From Bioinstrumentation to BioMEMS

research@ee.iitb.ac.in

ContentsEarly developments in bio-instrumentationCollaboration with other groupsSensor materialsSensor structuresbioMEMSWill give you a whiff of what we do and what we plan to do!

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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 inter-

disciplinary 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 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

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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

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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

Electrolyte

Silicon

Oxide

~ Two terminal device Ions attach to

surface sites, modify charge carriers in Si

Changes CV (note: small signal measurements required)

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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 Silicon

Antigen

Antibody

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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)

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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

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bioMEMS made in the ELab(2):Microelectroporator

SE

M &

op

tica

l m

icro

gra

phs

of

mic

ro p

ore

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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

Source

Sink

Dispersive drift channel

Detector system

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bioMEMS made in the ELab(5):CE

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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)

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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 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

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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