Roadshow Mikrofluidik 2013
Automatized Execution of Multivariate Experiments
in Microstructured Reactors
(Automatisierte Durchführung multivariater Experimente
in mikrostrukturierten Reaktoren)
Prof. Dr.-Ing. Werner Zang
CTO of HiTec Zang GmbH
Micro Technology
Motivation for Laboratory Automation
 Acceleration of development processes (time-to-market)
 Advanced reproducibility
 Increased reliability
 Increased safety
 Advanced process control
 Inline analytics
 Improvement of quality
 Cost savings:

Unattended operation
(overnight, weekend, ...)

Automated data
evaluation
 Resource savings:

Chemicals

Energy
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Automation
 Special conditions for automation in R&D labs
Constraint
Resultant claim
Tight deadlines
Flexible, modular experimental setup with
standardised components and connectors
Rare space
Compact technology
High cost pressure
Cost effective technique, low engineering
costs
For lack of qualified personnel:
Adaptation of changing tasks and operation
of automation technology by laboratory
personnel, as far as compatible with the
safety regulations
Easy to use technology for basic functions
(like connection of sensors, actuators and
standardised components …)
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Automation
 General requirements to Process Control Systems in R&D

Very easy handling

High flexibility

Modular construction of hardware and software

PC-based user interface

Low system costs compared to
automation of production
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Automation
 Special hardware requirements for R&D

Compact installation direct at the process plant

Flexible, standardised and potential-free interfaces (EMI robust)

Trouble-free interfacing with sensors, actuators and laboratory
apparatuses

High precision (20/24 bit resolution, absolute measurement
uncertainty <0.1% / <0.01%)

Integrated universal and specialized closed loop process controllers
with autotune functionality
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Automation
 Special software requirements for R&D

Drag and drop programming of the recipe schedule e.g. according to IEC
unit operation concept

Online configuration and parameterisation during plant operation

Large depth of processing data by using integrated control and analysis
programming language

Data export for external programs
(.xls, .csv, .txt, …)
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Accelerating the development process
 Previous methods:
Parallelisation of experiments in Batch Reactors
Typical Volume 0.1 to 5 Liter
 Advantages

Proven technology

Simplified scale-up
 Disadvantages

Relatively large space required

Possibly high safety expenses
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Accelerating the development process
 Previous methods:
Parallelisation of experiments in Synthesis Robots
Typical Volume 1 ml to 100 ml
 Advantages

Proven technology

Highest throughput by massively
parallel operation
 Disadvantages

Restricted in unit operations

Possibly high safety expenses

Very complicated for pressure or vacuum

No simple scale-up
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Accelerating the development process
 New paradigm in micro reaction plants:
Sequencing of experiments in Continuous Reactors
instead of parallelisation experiments in batch reactors
 Advantages

Only one single reaction system needed

Fewer restrictions in terms of
pressure and temperature

compatible to continous production

Relatively high throughput

Best reproducibility due to
automated operation
 Disadvantages

Not yet adopted everywhere

Not suitable for all syntheses
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Experimental setup
 PI flowsheet (example)

2 reaction steps

4 individualy controlled
feeds

5 individually controlled
temperatures
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Experimental setup
 Fully automated
TM

LabBox process-interface

LabVision® software with EasyBatch

AuotSam autosampler
TM
TM
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Instrumentation components
 Liquid conveyors



Gear pumps
Annular gear pumps
Syringe pumps
 Gravimetric control units


Balances
Mass flow meters
and controllers
 Autosamplers,
Liquid handling systems
and multi port valves

Upstream and downstream
processing
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Instrumentation components
 Standard sensors and actuators

T, p, pH,... / valves, heaters,...
 Tempering systems




Electrical heaters
Constant temperature circulators
Fourfold tempering System,
only one chiller required
Cryogenic system
down to - 180 ° C
 Inline analytical instruments


ATR-FTIR, NIR, UV spectr.
Liquid phase detector
(organic/anorganic)
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system hardware
 LabManager® (or LabBox ) process interface
TM

Standardised NAMUR connectors for sensors, actuators, laboratory
equipment and analytic instruments

Integrated closed loop controllers and power supplies

Extremly compact
(a small box instead of a bulky cabinet)
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system interfaces
 Analogue inputs
and outputs
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system interfaces
 Analogue inputs
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system interfaces
 Digital inputs and outputs
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system interfaces
 Heater drivers and serial interfaces
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Interface Example
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Automation system software
 LabVision®

Standard in laboratory automation software

Real NAMUR compliant R&D process control system

End to end data chain from experiment design
to ELN/LIMS database

User-friendly operation
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
LabVision™ Project Modules
 Automation project design via drag and drop
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Easy connection of sensors, actuators
and laboratory instruments
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Application oriented function blocks
 Operations (excerpt):

Surge doser

Batch amount doser

Batch rate doser

Conti doser

Refill device

Vacuum controller

Temperature
cascade controller
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Application oriented function blocks
 Example:

Gravimetric flow control

Balance and pump

Autotuning
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
EasyBatchTM sequential control
 Spreadsheet based programming of test procedures
 Self-explanatory
 Interactive operation and changes during runtime are possible
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
HiTextTM universal programming language
 Control
 Online evaluation
 Communication
 Special procedures
for EasyBatch
TM
 Multitasking
 Easy to use
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Notebook and
automatically generated documentation
 Functionality

Standardised
automated evaluation

Consistent presentation of parameters,
measured values,
analytic data and
results

Transfer of data
to a LIMS

Export as .pdf file
(manipulation-proof)

Export as .rtf file
(for post-processing)

WYSIWYG form designer
Automatized execution of multivariate experiments in microstructured reaction plants
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Micro Technology
Event report
 Complete report of the course of events
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Event report
 Complete report of measured data and set points
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Laboratory Information Management System
 Functionality





Planning and organising
Administration and documentation of recipe, batch-, educt-,
product- and sample-data
Search and retrieval
Comparison and analysis of data
Coupling devices
 Advantages







Support of daily laboratory work
Increases productivity
Error prevention
Protects sensitive information
Makes knowledge available to the user
Prevents information manipulation
Easy utilisation of information
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
SyrDos™ - syringe pump for mixing
and continuous operation
 All-purpose use
 Resistant to aggressive media
 Wetted materials: glass, PTFE,
KEL-F or PPF, opt. ceramics
 Compact high grade steel casing
 Syringes from 10µl up to 50 ml
 Optional pressure up to 90 bar
 48.000 steps, max. 10.000 steps/s
 Optional continuous conveyance
 Calibration in mg/min and ml/min
 Interfaces (RS232, RS485, MODBus,
4-20mA, 0-10V)
 Comfortable DosiMaster™ software
for dosing profiles, dispensing
and mixing purposes
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
AutoSamTM liquid handling system
 Applications

Sampling of specimens

Provision of reactants

Quenching, mixing and diluting

Liquid/Liquid extraction
 Properties and Procedures

Sample tubes with diaphragms
are easily processed

Bottling under inert gas possible

Exchangeable sample tray

Separate, large waste vessel

Programmable handling methods
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
GraviDos® - gravimetric controlled dosage
 High performance
 Low-cost
 Compact and robust
 Large dosing range
 Refilling without dosing interruption
 Increased control accuracy
compared to balances
 Resistant to aggressive media
 Easy to clean
 Available as platform- or overhead-balance
 Optionally stirring and heating
 Applicable as massflow and filling
quantity meter
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Phase detection and separation
 Detection of anorganic and organic liquid (and gaseous) phase
 Automated separation of anorganic and organic liquid phase
 Thermal measuring principle or
 Capacitive measuring principle
Automatized execution of multivariate experiments in microstructured reaction plants
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Micro Technology
Customised Solutions
 Mixed assembly applications

micro-mixers and glas
components

Continuous as well as
batch operation
 Totally integrated Automation
 Unattended operation
 Mobile
Automatized execution of multivariate experiments in microstructured reaction plants
HiTec Zang GmbH
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Micro Technology
Thanks a lot for your attention!
Fully Automated Execution of
Multivariate Experiments
on the example of
Microstructured Reactors
werner.zang@hitec-zang.de
www.hitec-zang.com
Automatized execution of multivariate experiments in microstructured reaction plants
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