Rapidly Adaptable and Mass-Producible Microscopic Chiplets for Minimally-Instrumented Respiratory Viral Screening

项目摘要 目的：呼吸道病毒感染每年影响数百万人。频频进行 广泛的病毒筛查测试可以通过快速识别感染者来遏制疫情的爆发。很遗憾，我不会 现有的筛查诊断平台能够在一年内每天对数亿人进行测试 大流行。这项提议是开发一种新的病毒筛查测试以填补这一空白的第一步。化验结果会 由含有场效应晶体管的微型电路组成，这些晶体管带有敏感的抗原特异性受体 对特定的病毒。这些小芯片--肉眼几乎看不见--将由光供电，并将传输 使用发光二极管的数据，这样一些就可以混合到提取的样品中，并用 手持设备，可立即产生效果。这种诊断将是可扩展的，并且成本低廉；数百万个微小的 芯片可以同时制造。它将是最少配备仪器的；一部带有闪光灯的普通手机 闪光灯和摄像头将与芯片连接。它将是灵活的、快速适应的和多路可复用的；受体 针对不同或新出现的病毒的特异性可以固定在不同的电路上，从而允许多种疾病 在单个患者样本中同时检测到。因此，这种诊断作为一个肿块是无与伦比的 可生产、简单使用、适应性强和高通量的工具，用于频繁和广泛的病毒筛查。 具体目标：拟议的诊断将通过追求以下具体目标来制定。 1.将生物场效应晶体管集成到现有的光无线集成电路平台中。 2.开发了一种与光无线集成电路交互的多路检测方案。 3.使用模拟临床标本在临床相关的定量范围内验证测试的可行性。 职业发展计划和职业目标：马修·坎贝尔博士是一名博士后 宾夕法尼亚大学工程与应用科学学院研究员，他在那里工作 专注于制造微电子机械系统。拟议的K25职业发展奖将 将他的纳米制造技能应用于生物传感器的开发，并将他的培训和接触扩展到两个 新领域：(1)生物医学实验，(2)医学生物学。这项提案包含了一个连贯的 导师和指导策略围绕这些领域展开，以加速他的研究之路 独立。完成这一多方面的培训计划将使坎贝尔博士成为跨学科的 成为生物医学传感诊断领域的领先研究人员所需的技能和专业知识。 导师和环境：坎贝尔博士得到了大学的热情支持和他强大的 指导团队。他的主要导师是微型制造专家(伊戈尔·巴加丁教授(博士))，他的合作伙伴是 导师们在微电路(Marc Miskin教授(博士))、场效应晶体管方面具有丰富的经验 Sensors(Charlie Johnson教授(博士))和Him Bau教授(博士))和病毒性呼吸道感染(教授。 罗纳德·科尔曼(医学博士)。这个小组将为坎贝尔博士开发这一检测方法提供理想的培训环境。

Project Summary Objective: Respiratory viral infections affect millions of individuals each year. Conducting frequent widespread viral screening tests can curb outbreaks by quickly identifying infectious persons. Unfortunately, no screening diagnostic platform exists with the capacity to test hundreds of millions of people daily during a pandemic. This proposal is the first step in developing a novel viral screening test to fill this gap. The assay will consist of microscopic circuits containing field effect transistors with antigen-specific receptors that are sensitive to particular viruses. These chiplets – barely visible to the human eye – will be powered by light and will transmit data using a light emitting diode, such that a few can be mixed into an extracted sample and illuminated with a handheld device to yield immediate results. This diagnostic will be scalable and inexpensive; millions of tiny chiplets can be fabricated simultaneously. It will be minimally instrumented; an ordinary cellphone with a strobe flash and camera will interface with the chips. It will be flexible, rapidly adaptable, and multiplexable; receptors specific to different or emerging viruses could be immobilized on distinct circuits, allowing multiple diseases to be detected simultaneously in a single patient sample. This diagnostic will thus be unmatched as a mass producible, simple to use, adaptable, and high throughput tool for frequent and widespread virus screening. Specific aims: The proposed diagnostic will be developed by pursuing the following specific aims. 1. Integrate biological field effect transistors into the existing optical wireless integrated circuit platform. 2. Develop a multiplexed detection scheme for interacting with optical wireless integrated circuits. 3. Demonstrate the test’s feasibility in a clinically relevant quantitative range using mock clinical specimens. Career development plan and career goals: Dr. Matthew Campbell (Ph.D., P.E.) is a postdoctoral researcher in the School of Engineering and Applied Science at the University of Pennsylvania, where his work is focused on fabricating microelectromechanical systems. The proposed K25 career development award will apply his nanofabrication skills toward biosensor development and extend his training and exposure into two new domains: (1) biomedical experimentation, and (2) medical biology. This proposal contains a cohesive mentorship and didactic strategy centered on these areas to accelerate his trajectory toward research independence. Completion of this multifaceted training plan will position Dr. Campbell with the cross-disciplinary skills and expertise necessary to become a leading investigator in the field of biomedical sensing diagnostics. Mentors and environment: Dr. Campbell is enthusiastically supported by the university and his strong mentoring team. His primary mentor is an expert in micromanufacturing (Prof. Igor Bargatin (Ph.D.)), and his co- mentors bring extensive experience in microscopic circuits (Prof. Marc Miskin (Ph.D.)), field effect transistor sensors (Prof. Charlie Johnson (Ph.D.) and Prof. Haim Bau (Ph.D.)), and viral respiratory tract infections (Prof. Ronald Collman (M.D.). This group will provide the ideal training situation for Dr. Campbell to develop this assay.