IGF::OT::IGF R&D- MEDICAL: BIOMEDICAL (BASIC RESEARCH)

基因突变导致关键生存途径的过度激活，导致对抗癌药物的耐药性。目前鉴定这些突变的技术可能以极低的频率存在，耗时和/或昂贵得令人望而却步。Lynntech提出将其基于对流PCR（cPCR）的便携式DNA扩增系统与基于硅纳米线（SiNW）的化学电阻器平台的高灵敏度相结合，以开发一种快速廉价的方法来检测低频突变。这项工作的主要创新是开发了一种用于多重生物测定的电化学检测平台。多重检测将允许使用单个cPCR反应评价突变组，特异性针对不同的癌症类型。对于本可行性研究，我们将开发一种cPCR检测方法，以在单个反应中检测两种独特的PIK 3CA突变。我们的目标是达到检测限，每个突变是0.01 - 0.02%的总DNA测定。然后，我们将开发一种新型的无机-有机混合化学电阻器装置来检测cPCR产物。最后，Lynntech的cPCR单元和化学电阻器模块将集成到一个设备中。成功完成拟议工作将产生一种研究工具/诊断测定，可能会在肿瘤护理设置中进行评估。

Genetic mutations causing hyperactivation of key survival pathways result in resistance to anti-cancer drugs. Current technologies to identify these mutations, which may be present in extremely low frequencies, are time consuming and/or prohibitively expensive. Lynntech proposes to combine its portable DNA amplification system based on convective PCR (cPCR) with the high sensitivity of a silicon nanowire (SiNW)-based chemresistor platform to develop a rapid and inexpensive means to detect low frequency mutations. The key innovation of this proposed work is the development of an electrochemical detection platform for a multiplexed biological assay. Multiplexing the assay will allow evaluation of mutation panels, specific for distinct cancer types with a single cPCR reaction. For this feasibility study, we will develop a cPCR assay to detect two unique PIK3CA mutations in a single reaction. We aim to achieve a limit-of-detection, for each mutation to be 0.01 – 0.02% of total DNA assayed. We will then develop a novel inorganic-organic hybrid chemresistor device to detect the cPCR products. Lastly, Lynntech’s cPCR unit and the chemresistor module will be integrated into a single device. Successful completion of the proposed work will result in a research tool/diagnostic assay which can potentially be evaluated in an oncology care setup.