents. The button "Predisposition reagents reader" is only activated in the not predisposed instruments for the use of the reagents barcode. BPC BIOSED srl - User's Manual Rev.1 En. 67 Maintenance- 6 Global 240/720 6 Maintenance In this chapter are described some operations of ordinary maintenance which can be performed by the end user to keep the instrument always in good operating conditions and achieve the best performance during the analytical routine. Moreover in this section is provided a list of the parts which are subject to to wear and which therefore it’s advisable to replace periodically, taking in account the time frame recommended. 6 .1 S c h e d u l e d P r e v e n t i v e M a i n t e n a n c e The following table lists the preventive maintenance to be performed on schedule, in order to maintain the analyzer in perfect operating condition. The most complex operations, with semiannual or annual basis, must be performed by qualified technicians authorized by BPC Biosed. SCHEDULED MAINTENANCE Global 240-720 Ref. code Working plane Action Time interval Cleaning: remove stains of liquind Daily Distil water reservoir 001016 Washing with Ipocleaning and rinse with distilled water Monthly Washing of cuvettes CO4020 Ipo Washing Daily CO4015 Extra Reading cuvettes 13-0055 Replacement 6 -12 months Photometer lamp 13-0003 Replacement 2000 h / 12 months 19-0009 Replacement 12 months MA000140 Replacement 6 months G2058/A Cleaning solution Daily 5202 Replacement 6 months 5207 5201 Replacement Replacement 6 months 6 months Electrode Li 5205 Replacement 6 months Electrode reference 5204 Replacement 6 months Pump tubing kit 001300 Replacement 6 - 12 months Replacement 12 months Replacement 12 months Replacement 24 - 36 months Sampling needle Needle cleaner R E S U Global 720 Cleaning + Electrode K - Electrode Cl + Electrode Na + Piston / glass syringe Dryer stump Kit tubes D E I F I L A U Q L E N N O 001542 S R 13-0052 E P 19-0028 BPC BIOSED srl - User's Manual Rev.1 En. 68 Maintenance- 6 Global 240/720 6.1.1 Washing of Cuvettes Cuvettes can be washed using only distilled water or o r with the two solutions supplied by BPC: Ipo and Extra Cleaning. The two solutions are poured in two containers of type C then positioned in the slots 28-29 of the tray. Washing with the two solutions is highly recommended as it has a function deproteinizing and helps to maintain the necessary transparency, indispensable for the correct measurement of the light signal. From the main screen click "Washing" then choose the type of washing: only with water (H2O) or with Ipo+Extra. The washing process takes about 20 minutes. Fill the two containers with at least 30 ml of the solutions IPO and Extra. The washing cycle uses 25 ml of each product. Containers and solutions are provided with the instrument. To keep the reaction cuvettes in perfect condition, it is recommended the daily use of cleaning solutions 6.1.2 How replace the photometer lamp The replacement of the lamp is i s needed when on the Alert Bar appear: Cuvette lamp failure! The sequence shows the steps to be performed 1 2 3 5 6 7 4 If during the replacement you accidently touch the bulb with your fingers, remove any impurity with acetone BPC BIOSED srl - User's Manual Rev.1 En. 69 Maintenance- 6 Global 240/720 6.1.3 How replace the cuvettes The sequence shows the steps to be performed 1 2 3 4 5 6 7 8 After replacing the cuvettes it is recommended to carry out a washing with IPO and Extra 6.1.4 How to replace the needle and the cleaner The sequence shows the steps to be performed: 1. switch off the instrument then remove r emove the samples and reagents tray for more space of movement 2. place the sampling arm above the refrigerated plate then remove the screw and the fastening nut 3. remove the 4 fixing screws of the 2 panels BPC BIOSED srl - User's Manual Rev.1 En. 70 Global 240/720 Maintenance- 6 4. Loosen the hex screw that secures the cleaner of the needle 5. push down the cleaner then remove a tube at a time and connect to the new cleaner 6. remove the needle with an Allen key 7. insert the new needle and tighten the lock nut first by hand then with the Allen key but only an eighth of a turn 8. 9. 10. 11. 12. thread the needle tip into the cleaner and gently lift until the cleaner is completely inserted pushing the cleaner upward, tighten the hexagonal fixing screw turn on the instrument and access ac cess the Service menu run a few cycles of Prime and make sure there are no water leaks reassemble the two panels covering the sampling arm ar m 6 . 2 M e c h a n i c a l A l i g n m e n t s A n d C o n t r o ls ls This section describes the following alignment and control procedures: – – – – Alignments of the needle Check of the volume dispensed Check of the reaction cuvettes c uvettes Check of the photometric reading main screen>Service>Set Steps>click red screen BPC BIOSED srl - User's Manual Rev.1 En. 71 Global 240/720 6.2.1 Maintenance- 6 Centering of the needles The following procedure allows you to align the sampling needle in the positions taken during the analysis process. – – Open the drop-down menu shown in the picture and click the option "All Adjustments" perform the alignment of the needle in each position moving with the two buttons "Plus" and "Minus". Click Save to store each adjustment 6.2.2 Rise from sample After aspiration of sample, the sampling needle moves up toward the home position but stops before, with the tip out of the cleaner, just to avoid dilution of the sample with the water inside the cleaner. – click "Ck Up Movement" and control the portion of needle that stays out of the cleaner – if necessary adjust the steps in the box up to meet the specification in the figure (increase the steps means increasing the portion of the needle that remains outside of the cleaner) – 6.2.3 change of steps is automatically saved Descent on sample and check of level sensor Regulates the maximum stroke of the needle into the sample cup – place an empty sample cup in the position 1 of the sample tray – click the button "Check Down Movement" then lift the cup gently, evaluating the gap of air between the tip of the needle BPC BIOSED srl - User's Manual Rev.1 En. 72 Maintenance- 6 Global 240/720 and the bottom of the cup. If necessary change the steps up to meet the specification shown in the figure – – change of steps is automatically saved fill the cup with 150 ul of total protein after that click again the button "Check Down Movement" – this time the needle stops below the liquid surface and on the display appears the image of the cup partially yellowed to simulate the presence of serum. The yellow cup confirms the correct functioning of the level sensor 6.2.4 Check of the volume dispensed It serves to verify the accuracy of the volume dispensed from the syringes. syringes. If the accuracy of the volume is confirmed, all the elements involved (syringe, valve, manifold, plexiglass, tubes, preheater and needle) are working properly. To perform the test, you need a 10 ml graduated cylinder or a graduated tube of same volume. Perform the following steps: 1. remove the reagents and samples tray 2. rotate the sampling arm until the needle is over the tray 3. lower the needle as shown in the figure 4. place a tube of 10 ml under the needle (10 ml must be marked) 5. access the screen "Service" 6. click "Prime" then enter 5 cycles (each cycle dispenses 999 µl of water) 7. repeat the previous step 8. the measured volume within the container must be approximately 10 ml 6.2.5 Check of the reaction cuvettes The cuvette where takes place the chemical reaction and shortly after the photometric reading is made, is one of the elements of the photometric channel that over time, undergoing the action of chemical products, changes the own transparency by reducing the amount of light that pass through. Daily washing with the two cleaning solutions IPO and Extra slows the action by extending the life of the cells and keeping the photometric system in proper operating condition. The state BPC BIOSED srl - User's Manual Rev.1 En. 73 Global 240/720 Maintenance- 6 control of the cuvette is realized by clicking the button "CK Cuvettes" in the Main screen. The software fill all the cuvettes with 500 µl of distilled water then reads the light passing through by all the wavelengths. At the end of the process after that the cuvettes were dried, the screen presents the data of the readings performed on the 50 cuvettes. For the first cuvette is visible the values in Volts while for all other cuvettes is shown the difference in Volt with respect to the cuvette number 1. This difference can be positive or negative. By highlighting one of the cuvettes and then pressing the key combination "alt gr-@" they are displayed some data resulting by the readings performed. The analysis of this data helps the user to evaluate the state of the cuvettes. As a general indication, it can be said that brand new cuvettes have a CV not exceeding 5%. This value, with daily use, is expected to grow due to the inevitable degradation. In fact, normally the readings have the first two or three digits equal to zero. Single cuvettes cuvettes with very high values are synonymous with dirty or scratched cuvettes. Often, after washing with IPO and Extra, the readings return within normal range, restoring a normal condition. 6.2.6 Check of the photometric reading Allows to check the value, stability and reproducibility of the photometric signal to the various wavelengths. main screen>Service>Reading ADC>select a cuvette BPC BIOSED srl - User's Manual Rev.1 En. 74 Global 240/720 Maintenance- 6 The Global asks which cuvette you want to check then fills it with about 500 ul of water and moves the cuvette in front of the light beam. The screen shows the following data: – – – photometric readings expressed in Volt, carried out in real time with all wave llenghts enghts offset: is the voltage in the absence of the light speed of rotation of the filters expressed in ms Verify the existence of the following conditions: Operating range – The range, which ensures the correct operation of the photometric system is 4 ÷ 8.5 V Stability of the readings – In regular operating conditions, only the two least least significant digits always drift Reproducibility of the reading – If you repeat the ADC reading 3 times with the same cuvette, you must get the same readings – In regular operating condition the Offset is within 0,002 - 0,006. Volt. You can accept a wider range with no effect on the reliability of results Offset Speed of the filters wheel – The speed of rotation is 40 ms. Values which deviate slightly from this value do not affect the proper instrument operation BPC BIOSED srl - User's Manual Rev.1 En. 75 Global 240/720 Maintenance- 6 6 .3 T r o u b l e s h o o t i n g This chapter discusses how to tackle any problems that can occur with the Global. Regular preventative maintenance is essential for optimum system performance. A significant number of problems outlined in this chapter are caused by the lack of the regular scheduled preventative maintenance. This chapter therefore goes hand in hand with paragraph 6.1 of this chapter. 6.3.1 Some tips Most of the time, in the face of anomalous results, it is common thought assign the responsibility to the instrument that is not working properly. Experience teaches us that in most cases the problem is caused by the lack of observance observance of the rules on Storage an and d handling of products, poor attention in the reconstitution of calibrators and control sera, poor cleaning and not use of disposable materials. In this section we list some tips that, if taken into account, greatly reduce the daily problems. Samples Issues Verify that the venous blood sampling was performed correctly. Avoid samples with: – Hemolysis: May cause overestimation or underestimation of some parameters for interference on the reaction colour or activation/inhibition of the enzyme activity. It is advisable to repeat the blood sampling and anyway indicate the presence of blood in the sample. Separate right away the serum / plasma from contact with the red blood cells via tubes with separator gel or granules or remove the serum / plasma from the suction tube. – TURBIDITY ': Decreases the photometric signal. Centrifuge further to eliminate the phenomenon – Lipemia: The presence of fibrin in the sample can cause the clogging of the needle. Take care of taking the supernatant only. – Avoid prolonged centrifugation at high speed which may cause hemolysis of the red blood cells. Centrifuge 5-10 minutes at 3000 RPM. – Make sure to use the correct anticoagulant. Do not use expired test tubes with anticoagulant. Pour the correct amount of sample into the tubes (respect the limit indicated – on the label). The sample of serum or plasma can be frozen for its conservation at -20 °. Once defrozen must not be refrozen – Avoid contamination between samples: use pipettes and disposable tips Reagents Issues – – – – Store the reagents at temperatures indicated on the label Do not use expired reagents Do not mix reagents from different lots Check that the optical densities of the reagents (reagent blank) are within the suggested range. Their value is an index of activity of the reagent. Discard if the values are higher or lower. – Run every day control sera normal and pathological. Ensure that the reconstitution volumes are correct and wait at least half an hour before use. If stored at 2-8 °C, they BPC BIOSED srl - User's Manual Rev.1 En. 76 Maintenance- 6 Global 240/720 can be used for a week, if frozen can be used for 1 month. The same informations also apply to the calibrators. 6.3.2 Troubleshooting the problem The following table summarizes the problems that arise most frequently when working with automatic analyzers. To facilitate the search, troubleshooting is differentiated according to the problem typology. Issue r e w o P ly p p u s s e l p m a S d n a s t n e g a e R Description The instrument does not power up up Checking Abnormal Results Explanation/Action Switch on the power switch be sure the power cable is connected to the power outlet be sure that the power outlet provides the required voltage Disconnect the power cable and check the integrity of the fuses(see par 2.2.3) Compare the test with the normal QC data and identify the differences Check the flags next to results See the reaction curve to compare the t he difference between normal and abnormal Optical Density related to the concentration values Use the Calibration curve to see the differences between OD readings and factor calculated in calibrations normal and abnormal Check for abnormal cuvettes, using Check Cuvettes monitor. Any cuvettes that show abnormal data are not in a suitable condition to be used and should be cleaned or replaced Check the mean SD, CV and ranges of the results from the Data Statistics If abnormal data is recognised: In a single test: Check parameters In some tests: Compare the parameters of the tests with the abnormal data to identify (a) common parameter(s) In all tests: Check the Calibrator material for expiry date Does the problem occur after a specific reagent is used? (Might indicate contamination of reagents) Samples have something in common that explains the cause of the problem? Was a certain anticoagulant used? If abnormal data is found in a single test: Compare normal calibration data with abnormal calibration data to identify the difference between them, using the Calibration curve. curve. Check the reagent blank and the parameters of calibration If abnormal data is found in some tests: test s: If all tests with abnormal results are calibrated using the same calibrator, the calibrator might be the cause of the abnormal data If abnormal data is found in all tests: There is a high possibility that the calibration analysis itself might result in abnormal data. Check the reagent probe or syringe, water, calibration material and common hardware. Check the Reaction When a single test is performing erratically, identify where the error has occurred in the data, using the reaction curve and the OD readings Check Cuvettes Check the cuvettes data, to identify an abnormality with cuvettes OD Sample Evaporation: High results might occur due to evaporation of the sample. Store samples properly and keep sample caps closed tightly if they need to be stored for a short period before analysis Use serum that is sufficiently free of blood clots and urine that is free of suspended matter to prevent the probe from becoming clogged clo gged and s e l p m a S d n a s t n e g a e R Troubleshoot abnormal Results Sample Problems Causing Abnormal Data BPC BIOSED srl - User's Manual Rev.1 En. 77 Maintenance- 6 Global 240/720 adversely affecting analysis Check that blood samples are sufficiently coagulated before serum separation. Remove the suspended fibrin before placing serum on the t he system If there is any suspended matter present in urine to be tested, perform centrifugal separation to precipitate precipita te the suspended matter before testing the samples If a sample requires pre-treatment depending on the t he analysis test, contact the reagent manufacturer or BPC local representative A minimum quantity of sample is required for analysis. Set up an appropriate quantity of sample for correct sampling in the system Liquid-level sensor has not functioned properly due to bubbles on the serum surface. Remove these bubbles and repeat analysis The sample cups might not be placed on the tray properly The parameters for reagents and samples are not accurate: Check Parameters setting Reagent Problems Causing Abnormal Data QC and Calibrator Problems Causing Abnormal Data Reagent not stored properly: The correct methods of storage, reagents calibrators and control sera are provided in each package insert. Follow the instructions. In case of not proper storage, results are biased even if used within effective periods Reagent expired: Consult the package insert, reagent manufacturer or local BPC representative for the stability of the opened product Reagents not placed into the system correctly: Check the position of the reagents in the trays with the help of the graphical interface Reagent interference between analysis tests If a reagent is contaminated by another reagent during analysis, results might be affected Reagent has not been prepared correctly: Replace the reagent. Refer to the package insert for preparation instructions Reagent has expired: Replace the reagent Liquid-level sensor has not functioned properly during reagent aspiration: This might be caused by bubbles in the reagent bottle. Remove bubbles Fresh reagent has been added to old reagent: Replace the reagent. Ensure the correct material is in the correct position in the tray Ensure the material was prepared correctly Check the open-bottle date and expiry date t he air for an extended period of Ensure the material has not been exposed to the time Results of Control N within the range, Pathological low: probable false negative on high values, the reagent is losing the original feature Results (one test) of Control N and P out of range: replace reagent then check calibration and control sera Results (all tests) of Control N and P out of range: replace control sera and check s m e l b o r P l a ic n a h c e M Syringe problems Needle problems Water leaking from syringes : check sampling needle, might be clogged. Contact your BPC local representative Bubbles in the syringe tubing: perform Prime cycles to eliminate bubbles; check the hoses of the water tank, they should not be throttled; Contact your BPC local representative Drop from the needle. The hydraulic system lost the original tightness. Check the hydraulic connections. Contact your BPC local representative The sample or reagent probe is clogged: use a thin teflon wire to unclog the needle The sample or reagent probe tip is bent or damaged: replace the needle and the cleaner BPC BIOSED srl - User's Manual Rev.1 En. 78 Maintenance- 6 Global 240/720 Cuvettes problems Reagent Refrigerator Problems Barcode Errors Errors Leaks from the Bottom of the System Reagent insufficient false Alarm Sample Insufficient false Alarm Distilled Water Software Water Tank Problems Abnormal data impossible to do some operations The sampling needle is incorrectly positioned: perform mechanical alignments (see par. 6.2.1); contact your BPC local representative Cuvettes stained or dirty: perform washes with IPO and Extra Cleaning Cuvette Wash Overflow: Overflow: one needle of the washing station might be clogged, use a thin teflon wire to unclog the needle; contact your BPC local representative Water remains in cuvettes after cleaning: one needle of the washing station might be clogged, use a thin steel wire to unclog the needle; contact your BPC local representative Reagent refrigerator temperature out-of-range: cover always the tray with the lid; remove condensate below tray; the room temperature is within the expected range? ; contact your BPC local representative Dirty barcode labels on sample cups or reagent bottles; barcode on sample tubes badly positioned; incorrect barcode setting for sample tubes Wash line obstructed: check for obstructions or bottlenecks in the waste container hoses; exaggerated condensate produced by the cooling of reagents, the room temperature is within the expected range? Sufficient reagent is in the bottles: run the test of par. 6.2.3; The liquid-level sensor might be faulty, contact your BPC local representative Sufficient sample is in the cup : ensure that the samples containers are well positioned; the liquid-level sensor might be faulty (see par. 6.2.3) Distilled water tank dirty or stained: wash the container with sodium hypochlorite and then rinse well with distilled water If Ca, Mg and Fe are abnormal: the distilled water conductivity might be greater than 2.0 mS/cm. you can not remove a test, change parameters or a profile: when samples already processed or to be processed stay in the memory of patients acceptance, editing and erasing operations are not allowed. Erase or save the patients in the archive (reset of automatic counter) 6.3.3 Alert messages The software of the Global alerts the user if a malfunction is in progress. The source of the fault comes from one of the following subsystems: – – – – – robotic photometric reading washing barcode reader communication Such a state in which the instrument is not able to operate or operates o perates only in part, is communicated to the user by messages of the following type: BPC BIOSED srl - User's Manual Rev.1 En. 79 Maintenance- 6 Global 240/720 µController 0 cannot communicate with µController 1 / Cuvettes Carousel motor does not rotate or cannot find its home position This message, which for most of people is not very indicative, is useful for the engineer that will carry out the assistance to which it is recommended notify the message. Initially, clicking on the message, the operator can groped to restore the normal operating state. If the error message reappears continuously, you should contact your local BPC representative. The following table summarizes the errors due to the malfunction of the hardware. The failure can be caused by a missed or incorrect positioning of a mechanical assembly or by a wrong operation of the reading system or by a not proper operating of the hydraulics. Also, because any mechanical movement is monitored by optical sensors, even the control system could be source of malfunction. The table allows the user to know the source of the fault. In fact, being each activity controlled by a microcontroller, it is simple back to the type of problem in progress. Rarely the problem is caused by a random malfunction of the instrument or incorrect utilization. However, in such circumstances it is advisable to consult the table in order to understand the nature of the problem after that remove any foreign object which might have generated the malfunction and reset the error. µ controller Failure Lack of communication between instrument and computer µ0 Failure of reading / writing of data from / to EEPROM Lack of communication with the barcode reader µ1 Cuvette carousel blocked or misplaced µ2 Sampling arm: horizontal movement blocked or malpositioned µ3 µ4 µ5 Sampling arm: vertical movement blocked or malpositioned Malfunction of the level sensor Sampling diluter blocked or misplaced Non-activation of the solenoid valve of the diluter The filter wheel is locked or the electronic control is not working Malfunction of the digital converter µ6 Samples and reagents tray blocked or misplaced µ9 Diluter of washing blocked or misplaced µ10 Non-activation of the solenoid waste valve µ11 Lack of communication with the ISE module µ13 Arm of the washing station blocked or misplaced (upper position) Arm of the washing station blocked or misplaced (lower position) BPC BIOSED srl - User's Manual Rev.1 En. 80 Global 240/720 6.3.4 Maintenance- 6 Runtime error The run-time error in the case of Global is similar to a fatal error or a problem that prevents the proper functioning of the program. The runtime error can be generated by a wrong operation of the user or by the corruption of raw files of the program. In such a situation the user can access to the Program folder of Global 4500DR (disk ( disk C:) and click one at a time the following exe files: METODICHE.EXE PAZIENTI.EXE Sometimes this operation is sufficient to restore the regular functioning. If the problem persists, contact your local BPC representative. BPC BIOSED srl - User's Manual Rev.1 En. 81 Global 240/720 ISE- 7 7 ISE (Ion Selective Electrodes) 7 .1 O v e r v i e w The ISE Module built-in the Global, measures lithium, sodium, potassium,and chloride in biological fluids, using ion-selective electrode technology. The flow-through sodium electrode uses a selective membrane, specially formulated to be sensitive to sodium ions. The potassium, lithium, and chloride electrodes employ similar designs with appropriate selective membrane materials. The potential of each electrode is measured relative to a fixed, stable voltage established by the reference electrode. An ion-selective electrode develops a voltage that varies with the concentration of the ion to which it responds. The relationship between the voltage developed and the concentration of the sensed ion is logarithmic, as expressed by the Nernst equation. A comparative method of measurement is used by comparing the potential developed the ions present in the sample with those produced by the calibrator with known concentrations. The difference between the two potentials is related logarithmically to the concentration of the measured ions in the sample divided by their respective concentrations in the calibrant solution. Since the difference in potentials and the concentration of the 4 electrolytes ions in the calibrant solution are known, the computer can calculate the concentration of the ions in the sample. ISE system includes three peristaltic pumps mounted within the Global analyzer. The ISE Module measures the concentration of Li+, Na+, K+, and Cl- in serum and plasma. An integral sample entry port is positioned on top of the ISE Module. This compact design allows for small sample size and fast operation. The Module requires a sample size of 80 µL. The ISE Module houses snap-in, snap-out electrodes which connect directly to an electronic board within the ISE Module. This eliminates the need for cables and minimizes electrical noise. Samples and calibrators are positioned in front of the electrodes by three peristaltic pumps. Two separate pumps move Calibrant A and Calibrant B into the ISE Module’s sample entry port and the waste pump positions samples and calibrants in front of the electrodes. The sample is deposited by the Global into the sample entry port. After each sample measurement, calibrant is pumped in front of the electrodes for a single-point calibration. The removal of protein build-up is accomplished by the use of cleaning solution. Cleaning solution is placed in a vial on the position 30 of the reagents tray, aspirated, and deposited into the sample entry port by the sampling probe of the Global . The ISE Module is completely self contained. All sample and calibrant positioning within the ISE Module is controlled by an integral microprocessor. The ISE Module’s microprocessor applies mathematical algorithms to electrode output voltages, converting them to clinical units of mmol/L. These data are communicated over serial communication lines to the Global analyzer. 7 .2 E l e c t r o d e s Electrodes are maintenance-free. maintenance-free. Electrode packages are marked with an “Install“Install -by date”. Cleaning solution is automatically used every 8 hours in order to minimize protein buildup in the fluid lines and in the electrodes. A pump calibration should be performed each day. A two-point calibration of BPC BIOSED srl - User's Manual Rev.1 En. 82 Global 240/720 ISE- 7 the ISE module is performed automatically every 8 hours regardless the instrument is in stand-by modality or in use. To ensure reliable operation, the ISE Module will perform calibrant sipping every 30 minutes after the last sample is run. This function is completely controlled by the ISE Module without any control by the Global analyzer or the operator. The ISE Module utilizes a doublejunction reference electrode. The reference electrode is filled with saturated KCl. If the concentration of the reference electrode reservoir r eservoir drops below 3.0M KCl, serious errors will result in the measured electrolyte concentrations. The reference electrode contains a small red sphere in the reservoir which normally resides on top of the filling solution. If the sphere begins to sink, the reference electrode must be replaced. When measuring urine, the sample must be accurately diluted (1 part sample to 9 parts urine diluent). The dilution must be performed before the sample is dispensed into the sample entry port. The reagent pack includes calibrant A and B packaged in foil pouches in addition to a waste container. 7 .3 F l u i d M a n a g e m e n t The sample is aspirated by the host analyzer from a sample cup and dispensed into the sample entry port on top of the ISE Module. The sample is then positioned in front of the electrodes for measurement. Four solutions are required to operate the ISE Module: 1. Calibrant A is used in both two-point and single-point calibrations for serum sample analysis. Calibrant A is pumped into the sample entry port by the Calibrant A pump and then positioned in front of the electrodes by the waste pump. Calibrant A solution is also used for Pump and Bubble Calibration. Calibrant A Solution Li+ 1.0 mmol/L Na+ 140 mmol/L K+ 4.0 mmol/L Cl- 125 mmol/L 2. Calibrant B is used in two-point and single-point calibrations for urine sample analysis. Calibrant B is pumped into the sample entry port by the Calibrant B pump and then positioned in front of the electrodes by the waste pump. Calibrant B Solution Li+ 0.4 mmol/L Na+ 70 mmol/L K+ 8.0 mmol/L Cl- 41 mmol/L 3. Cleaning Solution is used after any routine to prevent protein buildup on the electrodes and fluid path. 100 μL of cleaning solution are aspirated by the analyzer and dispensed into the sample entry port. The cleaning solution container must be covered with pieced cup to eliminate evaporation. BPC BIOSED srl - User's Manual Rev.1 En. 83 Global 240/720 ISE- 7 Cleaning solution must be prepared every four weeks and stored at 4° C 4. Urine Diluent. Urine samples must be diluted to perform urine measurement: 1 part urine sample to 9 parts urine diluent. The diluted specimen must be thoroughly mixed before aspirating a sample. 7 .4 M e c h a n i c a l F e a t u r e s The below figure shows the ISE Module. A bubble detector is included at the top of the electrodes to properly position the sample in front of the electrodes for measurement. A sample entry port is positioned at the top of the ISE Module. This permits a convenient sample entry location on the analyzer Global in which the ISE Module is mounted. The ISE Module is secured to the chemistry analyzer chassis by a bracket and 3 screws. This permits easy removal of the entire ISE Module from the analyzer for maintenance. Each of the electrodes can be easily installed or removed from the front of the housing pushing the compression plate. The pumps group that positions the sample and wash/calibrating solutions is situated on the left side of the analyzer. BPC BIOSED srl User s Manual Rev.1 En. 84 ISE- 7 Global 240/720 1 7 .5 Ins tal l ati on of IS E Global is not delivered with the ISE system ready to use. Being the electrodes consumer products, each one with their own shelf life, it is opportune to install them on delivery the instrument to the user. The pictures below show the Global once unpacked and ready to be installed: 1 2 3 4 7.5.1 Components of ISE system 1. Entry port where the sample is injected into the ISE Module. 2. Peristaltic pumps group. 3. Hydraulic and electrical manifold connecting the reagent pack to the pumps. 4. Tubes are unhooked to avoid their collapse when not used for long periodInstallation of the electrodes. The installation of the electrodes must be carried out with the instrument switched off and the power cable disconnected BPC BIOSED srl User s Manual Rev.1 En. 85 ISE- 7 Global 240/720 1. Remove the plastic caps and the 5 screws fixing the cover of the ISE compartment . 2. Remove the tubings of Std A and B (each tube in general is recognizable by means the label sticked. If not, label the tube before removing). Std A 3. Remove the 3 screws fixing the ISE module to the frame of the instrument. i nstrument. 4. With care, remove the connector of the flat cable shown in the sideways figure. 5. Lift the ISE module with care then remove the waste tube from below. 6. Take the ISE module out of the analyzer. 7. Remove the electrodes from the individual seal bag paying attention to the presence of one o-ring in each electrode. Std B BPC BIOSED srl User s Manual Rev.1 En. Global 240/720 86 ISE- 7 8. Depress the compression plate and insert the Reference electrode in the lower side of the module as shown in figure. figure. 9. Inset the remaining electrodes from the bottom upwards respecting the following order: Cl-, K+, Na+ and Li+. 10. Release the compression plate and be sure all the electrodes are well positioned and aligned. 11. Repeat the steps 1-6 in reverse order. 7.5.2 Reagent pack Calibrant A, Calibrant B and biological waste are packaged in foil pouches within the reagent pack. It is connected to the peristaltic pumps group by means the manifold supplied with the Global. The manifold, besides the three tubes connecting the peristaltic pumps, is equipped with an electric connector used as a data line between analyzer and reagent pack. The pack uses a memory that stores some important data. This memory is a write-once device. A part of this memory is used to store some factory parameters as expiration date, distributor code, module size, lot number, security key. Further data may be stored in the t he remaining space at the time of installation. The further data may include the install date, an updated count down of the volume usage. 1. Release button of manifold. The connector can be hooked or unhooked only when the Global is turned off. 2. Peristaltic pump of calibrant A. 3. Peristaltic pump of calibrant B. 4. Electric connection 5. Peristaltic pump used to position the calibrants and the sample in front of the electrodes in addition to lead the waste fluid into the reagent pack. BPC BIOSED srl User s Manual Rev.1 En. Global 240/720 87 ISE- 7 The install of the Reagent Pack must be carried out with the Global switched off 7.5.3 Installation of reagent pack 1. Remove the cover of the peristaltic pumps group. 2. Connect the reagents pack to the group of peristaltic pumps by means the manifold (on each tube is visible the stamping with the indication of the peristaltic pump where the tube has to be connected). 3. Insert and screw the electric connector co nnector into the female socket present on the Global. 4. Put back the tubes of the peristaltic pumps into their natural seat. Press the spring and put the tube around the roller. Pay attention to the correct placing of the tube and verify by hand the proper rotation of the pump (the tube must be not interlaced and wind round the middle of the roller). 5. Put back the cover of the pumps group. 7.5.4 Start-up of ISE system From the main menu click c lick the button "ISE Module". In case the key “ISE Module” of the Main Menu is inactive, inactive, activate through the button button “ISE Module” situated in the screen “Mechanical setup” The following list provides the explanation of the parameters displayed in the previous screen. BPC BIOSED srl - User s Manual Rev.1 En. Global 240/720 88 ISE- 7 ISE Rel. Software release of EPROM built-in the reagent pack. Reagents pack Identification code stamped on the pack. Date expiration Expiration date stamped on the pack. Installation date Date of the first installation of the reagent pack. Day left Days left to the expiration. Cal A left Residual volume in per cent of calibrant A. Cal B left Residual volume in per cent of calibrant B. Step STD. A Number of steps of peristaltic pump injecting the std A. Step STD. B Number of steps of peristaltic pump injecting the std B. Step Waste Number of steps of peristaltic pump moving the fluid in front of the Last ISE wet Date and time of the last fluid injected into the sample entry port of ISE. On the lower part of the screen is visible the command bar with the following keys: Calibrate STD B It makes access to the calibration menu Volume Pumps Calibration This calibration process ensures that the proper volumes of Calibrant A and Calibrant B are dispensed during subsequent calibrations and sample cycles. Also, the process counts the number of steps required for the Waste Pump to Prime Probe move the Calibrant A and calibrant B in front of the electrodes. Performs a series of washings with water and removes possible air bubbles Wash with STD B injects 100ul of Calibrant B into the ISE Module. The waste pump leads Calibrant B through the electrodes for washing. It is also used to eliminate the Wash with STD A air bubbles from the tube injects 100ul of Calibrant A into the ISE Module. The waste pump leads Calibrant A through the electrodes for washing. It is also used to eliminate the Remove Electrodes Clean with Solution air bubbles from the tube Removes fluid from the flow path of the ISE Module, and pauses the automatic washing cycle with STD A. Then runs the waste pump until the flow path is cleared of fluid. 100 µL of cleaning solution are aspirated by the sampling probe of Global and dispensed into the sample entry port. 1. Click several times on the keys “Wash with STD A and B” for filling of tubes In case it is displayed a warning such as “Air in Calibrant A-B”, repeat the step 1 several times up to the complete elimination of air in the tubes 2. Click the key “Volume Pumps 3. click "Calibration” to calibrate the peristaltic pumps. 4. Click the key “Calibrate STD B” to display the menu below. BPC BIOSED srl - User s Manual Rev.1 En. 89 ISE- 7 Global 240/720 5. Click “Run Calibration” and wait a few minutes up to the completion of the calibration. 6. When calibration is over, all the slopes calculated are displayed. Flags close to the slopes, warning the user about abnormal conditions occurred during the calibration process. 7. The table below shows the acceptable slope limit of each electrode Electrode Slope (mV/decade) Li+ Na+ K+ Cl- 47 – 64 52 – 64 52 – 64 40 - 55 8. In case one or more slopes are outside the range or flags are close to the slopes calculated, you are requested if you want to accept the calibration 7.5.5 Performance verification Control sera should be run after each calibration to ensure the reliability of the results. The option that allows to run C1 and C2 may be activated temporary or permanently through through two buttons situated in two different menu. BPC BIOSED srl - User s Manual Rev.1 En. Global 240/720 90 ISE- 7 Service/Set Steps/red page/ISE Setup/Execute C1-C2 ISE Automatic If the button “Execute C1C1 -C2 ISE Automatic” is green, C1 and C2 after any ISE calibration, will be automatically inserted in the list of tests to be run. The following image shows an example of the menu Details with the two controls C1 and C2 which will be processed with the next routine. If the automatic option is inactive, the user can run C1 and C2 following the path below: Methods/ISE Calibration/open floating menu/Run Controls 1. Onc Once e the two controls have been run, the button “Run Controls” is automatically disactivated 2. The screen “View Calibration” allows the user to review the data of the last ISE calibration. Select one of the electrodes present in the grid then click “View Calibration”. BPC BIOSED srl - User s Manual Rev.1 En. Global 240/720 91 ISE- 7 3. In case the values of C1 and C2 are not within the range expected, the user may modify the factor of the calibration curve entering the theoretic value of C1. 4. Click ”Modify Factor” then enter the expected value of C1. The factor is re-calculated and as a result C2 is updated as well. The new C1 will bring about the re-calculation of the factor and consequently the change of C2. Not always the new C2 is more accurate than the previous one so the user has to reach a proper compromise in order both C1 and C2 achieve the best accuracy 7.5.6 System integration notes Sample Matrix. The ISE Module is designed to analyze human serum and plasma. Surfactants. Virtually all surfactants can irreversibly harm ISE electrodes. Most oils, emulsions, many organic chemicals, as well as certain inorganic chemicals and buffers, can also harm the electrodes (sometimes irreversibly). QC Materials. Caution must be exercised when selecting quality control materials. QC materials specifically designed for use with ion-selective electrodes usually perform suitably. Sample Handling and Collection . BIOHAZARD: Human body fluid specimens may be contaminated with HIV or other pathogens. Treat all specimens and collection devices and equipment as biohazardous materials. Vacuum Collection Tubes: Serum: – Collect the specimen by venipuncture into an untreated tube. Fill the tube to at least 2/3 of the total volume. Note the time of collection. – Let blood stand for 20–30 minutes to allow clot formation. – Centrifuge the tube for 10–15 minutes and remove the serum to a clean specimen tube. – Serum may be analyzed immediately, stored at 4°C for 24 hours, or frozen at -20°C for up to one week. Samples must be brought to room temperature and mixed well before assaying. To obtain accurate results, samples should be free of any clots, fibrin, etc., which would obstruct sample flow and affect results. The use of a serum clearing agent is strongly recommended. If a serum separator tube is utilized, care must be taken to avoid inserting the sample probe into the gel layer. This can create obstructions in the sample probe and the fluid path. Plasma: Plasma samples offer an advantage over whole blood specimens when short term storage is a factor. If the sample is to be stored, serum specimens are preferable. – – – – – Collect the specimen by venipuncture into a Sodium-Heparin evacuated blood collection tube. The heparin level should not exceed 15 IU per mL of tube volume. Note the time of collection. DO NOT USE AMMONIUM HEPARIN, LITHIUM HEPARIN, EDTA, OR NaF TUBES. Mix the specimen by inverting the tube. Do not shake. Centrifuge the specimen within one hour of collection. Carefully remove the top plasma layer for analysis. Use a Pasteur pipette or a syringe fitted with a blunttipped needle for this procedure. procedure. Analyze plasma samples within 4 hours of collection. Refrigerated samples must be brought to room temperature and centrifuged prior to analysis. When using Sodium-Heparin collection tubes, collect a full tube of specimen to minimize the effect of sodium heparin on the ISE Module sodium measurement. BPC BIOSED srl - User s Manual Rev.1 En. 92 ISE- 7 Global 240/720 7 .6 M a i n t e n a n c e S c h e d u l e d The ISE Module has been designed to require very little user maintenance. The table below shows the maintenance to be carried out every day, every 6 months and annually. The only daily maintenance required is to run the cleaning solution after the last sample of the day but this operation is performed automatically by the Global. All other parts and expendables are replacement items. Use only BPC approved components. Recommended Schedule Maintenance ISE part ISE Module Type of operation Daily Cleaning • Pumps calibration Sample inlet port Monthly Six-Months/10,000 Six-Months/10,00 0 samples 12 Months • Cleaning • Li+ Electrode * Replacement • Na+ Electrode Replacement • K+ Electrode Replacement • Cl- electrode Replacement • Reference Electrode Replacement • Pump Tubing Replacement • Fluidic Tubing Replacement • *The recommended electrodes replacement is 3,000 samples monthly for high volume user, greater than 100 samples/day 7.6.1 Washing electrodes with cleaning solution It is used at the end of any routine to prevent protein buildup on the electrodes and fluid path. 100 µL of cleaning solution must be aspirated by the Global from a vial placed on the position 30 of the reagent tray and dispensed into the sample entry port. The vial must be corked to eliminate evaporation. Cleaning Solution must be prepared every four weeks and stored at 4ºC. 1. From the Main Menu click on the key ISE Module to display the ISE Module Maintenance screen. 2. Be sure the vial in the position 30 of the reagent tray is filled with cleaning solution. 3. Click the button “Clean with Solution” to start the washing of the electrodes with cleaning solution. In the Global 720 the position 30 of reagent tray is reserved reserved to the ISE Cleaning Solution BPC BIOSED srl - User's Manual Rev.1 En. Global 240/720 7.6.2 93 ISE- 7 Cleaning of sample inlet port To clean the sample inlet port showed in the picture below, use a cotton swab dipped in distilled water. Remove any residue of build up up protein sticked on the side of the entry entry port, being careful not to dislodge any particles that may obstruct the flow path. 7.6.3 Replacement of electrodes 1. From the “ISE Maintenance” menu click on the “Remove Electrodes” key. This function is used used to clear fluid from the flow path of the ISE Module. The ISE Module then runs the waste pump until the electrode flow path is cleared of fluid. 2. Switch the instrument off and disconnect the power cord. 3. Remove the cover showed in the sideways picture hiding hidi ng the ISE module. 4. Remove the tubes of Std A and B (the tubes should be recognizable by the label sticked, If not, make sure you be able to recognize them when you reset everything 5. Remove the 3 screws fixing the ISE module to the frame of the instrument. BPC BIOSED srl - User's Manual Rev.1 En. Global 240/720 94 ISE- 7 6. Pay attention when the 40 pin connector is being removed, pull out the connector with cautiousness, avoiding any bending as the pins could be damaged. 7. Lift slightly the ISE module as much as necessary to to remove the waste tube from below. 8. Depress the compression plate and remove all the electrodes. 9. Remove any traces of dried salt from the ISE module by taking another damp paper towel and wiping down the areas where the electrode contacts plug into the module. Follow this by removing the possible moisture with a dry paper towel and allow to dry. 10. When assured everything is properly dry, reinstall all the new electrodes each one with own o-ring. Make sure that all of the electrodes are seated properly and the o-rings are present. 11. Repeat the steps 2-7 in reverse order 12. Condition the new electrodes injecting Calibrant A and B solutions through the tubing from the reagent pack to the ISE Module. Click a few times on the “Wash with STD A” key and then on the “Wash with STD B” key. 13. Click on the “Volume Pumps Calibration” key to calibrate the peristaltic pumps. 14. Run the electrodes calibration. If the laboratory plans to store the ISE Module for a period greater than one week, during which the analyzer will not be connected to power, the procedure to preserve either the electrodes and the ISE module should be performed BPC BIOSED srl - User's Manual Rev.1 En. Global 240/720 7.6.4 95 ISE- 7 Shutdown procedure: preparing the ISE module for f or storage 1. Before the removal of the electrodes, from the main menu click on the “ISE Maintenance” key then click on the “Clean with Solution” key to wash the electrodes with the specific cleaning solution. 2. Click on the “Wash with STD A” key to purge the electrodes with standard A. Repeat the cycle 3 times. 3. Click on “Remove Electrodes” key to purge the ISE Modul Module e fluid path. 4. Execute the steps 2-9 2-9 of section 4.4 “Replacement of electrodes”. 5. Place the Reference, Na+ and Cl- electrodes into individual sealed bags. 6. Aspirate a small volume of Calibrant A from the top port of the reagent module into a syringe fitted with a blunt needle. 7. Inject sufficient Calibrant A into the lumen of the K+ and Li+ electrodes until fluid fills the lumen. 8. Cover both ends of the lumen (both sides of the K+ and Li+ electrodes) with tape to hold the Calibrant A in place. 9. Insert the K+ and Li+ electrodes into a sealed bag 10. Replace the module inside the instrument leaving the t he 40 pin cable disconnected. 11. Remove the reagent pack and discard 12. Execute the steps 2-9 2-9 of the procedure “Remove “ Remove electrodes” in reverse order. 7.6.5 ISE module re-activation 13. Switch the instrument off and disconnect the power cord. 14. Pull out the ISE Module from the instrument. 15. Remove all electrodes from sealed bags. 16. Remove tape from K+ and Li+ electrode. 17. If necessary, soak the reference electrode in warm water until the lumen of the electrode has been cleared of salt build-up. 18. Install electrodes into the ISE Module. 19. Connect new reagent pack to the Global analyzer. 20. Use the “Wash with STD AA-B” keys to prime the calibrants. 21. Calibrate the ISE electrodes. 7.6.6 Pump tube replacement 1. Remove the cover of the peristaltic pumps group. 2. Disconnect the pumps tubes from the reagent pack and from the ISE Module 3. Press down the platen opening and unhook the pump tubes from the rollers. BPC BIOSED srl - User's Manual Rev.1 En. Global 240/720 96 ISE- 7 4. While pressing down on the platen opening, thread the new platen pump tubes in the open space between the platen and the rollers 5. Connect reagent pack and ISE Module to fittings on the ends of new tube assemblies 6. Access the “ISE Module Maintenance” menu and do the following: a) A few washing cycles with calibrant A and B right to fill the tubes b) Calibration of the peristaltic pumps c) 7.6.7 Calibration of electrodes Alignment of the probe on the ISE entry entry port Main screen>Service>Set Steps>red page>ISE Setup The screen below is displayed : 1 Select the “Arm on ISE Module Adjustment” afterwards the Sampling probe of the Global moves over the entry port of the ISE Module. 2 Center the probe over the ISE entry port by by the keys "+" and "-" the then n click "Save" to store 7 .7 T r o u b l e s h o o t i n g To enhance trouble-free operation of the ISE system, it is important to follow the recommended component replacement schedule, listed in the maintenance section of this chapter. BPC BIOSED srl - User's Manual Rev.1 En. Global 240/720 97 ISE- 7 Troubleshooting can be categorized into three main areas. These areas are: fluid delivery, electrodes stability, and communication. Considering that normally the communication is stable and the data transmission is properly interpreted, troubleshooting should focus primarily on fluid delivery and electrode stability. As these are related, sometimes the same symptoms can have different causes. Most problems can be corrected without removing the ISE Module from the Global. However, in case of difficult, it may be necessary to remove the ISE Module from its own housing. 7.7.1 Fluid delivery t is necessary to perform a Pump Calibration cycle each day. This cycle will calibrate the pumps that dispense Cal A and Cal B, and position fluid in front of the electrodes. The waste pump moves solution from the Sample Entry port to the electrode area for measurement. Due to the wear of tubes of the peristaltic pumps, the positioning of the fluid in front of the elctrodes changes therefore pumps group must be often calibrated. The pump uses a stepper motor that counts how many steps it takes to move the solution to the correct position. By calibrating the pump each day, the ISE Module can now calculate the relationship between volume and pump steps. This will enable the pumps to dispense an accurate volume of calibrant, and for the solution to be accurately placed in the proper location for analysis. Problems can be caused by a partial obstruction from a clot in the tubing from the exit tube to the waste pump, a sharp bend in the waste tubing that restricts the flow, a misalignment of the electrodes. As the pump tries to pull the fluid from the sample entry port into the electrodes, a vacuum develops because of the restriction. The bubble detector detects the trailing edge of the solution (sample, calibrant, etc.) and stops the waste pump so that the solution is in front of the electrodes. The vacuum will cause the solution to travel after the pump stops. One of the first indications of a flow problem will be the lithium electrode response. If, however, the solution slowly moves out of the electrodes when the pump has not been activated, there is either a leak between the electrodes, or along the flow path. This can be tested by placing solution into the sample entry port by hand and watch to see if the fluid level changes. In either case, the symptoms would be similar similar— —the lithium or sodium millivolts would experience noise errors and the bubble detector would trigger an error. 7.7.2 ISE error messages Errors associated with electrode instability typically include drift, noise, and slope failures. While these errors may be caused by a failure of a particular electrode, it is necessary to explore other causes as well. Proper operation on a daily basis is the key to keeping the electrodes stable and the system working properly Each day, it is necessary to perform a Cleaning Cycle. The cleaning solution removes protein build-up in the flow paths of both the electrodes and the tubing. In high sample volume instances, it may be necessary to perform this cycle more than once in a single day. It is also necessary to replace the Reference Electrode every six months or when the red ball indicator no longer floats in the internal electrode solution, whichever comes first. Failure to replace the Reference Electrode at this interval will cause all three of the errors mentioned. BPC BIOSED srl - User's Manual Rev.1 En. 98 ISE- 7 Global 240/720 7.7.3 Troubleshooting guide The following table summarizes the actions to be taken in the presence of a malfunction limited only to the ISE system. It is assumed that the remaining parts of the analyzer are working regularly. Symptom System does not respond Low slope Problem Action 1. Communication failure 2. component failure on board Call Technical Service 1. Misalignment of electrodes Remove and replace electrodes, Turn off power a few minutes, reapply power inspect o-rings. Reassemble Na+ or K+ <52 mV/decade properly 2. Calibrator solutions Replace Calibrant B first and retest. If still low, replace Calibrant A and Cl- <40 mV/decade, retest Li+ <47 mV/decade High slope Na+, K+, Li+ >64 mV/decade Cl- >55 mV/decade 3. Electrode (low slope) Replace electrodes 4. Air bubble on reference Remove electrode, tap to dislodge electrode membrane 5. Reference electrode 6. ISE module or fluid temperature bubble, replace and recalibrate exceed 32° C (high slope) Replace reference electrode and retest Monitor temperature. Change Global location if ambient temperature is too great Noise Error Flag single 1. Electrode electrode Replace problem electrodes and recalibrate 2. 3. Electrical noise spike from Find source of spike and eliminate environmental source Check grounding of Global analyzer Component failure on ISE Call technical Service Replace reference electrode and Module board Noise Error Flag 1. Reference electrode Multiple electrodes recalibrate 2. Electrical noise spike from environmental source 3. Component failure on ISE Check for electrical noise coincident with activation Check grounding of Global analyzer Call Technical Service Purge the Calibrant A and Module board Drift Error Flag Single electrode 1. May occur when new electrode or Calibrant A is installed recalibrate the ISE Module. If the electrode is new it may initially drift as it rehydrates over the course of 15 minutes 2. Drift Error Flag (D) 1. Electrode May occur when new electrode or Calibrant A is installed on Replace the electrode and recalibrate Purge Calibrant A and recalibrate BPC BIOSED srl - User's Manual Rev.1 En. 99 ISE- 7 Global 240/720 Multiple electrodes 2. Reference electrode Replace reference electrode and recalibrate 3. 4. Electrical spike from Find source of spike and eliminate environmental source Check grounding of Global analyzer Component failure on ISE Call Technical Service Global must deliver 70ul. Check Module board Air in sample 1. Insufficient sample pipette into ISE Module sample entry port 2. Bubbles in Sample dispensed sample volume. check if the sampling needle dispenses the sample regularly 3. Fluid leaks Determine source of leak and resolve 4. Sample not positioned Electrodes not seated properly. Remove electrodes. Inspect o'rings and reassemble. Air in Sample and Replace pump tubing 5. Pump tubing obstructed Replace pump tubing. 1. Sample and Calibrant A are Electrodes are not properly seated segmented with air Calibrant A or compressed. Check compression plate, spring, and seal. Remove and reassemble electrodes 2. Fibrin or salt in plugging the Use Cleaning procedure electrode flow path Remove electrodes and clean or replace electrode with plugged flow path. Reinstall electrodes and recalibrate 3. Bubble detector is Call Technical Service malfunctioning Air in Calibrant B and 4. Waste pump is malfunctioning Call Technical Service 1. Calibrant B and Calibrant A are Electrodes are not properly seated. segmented with air Air in Calibrant A Check compression plate, spring and seal Ensure that all electrodes and orings are properly installed Ensure tubing between reagent pack and sample entry port is connected properly 2. Fibrin or salt is plugging the Use Cleaning procedure electrode flow path Remove electrodes and clean or replace electrode with plugged flow path. Reinstall electrodes and recalibrate Air in Calibrant A 3. Waste pump malfunction Call Technical Service 4. Bubble detector malfunction Call Technical Service 1. Calibrant A Replace reagent pack with a new BPC BIOSED srl - User's Manual Rev.1 En. 100 ISE- 7 Global 240/720 one, prime and recalibrate 2. Tubing from reagent pack is Reconnect or replace tubing Replace pump tubing disconnected, plugged, or crimped 3. Calibrant A pump is not working properly. 7.7.4 Call Technical Service Flag list The flags listed below indicate the operator that during calibration of the electrodes or during sample analysis occurred one or more disadvantages that may have affected the result. MS FLB FLS RA RB RS Missing sample Linearity error of calibrator B Linearity error of sample Noise affects the calibrant A measure Noise affects the calibrant B measure Noise affects the sample measure DA RPE Drift affects the measure of calibrant A Reagent pack expired 7 .8 I S E T h e o r y Electrolyte measurements in blood products were traditionally performed using flame photometry. The development of selective organic compounds for sodium, potassium, chloride, and other electrolytes has permitted the development of sensors capable of directly measuring biological fluids f luids throughout the physiological range. These sensors are known as ion-selective electrodes. The ISE Module measures lithium, sodium, potassium and chloride in biological fluids, using ion-selective electrode technology. The flow-through sodium electrode uses a selective membrane, specially formulated to be sensitive to sodium ions. The potassium, lithium, and chloride electrodes employ similar designs with appropriate selective membrane materials. The potential of each electrode is measured relative to a fixed, stable voltage established by the double-junction silver/silver chloride reference electrode. An ion-selective electrode develops a voltage that varies with the concentration of the ion to which it responds. The relationship between the voltage developed and the concentration of the sensed ion is logarithmic, as expressed by the Nernst equation: Ex = Es + RT/nF log (µ C) where: Ex = The potential of the electrode in sample solution Es = The potential developed under standard conditions co nditions RT/nF = A temperature dependent “constant”, termed the slope(s) log = Base ten logarithm function BPC BIOSED srl - User's Manual Rev.1 En. 101 ISE- 7 Global 240/720 C = Concentration of the measured ion in the solution A comparative method of measurement is utilized. First, the ISE Module measures the potentials developed when the sample is positioned in the electrodes. Next, Calibrant A is positioned in the electrodes. The difference in the two potentials is related logarithmically to the concentration of the measured ions in the sample divided by their respective concentrations in the calibrant solution. Since the difference in potentials and the concentration of the lithium, sodium, potassium, and chloride ions in the calibrant solution are known, the computer can calculate the concentration of the ions in the sample, in accordance with the Nernst equation, rewritten as: Ex - Es = S log (Cx / Cs) or Cx = Cs x 10^ [ (Ex-Es)/S ] where: Ex = ISE potential developed in sample solution Es = ISE potential developed in the calibrant solution S = Electrode slope calculated during calibration Cx = Concentration of ion in the sample Cs = Concentration of ion in the calibrant solution “S”, the slope, is determined during calibration using Calibrants A and B, which have known levels of lithium, sodium, potassium, and chloride. When a two-point calibration is initiated, the slope is calculated from the difference between the second Calibrant A reading and the Calibrant B reading. Excessive drift or noisy readings will be flagged and the appropriate error message sent to the Global from the ISE Module. BPC BIOSED srl - User's Manual Rev.1 En. 102 ISE- 7 Global 240/720 The slope is defined as: Slope = EB – EA / log (CB/CA) Where: CA = Calibration A concentration in mmol/L CB = Calibration B concentration in mmol/L EA = ISE potential developed in Calibrant A solution in mV EB = ISE potential developed in Calibrant B solution in mV The ISE Module’s electronic processor checks these slopes and an error code will be transmitted if they are outside the acceptable slope limits. Typical slopes are approximately 55 mV/decade for Li, Na and K and 45 mV/decade for Cl-. Acceptable slope limits are visible in the table below. Electrode Li+ Na+ K+ Cl- Slope (mV/decade) 47 – 64 52 – 64 52 – 64 40 - 55 In practice, electrode slopes may be higher than the ideally predicted value of 59.2 mV/decade at 25º C. Higher operating temperatures, interfering ions and other factors can raise the observed slope significantly. The slope changes significantly with temperature. Variations in temperature will resul in in changes to slope and sample results. BPC BIOSED srl - User's Manual Rev.1 En. 103 Global 240/720 Description Revision Rev.1 This manual conforms to the software revision 5.0 or higher REV. DATE DESCRIPTION WRITER CONTR. 1 2016/04/08 Global 240-720 F.Ballerini A.Ghironzi Title: Global 240-720 User's Manual 2 3 4 BPC Biosed srl Writer: F.Ballerini Controlled: A. Ghironzi Date: April 2016 Pages: 104
