An Integrated Optical DNA Detector for Portable PCR

描述（由申请人提供）：分子诊断是体外诊断市场中增长最快的部分。几乎所有的分子诊断分析都使用各种扩增技术，如聚合酶链反应（PCR），将特定序列片段扩增到易于检测的数量。然而，许多基于核酸技术（NAT）的检测仍然在集中地点进行，而不是像最初设想的那样作为即时检测形式进行。样品运输和等待足够的样品以启动高吞吐量系统所需的时间降低了这些NAT技术的能力。将NAT商业化用于非集中式实验室的最大问题之一是用于检测PCR扩增目标的设备的成本。在过去的几年中，已经发明了许多核酸传感器，具有各种光学，声学和电子检测方法。荧光检测一直是主要的方法，但是它需要复杂的光学检测系统，而且它们具有高成本/质量/功率要求。在非实验室情况下，确实需要将基于扩增的方法与简单且具有成本效益的分子诊断方法结合起来。最近也报道了利用纳米技术进行生物分析的各种方法。包括Lynntech在内的几家公司正在研究使用贵金属纳米颗粒和纳米结构作为生物分子结合事件的光学换能器。利用我们创新的基于金纳米颗粒的核酸检测技术，Lynntech旨在设计和开发一种多路复用、敏感且价格合理的体外诊断系统，用于非实验室环境，劳动强度最小。第一阶段的研究成功地证明了金纳米颗粒在一种检测DNA的新方法中的使用。新方法的独特之处在于其简单性，便于其在低成本的自动pcr分析中使用。该方法具有低成本的潜力，因为它使用一个简单的光学检测器，并且比传统的基于微生物学的方法快得多。第一阶段的研究还包括组装和测试硬件的初始工程设计，这些设计将与纳米颗粒DNA检测（NDD）分析一起使用。在这个II期项目中，Lynntech将扩展我们对DNA和金纳米颗粒之间形成的复合物的理解，并结合这些知识进一步优化快速检测。再加上来自我们的联盟伙伴Genaco Biomedical Products， Inc.的创新的高度多重PCR扩增技术，该系统将提供传染病的分子鉴别诊断。一旦成功开发，NDD分析将扩大扩增分子分析的应用范围，促进其在食品安全、生物武器检测、血液制品快速分析和环境监测等方面的应用。SARS和禽流感等高度传染性疾病是全球健康威胁。建立一个非实验室来对病人和动物进行测试，并在现场提供即时结果，可以在很大程度上帮助阻止疾病的传播。分子诊断是体外诊断市场中增长最快的部分。到2010年，美国市场预计将达到37亿美元，这是一个巨大的商业化机会。

DESCRIPTION (provided by applicant): Molecular diagnostics is the fastest-growing segment of the in-vitro diagnostics market. Nearly all molecular diagnostics assays use various amplification techniques such as polymerase chain reaction (PCR) to amplify specific sequence segments to easily detectable quantities. However, instead of being performed as a point-of-care format as originally envisioned, many of these nucleic acid technology based (NAT) tests are still performed at a centralized location. The time required for sample shipping and waiting for enough samples to start a high throughput system for cost-effective usage diminishes the power of these NAT techniques. One of the biggest problems of commercializing NAT for non-centralized laboratory is the cost of the device used to detect the target from PCR amplification. Over the past few years, many nucleic acid sensors have been invented with a variety of optical, acoustic, and electronic detection approaches. Fluorescent detection has been the dominating method, however it requires sophisticated optical detection systems, plus they have high cost/mass/power requirements. There is a genuine need to couple amplification-based methods with a simple and cost-effective method for molecular diagnostics in non-laboratory scenarios. Various approaches to exploit advances in nanotechnology for bioanalysis have also been recently reported. Several companies including Lynntech are investigating the use of noble metal nanoparticles and nanostructures as optical transducers of biomolecular binding events. Using our innovative gold nanoparticles based nucleic acid detection technology, Lynntech aims to design and develop a multiplexed, sensitive, and affordable in-vitro diagnostic system for use in non-laboratory settings with minimum labor intensity. The Phase I study successfully demonstrated the use of gold nanoparticles in a novel assay for the detection of DNA. The new method is unique in its simplicity, facilitating its use in a low-cost automated PCR-assay. The method has the potential to be low cost because it uses a simple optical detector and is significantly faster than conventional microbiology based methods. The Phase I study also included assembly and testing of initial engineering designs of the hardware to be used in conjunction with a nanoparticle DNA detection (NDD) assay. In this Phase II proposal, Lynntech will expand our understanding of complexes that form between DNA and gold nanoparticles and incorporate this knowledge to further optimize the rapid assay. Coupled with an innovative highly multiplexed PCR amplification technology from our alliance partner, Genaco Biomedical Products, Inc., the system will provide molecular differential diagnostics of infectious diseases. When successfully developed, the NDD assay will expand the range of applications for amplification based molecular assays, facilitating its use in food safety, detection of biological weapons, rapid analysis of blood products and environmental monitoring, etc. Highly infectious diseases such as SARS and bird flu are global health threats. Having a non-laboratory set up to test the patients and animals and to provide immediate results on location can help stopping the spread of the diseases a great deal. Molecular diagnostics is the fastest-growing segment of the in-vitro diagnostics market. By 2010, a U.S. market of $3.7 billion is expected, representing a significant opportunity for commercialization.