1
BME 4490 Sensors & Instruments Homework
Due: February 21, 2001
The following set of problems is intended to help you think about biosensor design. Please feel
free to contact Professor Stenken (stenkj@rpi.edu) immediately if you have a question or feel
confused about the assignment.
Pick two of the following clinically important analytes and answer the following questions.
Analytes:
H+
Ca2+
Na+
K+
Glucose
Lactic Acid
Glycerol
O2
Dopamine
Serotonin
Glutamate
Theophylline
Acetylcholine
Nitric Oxide (NO)
(a) What is the clinical importance of this analyte? (Hint: Look in either a physiology or
biochemistry textbook.) The chemical structures of these compounds can be found in the
Merck Index, a reference book available in the RPI library.
(b) For your analyte, think about the following. How can you go from "recognition" of
the analyte in a sample to "detection"? See Figure 1. What is the matrix that your
sample resides in (blood, urine, tissue, etc.) ? Will you be drawing a biological fluid to
perform an in vitro analysis (blood or urine) or will you detect continuously in vivo?
How fast does your sensor need to respond? (Hint – are there processes associated with
this analyte that might make it have concentrations that are rapidly changing?)
(c) Keeping in mind the sensor concepts discussed in class, suggest a sensor design
keeping the above points in mind and including the following information. (Note there is
no "right" or "wrong" answer here. Be creative and see what you can come up with in
terms of a sensor.)
(i) Which energy transducer will you use? (Electrochemical, Thermal, Optical,
etc.)
(ii) How will you couple the chemical selective layer (molecular recognition) to
the transducer?
2
(iii) Will you need a protective cover over the sensor? If so, could this prevent
your analyte from reaching the transducer?
(d) Compare your design to a recently published design for this analyte. I have included
a variety of sensor references. Many of these articles are available either on-line or in the
library. You are certainly welcome to search the scientific literature to come up with
new ideas.
Adapted from: AJ Cunninham, pg 12
Introduction to Bioanalytical Sensors
Wiley, 1998
Protective Membrane
Chemical Selective
Layer
Diffusion
A
Analyte (A)
Chemical
Reaction or
Binding Reaction
P
Interferent (I)
Transducer
Diffusion
Signal
P
R
Transducers:
Electrochemical
Optical
Thermal
Mass-Sensitive
Selective Layer
Molecular Recognition
Ionophore
Enzyme, Cell, Tissue
Antibody
Abiotic
P = Product
R = Transducer Product –
Amperometric
Figure 1. An overview of a biological sensor configuration.
Reference Sources:
E. Lindner, V. V. Cosofret, S. Ufer, R. P. Buck, W. J. Kao, M. R. Neuman, and J. M. Anderson, "Ion-selective
membranes with low plasticizer content: Electroanalytical characterization and biocompatibility studies," J. Biomed.
Mater. Res., vol. 28, pp. 591-601, 1994.
M. E. Collison and M. E. Meyerhoff, "Chemical sensors for bedside monitoring of critically ill patients,"
Anal.Chem., vol. 62, pp. 425A-437A, 1990.
B. Aussedat, M. Dupire-Angel, R. Gifford, J. C. Klein, G. S. Wilson, and G. Reach, "Interstital glucose
concentration and glycemia: implications for continuous subcutaneous glucose monitoring," Am. J. Physiol.
Endocrinol. Metab. , vol. 278, pp. E716-E728, 2000.
D. A. Baker and D. A. Gough, "Dynamic delay and maximal dynamic error in continous biosensors," Anal.Chem.,
vol. 68, pp. 1292-1297, 1996.
3
R. Ballerstadt and J. S. Schultz, "A fluorescence affinity hollow fiber sensor for continuous transdermal glucose
monitoring," Anal.Chem., vol. Aug 8, 2000, pp. A-H, 2000.
M. G. Boutelle, L. K. Fellows, and C. Cook, "Enzyme packed bed system for the on-line measurement of glucose,
glutamate, and lactate in brain microdialysate," Anal.Chem., vol. 64, pp. 1790-1794, 1992.
J. J. Burmeister, K. Moxon, and G. A. Gerhardt, "Ceramic-based multisite microelectrodes for electrochemical
recordings," Anal.Chem., vol. 72, pp. 187-192, 2000.
B. D. Cameron and G. L. Coté, "Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,"
IEEE Trans. Biomed. Eng. , vol. 44, pp. 1221-1227, 1997.
T. Carlsson, U. Adamson, Per-E. Lins, and B. Danielsson, "Use of an emzyme thermistor for semi-continuous blood
glucose measurements," Clin. Chim. Acta, vol. 251, pp. 187-200, 1996.
T. Chen, K. A. Friedman, I. Lei, and A. Heller, "In situ assembled mass-transport controlling micromembranes and
their application in implanted amperometric glucose sensors," Anal.Chem., vol. ASAP, pp. A-F, 2000.
H. A. Clark, M. Hoyer, M. A. Philbert, and R. Kopelman, "Optical nanosensors for chemical analysis inside single
living cells. 1. Fabrication, characterization, and methods for intracellular delivery of PEBBLE sensors,"
Anal.Chem., vol. 71, pp. 4831-4836, 1999.
H. A. Clark, R. Kopelman, R. Tjalkens, and M. A. Philbert, "Optical nanosensors for chemical analysis inside single
living cells. 2. Sensors for pH and calcium and the intracellular application of PEBBLE sensors," Anal.Chem., vol.
71, pp. 4837-4843, 1999.
H. R. Clark, T. A. Barbari, and G. Rao, "Modeling the response time of an in vivo glucose affinity sensor,"
Biotechnol. Prog., vol. 15, pp. 259-266, 1999.
V. V. Cosofret, M. Erdösy, T. A. Johnson, R. P. Buck, R. B. Ash, and M. R. Neuman, "Microfabricated sensor
arrays sensitive to pH and K+ for ionic distribution measurements in the beating heart," Anal.Chem., vol. 67, pp.
1647-1653, 1995.
E. Csöregi, C. P. Quinn, D. W. Schmidtke, Sten-E. Lindquist, M. V. Pishko, L. Ye, I. Katakis, J. A. Hubbell, and A.
Heller, "Design, characterization, and one-point in vivo calibration of a subcutaneously implanted glucose
electrode," Anal.Chem., vol. 66, pp. 3131-3138, 1994.
Q. Ding, G. W. Small, and M. A. Arnold, "Evaluation of nonlinear model building strategies for the determination
of glucose in biological matrices by near-infrared spectroscopy," Anal. Chim. Acta, vol. 384, pp. 333-343, 1999.
R. Levi, S. McNiven, S. A. Piletsky, S.-H. Cheong, K. Yano, and I. Karube, "Optical detection of chloramphenicol
using molecularly imprinted polymers," Anal.Chem., vol. 69, pp. 2017-2021, 1997.
R. C. Mercado and F. Moussy, "In vitro and in vivo mineralization of Nafion membrane used for implantable
glucose sensors," Biosensors Bioelectron., vol. 13, pp. 133-145, 1998.
M. E. Meyerhoff, B. Fu, E. Bakker, J.-H. Yun, and V. C. Yang, "Polyion-sensitive membrane electrodes for
biomedical analysis," Anal.Chem., vol. 68, pp. 168A-175A, 1996.
M. H. Schoenfisch, K. A. Mowery, M. V. Rader, N. Baliga, J. A. Wahr, and M. E. Meyerhoff, "Improving the
thromboresistivity of chemical sensors via nitric oxide release: Fabrication and in vivo evaluation of NO-releasing
oxygen-sensing catheters," Anal.Chem., vol. 72, pp. 1119-1126, 2000.