1. BioSensors Yang Yang 9/28/2004

2. Outlines BioMEMS Enzyme-coated carbon nanotubes Microcantilever biosensor with environmentally responsive hydrogel Cantilever array based nanotechnology olfactory sensors Conclusion

3. BioMEMS Inetegration of life science/biomedical Disciplines with micro- and nano- Scale systems and materials.

4. BioMEMS Materials used for fabricationBiosensors Biosensors are analytical devices that combine a biologically sensitive Element with a physical or chemical transducer to selectively and quan- Titatively detect the presence of specific compounds in a given external environment.

5. BioMEMS Biosensor—Mechanical detection Mass mode cantilever sensorStress mode cantilever sensor

6. BioMEMS Biosensor-- Electrical detection Ampero, monitors formation of H+ in a redox process Potentio, measures the potential at an electrode in reference to another Conducto, measures the changes in Electrical impedance between 2 electrodes. Both ampero- and potentio- need reference electrodes, which makes the fabrication difficult. Conducto- does not.

7. BioMEMS Biosensor-- Optical detection Based on fluorescence or chemiluminescence. Fluorescence- fluorescent markers emits light at specific wavelengths, thus any change in optical signal indicates a binding reaction. Chemiluminescence- light is generated by the release of energy as a result of a chemical reaction. Cited paper R. Bashir, BioMEMS: state-of-the-art in detection, opportunities and prospects, Advanced drug delivery reviews, 56 (2004) 1565-1586

8. Enzyme-Coated Carbon Nanotubes Manufacturing method

9. Enzyme-Coated Carbon Nanotubes Effects of GOx immobilization After immobilization 1.AFM height: 5 nm → 8 nm; 2.1 GOx molecule per 12 nm; 3.Conductance of SWNT decreases significantly (black → cyan); 50 GOx molecules on SWNT bare SWNT 4. pH dependent;

10. Enzyme-Coated Carbon Nanotubes Effects of GOx immobilization 5. Glucose sensitive. Pros Very sensitive to testing entities. 1.Excellent nanosize pH sensor: can measure pH as low as 0.1; 2.Enzyme detector: can measure the enzymatic activity of a single redox enzyme. Cited paper K. Besteman, et al, Enzyme-coated Carbon nanotubes as single- Molecule biosensors, vol. 3, no. 6,727-730, 2003

11. Microcantilever Biosensor with Environmentally Responsive Hydrogel Method of fabrication Silicon-On Insulator (SOI) wafer Oxide layer Silicon layer Buried silicon layer Etch using photoresist mask Etch out 3 layers at selected locations Grown oxide Dry etch out oxide on substrate Use tetramethylammonium hydroxide to etch the silicon substrate and to form the Cantilever/oxide composite Cantilever/oxide combo Soaked in hydro- Fluoric acid to etch Off all oxide Released cantilever Soaked in organosilane gaining bonding between polymers and cantilever Precise photo-etching to form coated cantilever

12. Microcantilever Biosensor with Environmentally Responsive Hydrogel Testing results Hydrogel film capable of Sensing the change in pH; Sensitivity of pH is Per 1 nm bending Increasing pH path Decreasing pH path

13. Microcantilever Biosensor with Environmentally Responsive Hydrogel Pros 1.Very sensitive to changes in pH; 2.Response features can be controlled by modifying swelling properties of the coating material, by changing the dimension of cantilever, etc; 3.Can be testing sample specific by bonding other environmentally responsive hydrogels. Cited paper J.Z. Hilt, et al, Ultrasensitive biomems sensors based on microcantilevers Patterned with environmentally responsive hydrogels, Biomedical microdevice 5:3, 177-184, 2003

14. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Cantilever sensors array and polymer coatings Cantilever length: thickness: width:

15. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Schematic setup

16. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Data acquisition Signal magnitude for each one of the 8 cantilevers at 5 acquisition Instants with the injection of etha- nol

17. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Data processing (Principal Compo- nents Analysis) PCA is a statistical method that rotates a data set such that the max. variability is visible and the Most important gradients are Identifiedmore.more

18. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Differential measurement in liquids Noises occur in liquid envir. measurement: changes in pH; Ion concentration; temperature and etc.

19. Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE) Pros and Cons Reference sensors can be used for differential measurements; It can be used in various media; High sensitivity over a wide range of operating temperatures; It can be integrated into other systems; Relatively long response time. Cited paper M.K. Baller, et al, A cantilever array-based artificial nose, Ultramicroscopy, 82 (2000) 1-9

20. Conclusion Biosensors are very small, very sensitive and can be transplanted to human body; Dramatically improve efficiency in drug discovery research; Multidisciplinary