Facile screening for esophageal cancer in LMICs

食道鳞状细胞癌(ESCC)在全球所有癌症中排名第六，新增45万人 每年确诊7例，预后非常差。低成本、微创的护理地点人群 食管癌的筛查是非常必要的，特别是在低度微血管内胆囊癌，那里的5年食管癌存活率不到10%。 甲基化改变经常发生在包括EC在内的人类恶性肿瘤中，构成了一种早期事件 可以作为早期癌症检测的生物标志物。然而，对于以这种方式使用的DNA甲基化， 我们需要性价比高、用户友好和可靠的测试，以允许在LMIC中进行临床翻译。我们提出了一个 早期食管鳞癌诊断策略包括收集食道标本的一次性吞咽海绵 再加上智能手机操控的微流控芯片，用于自动处理样品和甲基化 侦测。该策略不需要内窥镜检查(EGD)，可由医护人员实施 没有医学学位，使用手机上的分析应用程序。海绵更便宜(约30美元) 每个)，侵入性更小，比EGD更容易执行(总成本1500美元，包括设施费)；没有 房费，不像EGD。该微芯片集成了DNA提取、亚硫酸氢盐DNA转化和 在单个设备中进行甲基化分析。此外，对于这两种设备，微芯片都与手机接口 控制和甲基化检测和分析。该集成设备能够检测DNA甲基化 以样本到答案的方式从粗略样本中提取数据，而无需将数据发送回分析器 场外中心。因此，所提出的平台承诺了一种经济高效且用户友好的早期PoC策略 可在LMIC中实现的ESCC检测。我们还汇集了一支才华横溢的跨学科， 洲际团队执行这一战略。我们的任务将分两个阶段完成，目标如下： UG3阶段：目标1：评估样本收集、处理和甲基化的简化方案 侦测。目标二：在手机中实现DNA样本处理和甲基化检测- 操纵式微流控芯片系统。目标3：测试整合了DNA的ESCC诊断策略原型 甲基化检测系统用吞咽的海绵进行样本采集。UH3阶段：目标1：至 提高甲基化诊断系统用于低分子集成电路的成本效益和稳健性。目标2： 开发一种用于常温芯片存储的方法，并执行芯片上的质控测试以验证分析功能。目标 3：使用我们的护理点策略在乌干达进行ESCC诊断试验。

Esophageal squamous cell carcinoma (ESCC) ranks sixth among all cancers worldwide, with 450,000 new cases diagnosed per year and a very poor prognosis. Low-cost, minimally invasive point-of-care population screening for ESCC is badly needed, particularly in LMICs, where 5-year ESCC survival is less than 10%. Altered methylation occurs frequently in human malignancies, including EC, constituting an early event that can serve as an early cancer detection biomarker. However, for DNA methylation to be used in this manner, we need cost-effective, user-friendly and robust tests that permit clinical translation in LMICs. We propose an early ESCC diagnostic strategy comprising a single-use, swallowable sponge to collect esophageal specimens coupled with a smartphone-manipulated microfluidic chip for automated sample processing and methylation detection. This strategy does not require endoscopy (EGD), can be administered by healthcare workers without medical degrees, and uses an on-phone analytic app. The sponge is cheaper (approximately $30 each), less invasive, and easier to perform than EGD ($1500 total cost, including facility fees); there are no room charges, unlike EGD. The microchip integrates DNA extraction, bisulfite DNA conversion, and methylation analysis into a single device. In addition, the microchip interfaces with a cellphone, for both device control and methylation detection and analysis. The integrated device enables detection of DNA methylation from crude samples in a “sample-to-answer” manner, without the need for sending data back to an analytic center off-site. Thus, the proposed platform promises a cost-effective and user-friendly POC strategy for early ESCC detection that is implementable in LMICs. We have also assembled a talented interdisciplinary, intercontinental team to execute this strategy. Our task will be achieved in 2 phases via the following Aims: UG3 PHASE: Aim 1: To assess a streamlined protocol for sample collection, processing and methylation detection. Aim 2: To implement DNA sample processing and methylation detection into a mobile phone- manipulated microfluidic chip system. Aim 3: To test a prototype ESCC diagnostic strategy integrating the DNA methylation detection system with the swallowable sponge for sample collection. UH3 PHASE: Aim 1: To improve the cost-effectiveness and robustness of the methylation diagnostic system for use in LMICs. Aim 2: To develop a method for ambient chip storage and perform on-chip QC tests to verify assay functionality. Aim 3: To conduct an ESCC diagnostic trial in Uganda using our point-of-care strategy.