MAQDOTS: Multi-Analyte Quantum Dot Test Strips

描述(由申请人提供)： 每年有500多万患者因疑似急性心肌梗死(AMI)而被送往心脏监护病房(CCU)。这些患者中的大多数被排除在急性心肌梗死之外，随后出院。一种诊断急性心肌梗死患者与其他疾病患者的简单方法将节省数十亿美元，为急性心肌梗死患者腾出CCU单元，提供一流的护理，并挽救患者的生命。美国国家临床生物化学家学会建议，从血液或血清等体液中以极高的精确度在症状出现后几小时内对一组心脏标志物进行定量测量，可以提高急性心肌梗死的诊断水平。然而，用于监测指示急性心肌梗死的心脏标志物的定量、易用、准确、快速的测试单元并不是现成的。这在很大程度上是由于缺乏负担得起的、足够灵敏的便携式检测系统。为了解决这一重要问题，智能光学系统公司与斯克里普斯实验室合作，提议开发基于半导体核晶体(量子点)的横向流动测试条，并结合灵敏且廉价的读出设备，用于检测和定量体液样本中的多种阿里亚利特。LOS提出的方法是将纳米材料用于体外诊断的一种新方法，预计将扩大侧向流动测试条的范围和能力。在第一阶段，将通过制造所需的传感纳米材料、设计适当的测试条、构建光学读取器来测量测试条的响应，然后通过将其性能与当前的临床标准进行比较来测试和验证该原理的可行性。在第一阶段，将使用包括肌红蛋白、CK-MB和血清中添加的肌钙蛋白I在内的心脏标志物来证明这一原理的可行性。这项建议的总体目标是开发一种新的横向流动测试条开发的技术方法，这种基本方法还可以导致开发用于其他重要生物医学、过程监测和环境传感应用的测试套件，以及其他体液测试，如尿液和唾液。这些在临床诊断方面的巨大进步也将对环境监测、国土防御和生物安全检测产生深远的好处。在第二阶段，我们将继续优化膜化学和量子点的生物标记，以实现更灵敏和准确的多分析测试条。将开发和优化一个原型光学检测系统，以实现高灵敏度和合适的动态范围。第二阶段的工作还将包括用更大的样本面板进行广泛的测试和临床试验，以了解该设备用于急性心肌梗死诊断的可靠性。

DESCRIPTION (provided by applicant): Over five million patients are admitted annually to cardiac care units (CCU) for suspected acute myocardial infraction (AMI). The majority of these patients are ruled out of AMI and are subsequently released. A simple method to diagnose patients suffering from AMI from those with other ailments would save billions of dollars, free up CCU units for AMI patients, offer superior care, and save lives of patients. The National Academy of Clinical Biochemists recommended that a quantitative measurement of a panel of cardiac markers within a few hours of the onset of symptoms at excellent precision from body fluids such as blood or serum could improve AMI diagnosis. However, a quantitative, easy-to-use, precise, rapid, test unit for monitoring cardiac markers indicative of AMI is not readily available. This has largely been due to the lack of an affordable, sufficiently sensitive, portable detection system. To solve this important problem, Intelligent Optical Systems, in collaboration with Scripps Laboratories, proposes to develop semiconductor rianocrystal (Quantum Dot) based lateral flow test strips, combined with a sensitive and inexpensive readout device, for detecting and quantifying multiple arialytes in body fluid samples. lOS's proposed approach is a novel use of nanomaterials for in vitro diagnostics, and is expected to expand the scope and capabilities of lateral flow test strips. In Phase I, the feasibility of the principle will be demonstrated by fabricating the required sensing nanomaterials, designing appropriate test strips, constructing an optical reader to measure the response from the test strips, and then testing and validating the strips by comparing their performance against current clinical standards. In Phase I, cardiac markers, including Myoglobin, CK-MB, and Troponin I spiked in serum will be used to demonstrate the feasibility of the principle. The overall goal of this proposal is to develop a new technical approach for lateral flow test strip development and this basic approach can also lead to the development of test kits for other important biomedical, process monitoring, and environmental sensing applications, as well as in other testing of body fluids, such as urine and saliva. These dramatic improvements in clinical diagnostics will also have far reaching benefits to environmental monitoring, homeland defense, and biothreat detection. In Phase II, we will continue to optimize the membrane chemistry and the biolabeling of QDs to achieve more sensitive and precise multianalyte test strips. A prototype optical detection system will be developed and optimized to achieve high sensitivity and a suitable dynamic range. Phase II work will also involve extensive testing with a larger panel of samples and clinical trials to understand the reliability of the device for AMI diagnosis.