SBIR Phase I: Thermoelectric DNA Sequencer for Mutation Detection

这个小型企业创新研究(SBIR)第一阶段项目建议开发一种高度创新的、热电的、微流控的DNA测序方法，用于突变检测(例如，SNPs)，用于个性化医学应用。总体目标是优化操作参数和微流控装置设计变量，以克服限制测序方法准确性的三个因素。为实现这一总体目标，该项目将涉及以下三个技术目标：技术目标1，优化参数，以确保在单核苷酸注射过程中所有可用核苷酸位点得到扩展；技术目标2，优化参数，以减少dNTP误结合水平；以及技术目标3，制定改进的战略，对涉及同源多聚体区域的突变进行测序。单核苷酸多态(SNPs)是基因组中的单碱基对变异，是特定疾病遗传易感性的重要指标。在个体化药物领域，存在着对更便宜、更高效、简单和灵敏的SNP检测方法的巨大医疗需求和商业市场。热电DNA测序是一项不连续的创新，不同于任何现有的DNA测序方法。尽管热电测序的风险很高，但成功的商业化将为突变检测提供一种变革性的、廉价的、简单的方法。如果成功，这个项目的更广泛的影响/商业潜力将是个性化医学。SNPs是一类最丰富的多态现象，它使个体易患特定的疾病，并影响其对药物的反应。对人群进行广泛的基因突变筛查(例如SNPs)将大大降低医疗保健成本，并通过及早发现遗传病、更有效和及时地治疗以及降低人群的死亡率和发病率，产生显著的积极社会影响。热电测序通过将基因测试扩展到临床实验室和医生办公室，提供了改变个性化医学领域的潜力。基因检测识别出在症状出现之前就有疾病易感性的个体。例如，癌症是美国主要的死亡原因之一，每年导致558,644人死亡。据估计，每年癌症治疗的成本为1041亿美元，这增加了美国令人震惊的医疗成本。美国每年的医疗费用为2.199万亿美元，占该国GDP的16%。早期诊断可以进行早期干预，提高这些人的生活质量，并降低卫生保健成本。

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.