biosensors yang yang 9/28/2004. outlines biomems enzyme-coated carbon nanotubes microcantilever...
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BioSensors
Yang Yang
9/28/2004
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Outlines
BioMEMS
Enzyme-coated carbon nanotubes
Microcantilever biosensor with environmentally responsive hydrogel
Cantilever array based nanotechnology olfactory sensors
Conclusion
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BioMEMS
Inetegration of lifescience/biomedicalDisciplines with micro- and nano-Scale systems andmaterials.
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BioMEMS
Materials used for fabricationBiosensors
Biosensors are analytical devicesthat combine a biologically sensitiveElement with a physical or chemical transducer to selectively and quan-Titatively detect the presence of specific compounds in a given external environment.
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BioMEMSBiosensor—Mechanical detection
Mass mode cantilever sensor Stress mode cantilever sensor
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BioMEMSBiosensor-- Electrical detection
Ampero, monitors formation of H+ in a redox process
Potentio, measures the potentialat an electrode in reference to another
Conducto, measures the changes in Electrical impedance between 2 electrodes. Both ampero- and potentio-
need reference electrodes,which makes the fabricationdifficult. Conducto- does not.
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BioMEMSBiosensor-- 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
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Enzyme-Coated Carbon Nanotubes
Chemical VaporDeposit(CVD)
Manufacturing method
Semi-conducting CarbonNanotubes(SWNTs)
Immobize SWNTs
Soaking and Washingin solution
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Enzyme-Coated Carbon NanotubesEffects of GOx immobilization
After immobilization1. AFM height: 5 nm → 8 nm;2. 1 GOx molecule per 12 nm;3. Conductance of SWNT decreases significantly (black → cyan);
50 GOx molecules on SWNT
bare SWNT
4. pH dependent;
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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 paperK. Besteman, et al, Enzyme-coatedCarbon nanotubes as single-Molecule biosensors, vol. 3, no. 6,727-730, 2003
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Microcantilever Biosensor withEnvironmentally Responsive Hydrogel
Method of fabrication
Silicon-On Insulator (SOI) wafer
Oxide layer
Silicon layer
Buried silicon layer
Etch using photoresist mask
Etch out 3 layers at selected locations
Grown oxide
Dry etch out oxide on substrate
Use tetramethylammonium hydroxide to etch the silicon substrate and to form theCantilever/oxide composite
Cantilever/oxide combo
Soaked in hydro-Fluoric acid to etchOff all oxide
Released cantilever
Soaked in organosilanegaining bonding betweenpolymers and cantilever
Precise photo-etchingto form coated cantilever
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Microcantilever Biosensor withEnvironmentally Responsive Hydrogel
Testing results
Hydrogel film capable ofSensing the change in pH;
Sensitivity of pH isPer 1 nm bending
Increasing pH path
Decreasing pH path
pH 5105
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Microcantilever Biosensor withEnvironmentally 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 microcantileversPatterned with environmentally responsive hydrogels, Biomedical microdevice5:3, 177-184, 2003
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
m1
Cantilever sensors array and polymer coatings
Cantilever length: m500
m100
thickness:
width:
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
Schematic setup
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
Data acquisition
Signal magnitude for each one of the 8 cantilevers at 5 acquisitionInstants with the injection of etha-nol
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
Data processing (Principal Compo-nents Analysis)
PCA is a statistical method that rotates a data set such that themax. variability is visible and theMost important gradients areIdentifiedmore.
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
Raw data
Differential measurement in liquids
Noises occur in liquid envir. measurement:changes in pH;Ion concentration;temperature and etc.
Compen. data
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Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)
Pros and ConsReference 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
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Conclusion
Biosensors are very small, very sensitive and
can be transplanted to human body; Dramatically improve efficiency in drug
discovery research; Multidisciplinary