A Nanotechnology Enabled Point of Care Diagnostic Platform for Early Stage Cancer

描述（由申请人提供）：本申请的目的是开发、评估和验证一种可靠、高灵敏度、即时诊断（poc）系统，用于前列腺癌的早期检测和后续监测。在男性癌症中，最常见的是前列腺癌，概率为六分之一。在所有男性癌症病例中，约29%（218,890例）是前列腺癌，预计死亡人数为27,050人。将前列腺癌诊断带到护理点，并将一组更大、更具体的生物标志物的测试结合到一个低成本的一次性平台上，将显著提高生存率，降低治疗成本。技术创新。这个项目是在蛋白质微阵列分析中使用纳米粒子生物芯片表面的创新。我们的目标是利用Inanovate开发的纳米颗粒附着方法，以及Brigham and Women's Hospital （BWH）开发的天然抗原反向捕获方法，获得与前列腺癌非常高的相关性。最后，将这两种创新与实时读出相结合，可以在护理点执行测试。长期目标。长期目标是提供一个可以在早期发现癌症并在治疗后和治疗期间监测癌症的主要平台。实现这一目标的第一个例子将是推出一种前列腺癌筛查测试，这种测试将既灵敏、准确，又能在护理点广泛使用。第一阶段总结。目的是证明使用基于纳米颗粒的生物芯片底物与实时荧光成像相结合来测量多种自身抗体生物标志物浓度的可行性，用于前列腺癌的早期检测。第一阶段的具体目标。目标1是在纳米颗粒生物芯片底物的背景下优化终点分析性能。将使用在BWH鉴定的28个生物标志物进行分析开发实验。目标2是开发一种实时荧光检测系统，专门适用于BWH方法。目的3是显示与目的1中收集的终点数据的直接比较，以及在实时模式下检测先前确定的前列腺癌相关特征的能力。II期目标：1)将自动化样品制备和标签集成到平台模块中，并准备器械主备案（DMF）。2)简化一次性芯片中诱饵蛋白的供应和掺入。3)与BWH合作完成生物标志物面板验证，并为上市前批准（PMA）设计多地点临床试验。在合作伙伴的支持下启动DMF和PMA。商业机会。P.O.C前列腺癌筛查的潜在市场估计每年超过20亿美元。此外，通过帮助每个人都能获得和负担得起准确的癌症筛查，我们看到本文提出的潜在诊断平台在将健康行业的重点从低效的晚期治疗转向早期诊断和低成本治疗方面发挥了关键作用。公共卫生相关性：大多数癌症都有治疗方法；然而，存活率很大程度上取决于癌症的诊断阶段。这个问题不仅与进行准确的测试有关，还与这种测试的成本和广泛可用性有关。我们建议开发一种基于纳米技术的基于蛋白质特征的前列腺癌诊断测试，可用于初级保健点。

DESCRIPTION (provided by applicant): The objective of this proposal is the development, evaluation and validation of a reliable, highly sensitive, point-of-care (P.O.C) diagnostic system, for the early detection and subsequent monitoring of prostate cancer. Of cancers in males, the most common is prostate, with a probability of 1 in 6. Approximately 29% (218,890) of all cancer cases in males are prostate cancer with 27,050 deaths expected. Taking prostate cancer diagnosis to the point-of-care, and incorporating a test for a larger, more specific set of biomarkers, onto a low cost disposable platform would significantly increase survival rates and reduce treatment costs. Technological Innovation. This project is innovative in the use of a nano-particle biochip surface in the context of a protein microarray assay. We aim to exploit the nano-particle attachment approach developed by Inanovate, with the native antigen reverse-capture method developed at Brigham and Women's Hospital (BWH) to obtain very high correlation rates to prostate cancer. Finally the combination of these two innovations with a real-time read-out enables the test to be performed at point-of-care. Long-Term Goal. The long term goal is to provide a premier platform from which cancer can be detected at an early stage and monitored after and during treatment. The first example of this goal will be the launch of a screening test for prostate cancer that will be both sensitive, accurate, and widely available at the point-of-care. Phase I Summary. The objective is to demonstrate the feasibility of using a nano-particle based biochip substrate in combination with real-time florescent imaging to measure the concentration of multiple autoantibody biomarkers for early stage detection of prostate cancer. Specific Aims for Phase I. Aim 1 is to optimize end-point assay performance within the context of the nano- particle biochip substrate. Assay development experiments will be performed with the 28 biomarkers identified at BWH. Aim 2 is to develop a real-time fluorescent detection systems specifically suited for the BWH approach. Aim 3 is to show direct comparisons to the end-point data collected in Aim 1 and the ability to detect previously identified prostate cancer correlation signatures in the real-time mode. Phase II Objectives. 1) Integrate automated sample preparation and labeling into platform module, and prepare for Device Master Filing (DMF). 2) Streamline supply and incorporation of bait proteins into disposable chip. 3) Finalize biomarker panel validation in collaboration with BWH, and design multi-site clinical trial for Pre-Market Approval (PMA). 4) Initiate DMF and PMA with support from partners. Commercial Opportunity. The potential market for P.O.C prostate cancer screening is estimated at over $2B p.a. Furthermore, by helping make accurate cancer screening available and affordable to everyone, we see the underlying diagnostic platform proposed herein playing a key role in moving the health industry's focus away from inefficient late stage treatments, towards early stage diagnosis and lower cost therapies. PUBLIC HEALTH RELEVANCE: Treatments are available for most cancers; however, survival rates depend largely on the stage at which the cancer is diagnosed. The problem is related to having an accurate test, but also related to the cost and widespread availability of such a test. We propose to develop a nanotechnology enabled protein signature based diagnostic test for prostate cancer available at the point of primary care.