Nano-bridge biosensors for DNA hybridization detection [electronic resource]

Biosensors are used for detecting biological molecules such as proteins and nucleic acids. Traditional techniques, such as Enzyme-linked Immuno-sorbent Assay (ELISA) are sensitive but require several hours to yield results and usually require attaching a fluorophore molecule to the target molecule. The creation of label-free, fast, more accurate and integrated detection devices is imperative and we are increasingly looking to the nano-world for such technology. Micro-machined biosensors that employ electrical detection are now being developed. Impedance biosensor is a class of electrical biosensors that shows promise for point-of-care and other applications due to low cost, ease of miniaturization and label-free operation. Critically important component of any bio-detection system is the core biosensor device. Here we have designed, developed, tested and optimized a nano-biosensor that is configured and fabricated using silicon process technology. Electrical nano-sensors rely on label free detection of biochemical reactions in real time. These electrical sensors can measure impedance change as an electrical 'signature' of the nucleic acid or proteins interactions via a number of different mechanisms that are determined by their specific design and geometry. These nano-sensor designs will lead to an improvement in sensitivity by increasing the signal to noise ratio which results in more accurate readings through a reduction of spurious signal generation. We have developed a nano-bridge biosensor with a depletion-mode silicon 'nano-resistor' for the detection of DNA and protein at very low concentrations. In order to achieve higher sensitivity the sensing surface area is significantly increased as well as doping profile of impurities in silicon nano-resistor is optimized.. In contrast to a conventional Si enhancement mode MOSFET, this device behaves similar to depletion mode MOSFET, thereby it is always in the "ON" state, and no threshold voltage is needed to turn it into the active sensing mode. In addition signal calibration is not required due to a linear I-Vg characteristic at low Vg. The nano-bridge design has been optimized for maximal [Delta]I/I. The linearity of the response shows that the design will allow measurement of charge induced changes over a wide range with no threshold and high signal to noise ratios. To increase sensing throughput we will flow the solution containing the target molecules over an array of such sensing structures each of which has its own integrated readout circuitry that will offer 'real-time' detection (i.e. several minutes) of un-labeled molecules without sacrificing sensitivity. These electrical nano-biosensors are much more suited for the development of affordable bio-detection platforms, because they do not require expensive labeling reagents, rely on fabrication processes well established in the semiconductor IC industry, do not need bulky, expensive optical readout systems, and more importantly, can generate data on real time. One of the most important issues in the design of these sensor devices is to achieve high signal to noise ratio in order to make them amenable to sensitive detection of biological events, molecular interactions or chemical reactions. In order to improve the sensitivity and signal to noise ratio and to address the need for high density array construction we have designed and partially tested a nano-scale sensor with spatial structure, type and signal detection principles. The nano-bridge sensor is a double-gated depletion-mode semiconductor nano-resistive sensor. The structure and fabrication of these sensors will lead to improved sensitivity and greater accuracy of DNA hybridization detection up to 10 fM.

Keywords: Electrical Engineering
Advisor: Nishi Yoshio
Dutton Robert W. advisor. Thesis advisor
Melosh Nicholas A. advisor. Thesis advisor