A Nanotechnology Enabled Diagnostic Platform for Early Stage Cancer Detection

描述(由申请人提供)：这项建议的目标是开发、评估和验证一种准确、低成本的诊断测试，该测试可以区分前列腺癌和良性前列腺增生症，特异性为85%，敏感性为85%。前列腺癌是男性最常见的癌症，概率为六分之一。在男性所有癌症病例中，约有29%是前列腺癌，2009年估计有27,050人死亡。与大多数癌症一样，早期准确的检测可以挽救生命。然而，目前前列腺癌筛查测试PSA的一个主要缺陷是，它没有区分癌症和一种常见的良性疾病：良性前列腺增生症(BPH)。事实上，88%的阳性PSA检测归因于BPH。尽管BPH是一种无威胁的疾病，但只有昂贵的活检才能将其与前列腺癌区分开来。技术创新。Inanovate与布里格姆妇女医院(BWH)的研究人员合作，确定了一系列能够区分前列腺癌和前列腺增生症的自身抗体生物标志物，其特异性为85%，敏感性为85%。建议的诊断测试将该生物标记物小组与一种新型生物芯片平台相结合，能够在护理点准确地从血液样本中筛选多种低浓度蛋白质。该平台包括纳米颗粒表面技术，它通过控制蛋白质在生物芯片表面的分布和方向来提高分析灵敏度；以及实时荧光生物芯片扫描仪和分析方法，能够区分“特定”(真)生物标记物信号和“非特定”(假)信号。第一阶段总结。其目的是论证使用纳米颗粒生物芯片表面技术结合实时荧光成像技术来测量多种自身抗体生物标志物浓度以准确检测前列腺癌的可行性。在第一阶段，开发并测试了一个原型系统。在审查员对原始第二阶段提交的意见提出批评后，原型平台已进行了实质性的重新设计，性能显著提高。通过第二阶段，该系统将被推进用于护理点(PoC)，同时验证自身抗体生物标记物小组，为多地点临床试验做准备。第二阶段目标。1)开发基于实时流的筛查平台的PoC版本，2)使用实时测量验证生物标志物，3)为临床试验准备监管/商业计划。商机。据估计，治疗点前列腺癌筛查的潜在市场每年超过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，我们看到这里提出的基本诊断平台在将卫生行业的重点从低效的晚期治疗转移到早期诊断和低成本治疗方面发挥了关键作用。 与公共卫生相关：男性最常见的癌症是前列腺癌，其终生概率为六分之一。每年约有20万新前列腺癌病例被诊断出来，其中近3万人死亡。目前FDA批准的前列腺癌诊断试验(PSA)存在局限性，前列腺癌和良性前列腺增生症(BPH)患者的血清PSA水平均升高。大多数PSA水平升高的男性最终被证明没有患癌症；多达88%的男性(每年超过100万人)接受了不必要的活检，每年的费用为20亿美元。美国的医疗系统。迫切需要一种能够准确区分前列腺癌和前列腺增生症的低成本检测方法。

DESCRIPTION (provided by applicant): The objective of this proposal is the development, evaluation and validation of an accurate, low cost diagnostic test that can discriminate prostate cancer from benign prostatic hyperplasia to a Specificity of 85% at a Sensitivity of 85%. Prostate cancer is the most common cancer in men, with a probability of 1 in 6. Approximately 29% of all cancer cases in males are prostate cancer with 27,050 deaths estimated in 2009. As in most cancers, early and accurate detection can be life saving. However, a major deficiency of the current prostate cancer screening test, PSA, is that it does not discriminate between cancer and a common benign condition; benign prostatic hyperplasia (BPH). In fact, 88% of positive PSA tests are attributed to BPH. Although BPH is a non-threatening condition, only expensive biopsies can distinguish it from prostate cancer. Technological Innovation. Inanovate has partnered with investigators at Brigham and Women's Hospital (BWH) to identify a series of auto-antibody biomarkers capable of distinguishing prostate cancer from BPH to a Specificity of 85% at a Sensitivity of 85%. The proposed diagnostic test integrates this biomarker panel with a novel biochip platform capable of accurately screening multiple low concentration proteins from blood samples at the point of care. The platform includes a nano-particle surface technology that improves assay sensitivity by controlling the distribution and orientation of proteins across the biochip surface; and a real-time fluorescent biochip scanner and analysis methodology that enables the discrimination of 'specific' (true) biomarker signals from 'non-specific' (false) signals. Phase I Summary. The objective was to demonstrate the feasibility of using a nano-particle biochip surface technology in combination with real-time florescent imaging to measure the concentration of multiple autoantibody biomarkers for accurate detection of prostate cancer. In Phase I a prototype system was developed and tested. Following reviewer critiques from the original Phase II submission, the prototype platform has been substantially re-engineered, and the performance significantly improved. Through Phase II, this system will be advanced for point-of-care (PoC) use, in parallel with validation of the auto-antibody biomarker panel in preparation for multi-site clinical trials. Phase II Objectives. 1) Develop PoC version of the real-time flow-based screening platform, 2) Validate biomarkers using real-time measurement, 3) Prepare regulatory/commercial plans for clinical trials. Commercial Opportunity. The potential market for a point-of-care 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: The most common cancer in men is prostate cancer, with a lifetime probability of 1 in 6. Approximately 200,000 new cases of prostate cancer are diagnosed per year with nearly 30,000 deaths. The current FDA approved diagnostic test for prostate cancer (PSA) has a limitation in that serum levels of PSA are elevated in both prostate cancer and Benign Prostatic Hyperplasia (BPH). Most men with an elevated PSA level turn out to not have cancer; with unnecessary biopsies performed in as many as 88% of men (over 1 million each year) at a cost of $2 billion p.a. to the US health system. A low cost test which can accurately distinguish prostate cancer from BPH is critically needed.