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会导致抗癌药物的耐药性。目前用于识别这些突变的技术可能以极低的频率出现，耗时和/或昂贵得令人望而却步。Lynntech建议将其基于对流聚合酶链式反应(CPCR)的便携式DNA扩增系统与基于硅纳米线(SiNW)的化学电阻平台的高灵敏度相结合，以开发一种快速且廉价的方法来检测低频突变。这项工作的关键创新点是开发了一种用于多路生物检测的电化学检测平台。多重检测将允许对突变面板进行评估，这些面板针对不同的癌症类型，只需一次CPCR反应。在这项可行性研究中，我们将建立一种CPCR方法，在一次反应中检测两个独特的PIK3CA突变。我们的目标是实现检测极限，每个突变占所检测总DNA的0.01-0.02%。然后，我们将开发一种新型的无机-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。拟议工作的成功完成将产生一种研究工具/诊断分析，它可能会在肿瘤学护理机构中进行评估。

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.