A novel, reliable and sensitive optical detection platform for ovarian cancer.

癌症是一种致命的疾病，每年夺去五十万美国人的生命。在许多类型的癌症中，卵巢癌是一种特别严重的疾病，因为它通常不会出现很多症状，而当出现时，通常为时已晚。与许多其他癌症一样，理论上可以通过检测患者血液样本中的某些分子来检测卵巢癌。有许多这样的“分子标记”可以测量。然而，大多数当前平台的灵敏度不够高，无法检测血液中的大多数标记物。那些敏感的产品非常复杂、不可靠且昂贵。这项特殊的研究旨在开发一种非常灵敏、成本低廉且能够非常快速地同时执行多项测试的生物分子检测器。该平台将能够通过微创血液测试来分析癌症患者对治疗的反应。由于与计算机断层扫描和活检相比，这些测试相对简单且便宜，因此可以更频繁地进行测试，并帮助临床医生快速了解患者对治疗的反应，并在必要时增加剂量、修改或停止治疗。此外，该平台为卵巢癌的早期诊断铺平了道路，并且可以适用于许多其他癌症。拟议的研究还包括教育活动，向高中生传授衍射和光学现象，从而使拟议的平台能够运行。所提出的平台集成了三个要素：a）基于免疫磁珠的分离，通过从大样本量中捕获稀有分子，将少量分子浓缩到功能化生物芯片表面上；b）光学衍射法，用于检测自组装珠光栅产生的信号；c）高速旋转盘干涉法，询问多个芯片以实现快速和高灵敏度的多路复用。该研究涉及构建系统，通过模拟和实验优化其性能，并使用卵巢癌的三种分子标记物（血管内皮生长因子、血小板源性生长因子、碱性成纤维细胞生长因子）进行测试，这些标记物使用当今的技术通常很难检测到，因此尚未在卵巢癌的背景下进行广泛研究。拟议的系统将从卵巢癌患者的血液样本中以亚皮摩尔浓度检测这些标记物，最重要的是，同时检测所有这些标记物。与大多数现有的生物传感平台通常只有一个主要优点但有很多缺点不同，所提出的生物分子检测系统将具有高通量、高灵敏度、鲁棒性、检测芯片可存档以供将来分析的能力，而不需要荧光或显微镜。

Cancer is a deadly disease and costs us half a million American lives every year. Among many types of cancers, ovarian cancer is a particularly severe disease because it usually does not present many symptoms and when it does, it is usually too late. Ovarian cancer, like many other cancers, can theoretically be detected by sensing certain molecules in the blood sample of a patient. There are a number of such 'molecular markers' that could be measured. However, most current platforms are not sensitive enough to detect most of these markers in blood. Those that are sensitive are highly complicated, unreliable and expensive. This particular study aims to develop biomolecular detector that is very sensitive, low cost and capable to performing multiple tests at the same time very quickly. The prosed platform will have the capability of analyzing how a cancer patient responds to therapy using a minimally invasive blood test. Since these tests are relatively simple and cheap as compared to computed tomography scans and biopsies, the tests can be performed more frequently and help clinicians quickly see how the patient is responding to therapy and if necessary, increase the dosage, modify or stop the therapy. In addition, the platform paves the way to early diagnosis of ovarian cancer and can be adapted to many other cancers. The proposed study also includes educational activities that will teach high school students about diffraction and optical phenomenon that enables the operation of the proposed platform. The proposed platform integrates three elements: a) immunomagnetic bead-based separation that concentrates small number of molecules onto a functionalized biochip surface by capturing rare molecules from large sample volumes, b) optical diffractometry to detect signals generated by self-assembled bead gratings, and c) high-speed spinning disk interferometry that interrogates multiple chips for fast and highly sensitive multiplexing. The study involves building the system, optimizing its performance via simulations and experimentation, and testing with three molecular markers of the ovarian cancer (vascular endothelial growth factor, platelet-derived growth factor, basic-fibroblast growth factor) that are generally difficult to detect using today's technology and hence have not been extensively studied in the context of ovarian cancer. The proposed system will detect these markers from the blood samples of ovarian cancer patients at sub-picomolar concentrations and most importantly, detect all of them at the same time. Unlike most current biosensing platforms that usually have one main strength but a lot of shortcomings, the proposed biomolecular detector system will have the capability of high throughput, high sensitivity, robustness, archivability of the detection chips for future analysis, without the need for fluorescence or microscopy.