Modeling and Simulation of Electrochemical DNA Biosensors in CMOS Technology

Abstract

<p> Early detection of pathogens in food and water samples is essential in containing and preventing the spread of various diseases, such as campylobacter jejuni or E-coli. In the food processing industry, fast and reliable methods for testing products against contamination would mean faster delivery and better food quality. The pairing specificity of complementary DNA strands provides a highly selective means of detecting pathogens based on their genomic content. Recently, a lot of research has been directed towards the use of mainstream semiconductor technology to build highly sensitive and cheap DNA hybridization sensors. Typically, the gate of a metal-oxide-semiconductor (MOS) transistor is removed, and probe single-stranded DNA molecules are added to the exposed insulator. Complementary DNA hybridization from a solution sample can then be sensed electrostatically by the underlying Field-Effect transistor (FET). </p> <p> The work in this thesis is concerned with the mathematical modeling of FET based biosensors, named BioFETs. Modeling will enable the assessment of the sensitivity of such devices, as well as the potential for using the BioFETs in creating fully electronic microarrays. The mathematical model presented here captures the effects of ionic charge screening of the DNA charges by counterions in the ambient solution, and the effects of surface adsorption that can also aid in the charge screening process. The effects of varying different parameters on the sensitivity of the BioFET are investigated, and the noise contributed by the FET structure is incorporated into the analysis to quantify the expected signal-to-noise ratio (SNR) ofthe BioFET. </p> <p> In order to gain further insight into the operation of the BioFET, linear approximations are applied to the different regions of the BioFET to arrive at an analytic expression that approximates its expected response to DNA hybridization. The approximations are verified by comparing them against the results obtained from the physical model. Finally, different circuit configurations are presented that allow for highly sensitive biosensors to be realized using the BioFET, and a description of a fabricated electronic DNA microarray chip in standard CMOS 0.8 μm is presented. </p>