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
Filter
Recognition Transducer Electronics Signal
(analyte) Layer

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Introduction

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

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Electrochemical DNA Sensors

 Harnesses specificity of DNA

 Simple assembly
 Customizable
 Vast uses for small cost

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 DNA Structure

 DNA structures---double
helix
 4 complementary
bases:
Adenine (A), Guanine (G),
Thymine (T), and Cytosine (C)

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 DNA Specificity
 Hydrogen bonding between base pairs

 Stacking interaction between bases along axis

of double-helix
 Animation

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Principles of DNA biosensors
 Nucleic acid hybridization

(Target Sequence)

(Hybridization)

ssDNA (Probe) (Stable dsDNA)

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

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 E-DNA Sensor Structure

“Stem-loop”

Gold electrode

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 E-DNA Sensor Structure
Target

“Stem-loop”

Gold electrode

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 E-DNA Sensor Structure

(Open, extended)

(Stem-loop)

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

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Carbon Nanotube Biosensor

Image: www.cnano-rhone-alpes.org

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 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

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 CNT Biosensor Structure

Succinimidyl ester

Source: Chen et al., 2001

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 CNT Uncoated vs. Coated

Source: Chen et al., 2001

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 CNT Biosensor Signal Detection

Glucose
O2
Gluconic Acid
H2O2
e-

Source: Besteman et al., 2003

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 CNT Biosensor Signal Detection

e- e- e-

e-

Effectively increases electrical current

Source: Besteman et al., 2003

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 CNT Biosensor Results

160 mM

60 mM

20 mM

0 mM

Source: Besteman et al., 2003

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 BioFET
 Draws upon versatility of common electronic
component (Field-Effect Transistor)
 Well understood expectations/results

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 FET
+

Drain Gate
Insulator Source
+ + + +
(Not conductive enough)
(Electron Channel)

- - -
- -

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 FET
+

-
Threshold Voltage
Drain Gate
Insulator Source
+ + + +

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 FET
+

Drain Gate
Insulator Source
++ +++ + ++
- - - - - -
- -
- - -
- -

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 BioFET

Source: Im et al., 2007

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 BioFET

Source: Im et al., 2007

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 BioFET Results
Gate (before)

Source: Im et al., 2007

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 BioFET Results
Gate
(w/Gate
complete
(afterBiomolecule)
etch, w/biotin)

Source: Im et al., 2007

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Whole Cell Sensors

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

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

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

 Temperature/pH sensitive
 Short shelf-life

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Whole Cell Sensors

Source: Daunert et al., 2000

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Action-Potential Biosensor

Source: Tonomura et al., 2006

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Action-Potential Biosensor

(Side view)

Source: Tonomura et al., 2006

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Action-Potential Biosensor

Suction

Source: Tonomura et al., 2006

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Action-Potential Biosensor

Suction

Source: Tonomura et al., 2006

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Action-Potential Biosensor

Source: Tonomura et al., 2006

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Summary
 Use of biomolecules in sensors offers:
 Extreme sensitivity
 Flexibility of use
 Wide array of detection
 Universal application

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

 Summary
 But still maintains challenges of:
 pH/Temperature sensitivity
 Degradation
 Repeatable use

 Regardless of challenges:
 Biosensors will permeate future society

Introduction E-DNA Carbon N-T BioFET 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?

Introduction E-DNA Carbon N-T BioFET Whole Cell Summary