Glucose Biosensors

1
Glucose Biosensors
Presented by
Jay Leitch
2
What are Glucose Biosensor?

• Immobilized biological components fixed on
  ordinary analytical detectors
• Selectively detects and quantifies the analyte
  in a natural matrix without requiring any
  separation
• Ideal Sensor

• Highly Specific
• Linearity in signal response
• Independent of hydrodynamics
• Independent of co-substrates
• Requires minimal calibration

• Biocompatible
• Long lifespan
• Low cost
• Can be scaled down

3
Biosensor Components

• Membranes
• Used to protect immobilized GOD electrodes from
  high metabolite concentration. Extends linearity
  of sensor by limiting glucose, but not O2
  diffusion
• E.g. Polyurethane (PU), Perforated, Polycarbonate
• Transducers
• Thermometric
• Optical fluorescence, chemiluminescence,
  optical rotation
• Electrochemical potentiometric, voltammetric,
  amperometric
• Biological Component
• Biocatalytic Mediator enzyme/antibody etc. that
  interacts with the desired analyte

4
Enzymatic Reactions for Glucose Analysis
?H
glucose oxidase

• Glucose O2 Gluconic acid H2O2 19 kcal
• H2O2 ½ O2 H2O 24 kcal
• Total Reaction
• Glucose ½ O2 Gluconic acid H2O 43 kcal
• Glucose oxidase (GOD) is commonly used since it
  fairly stable requires no cofactors or
  coenzymes

catalase
GOD
catalase
5
Thermometric Sensors

• Measures heat changes caused by enzymatic
  reactions
• Limited to in vitro analysis
• Transducers
• Thermistor very sensitive, but excitation
  electricity causes a raise in thermister
  temperature, thus strict control over ambient
  temperatures is needed
• Thermocouple no excitation electricity, but
  low sensitivity
• Thermopile Antimony and Bismuth evaporated
  in thin film creating a series array of
  thermocouple junctions. Sensitivity increases
  with the number of junctions. Do not require
  excitation electricity

6
Thermopile-based Enzyme Probe
7
Optical Sensors

• Can measure aqueous glucose concentrations by
  optical emissions by using fluorescence,
  chemiluminescence and optical rotation of
  molecules
• Advantages
• Electrical isolation from patient
• Eliminates electrical interference
• No need for a reference electrode
• Easily miniaturized due to advances in fiber
  optics

Bioaffinity glucose sensor glucose binds to con
A (concanavalin A) releasing a fluoroesceinated
dextran. Range of measureable glucose levels
2.8-22 mM. Response time 5-7 min.
8
Electrochemical Sensors

• commonly measured by amperometric or
  potentiometric methods
• composed of electrode with enzyme, such as GOD
  immobilized and surrounded by PU membrane
• can monitor glucose levels by examining reaction
  substrates or products
• can be miniaturized easily and produce effective
  signals

9
So Why Is This Useful?

• Many individuals in the world are diagnosed with
  Diabetes Mellitus
• Diabetes mellitus is a disease that affects the
  production or release of insulin
• Chronic elevations of blood glucose can lead to
  renal, retinal and neural complications
• Traditionally glucose levels could be monitored
  using capillary blood from finger prick and using
  GOD/peroxidase dry reagent strips and insulin
  injections
• Implantable glucose sensors could be a solution
  to prevent insulin shock and diabetic coma

10
Implantable Glucose Sensors

• Continuous monitoring of analyte concentration
• Sensor signal coupled to an infusion pump for a
  closed-loop insulin delivery (i.e. forming an
  artificial pancrease)
• Usually implanted in subcutaneous tissue
• Based on electrochemical or optical techniques
• 3 Basic Designs vessel-shaped blood flows
  through it
• needle type injected by needle
• plane-geometry see figure below

11
Glucose Sensor Implant Results

• Implant showed a linear trend between sensor
  output and glucose concentration
• 95 accurate
• Only a slight lag (60 secs.) between increased
  glucose and signal
• Fairly Sensitive
• Showed no effects in the presence of inhibitors

• Problems
• Short lifespan performance impaired in 3-7
  days and need replacing after 4 weeks
• Eliminating lag would be ideal since high
  glucose levels for even one minute good
  potentially cause damage
• Glucose concentration is lower in subcutaneous
  interstitial fluids than in bloodstream

12
References

1. Cunningham, A. Introduction to bioanalytical
   sensors. New York John Wiley Sons, Inc.
   1998, pp.159-62
2. Turner,A. Advances in Biosensors. Vol.1 England
   Jai Press Ltd. 1991, pp.67-72.
3. Ward, W. et. al. A new amperometric glucose
   microsensor in vitro and short-term in vivo
   evaluation. Elsevier Science. Biosensors
   Bioelectronics 17 (2002) 181-189.
4. Wilson, G. et. al. Biosensors Fundamentals and
   Applications. New York Oxford University Press,
   1989, pp.390-405.
5. Wise, L. Bioinstrumentation and Biosensors. New
   York Marcel Dekker, Inc., 1991, pp.229-45.
6. Wise, L. Applied Biosensors. Boston
   Butterworth Publishers, 1989, pp.227-44.