1. Selected Biosensors Yu Cao Oct 28, 2008

2. Yu Cao Outline Two categories of biosensors –I: Electrical sensors –II: Optical sensors

3. Yu Cao Using the surface effect of a transistor Al 0.3 GaN/GaN 2DEG Surface charge +σs+σs -σs-σs z

4. I: Electrolyte Gate HEMT Sensors Site-binding model: Atoms in the AlGaN surface are acting as amphoteres in contact with an electrolyte. High concentration of H 3 O + High concentration of OH - Oxidized AlGaN surface

5. Yu Cao I: Electrolyte Gate HEMT Sensors (cont.) V ds =1.0V V ref =0.0V pH values Transient behavior of Ids during changes of the pH by titration with NaOH Given constant I ds, sensitivity is defined as dV ref /d(pH), ~50mV/pH

6. Yu Cao I: Polar Liquids Sensors Adsorption of polar molecules  corresponding variation of the surface potential Dipoles superimposing the electrical field inside the barrier and modulate the 2DEG density and current isopropanal acetone methanol

7. Yu Cao I: Polar Liquids Sensors (cont.) Size sensor for water droplet

8. Yu Cao I: Biosensors

9. Yu Cao I: Biosensor – Direct Monitoring of Cell Activity The survival of living cells on the substrate or the sensor surface –Si is attacked by many biological agents, but an oxidized surface can help an appropriate cell growth –Other semiconductors require a passivation, e.g. GaAs Advantages of group-III-nitrides based HEMTs –Chemically stable –Nontoxic to living cells –Good properties for sensor applications in liquid and electrolyte environments

10. Yu Cao I: Biosensor – Direct Monitoring of Cell Activity (cont.) Cardiac myocyte syncytium clutivated on the device surface of an AlGaN/GaN electrolyte gate FET array Extracellular potential of a spontaneously beating cardiac myocyte syncytium recorded with an AlGaN/GaN electrolyte gate FET (reasons? Unknow yet!) Voltage in the junction area between transistor gate and cell

11. Yu Cao I: Biosensor – Indirect monitoring of bioreactions through pH Value Enzyme can break down lipids, releasing some acid and changing pH value.

12. Yu Cao I: Biosensor – Site-specific, selective detection of biomolecules Au-thiol group chemistry: to bound thiol-modified oligonucleotides with 5nm Au for HEMT based DNA sensing

13. Yu Cao II: Biosensor – Laser-induced Fluorescence (LIF)

14. Yu Cao II: Biosensor – Laser-induced Fluorescence (LIF)

15. Yu Cao Notes: Dye Laser A dye laser is a laser which uses an organic dye as the lasing medium, usually as a liquid solution. Compared to gases and most solid state lasing media, a dye can usually be used for a much wider range of wavelengths. The wide bandwidth makes them particularly suitable for tunable lasers and pulsed lasers. Moreover, the dye can be replaced by another type in order to generate different wavelengths with the same laser, although this usually requires replacing other optical components in the laser as well.laserorganicdye lasing mediumliquidsolution gasessolid statewavelengthstunable lasers

16. Yu Cao II: Biosensor – Laser-induced Fluorescence (LIF) Advantages LIF measurements are conducted during routine gastrointestinal endoscopy examinations The fiberoptic probe only touches the surface of the tissue An LIF measurement is completed in approximately 0.6 seconds No biopsies of the tissues are needed Greatly improves the accuracy of diagnosis for malignant tissue

17. Yu Cao II: Biosensor – optical sensors for cell Pulled nanosensors have tip diameters of ~ 40-50 nm Final coated fibers are ~ 200 nm diameter Antibody coated tips for specificity in binding Nanometer diameter tip provides near-field excitation

18. Yu Cao II: Biosensor – optical sensors for cell 325 nm line of a HeCd laser used for excitation of BPT and BaP Inverted microscope used for monitoring insertion of fiber optic probe into single cell Fluorescent light is collected by microscope objective and detected using a photon counting photo multiplier tube (PMT)

19. Yu Cao Notes: Inverted microscope An inverted microscope is a microscope with its light source and condenser on the top, above the stage pointing down, while the objectives and turret are below the stage pointing up. It was invented in 1850 by J. Lawrence Smith, a faculty member of Tulane University (then named the Medical College of Louisiana). microscopelight source condenserobjectivesTulane University Inverted microscopes are useful for observing living cells or organisms at the bottom of a large container (e.g. a tissue culture flask) under more natural conditions than on a glass slide, as is the case with a conventional microscope.cellsorganisms tissue culture

20. Yu Cao II: Biosensor – optical sensors for cell Small size of nanosensor allows for insertion into typical mammalian cells with no apparent damage Capable of detecting only a few molecules of BPT in a single cell Typical incubation time in a cell is five minutes If toxic chemicals like BPT or BaP exist in the cell with picomolar concentrations, they can be measured quantitatively

21. Yu Cao Questions?