Transcript BioelectronicSystem_bioMS - Department of Electrical Engineering

Bioelectronic Systems & bioMS
@ee.iitb
M B Patil
Convener Microelectronics Group
IIT Bombay
Definitions
Bioelectronic Systems: Systems that
utilize a bio-object or operate on bioobjects for their function.
 BioMS: Microfabricated systems (MS)
that utilize bio-objects or operate on bioobjects for their function.
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Concluding Remarks about this
area in AIM 2002
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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  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 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
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FOR MORE INFO...
A site on iSens will soon be up
iSens Project Goals
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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 Markers

Enzymatic markers
– Creatine kinase-Total (CK)
– Creatine kinase MB (CK-MB)
– Lactate dehydrogenase (LDH)
– Aspartate aminotransferase (AST)
– Glycogen phosphorylase isoenzyme BB (GPBB)
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Protein molecules
– Troponin
– Myoglobin
Cell-free DNA fragments
Will try the molecules in blue
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Conventional Approaches
Sequential assays
 Immunoassays:
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– ELISA (Enzyme Linked ImmunoSorbant Assay)
– Radioimmunoassay
– Immunoprecipitation
Chromatography (!)
 Electrophoresis for separating isomers and
then looking for activity (for lab (skilled labor,
time consuming))
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New approaches
Biosensor array based or microfabricated
sequential assay system based
 General approach is to use affinity sensors
 Some modern direct affinity sensors:
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– Quartz crystal microbalance
– Surface plasmon resonance
– Affinity cantilevers
– Conducting polymer devices
– EIS capacitors
Functional Architecture of iSens
Sample
Input Filter
Reactor
Reagent
Biosensor
Array
Control + Processing
Electronics
Signal
Conditioning
+
Display
Flavour of Biosensor Array:
Affinity Cantilevers
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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
Mirror
Silicon
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
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Analyte
Bipotentiostat
Polymer bridging gold
electrodes
CE
Au
WE1
RE
Au
Substrate
WE2
Flavour of Biosensor Array:
ISFET based
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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
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Could be used in the
constant drain current
mode or constant gate
voltage mode
Encapsulation
Metal Contacts
RE
+
+
Source
N+
+
+ +
+ + + +
+
Drain
H+
+++++
Analyte
- - - - electrons
[SiO2+Si3N4]
P-type silicon
N+
Team & Resources
People: A team of about 24
Equipment: About Rs 2 crore for
equipment, includes e-beam
lithography, AFM, HWCVD,…
Status
Have got started &
working to have the
devices ready
 This is how a
microcantilever
looks
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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
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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
Porphyrin Molecules
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Porphyrin Molecule
attatched with a thiol
group protected by an
acetate group
Formation of SAM: insitu 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 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)
120.00
I-V curve
100.00
70.00
80.00
60.00
60.00
50.00
40.00
20.00
-1.50
-1.00
0.00
-0.50
0.00
-20.00
0.50
1.00
1.50
Current (nA)
Current (nA)
I-V curves obtained
40.00
30.00
20.00
10.00
-40.00
-60.00
-1.50
-80.00
Voltage (V)
-1.00
-0.50
0.00
0.00
-10.00
0.50
Voltage (V)
Diode type characteristics with a barrier potential
Measurements taken on the hill shown before
1.00
1.50
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
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