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

导致关键生存通路过度激活的基因突变导致对抗癌药物的耐药性。目前识别这些突变的技术，可能以极低的频率出现，既耗时又昂贵。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）的高灵敏度化学电阻平台结合起来，开发一种快速且廉价的检测低频突变的方法。这项工作的关键创新是开发了一种用于多重生物测定的电化学检测平台。多路分析将允许评估突变面板，特定于不同的癌症类型与单一的cPCR反应。为了这项可行性研究，我们将开发一种cPCR检测方法来检测单个反应中两个独特的PIK3CA突变。我们的目标是达到检测限，每个突变为总DNA的0.01 - 0.02%。然后，我们将开发一种新的无机-有机混合化学电阻装置来检测cPCR产物。最后，Lynntech的cPCR单元和化学电阻模块将集成到一个设备中。这项工作的成功完成将产生一种研究工具/诊断分析方法，可以潜在地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.