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Biosensors

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.

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Biosensors

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  1. Biosensors Christopher Byrd ENPM808B University of Maryland, College Park December 4, 2007

  2. Outline • Introduction • 4 Specific Types of Biosensors • Electrochemical (DNA) • Carbon nanotube • BioFET • Whole Cell • Basic functionality • Benefits/Challenges • Summary • References

  3. Introduction • Biosensor: Incorporation of a biomolecule in order to detect something Species to be detected (analyte) Filter Recognition Layer Recognition Layer Transducer Electronics Signal Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  4. Introduction • Biosensors ~ $3B • 90% → Glucose testing • 8% - 10% increase in industry per year Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  5. 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

  6. 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

  7. 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

  8. Principles of DNA biosensors • Nucleic acid hybridization (Target Sequence) (Hybridization) (Stable dsDNA) ssDNA (Probe) Source: http://cswww.essex.ac.uk Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  9. E-DNA Sensor Structure “Stem-loop” s Gold electrode Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  10. E-DNA Sensor Structure Target “Stem-loop” s Gold electrode Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  11. 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

  12. Carbon Nanotube Biosensor Image: www.cnano-rhone-alpes.org Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  13. 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

  14. CNT Biosensor Structure Succinimidyl ester Source: Chen et al., 2001 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  15. CNT Uncoated vs. Coated Source: Chen et al., 2001 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  16. 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

  17. CNT Biosensor Signal Detection e- e- e- e- e- Effectively increases electrical current Source: Besteman et al., 2003 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  18. 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

  19. 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

  20. FET + - Drain Gate Insulator Source + + + + (Not conductive enough) (Electron Channel) - - - - - Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  21. FET + - Threshold Voltage Drain Gate Insulator Source + + + + Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  22. FET + - Drain Gate Insulator Source + + + + + + + + - - - - - - - - - - - - - Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  23. BioFET Source: Im et al., 2007 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  24. BioFET Source: Im et al., 2007 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  25. BioFET Results Gate (before) Source: Im et al., 2007 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  26. d BioFET Results Gate (w/ complete Biomolecule) Gate (after etch, w/biotin) Source: Im et al., 2007 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  27. Whole Cell Sensors Source: http://www.whatsnextnetwork.com/technology/media/cell_adhesion.jpg Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  28. 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

  29. Whole Cell Sensors Source: Daunert et al., 2000 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  30. Action-Potential Biosensor Source: Tonomura et al., 2006 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  31. Action-Potential Biosensor (Side view) Source: Tonomura et al., 2006 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  32. Action-Potential Biosensor Suction Source: Tonomura et al., 2006 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  33. Action-Potential Biosensor Suction Source: Tonomura et al., 2006 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  34. Action-Potential Biosensor Source: Tonomura et al., 2006 Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

  35. 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

  36. 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

  37. 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.

  38. Questions? Introduction E-DNA Carbon N-T BioFET Whole Cell Summary

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