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From Bioinstrumentation to BioMEMS
ContentsEarly developments in bio-instrumentationCollaboration with other groupsSensor materialsSensor structuresbioMEMSWill give you a whiff of what we do and what we plan to do!
21 June 200221 June 2002 AIM 2002AIM 2002 22
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)
21 June 200221 June 2002 AIM 2002AIM 2002 33
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
21 June 200221 June 2002 AIM 2002AIM 2002 44
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
21 June 200221 June 2002 AIM 2002AIM 2002 55
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
21 June 200221 June 2002 AIM 2002AIM 2002 66
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
21 June 200221 June 2002 AIM 2002AIM 2002 77
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
21 June 200221 June 2002 AIM 2002AIM 2002 88
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
21 June 200221 June 2002 AIM 2002AIM 2002 99
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)
21 June 200221 June 2002 AIM 2002AIM 2002 1010
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)
21 June 200221 June 2002 AIM 2002AIM 2002 1111
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]
21 June 200221 June 2002 AIM 2002AIM 2002 1212
Why Conducting Polymers?
Assaying ions & molecules in aqueous Assaying ions & molecules in aqueous solutions is important for observing solutions is important for observing biological phenomenabiological 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
21 June 200221 June 2002 AIM 2002AIM 2002 1313
Conducting polymer ENFET
SubstrateSource Drain
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
21 June 200221 June 2002 AIM 2002AIM 2002 1414
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
21 June 200221 June 2002 AIM 2002AIM 2002 1515
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
21 June 200221 June 2002 AIM 2002AIM 2002 1616
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
21 June 200221 June 2002 AIM 2002AIM 2002 1717
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
21 June 200221 June 2002 AIM 2002AIM 2002 1818
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,..)
21 June 200221 June 2002 AIM 2002AIM 2002 1919
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
21 June 200221 June 2002 AIM 2002AIM 2002 2020
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 June 200221 June 2002 AIM 2002AIM 2002 2121
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
21 June 200221 June 2002 AIM 2002AIM 2002 2222
ISFET
P-type silicon
N+ N+
+ + + + +
-- -- -- -- --
Source Drain
Encapsulation Metal Contacts
electrons
+
[SiO2+Si3N4]
+Analyte+
+++ +
+
H++
+
RE 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)
21 June 200221 June 2002 AIM 2002AIM 2002 2323
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
21 June 200221 June 2002 AIM 2002AIM 2002 2424
bioMEMS made in the ELab(2):Microelectroporator
SE
M &
op
tica
l m
icro
gra
phs
of
mic
ro p
ore
21 June 200221 June 2002 AIM 2002AIM 2002 2525
bioMEMS made in the ELab(3):Microelectroporator
Electroporator Cell
Pulse output due to a ~15 m particle
21 June 200221 June 2002 AIM 2002AIM 2002 2626
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
21 June 200221 June 2002 AIM 2002AIM 2002 2727
bioMEMS made in the ELab(5):CE
21 June 200221 June 2002 AIM 2002AIM 2002 2828
bioMEMS made in the ELab(6):CE
0 20 40 60 80 100 120 140 160300
305
310
315
320
325
330
335
340
345
350
MUPP 1.5X
MUPP 2X
1&DS&2
S&1AND2&1
CE9_R5DNA 500bp ladderDUPP 2Xf=70kHz
Capacita
nce (
pf)
Time (min)
21 June 200221 June 2002 AIM 2002AIM 2002 2929
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
21 June 200221 June 2002 AIM 2002AIM 2002 3030
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
21 June 200221 June 2002 AIM 2002AIM 2002 3131
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