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Invivo Glucose Biosensors

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Easy to fabricate. Disadvantages. Oxygen consumption(solved) Protein adsorption ... Fabricate outer membrane surface of electrodes. Self Assembled monolayer (SAMs) ... – PowerPoint PPT presentation

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Title: Invivo Glucose Biosensors


1
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

2
Outline
  • Introduction
  • Diabetes
  • Biosensors
  • Types/Principle of in-vivo glucose biosensor
  • Electrochemical
  • Fluorescence
  • Challenges of in-vivo use
  • Biocompatibility
  • Future of Glucose biosensors
  • Summary

3
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

4
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

5
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/
6
Glucose monitors
http//www.diabeticexpress.com/content/ProductHome
.aspx?CategoryID25 http//www.drgreene.com/21_139
3.html
7
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

8
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
9
Types of Glucose sensors
Wickramasinghe Y., Yang, and Spencer A.S., (2004)
Journal of Fluorescence.14, 513-520
10
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

11
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.
12
Hydrogen peroxide based
http//www.msn/ccyeo/topics/Biosensors.html
13
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.
14
Amperometric Biosensor
  • Advantages
  • Simple design
  • Easy to fabricate
  • Disadvantages
  • Oxygen consumption(solved)
  • Protein adsorption
  • Electrochemical interferences

15
Fluorescence-based Biosensors
  • Lectin-based
  • Concanavalin A
  • Enzyme-based
  • Glucose oxidase / dehydogenase
  • Hexokinase / Glucokinase
  • Bacterial glucose-binding protein
  • Boronic-Acid derivatives

16
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.
17
Fluorescence-based Biosensors
  • Advantages
  • More sensitive
  • Safe
  • Less interferences
  • Disadvantages
  • Need stable glucose indicators
  • Expensive

18
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

19
Biofouling
Wisniewski N., and Reichert M.(2000) Colliods
Surfa.18,197-219.
20
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.
21
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.
22
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

23
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

24
Acknowledgements
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