biosensors christopher byrd enpm808b university of maryland, college park december 4, 2007

Biosensors

Christopher Byrd

ENPM808B University of Maryland, College Park

December 4, 2007

Outline

Introduction

4 Specific Types of Biosensors Electrochemical (DNA)

Carbon nanotube

BioFET

Whole Cell Basic functionality

Benefits/Challenges

Summary

References

Introduction

Biosensor:

Incorporation of a biomolecule in order to detect something

Species to be detected (analyte)

FilterRecognition Layer

Transducer Electronics SignalRecognition Layer

Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction

Introduction

Biosensors ~ $3B 90% → Glucose testing 8% - 10% increase in industry per year


Electrochemical DNA Sensors

Harnesses specificity of DNA Simple assembly Customizable Vast uses for small cost


DNA Structure

DNA structures---double helix

4 complementary bases:

Adenine (A), Guanine (G),

Thymine (T), and Cytosine (C)


DNA Specificity

Hydrogen bonding between base pairs

Stacking interaction between bases along axis of double-helix

Animation


Principles of DNA biosensors Nucleic acid hybridization


Source: http://cswww.essex.ac.uk

ssDNA (Probe)

(Target Sequence)

(Hybridization)

(Stable dsDNA)

E-DNA Sensor Structure

“Stem-loop”

s

Gold electrode



“Stem-loop”

Target

s

Gold electrode




Source: Ricci et al., Langmuir, 2007, 23, 6827-6834

(Stem-loop)

(Open, extended)

Carbon Nanotube Biosensor


Image: www.cnano-rhone-alpes.org

Carbon Nanotube Biosensor


One atom thick One nanometer diameter Ability to be functionalized

Electrical conductivity as high as copper, thermal conductivity as high as diamond

CNT Biosensor Structure


Succinimidyl ester

Source: Chen et al., 2001

CNT Uncoated vs. Coated


Source: Chen et al., 2001

CNT Biosensor Signal Detection


Source: Besteman et al., 2003

O2

H2O2

Glucose

Gluconic Acid

e-



e-

e- e-e-

e-

Effectively increases electrical current

CNT Biosensor Signal Detection

CNT Biosensor Results



0 mM

20 mM

60 mM

160 mM


BioFET Draws upon versatility of common electronic

component (Field-Effect Transistor) Well understood expectations/results


FET

Drain Gate

Source

-

-

-

-

-

-

Insulator

+

+ + + +

(Electron Channel)(Not conductive enough)


FET

Drain Gate

Source

-

Insulator

+

+ + + +

Threshold Voltage


FET

Drain Gate

Source

-

-

-

-

-

-

- -

Insulator

+ + + +

+

+ + + +

- -- -- -


Source: Im et al., 2007

BioFET



BioFET Results

Gate (before)



BioFET ResultsGate

(after etch, w/biotin)

Gate (w/ complete Biomolecule)

d


Source: http://www.whatsnextnetwork.com/technology/media/cell_adhesion.jpg

Whole Cell Sensors


Whole Cell Sensors Harness normal genetic processes May detect dozens of pathogens Modifiable/customizable Reports bioavailability

Temperature/pH sensitive Short shelf-life


Source: Daunert et al., 2000

Whole Cell Sensors


Source: Tonomura et al., 2006

Action-Potential Biosensor




(Side view)




Suction

Carbon N-T E-DNA BioFETIntroduction

Summary Use of biomolecules in sensors offers:

Extreme sensitivity Flexibility of use Wide array of detection Universal application

Whole Cell Summary

Summary But still maintains challenges of:

pH/Temperature sensitivity Degradation Repeatable use

Regardless of challenges: Biosensors will permeate future

society

Carbon N-T E-DNA BioFETIntroduction Whole Cell Summary

References K McKimmie. “What’s a Biosensor, Anyway?”, Indiana Business Magazine, 2005, 49, 1:18-23. N Zimmerman. “Chemical Sensors Market Still Dominating Sensors”, Materials Management in Health Care, 2006, 2, 54. K Odenthal, J Gooding. “An introduction to electrochemical DNA biosensors”, Analyst, 2007, 132, 603–610. S V Lemeshko, T Powdrill, Y Belosludtsev, M Hogan, “Oligonucleotides form a duplex with non-helical properties on a positively charged surface”, Nucleic

Acids Res., 2001, 29, 3051–3058. F Ricci, R Lai, A Heeger, K Plaxco, J Sumner. “Effect of Molecular Crowding on the Response of an Electrochemical DNA Sensor”, Langmuir, 2007, 23,

6827-6834. M Heller. “DNA Microarray Technology”, Annual Review of Biomedical Engineering, 2002, 4, 129-153. E Boon, D Ceres, T Drummond, M Hill, J Barton, “Mutation Detection by DNA electrocatalysis at DNA-modified electrodes”, Nat. Biotechnol. 2000, 18, 1096-

1100. S Timur, U Anik, D Odaci, L Gorton, “Development of a microbial biosensor based on carbon nanotube (CNT) modified electrodes”,

Electrochemistry Communications, 2007, 9, 1810-1815. K Besteman, J Lee, F Wiertz, H Heering, C Dekker. “Enzyme-Coated Carbon Nanotubes as Single-Molecule Biosensors”, Nano Letters, 2003, 3, 6: 727-730. R Chen, Y Zhang, D Wang, H Dai. “Noncovalent Sidewall Functionalization of Single-Walled Carbon Nanotubes for Protein Immobilization”, J. Am. Chem.

Soc., 2001, 123, 16: 3838 -3839. K Balasubramanian, M Burghard. “Biosensors based on carbon nanotubes”, Anal. Bioanal. Chem., 2005, 385, 452-468. Hayes & Horowitz, Student Manual for the Art of Electronics, Cambridge Univ. Press, 1989. I Hyungsoon, H Xing-Jiu, G Bonsang, C Yang-Kyu. “A dielectric-modulated field-effect transistor for biosensing”, Nature Nanotechnology, 2007, 2, 430 –

434. D Therriault. “Filling the Gap”, Nature Nanotechnology, 2007, 2, 393 - 394. S Daunert, GBarrett, J Feliciano, R Shetty, S Shrestha, W Smith-Spencer. “Genetically Engineered Whole-Cell Sensing Systems: Coupling Biological

Recognition with Reporter Genes”, Chem. Rev. 2000, 100, 2705-2738. T Petänen, M Romantschuk. “Measurement of bioavailability of mercury and arsenite using bacterial biosensors”, Chemosphere, 2003, 50, 409-413. F Roberto, J Barnes, D Bruhn. “Evaluation of a GFP Reporter Gene Construct for Environmental Arsenic Detection.”, Talanta. 2002, 58, 1:181-188. W Tonomura, R Kitazawa, T Ueyama, H Okamura, S Konishi. “Electrophysiological biosensor with Micro Channel Array for Sensing Signals from Single

Cells”, IEEE Sensors, 2006, 140-143. R Leois, J Rae. “Low-noise patch-clamp techniques”, Meth. Enzym. 1998, 293: 218-266. [1] A Vikas, C S Pundir. “Biosensors: Future Analytical Tools”, Sensors and Transducers, 2007, 2, 935-944.

Questions?

Carbon N-T E-DNA BioFETIntroduction Whole Cell Summary

biosensors christopher byrd enpm808b university of maryland, college park december 4, 2007

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