Download Electrical Biosensors in Microfluidic for High Throughput Genomics and Proteomics   

Electrical Biosensors in Microfluidic for High Throughput Genomics and Proteomics Stanford University Ph.D. Thesis Defense Hesaam Esfandyarpour ([email protected]) Research Advisor: Professor Ronald Davis Department of Electrical Engineering December 3, 2009 @ 9:00 AM (Refreshments served at 8:45 AM) Clark Center Auditorium (Basement, entrance across from Nexus) Abstract Biosensors are used for detecting biochemical molecules such as proteins and nucleic acids. The development of vastly improved DNA sequence determination for personalized medicine and ecological studies could complete the revolution initiated by the Human Genome Project. In the first part, a novel method for DNA sequencing, called Thermosequencing based on direct heat or pH measurement will be introduced. The development of a high‐sensitivity calorimeter that can be scaled to automated, highly multiplexed array architectures will be discussed. This detection part is made of a dual‐sided on‐chip calorimeter with polysilicon sensors microfabricated on Si3N4 suspended membranes; the injection part is made of an on‐chip microfluidic unit based on PDMS valve controlling technology. Experimental results for sequencing and other biological applications will be presented. In the second part, the development of a micromachined biosensor based on a nanoneedle structure that employ electrical detection would be presented. Traditional techniques, such as Enzyme‐linked Immuno‐sorbent Assay (ELISA) are sensitive but require several hours to yield an assay and usually require attaching a fluorophore molecule to the target molecule. The key element in our device is a 10nm wide (annular) gap on the end of the needle of total diameter/thickness about 100nm. Any change in the population of molecules in this gap results in a change of impedance across the gap. To increase throughput we can flow the solution containing the target molecules over an array of such structures each with its own integrated readout circuitry that should offer ‘real‐time’ detection (i.e. several minutes) of un‐labeled molecules without sacrificing sensitivity. Preliminary measurements on individual needle structures for detection of biomolecules are consistent with the design.