From Bioinstrumentation to BioMEMS research@ee.iitb.ac

1. From Bioinstrumentation to BioMEMSresearch@ee.iitb.ac.in Contents Early developments in bio-instrumentation Collaboration with other groups Sensor materials Sensor structures bioMEMS Will give you a whiff of what we do and what we plan to do!

2. Early history of bioinstrumentation @ IITB • Began with work in the Electrical Department • Electro-oculography, electromyography, ECG, microprocessor based ECG analyzer, .. • Other departments • Mechanical & aeronautical: fluid dynamics & flow (theory and some instrumentation) • Physics: X-ray imaging & laser applications (mainly theoretical) AIM 2002

3. Subsequent Developments • New developments in EE in bioinstrumentation • Setting up of the School of Biomedical Engineering • ~ 1987 IITB Senate takes a landmark decision to admit medical graduates in its post-graduate program in BME • Synergistic development of bio-instrumentation with BME • Biosensor work with Chemistry & Materials Science • Sensor & biosensor research in Microelectronics AIM 2002

4. New developments in EE (1) • Mid to late eighties faculty joined with research interests in instrumentation, microelectronics, signal & image processing • They also had interests in bio-related application areas • The administration encouraged inter-disciplinary work AIM 2002

5. New developments in EE (2) • Several projects executed on: • Audiometry • PC based patient monitoring system • ECG telemetry & ECG data compression • Speech recognition • Aids for the visually challenged • MRI image enhancement AIM 2002

6. New developments in EE (3) • Electronic Design Laboratory (EDL) projects: • Prosthetic hand/wrist based on (a) EMG activity (b) Simple audio cues • Aids for the visually challenged (a)A clock that reads out time based on audio/inputs (b) Several projects on ultrasonic object detectors • Low cost devices for web-based healthcare delivery (a) ECG and other physiological parameters (b) mobile acquisition system for physiological parameter • Electronic sensing systems for rice polish evaluation AIM 2002

7. New developments in EE (4) • EDL projects (contd): • ECG recording using a sound card • Battery driven high-voltage isolated stimulator. • Water & air quality monitor (a)System to measure water quality in Powai lake (b) System to measure air quality and noise .. (c) Transceiver and PC data acquisition equipment • Impedance tomography system • System for single cell electroporation AIM 2002

8. Bio-instrumentation with SBME • Several core faculty members in SBME had interest in instrumentation for their research • Interaction between EE & SBME faculty and students lead to more realistic projects • Having SBME on campus increased the engineering faculty’s interaction with doctors and hospitals AIM 2002

9. Bio-instrumentation with SBME (2) • Within SBME: • Great interest in instrumentation for electrophysiology: a slew of stimulators & signal capture modules (an EMG analyzer sold to industry and is undergoing field trials) • Biopotential amplifiers • Instrumentation for hemorheological studies • Prosthetic hand • Tele-medicine (several faculty across the institute) AIM 2002

10. Bio-instrumentation with SBME (3) • Jointly EE & SBME: • Instrumentation for tissue impedance study • Pulse oximetry • Audiometry • Silicon microprobe for potential and strain measurement (an early anisotropic etching project in the country) • Medical imaging: Diagnostic support for mamography (more info in the communications group site) AIM 2002

11. Biosensor work with Chemistry • Pioneering work on conducting polymers has been conducted in the electrochemistry lab in the Department of Chemistry • There has been collaborative work with EE to convert some of this knowledge to conducting polymer microsensors & biosensors • Sensors & instrumentation for: ions & biomolecules realized [Major Media Lab & DBT projects in this area now on] AIM 2002

12. Why Conducting Polymers? Assaying ions & molecules in aqueous solutions is important for observing biological phenomena Problem: Conventional semiconductor chemical sensors are: • 2D devices with a planar interface (gives poor sensitivity) or poly-crystalline devices, & • Have poor stability in aqueous environments AIM 2002

13. 0.30 0.25 0.20 0.15 0.10 0.05 Substrate H+ Enzyme catalyzed reaction H+ /   / Enzyme Substrate Source Drain 0 10 20 30 40 50 60 Conducting polymer ENFET Cross-section of a biosensor Sensor response AIM 2002

14. Sensor materials & Sensors work in the ELab • For the last two decades faculty in EE have been interested in materials and structures for sensors which has lead on to bioMEMS • Early interest in materials and structures for physical sensors which moved on to chemical and biochemical sensors AIM 2002

15. Sensor materials • Some materials related work: • ITO for reducing gas sensors • Cadmium oxide films by ARE for photometry • Indium doping of silicon for IR sensors AIM 2002

16. Some biosensors in ELab • MOS capacitor based radiation sensors • EOS based sensors • ISFET • Capacitive immunosensor • bioMEMS • Silicon micro-electrodes & cantilevers • Silicon electroporation transducer • Capillary electrophoresis AIM 2002

17. Why EOS? • Compatible with standard microelectronic processing, therefore the possibility of monolithic systems • Oxide compatible and used as an containment medium for various bio-objects • Problems: • Leaky to proton drifts • Some cases interface properties not optimum AIM 2002

18. Sensors (EOS system based) • EOS Capacitors • For ions & biomolecules (mainly affinity BS) • ISFETs • For ions & biomolecules (mainly catalytic BS) • Sensing systems • Arrays (proteins, DNA fragments,…) • Capillary Electrophoresis (proteins, DNA,…) • Dielectrophoretic systems (cells, organelles,..) AIM 2002

19. What can be exploited in EOS systems for Biosensors? • In MOS Capacitors • Change of surface charge can modify what is called the high-frequency CV • For affinity biosensors, change of effective dielectric thickness can be exploited • In ISFETs • Change of surface charge can modify the channel charge • This can be probed as a change of the threshold voltage AIM 2002

20. ~ Electrolyte Oxide Silicon Example: EOS capacitor EOS Capacitor • Two terminal device • Ions attach to surface sites, modify charge carriers in Si • Changes CV (note: small signal measurements required) AIM 2002

21. Antigen Antibody Silicon Capacitive affinity biosensors • Surface of oxide coated with antibody • When antigen in analyte present, they diffuse and attach • Observe change of capacitance • Using porous silicon improves sensitivity AIM 2002

22. Encapsulation Metal Contacts RE Analyte + + + + + + + + + Source H+ Drain + + + + + + N+ - - - - - N+ [SiO2+Si3N4] electrons P-type silicon A Example: The ISFET ISFET • A field effect device • Ions attaching to surface sites modify channel charge • Channel current therefore modulated (note: DC measurements fine  more complex device but simpler instrumentation) AIM 2002

23. bioMEMS made in the Elab:Microelectroporator • Single cell micro-electroporator • Pore etched in silicon so that impedance change can be observed for single cells passing through the pore • Electroporate when threshold reached AIM 2002

24. bioMEMS made in the ELab(2):Microelectroporator SEM & optical micrographs of micro pore AIM 2002

25. bioMEMS made in the ELab(3):Microelectroporator Electroporator Cell Pulse output due to a ~15 m particle AIM 2002

26. Source Dispersive drift channel Detector system Sink bioMEMS made in the ELab(5):CE • Since biomolecules often charged, they drift in an electric field • Drift velocity different for different sized molecules or made different using dispersive media • Different transit times between source & sink used to detect different molecules AIM 2002

27. bioMEMS made in the ELab(5):CE AIM 2002

28. bioMEMS made in the ELab(6):CE AIM 2002

29. A whiff off what we plan to do • Affinity cantilevers for biomolecules • Conducting polymer arrays for diseases • Microbial sensors • “Silicon locket” for cardiovascular monitoring • Radiation sensors AIM 2002

30. Conclusions • IITB is one of the few places in the country which has demonstrated collaborative work in the area of bio-instrumentation & bio-sensing systems • These have been demonstrated by student projects and modest consultancy and sponsored projects • Need projects with critical funding levels to take these ideas to the field and is actively seeking funding and collaboration • The academic-research structure in the institute is conducive for the realization of the above objective that would create both locally useful bioMEMS based diagnostic systems and globally appreciated new knowledge AIM 2002

31. The Team (or shall we say morphing teams!) • Faculty: • EE: T Anjaneyulu, SD Agashe, AN Chandorkar, UB Desai, V Gadre, R Lal, PC Pandey, M Patil, R Rao, DK Sharma, J Vasi • SBME: S Devasahayam, R Manchanda, S Mukherji • Chemistry: AQ Contractor • Materials Science: R Srinivasa (Expanding as new faculty join with interests in related areas and as we look more seriously at systems on a chip) • Students: • Doctoral: M Reddy, G Pathak, S Kolluri, M Mitra, A Topkar, B Prasad, A Betty, A Shastry, …(just the E students more from other groups) • M Techs & Dual Degree: ~ a dozen • B Techs: ~a dozen AIM 2002