Bioelectronic Systems & bioMS @ee.iitb

1. Bioelectronic Systems & bioMS@ee.iitb M B Patil Convener Microelectronics Group IIT Bombay

2. Definitions • 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.

3. Concluding Remarks about this area 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

4. Projects 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

5. iSens 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

6. Molecular 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

7. Conventional 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))

8. New 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

9. Functional Architecture of iSens Input Filter Sample Signal Conditioning + Display Biosensor Array Reactor Control + Processing Electronics Reagent

10. Antibodies Mirror Silicon Flavour of Biosensor Array: Affinity 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

11. Bipotentiostat Analyte Polymer bridging gold electrodes CE RE Au Au Substrate WE1 WE2 Flavour of BiosensorArray: Conducting 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

12. Encapsulation Metal Contacts RE Analyte + + + + + + + + + Source H+ Drain + + + + + + N+ - - - - - N+ [SiO2+Si3N4] electrons P-type silicon A Flavour of Biosensor Array: ISFET 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

13. Team & Resources People: A team of about 24 Equipment: About Rs 2 crore for equipment, includes e-beam lithography, AFM, HWCVD,…

14. Status • Have got started & working to have the devices ready • This is how a microcantilever looks

15. A 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

16. Preparation and Characterization of the 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

17. Porphyrin 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

18. STM 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)

19. I-V curves obtained Diode type characteristics with a barrier potential Measurements taken on the hill shown before

20. In 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