Transcript From Bioinstrumentation to BioMEMS Contents

From Bioinstrumentation to BioMEMS
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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!
Early history of
bioinstrumentation @ IITB
 Began with work in the Electrical Department
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Electro-oculography, electromyography, ECG,
microprocessor based ECG analyzer, ..
 Other departments
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Mechanical & aeronautical: fluid dynamics & flow
(theory and some instrumentation)
Physics: X-ray imaging & laser applications (mainly
theoretical)
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Subsequent Developments
 New developments in EE in bioinstrumentation
 Setting up of the School of Biomedical Engineering
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~ 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
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New developments in EE (1)
 Mid to late eighties faculty joined with
research interests in instrumentation,
microelectronics, signal & image processing
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They also had interests in bio-related
application areas
The administration encouraged interdisciplinary work
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New developments in EE (2)
 Several projects executed on:
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Audiometry
PC based patient monitoring system
ECG telemetry & ECG data compression
Speech recognition
Aids for the visually challenged
MRI image enhancement
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New developments in EE (3)
 Electronic Design Laboratory (EDL) projects:
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Prosthetic hand/wrist based on
(a) EMG activity (b) Simple audio cues
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Aids for the visually challenged
(a)A clock that reads out time based on audio/inputs
(b) Several projects on ultrasonic object detectors
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Low cost devices for web-based healthcare delivery
(a) ECG and other physiological parameters (b) mobile
acquisition system for physiological parameter
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Electronic sensing systems for rice polish evaluation
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New developments in EE (4)
 EDL projects (contd):
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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
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Impedance tomography system
System for single cell electroporation
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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
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Bio-instrumentation with SBME (2)
 Within SBME:
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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)
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Bio-instrumentation with SBME (3)
 Jointly EE & SBME:
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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)
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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]
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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
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Conducting polymer ENFET
0.30
Substrate
H+
0.25
Enzyme
Enzyme catalyzed reaction
H+ /
  /
0.20
0.15
0.10
Source
Substrate
Drain
0.05
0
10
20
30
40
50
60
Cross-section of a biosensor
Sensor response
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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
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Sensor materials
 Some materials related work:
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ITO for reducing gas sensors
Cadmium oxide films by ARE for
photometry
Indium doping of silicon for IR sensors
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Some biosensors in ELab
 MOS capacitor based radiation sensors
 EOS based sensors
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ISFET
Capacitive immunosensor
 bioMEMS
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Silicon micro-electrodes & cantilevers
Silicon electroporation transducer
Capillary electrophoresis
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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
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Sensors (EOS system based)
 EOS Capacitors
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For ions & biomolecules (mainly affinity BS)
 ISFETs
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For ions & biomolecules (mainly catalytic BS)
 Sensing systems
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Arrays (proteins, DNA fragments,…)
Capillary Electrophoresis (proteins, DNA,…)
Dielectrophoretic systems (cells, organelles,..)
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What can be exploited in EOS
systems for Biosensors?
 In MOS Capacitors
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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
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Change of surface charge can modify the channel
charge
This can be probed as a change of the threshold
voltage
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EOS Capacitor
 Two terminal device
 Ions attach to
surface sites, modify
charge carriers in Si
 Changes CV
(note: small signal
measurements
required)
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Oxide
Electrolyte
Silicon
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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
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Antigen
Antibody
Silicon
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ISFET
 A field effect device
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Ions attaching to
surface sites modify
channel charge
Channel current
therefore modulated
Encapsulation
Metal Contacts
RE
+
+
Source
N+
+
+ +
+ + + +
+
Drain
H+
+++++
Analyte
- - - - -
N+
electrons
[SiO2+Si3N4]
P-type silicon
(note: DC measurements
fine  more complex
device but simpler
instrumentation)
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bioMEMS made in the Elab:
Microelectroporator
 Single cell microelectroporator
 Pore etched in silicon
so that impedance
change can be observed
for single cells passing
through the pore
 Electroporate when
threshold reached
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SEM & optical micrographs of micro pore
bioMEMS made in the ELab(2):
Microelectroporator
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bioMEMS made in the ELab(3):
Microelectroporator
Electroporator Cell
Pulse output due to a ~15 m particle
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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
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Source
Dispersive
drift channel
Detector system
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Sink
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bioMEMS made in the ELab(5):
CE
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bioMEMS made in the ELab(6):
CE
350
S&1
AND S&21&D
2&1
MUPP
1.5X
345
Capacitance (pf)
340
335
330
MUPP
2X
325
CE9_R5
DNA 500bp ladder
DUPP 2X
f=70kHz
320
315
310
305
300
0
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40
60 80 100 120 140 160
Time (min)
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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
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Conclusions
 IITB is one of the few places in the country which has
demonstrated collaborative work in the area of bioinstrumentation & 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
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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
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SBME: S Devasahayam, R Manchanda, S Mukherji
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Chemistry: AQ Contractor
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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)
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 Students:
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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
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