From Bioinstrumentation to BioMEMS Contents
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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
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)
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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
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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 interdisciplinary work
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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
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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
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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
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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:
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:
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:
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
ISFET
Capacitive immunosensor
bioMEMS
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
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,..)
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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
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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
20
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
21
ISFET
A field effect device
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
26
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
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
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