Invivo Glucose Biosensors

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In-vivo Glucose Biosensors
http//pubs.acs.org/hotartcl/ac/98/sep/skin.html

• Simuli L. Wabuyele
• Rensselear Polytechnic Institute
• Department of Chemistry and Chemical Biology
• 11/22/2005

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Outline

• Introduction
• Diabetes
• Biosensors
• Types/Principle of in-vivo glucose biosensor
• Electrochemical
• Fluorescence
• Challenges of in-vivo use
• Biocompatibility
• Future of Glucose biosensors
• Summary

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Introduction

• Glucose
• -Sugar that provides energy to all body cells
• -Maintained at constant level (70-110mg/dl)
• Insulin
• Glucagon
• Diabetes Mellitus
• -Disease that affects your body's ability to use
  glucose
• -One of the leading causes of deaths
• Serious complications i.e. blindness, nerve
  damage, kidney and heart diseases

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Types of Diabetes

• Diabetes type 1
• -Genetic disorder
• -Insulin- independent (not produced)
• -Found in 5-10 diabetics
• Diabetes type 2
• -insulin resistant (not used)
• -Occurs in 90-95 diabetics
• Gestational diabetes
• -Occurs in pregnant women
• -Hormones partially block the action of insulin
• -Goes away after delivery

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Prevalence of Diabetes
By the year 2025 the number of subjects with
diabetes will have increased approximately
10-fold compared to figures observed in 1985.
http//www.sanger.ac.uk/Teams/Team35/
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Glucose monitors
http//www.diabeticexpress.com/content/ProductHome
.aspx?CategoryID25 http//www.drgreene.com/21_139
3.html
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Need of a better device

• Technique required
• less painful
• simple and easy to use
• single time use
• continuously monitors glucose levels
• operates for a long period of time
• Thus reliable
• Such as A BIOSENSOR

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What is a Biosensor?
A device thats designed to detect changes in the
level of analyte measure
http//www.must.edu.my/ccyeo/topics/Biosensors.ht
ml
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Types of Glucose sensors
Wickramasinghe Y., Yang, and Spencer A.S., (2004)
Journal of Fluorescence.14, 513-520
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Electrochemical Biosensors

• Amperometric
• Enzyme electrodesGlucose Oxidase (GOx /GOD)
• Measure electric current as a result of electron
  exchange between the biological component and an
  electrode
• Potentiometric
• Ion selective electrodes
• Measure change in concentration of particular
  ions
• Conductometric
• Platinum/gold electrodes
• Measure change in conductivity of solution due to
  ions

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Amperometric Biosensor
Outer membrane (polyurethane)-control diffusion
of glucose - biocompatibility Inner membrane
(cellulose acetate)-filter interfering substances
Pickup J., McCartney L., Rolinski O., and Birch
D. (1999) BMJ.319, 1289.
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Hydrogen peroxide based
http//www.msn/ccyeo/topics/Biosensors.html
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Mediated glucose sensors

• -Oxidized/reduced mediator couple Ferrocenium
  /ferrocene
• -avoid oxygen consumption
• Reduced form of enzyme reacts with mediators
  regenerate enzyme
• -mediator re-oxidized at less extreme potential
  reducing interferences

Wang J. (2001) Electroanalysis. 13, 12,983-988.
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Amperometric Biosensor

• Advantages
• Simple design
• Easy to fabricate
• Disadvantages
• Oxygen consumption(solved)
• Protein adsorption
• Electrochemical interferences

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Fluorescence-based Biosensors

• Lectin-based
• Concanavalin A
• Enzyme-based
• Glucose oxidase / dehydogenase
• Hexokinase / Glucokinase
• Bacterial glucose-binding protein
• Boronic-Acid derivatives

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Fluorescence-Based Biosensor
-Concanavalin A competitively binds glucose and
dextran -FRET occurs -Displacement reduces FRET,
increasing intensity
Pickup J., McCartney L., Rolinski O., and Birch
D. (1999) BMJ.319, 1289.
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Fluorescence-based Biosensors

• Advantages
• More sensitive
• Safe
• Less interferences
• Disadvantages
• Need stable glucose indicators
• Expensive

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Challenges of in-vivo biosensors

• Biocompatibility
• Body's reaction to implanted sensor and sensor
  reaction to the body
• -Inflammatory response
• -Encapsulation
• -reduction in sensor reliability
• Interferences in sensor environment
• Non-specific adsorption
• Affect sensor stability and lifetime
• Difficult to calibration sensor in-vivo
• Some sensors have not been tested in-vivo

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Biofouling
Wisniewski N., and Reichert M.(2000) Colliods
Surfa.18,197-219.
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To improve biocompatibility

• Fabricate outer membrane surface of electrodes
• Self Assembled monolayer (SAMs)
• -Alkane thiolates
• Polymeric Coatings
• -Polyacryamide
• -Polyethylene oxide/PEG
• Microperfusion
• flow aqueous film around the tip of electrode
• Use an anti-fouling agent
• Nitric Oxide (NO)
• Replace the implanted biosensor

Mukhopadhyay,R.(2005)Anal.chemA.429-432 and
Pickup J. et. Al (1999) BMJ.319, 1289.
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Anti-fouling agent

• Sensor that release NO to prevent thrombus
  formation
• SEM images

Frost C.M., and Meyerhoff. (2002) Current
Opinions in Chemical Biology.6, 633-641.
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Future of Glucose biosensors

• Improve sensitivy ,stability and selectivity
• Use Sol-gel systems to immobilize GOx -Reduce
  leaching
• Use of hybrid films to improve stability of Gox
  and permselectivity of membrane
• Enhance biocompatibility of implanted biosensors
• Sensor modifications
• -Biomimetrics- phospholipids
• Explore fluorescence techniques further
• Fluorescence decay lifetimes
• Quantum dots
• Develop implantable biosensors for clinical use

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Summary

• Tight control of blood glucose is required for
  the management of diabetes mellitus
• There various methods used for glucose monitoring
• In-vivo glucose biosensors offer a continuous,
  long-term monitoring technique
• Biofouling remains a major challenge in the
  implantable biosensors
• With the on-going research , in-vivo glucose
  biosensors are a potential for the future use

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Acknowledgements