This Small Business Innovation Research (SBIR) Phase I project proposes to develop a highly innovative, thermoelectric, microfluidic DNA sequencing method for mutation detection (e.g., SNPs) for applications in personalized medicine. The overall objective is to optimize operational parameters and microfluidic device design variables to overcome three factors that limit the accuracy of the sequencing method. To achieve this overall objective, the project will address the following three technical objectives: Technical objective 1, optimize parameters to ensure that all available nucleotide sites are extended during a single nucleotide injection, technical objective 2, optimize parameters to reduce the level of dNTP misincorporation, and technical objective 3, develop improved strategies for sequencing mutations involving homopolymeric regions. Single nucleotide polymorphisms (SNPs) are single base pair variations within the genome that are important indicators of genetic predisposition towards specific diseases. There is a significant medical need and commercial market in the field of personalized medicine for a less expensive, more efficient, simple and sensitive SNP detection assay. Thermoelectric DNA sequencing is a discontinuous innovation, unlike any existing method for sequencing DNA. Despite the high-risk, successful commercialization of thermoelectric sequencing will provide a transformative, inexpensive, simple method for mutation detection. The broader impact/commercial potential of this project, if successful, is in personalized medicine. SNPs are the most abundant class of polymorphism and predispose individuals to specific diseases and influence their response to drugs. Wide-spread screening of the population for genetic mutations (e.g. SNPs) will dramatically decrease health care costs and produce significant positive social impact by enabling the early detection of inherited disease, more effective and timely treatment, and lower mortality and morbidity among the population. Thermoelectric sequencing offers the potential to transform the field of personalized medicine by extending genetic testing into the clinical laboratory and doctor's office. Genetic testing identifies individuals who have predisposition to diseases before the onset of the symptoms. Cancer for example, one of the leading causes of mortality in the United States, causes 558,644 deaths per year. The cost of cancer treatment is estimated to be $104.1 billion per year that adds to the staggering cost of healthcare in the United States. The cost of healthcare in the United States is $2.199 trillion per year that is 16% of the GDP of the country. Early diagnosis allows early intervention, increases the quality of life of these individuals, and reduces the cost of health care
