1. From Bioinstrumentation to BioMEMS research@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. 21 June 2002 AIM 2002 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)

3. 21 June 2002 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

4. 21 June 2002 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

5. 21 June 2002 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

6. 21 June 2002 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

7. 21 June 2002 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

8. 21 June 2002 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

9. 21 June 2002 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)

10. 21 June 2002 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)

11. 21 June 2002 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]

12. 21 June 2002 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

13. 21 June 2002 AIM 2002 13 Conducting polymer ENFET Substrate Source Drain H+H+ Enzyme Enzyme catalyzed reaction  H +  /     /  Substrate 0 10 20 30 40 50 60 0.30 0.25 0.20 0.15 0.10 0.05 Cross-section of a biosensor Sensor response

14. 21 June 2002 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

15. 21 June 2002 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

16. 21 June 2002 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

17. 21 June 2002 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

18. 21 June 2002 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,..)

19. 21 June 2002 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

20. 21 June 2002 AIM 2002 20 EOS Capacitor Electrolyte Silicon Oxide ~  Two terminal device Ions attach to surface sites, modify charge carriers in Si Changes CV (note: small signal measurements required)

21. 21 June 2002 AIM 2002 21 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 Silicon Antigen Antibody

22. 21 June 2002 AIM 2002 22 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)

23. 21 June 2002 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

24. 21 June 2002 AIM 2002 24 bioMEMS made in the  ELab(2): Microelectroporator SEM & optical micrographs of micro pore

25. 21 June 2002 AIM 2002 25 bioMEMS made in the  ELab(3): Microelectroporator Electroporator Cell Pulse output due to a ~15  m particle

26. 21 June 2002 AIM 2002 26 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 Source Sink Dispersive drift channel Detector system

27. 21 June 2002 AIM 2002 27 bioMEMS made in the  ELab(5):  CE

28. 21 June 2002 AIM 2002 28 bioMEMS made in the  ELab(6):  CE

29. 21 June 2002 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

30. 21 June 2002 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

31. 21 June 2002 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