biosensor boot camp part 2 david e williams. title: electrode systems for continuous monitoring in...
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Title: ELECTRODE SYSTEMS FOR CONTINUOUS MONITORING IN CARDIOVASCULAR SURGERYAuthor(s): CLARK, LC; LYONS, CSource: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Volume: 102 Issue: 1 Pages: 29-& DOI: 10.1111/j.1749-6632.1962.tb13623.x Published: 1962Times Cited: 1,093 (from Web of Science
Glucose oxidase-containing membrane
glucose oxygen
Gox-containing membrane
Ag anode
Pt cathode
Signal decreases as glucose increases in this configuration
This model was the first whole-blood glucose analyzer. The instrument directly measures the whole-blood glucose level from a 25-microliter sample within a ±2% accuracy. The sensor created for the Model 23A was the first commercial biosensor and was used in the Miles Biostator, the first artificial pancreas. The U.S. Food and Drug Administration has identified the YSI Model 23A and subsequent designs as the reference standard for measuring glucose.
In 1970, Dr. Clark demonstrated the enzyme-activated polarographic measurement of glucose in water and pointed out that glucose could be measured in whole blood with the presence of the glucose oxidase enzyme. Within a couple of years, YSI was able to market its pioneering Model 23 Glucose Analyzer with a polarographic electrode.
http://www.ysi.com/history.php
http://www.chemheritage.org/discover/collections/collection-items/scientific-instruments/ysi-blood-glucose-analyzer-model-23a.aspx
Hydrogen peroxide readily depolarizes the polarographic anode and current flow, at a given applied voltage (usually about 0.9 volt), is proportional to the hydrogen peroxide concentration. If glucose were to be measured in blood by mixing the enzyme and the blood, no glucose would be detected because blood contains the enzyme, catalase, which destroys hydrogen peroxide at a very fast rate. This difficulty, and others, are circumvented through the use of a cellulose or other membrane which is permeable to small molecules, such as glucose, but is impermeable to proteins. The membrane serves to keep the glucose oxidase on the side of the membrane with the anode and at the same time to keep other enzymes, some of which, such as catalase, would ruin the reaction, on the other side of the membrane. Glucose has a molecular weight of 180 and can freely diffuse through the membrane. The product of the reaction, hydrogen peroxide, has a low molecular weight, only 34, but by virtue of the design of the present invention is formed directly on the platinum electrode surface where it is detected, and in the process of being detected is, in part at least converted to H20 and oxygen.
Pt anode: H2O2 oxidation
Ag/AgCl cathode
This model was the first whole-blood glucose analyzer. The instrument directly measures the whole-blood glucose level from a 25-microliter sample within a ±2% accuracy. The sensor created for the Model 23A was the first commercial biosensor and was used in the Miles Biostator, the first artificial pancreas. The U.S. Food and Drug Administration has identified the YSI Model 23A and subsequent designs as the reference standard for measuring glucose.
In 1970, Dr. Clark demonstrated the enzyme-activated polarographic measurement of glucose in water and pointed out that glucose could be measured in whole blood with the presence of the glucose oxidase enzyme. Within a couple of years, YSI was able to market its pioneering Model 23 Glucose Analyzer with a polarographic electrode.
http://www.ysi.com/history.php
http://www.chemheritage.org/discover/collections/collection-items/scientific-instruments/ysi-blood-glucose-analyzer-model-23a.aspx
Think a bit… the assumptions connecting the measurement to the desired quantity
conc
entr
ation
position
In the space: Glucose + O2 -> H2O2
Glucose conc
At the electrode: H2O2 -> O2
Oxygen conc
H2O2 conc
Small gap underneath membrane relative to membrane thickness
Gap is controlled – another membrane
Large excess of Gox – fast reaction
Current ~ gradient of H2O2 at electrode
Development of the home-use glucose sensorFerrocene-Mediated Enzyme Electrode for Amperometric Determination of GlucoseAnthony E. G. Cass,’ Graham Davis, Graeme D. Francis, and H. Allen 0. Hill*Inorganic Chemistry Laboratory, University of Oxford, Oxford OX1 3QR, United KingdomWilliam J. Aston, I. John Higgins, Elliot V. Plotkin, Lesley D. L. Scott, and Anthony P. F. TurnerBiotechnology Centre, Cranfield Institute of Technology, Bedford MK43 OAL, United Kingdom
Anal. Chem., 1984, 56 (4), pp 667–671
Fcor Fc + glucoseor Fc + GOx
Fc + glucose + GOx
Removes oxygen dependence
Eliminates uric acid and ascorbate interference
Concept for a single use, batch calibrated device
the reaction : Fc+ + glucose + GOxregenerates Fc near the electrode so current doesn’t decrease
Fc → Fc+ + e-
anodic current decreases when Fc is depleted near the electrode
glucose + M(ox) gluconolactone + M(red)GOx
Fc+ Fc
for glucose measurement, hold potential constant at ~ 0.4 V and measure current
The reaction of Fc+ and GOx(red): a classic ErCi’ system
E = electrochemical stepC’ = homogeneous catalytic chemical reactionr = reversiblei = irreversible
Examples of some other classic mechanisms:ErCr
ErCiEr
CrEi
(C = homogeneous chemical reaction)
Fc/GOx system
R (Fc) O (Fc+) + e
O (Fc+) + Z (glucose) R + Y (gluconolactone) k’
bulk concentrations, i.e. what’s added at the start
A.J. Bard, L.R. Faulkner, Electrochemical Methods: Fundamentals and Applications, ed. John Wiley: New York, 2001; Chapter 12.
R (Fc) O (Fc+) + e
O (Fc+) + Z (glucose) R + Y (gluconolactone) k’
Reaction consumes ‘O’ and regenerates ‘R’ in the boundary layer near the electrode as ‘O’ is produced at the electrode
Technology and market drivers
• Lower blood volume• More precision• Avoiding other peoples’ patents
• -> coulometers• -> high concentration solutions of enzyme and
mediator• -> old (ferrocyanide) and new (osmium)
mediators
Chamber of precisely known volume, capillary fill
Dried reagents give high concentration solutions
Complete conversion of glucose in sample to gluconolactone with equivalent reduction of ferricyanide
Coulometric determination of amount of ferrocyanide produced
Precision determined by precision of manufacture of the defined sample volume
Electrodes in chamber
spacer
reagents
100um gap
Lifescan ‘one-touch’
~1uL sample volume; 5s measurement; made by web printing process : 106 / hr
Therasense : Adam Heller
http://ubimon.doc.ic.ac.uk/bsn/public/bsn-2005-Heller.pdf
Glucose gluconolactone
GoX
Os(III) Os(II)
http://www.boots.com/en/Pharmacy-Health/Health-shop/Diagnostics-electrical-health/Blood-glucose-monitors/
Random Thoughts list
• Strep – antigen extraction• Glucose – how devices changed and the
assumptions behind operation• Flow injection, protective membranes,
Bourtelle and Albery, one shot• Microfluidics• Surfaces and interactions• Immunoassay theory