Bioelectronic Systems & bioMSBioelectronic Systems & bioMS@ee.iitb@ee.iitb

M B Patil

Convener Microelectronics Group

IIT Bombay

DefinitionsDefinitions

Bioelectronic Systems: Systems that utilize a bio-object or operate on bio-objects for their function.

BioMS: Microfabricated systems (MS) that utilize bio-objects or operate on bio-objects for their function.

Concluding Remarks about this Concluding Remarks about this area in AIM 2002area in AIM 2002 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 We have got this support this year

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

Projects in this areaProjects in this area

A major sponsored project by NPSM on ‘bioMS for Cardiac Markers’ [we have called this sensing system iSens]

Smaller and internally funded projects in biomolecular electronics and electroporation FOR MORE INFO...

A site on iSens will soon be up

iSens Project GoalsiSens Project Goals

The ultimate goal of the project is to design & prototype: A Point of Care Assay System for Molecular Markers for

Myocardial Infarction Would involve:

– Design & prototype of processes– Design & prototype of structures – Integration of system for quick assay of cardiac markers– Testing of the devices and systems at various stages of

the development– Overall protocol testing

Team & Timeframe:– Multi-departmental team– Project duration 30 months

Molecular MarkersMolecular Markers

Enzymatic markers– Creatine kinase-Total (CK)– Creatine kinase MB (CK-MB)– Lactate dehydrogenase (LDH)– Aspartate aminotransferase (AST)– Glycogen phosphorylase isoenzyme BB (GPBB)

Protein molecules– Troponin– Myoglobin

Cell-free DNA fragments Will try the molecules in blue

Conventional ApproachesConventional Approaches

Sequential assays Immunoassays:

– ELISA (Enzyme Linked ImmunoSorbant Assay)

– Radioimmunoassay– Immunoprecipitation

Chromatography (!) Electrophoresis for separating isomers

and then looking for activity (for lab (skilled labor, time consuming))

New approachesNew approaches

Biosensor array based or microfabricated sequential assay system based

General approach is to use affinity sensors

Some modern direct affinity sensors:– Quartz crystal microbalance– Surface plasmon resonance– Affinity cantilevers– Conducting polymer devices– EIS capacitors

Functional Architecture of iSensFunctional Architecture of iSens

Input Filter

ReactorBiosensor

Array

Reagent

Sample

Signal Conditioning

+Display

Control + ProcessingElectronics

Flavour of Biosensor Array: Flavour of Biosensor Array: Affinity CantileversAffinity Cantilevers

Based on resonating structure 0r deflection: Attachment changes mass

or stiffness of resonating structure and thence resonant frequency

Attachment changes bending of the cantilever

Antibodies

Silicon

Mirror

Flavour of Flavour of BiosensorArray: BiosensorArray: Conducting polymer FETsConducting polymer FETs

Inter-digitated noble metal electrode covered with conducting polymer

Conductance change occurs with change of state (such as change of pH in enzyme catalyzed or affinity reaction) that can be used for sensing

CE RE

WE1

Analyte Bipotentiostat

Polymer bridging gold electrodes

Substrate WE2

AuAu

Flavour of Flavour of Biosensor Array: Biosensor Array: ISFET basedISFET based Attachment of ions to

naturally occurring surface sites or ionophores attached to the surface of the dielectric of a FET-like device Changes channel charge

& thence drain current Could be used in the

constant drain current mode or constant gate voltage mode

P-type silicon

N+ N+

+ + + + +

-- -- -- -- --

Source Drain

Encapsulation Metal Contacts

electrons

+

[SiO2+Si3N4]

+Analyte+

+++ +

+

H++

+

RE

Team & ResourcesTeam & Resources

People: A team of about 24Equipment: About Rs 2 crore for

equipment, includes e-beam lithography, AFM, HWCVD,…

StatusStatus

Have got started & working to have the devices ready

This is how a microcantilever looks

A whiff of a smaller projectA whiff of a smaller project

A student project, but with faculty and research scholar support form Chemistry & Electrical Engineering

Aim: Try to see how a gold-single molecule (a porphyrin synthesized in Chemistry) behaves as a diode

Deposit gold on SiO2, Deposit a SAM monolayer, study IV characteristics with a STM

Preparation and Characterization of Preparation and Characterization of the gold filmthe gold film

- Prepared using Physical Vapor deposition process

-Cleaned using the Piranha solution to remove organic impurities

-XRD spectrum taken to analyse the crystal structure

-<111> crystal structure observed

-STM/AFM pictures taken to gauge surface smoothness

1000nm x 1000nm scan

Features height < 1nm

Porphyrin MoleculesPorphyrin Molecules

Porphyrin Molecule attatched with a thiol group protected by an acetate group

Formation of SAM: in-situ cleavage of the S-Ac bond

Metallo-porphyrin selected due to its intercalating properties with DNA

The methyl groups attached make the porphyrin water soluble

Tetra Methyl Pyridyl Zinc Porphyrin Thiol Acetate

STM ImagesSTM Images

Ridges type structure obtained in the first figure (10nm x 10nm scan)

Valley of depth ~1nm observed in the second image (50nm x 50nm scan)

I-V curves obtainedI-V curves obtained

-80.00

-60.00

-40.00

-20.00

0.00

20.00

40.00

60.00

80.00

100.00

120.00

-1.50 -1.00 -0.50 0.00 0.50 1.00 1.50

Voltage (V)

Cu

rre

nt

(nA

)

I-V curve

-10.00

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

-1.50 -1.00 -0.50 0.00 0.50 1.00 1.50

Voltage (V)

Cu

rre

nt

(nA

)

Diode type characteristics with a barrier potential

Measurements taken on the hill shown before

In conclusionIn conclusion

There is frenetic activity in the bioelectronics and bioMS area at IITB

Need to create more awareness of the applications of this new area

Need to increase interaction with user agencies