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BioSensors
Yang Yang
9/28/2004
Outlines
BioMEMS
Enzyme-coated carbon nanotubes
Microcantilever biosensor with environmentally responsive hydrogel
Cantilever array based nanotechnology olfactory sensors
Conclusion
BioMEMS
Inetegration of life
science/biomedical
Disciplines with
micro- and nanoScale systems and
materials.
BioMEMS
Biosensors
Biosensors are analytical devices
that combine a biologically sensitive
Element with a physical or chemical
transducer to selectively and quanTitatively detect the presence of
specific compounds in a given
external environment.
Materials used for fabrication
BioMEMS
Biosensor—Mechanical detection
Mass mode cantilever sensor
Stress mode cantilever sensor
BioMEMS
Biosensor-- Electrical detection
Ampero, monitors formation of H+ in
a redox process
Potentio, measures the potential
at an electrode in reference to
another
Conducto, measures the changes in
Electrical impedance between 2 electrodes.
Both ampero- and potentioneed reference electrodes,
which makes the fabrication
difficult. Conducto- does not.
BioMEMS
Biosensor-- Optical detection
Based on fluorescence or chemiluminescence.
Fluorescence- fluorescent markers emits light at
specific wavelengths, thus any
change in optical signal indicates
a binding reaction.
Chemiluminescence- light is generated by the
release of energy as a result of a
chemical reaction.
Cited paper
R. Bashir, BioMEMS: state-of-the-art in detection, opportunities and prospects,
Advanced drug delivery reviews, 56 (2004) 1565-1586
Enzyme-Coated Carbon
Nanotubes
Manufacturing method
Chemical Vapor
Deposit
(CVD)
Semi-conducting Carbon
Nanotubes(SWNTs)
Immobize SWNTs
Soaking and Washing
in solution
Enzyme-Coated Carbon
Nanotubes
Effects of GOx immobilization
After immobilization
1. AFM height: 5 nm → 8 nm;
2. 1 GOx molecule per 12 nm;
3. Conductance of SWNT decreases
significantly (black → cyan);
bare SWNT
50 GOx
molecules
on SWNT
4. pH dependent;
Enzyme-Coated Carbon
Nanotubes
Effects of GOx immobilization
5. Glucose sensitive.
Pros
Very sensitive to testing entities.
1. Excellent nanosize pH sensor:
can measure pH as low as 0.1;
2. Enzyme detector:
can measure the enzymatic
activity of a single redox enzyme.
Cited paper
K. Besteman, et al, Enzyme-coated
Carbon nanotubes as singleMolecule biosensors, vol. 3, no. 6
,727-730, 2003
Microcantilever Biosensor with
Environmentally Responsive
Hydrogel
Method of fabrication
Released cantilever
Oxide layer
Silicon layer
Silicon-On Insulator
(SOI) wafer
Buried
silicon
layer
Etch using photoresist mask
Soaked in hydroFluoric acid to etch
Off all oxide
Etch out 3 layers at
selected locations
Dry etch out
oxide on
substrate
Soaked in organosilane
gaining bonding between
polymers and cantilever
Grown oxide
Use tetramethylammonium
hydroxide to etch the silicon
substrate and to form the
Cantilever/oxide composite
Precise photo-etching
to form coated cantilever
Cantilever/oxide
combo
Microcantilever Biosensor with
Environmentally Responsive
Hydrogel
Testing results
Hydrogel film capable of
Sensing the change in pH;
5
Sensitivity of pH is 5 10 pH
Per 1 nm bending
Increasing pH path
Decreasing pH path
Microcantilever Biosensor with
Environmentally Responsive
Hydrogel
Pros
1. Very sensitive to changes in pH;
2. Response features can be controlled
by modifying swelling properties of the
coating material, by changing the dimension
of cantilever, etc;
3. Can be testing sample specific by bonding
other environmentally responsive hydrogels.
Cited paper
J.Z. Hilt, et al, Ultrasensitive biomems sensors based on microcantilevers
Patterned with environmentally responsive hydrogels, Biomedical microdevice
5:3, 177-184, 2003
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Cantilever sensors array and polymer coatings
Cantilever length: 500m
thickness: 1m
width: 100m
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Schematic setup
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Data acquisition
Signal magnitude for each one
of the 8 cantilevers at 5 acquisition
Instants with the injection of ethanol
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Data processing (Principal Components Analysis)
PCA is a statistical method that
rotates a data set such that the
max. variability is visible and the
Most important gradients are
Identifiedmore.
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Differential measurement in liquids
Noises occur in liquid
envir. measurement:
changes in pH;
Ion concentration;
temperature and etc.
Raw data
Compen. data
Cantilever Array Based
Nanotechnology Olfactory
Sensors (NOSE)
Pros and Cons
Reference sensors can be used for differential measurements;
It can be used in various media;
High sensitivity over a wide range of operating temperatures;
It can be integrated into other systems;
Relatively long response time.
Cited paper
M.K. Baller, et al, A cantilever array-based artificial nose, Ultramicroscopy,
82 (2000) 1-9
Conclusion



Biosensors are very small, very sensitive and
can be transplanted to human body;
Dramatically improve efficiency in drug
discovery research;
Multidisciplinary