biosensors christopher byrd enpm808b university of maryland, college park december 4, 2007
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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
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Electrochemical DNA Sensors
Harnesses specificity of DNA Simple assembly Customizable Vast uses for small cost
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
DNA Structure
DNA structures---double helix
4 complementary bases:
Adenine (A), Guanine (G),
Thymine (T), and Cytosine (C)
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
DNA Specificity
Hydrogen bonding between base pairs
Stacking interaction between bases along axis of double-helix
Animation
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Principles of DNA biosensors Nucleic acid hybridization
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: http://cswww.essex.ac.uk
ssDNA (Probe)
(Target Sequence)
(Hybridization)
(Stable dsDNA)
E-DNA Sensor Structure
“Stem-loop”
s
Gold electrode
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
E-DNA Sensor Structure
“Stem-loop”
Target
s
Gold electrode
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
E-DNA Sensor Structure
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Ricci et al., Langmuir, 2007, 23, 6827-6834
(Stem-loop)
(Open, extended)
Carbon Nanotube Biosensor
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Image: www.cnano-rhone-alpes.org
Carbon Nanotube Biosensor
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
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
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Succinimidyl ester
Source: Chen et al., 2001
CNT Uncoated vs. Coated
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Chen et al., 2001
CNT Biosensor Signal Detection
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Besteman et al., 2003
O2
H2O2
Glucose
Gluconic Acid
e-
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Besteman et al., 2003
e-
e- e-e-
e-
Effectively increases electrical current
CNT Biosensor Signal Detection
CNT Biosensor Results
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Besteman et al., 2003
0 mM
20 mM
60 mM
160 mM
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
BioFET Draws upon versatility of common electronic
component (Field-Effect Transistor) Well understood expectations/results
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
FET
Drain Gate
Source
-
-
-
-
-
-
Insulator
+
+ + + +
(Electron Channel)(Not conductive enough)
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
FET
Drain Gate
Source
-
Insulator
+
+ + + +
Threshold Voltage
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
FET
Drain Gate
Source
-
-
-
-
-
-
- -
Insulator
+ + + +
+
+ + + +
- -- -- -
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Im et al., 2007
BioFET
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Im et al., 2007
BioFET
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Im et al., 2007
BioFET Results
Gate (before)
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Im et al., 2007
BioFET ResultsGate
(after etch, w/biotin)
Gate (w/ complete Biomolecule)
d
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: http://www.whatsnextnetwork.com/technology/media/cell_adhesion.jpg
Whole Cell Sensors
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Whole Cell Sensors Harness normal genetic processes May detect dozens of pathogens Modifiable/customizable Reports bioavailability
Temperature/pH sensitive Short shelf-life
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Daunert et al., 2000
Whole Cell Sensors
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Tonomura et al., 2006
Action-Potential Biosensor
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Tonomura et al., 2006
Action-Potential Biosensor
(Side view)
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Tonomura et al., 2006
Action-Potential Biosensor
Suction
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Tonomura et al., 2006
Action-Potential Biosensor
Suction
Carbon N-T E-DNA BioFET Whole Cell SummaryIntroduction
Source: Tonomura et al., 2006
Action-Potential Biosensor
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