biosensors yang yang 9/28/2004. outlines biomems enzyme-coated carbon nanotubes microcantilever...

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 lifescience/biomedicalDisciplines with micro- and nano-Scale systems andmaterials.

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.

BioMEMSBiosensor—Mechanical detection

Mass mode cantilever sensor Stress mode cantilever sensor

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.

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

Enzyme-Coated Carbon Nanotubes

Chemical VaporDeposit(CVD)

Manufacturing method

Semi-conducting CarbonNanotubes(SWNTs)

Immobize SWNTs

Soaking and Washingin solution

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;

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

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

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

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

Cantilever Array Based Nanotechnology Olfactory Sensors (NOSE)

m1

Cantilever sensors array and polymer coatings

Cantilever length: m500

m100

thickness:

width:

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 acquisitionInstants with the injection of etha-nol

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.

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

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

Conclusion

Biosensors are very small, very sensitive and

can be transplanted to human body; Dramatically improve efficiency in drug

discovery research; Multidisciplinary