Ultrasensitive PSA Quantitation Using Smartphone to Reduce Prostate Cancer Monitoring Disparities

项目摘要 前列腺癌是医疗服务不足男性癌症死亡的主要原因 获得优质卫生保健资源的机会有限。对极低血进行纵向监测 前列腺特异性抗原(PSA)浓度(数十pg/ml)是临床诊断前列腺癌的重要手段 前列腺癌根治术或根治性放射治疗后患者的监测。这样的监控 需要高灵敏度的诊断化验。然而，对于未得到充分服务的患者来说，这是一个挑战 为了获得最先进的诊断资源，遭受健康差距的人。缺乏 适当的资源和基础设施会导致失访，增加肿瘤 未经监测的复发和转移。唐人街社区的居民 美国代表着这些医疗服务不足的人群，他们遭受着健康差距，原因是 语言、文化和经济障碍。 我们的目标是减少前列腺癌治疗的差距，通过提供 以最小的基础设施需求进行灵敏度PSA测量，通过进一步开发和 一种超灵敏、方便、低成本、可广泛部署的微泡PSA的验证 站台。该平台建立在我们创新的微泡数字分析技术基础上，能够 对各种生物体液中蛋白质生物标记物的毫微摩尔浓度进行定量， 包括血液，使用智能手机。我们已经证明了这一点，使用来自 前列腺癌患者的微泡PSA检测具有相当的准确性，但~200倍 比中心实验室最先进的灵敏度更高。本研究的临床可行性和可行性。 这项技术还被成功地用于各种临床应用，包括BHCG 检测和RADx资助以及FDA EUA提交的SARS-CoV-2抗原检测。此外, 我们已经开发并证明了一种自动化微流控平台的可行性 集成了所有的微泡分析步骤。 我们建议(目标1)将微泡PSA检测集成到自动化的 适合家庭或泌尿外科医生办公室使用的微流体平台，无需基础设施或 复杂的仪器需求。这个平台只需要几滴指甲血就可以了 输入和智能手机，可在20分钟内读取高灵敏度的PSA定量数据。(目标2)由 与宾夕法尼亚大学医院的中心临床实验室合作，我们 将通过与FDA的比较来验证微泡PSA平台的临床性能 经批准的最先进技术，使用临床血样。此外，我们还将与Dr. 金文武，泌尿科医生，外科主任，在旧金山中医院执业的当地专家 旧金山唐人街将验证该平台在医疗服务不足的唐人街的可用性 居民。

Project Summary Prostate cancer is a leading cause of cancer mortality in medically underserved men, due to limited access to quality health care resources. Longitudinal monitoring of very low blood prostate specific antigen (PSA) concentrations (tens of pg/mL) is an important tool for clinical surveillance of patients post radical prostatectomy or radical radiotherapy. Such monitoring requires high sensitivity diagnostic assays. However, it is challenging for underserved patients suffering from health disparities to get access to the state-of-the-art diagnostic resources. Lacking the appropriate resources and infrastructure results in loss-to-follow-up, increased tumor recurrence and metastasis without surveillance. Residents in Chinatown communities across the US represent such medically underserved populations suffering from health disparities, due to language, cultural and economic barriers. Our goal is to reduce prostate cancer care disparities by providing access to high sensitivity PSA measurement with minimal infrastructure needs, by further developing and validating an ultrasensitive, convenient, low-cost and widely deployable Microbubbling PSA Platform. This platform builds on our innovative Microbubbling Digital Assay technology, capable of quantitating femtomolar concentrations of protein biomarkers in various biological fluids, including blood, using smartphones. We have demonstrated that, using blood samples from prostate cancer patients, the Microbubbling PSA assay has comparable accuracy, but ~200 fold higher sensitivity than central laboratory state-of-the-art. The clinical feasibility and viability of the technology has also been successfully proven for various clinical applications, including bhCG detection and RADx-funded and FDA EUA-submitted SARS-CoV-2 antigen detection. In addition, we have developed and demonstrated feasibility of an automated microfluidics platform that integrates all Microbubbling assay steps. We propose to (Aim 1) integrate the Microbubbling PSA Assay into the automated microfluidics platform suitable for home or urologist office use, without infrastructure or sophisticated instrument needs. This platform only requires a few drops of fingerstick blood as input and a smartphone for high sensitivity quantitative PSA readout in 20 min. (Aim 2) By collaborating with the central clinical laboratory at Hospital of the University of Pennsylvania, we will validate the clinical performance of the Microbubbling PSA Platform by comparing with FDA- approved state-of-the-art, using clinical blood samples. Furthermore, we will collaborate with Dr. Wenwu Jin, a urologist, Chief of Surgery and local expert practicing in Chinese Hospital in San Francisco Chinatown to validate the usability of the platform in medically underserved Chinatown residents.