Electrical Detection of Small Molecule Binding to Biological Receptors using Organic Thin Film Transistors : A new approach for label free assays

尽管我们对人类生物学的知识不断进步，伴随而来的是对新发现的生物途径进行治疗干预的机会，制药行业面临着许多重大挑战。其中最重要的是需要提高药物发现的效率，减少新药上市的时间，并减少药物开发后期阶段的自然减员。对药物“候选”化合物与其所需或不所需的生物目标之间相互作用的测量方法的优化在这方面发挥了关键作用。无标记分析方法仍然长期流行，因为它们可以提供对这些相互作用的直接测量；目前，这些方法涉及使用精密仪器的光学检测。目前技术水平的缺点包括较高的仪器和操作成本以及有限的样品吞吐量(一天内可以测量的候选化合物的数量)。也可以考虑非光学检测方法。该项目旨在引入一种基于有机薄膜晶体管(OTFT)生物传感器的颠覆性技术方法进行无标记分析，其中检测本质上是电气的。OTFT提供了一条低成本制造生物传感器阵列的途径，灵感来自最初为消费电子行业设计的低温、添加剂制造方法。使用OTFT的电子检测承诺通过不使用光学仪器来颠覆无标签分析市场，并将实现与当前技术相比的大规模并行化，从而降低成本，并使制药行业最终用户的生产率发生阶段性变化。该项目将演示使用OTFT生物传感器进行无标记分析的可行性，使用与药物发现过程相关而选择的示范系统。

Despite continual advances in our knowledge of human biology, with the attendant opportunity for therapeutic interventions in newly discovered biological pathways, the pharmaceutical industry faces a number of significant challenges. Foremost amongst these is a need to improve the efficiency of drug discovery, reducing the time to market for new medicines and lowering attrition in the later stages of drug development. Optimisation of methods for the measurement of the interaction between drug 'candidate' compounds and their desired or undesired biological targets have a critical role to play in this. Label free analysis approaches remain enduringly popular, as they can provide a direct measure of these interactions; at the current time these approaches involve optical detection using precision instrumentation. Drawbacks of the current state of the art include high instrumentation and operating costs and limited sample throughput (the number of 'candidate' compounds that can be measured in a day). Non-optical detection approaches can also be considered. This project aims to introduce a disruptive technology approach for label free analysis, based on the use of organic thin film transistor (OTFT) biosensors, where the detection is electrical in nature. OTFT offers a route to low cost fabrication of biosensor arrays, inspired by low temperature, additive fabrication methods originally designed for the consumer electronics industries. Electrical detection using OTFT promises to disrupt the label free analysis market by dispensing with optical instrumentation and will enable massive parallelisation compared to current technologies, resulting in lowered costs and a step change in productivity for end users within the pharmaceutical industry. The project will demonstrate the feasibility of using OTFT biosensors for label free analysis, using exemplifying systems selected for their relevance to the drug discovery process.