CAREER: Rapid and Ultrasensitive Critical Care Testing at the Point of Need using Multiplexed Transient-State Digital Assays

职业：使用多重瞬态数字化验在需要时进行快速、超灵敏的重症监护测试

• 批准号: 2047842
• 负责人: Ramses Martinez
• 金额: $ 51.75万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2047842&HistoricalAwards=false
• 关键词: CAREER; Rapid; Ultrasensitive; Critical; Care

The detection of multiple biomarkers with high sensitivity and selectivity is essential to guide personalized treatment of diseases, such as respiratory infections, immune reactions, or cancer. Unfortunately, current clinical testing techniques require days to weeks to be completed, impeding treatment. This Faculty Early Career Development (CAREER) grant supports research investigating the mechanisms behind a novel antigen detection approach that leverages millions of rotating nanorobots. These platforms will enhance testing capabilities and enable the rapid development of life-saving personalized treatments, supporting NSF’s mission of advancing the national health. This CAREER project supports a new educational program called “Revolutionizing Healthcare Diagnostics”, which utilizes easy-to-use computer aided design software and 3D printing to introduce underrepresented students to the design and manufacture of cost-effective medical tools and diagnostic devices.The goal of this CAREER award is to develop a new kind of ultrasensitive portable immunoassay, called Transient State Digital Assays (TSDAs), which combine magnetically controlled rotating nanorobots and nanogap-enhanced Raman scattering nanoprobes to enable near-the-patient concurrent quantification of circulating blood cytokine biomarkers with the combination of high speed, sensitivity, accuracy, and multiplexity. A solid theoretical foundation for TSDAs will be established through the development of a multiphysics model accounting swirl flows, mass transport, binding kinetics, and single-molecule digital signal transduction. The experimental validation of this model will unveil the fundamental mechanisms and key parameters behind the nanoswirl-based transient-state biorecognition. This fundamental knowledge will allow the development of optimization guidelines for the TSDA biosensing of multiple analytes in different sample media, significantly improving the speed and sensitivity of existing microarray assays. The implementation of TSDA in microarray chips compatible with fast and portable laser scanning optics will achieve unprecedented high assay speeds, low limits of detection (LOD=0.05-1pg/mL), large dynamic ranges, and multiplexity (up to 24 biomarkers) in the same portable platform. The optimal control of the nanorobots during TSDA using a compact magnetic actuation system will result in assay reaction times as short as 1 min, which is more than 100 times shorter than those of conventional ELISA kits. The educational program complementing this research will support STEM engagement in schools, provide research opportunities to underrepresented groups, and train students in state-of-the-art nanorobotics, biology, and diagnostics techniques, enhancing future engineering workforce.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

具有高灵敏度和高选择性的多个生物标志物的检测对于指导呼吸道感染、免疫反应或癌症等疾病的个性化治疗至关重要。不幸的是，目前的临床测试技术需要几天到几周的时间才能完成，这阻碍了治疗。这笔学院早期职业发展(Career)补助金支持研究一种利用数百万旋转纳米机器人的新型抗原检测方法背后的机制。这些平台将增强检测能力，使挽救生命的个性化治疗快速发展，支持NSF推进国民健康的使命。该职业项目支持一个名为“医疗诊断革命”的新教育项目，该项目利用简单易用的计算机辅助设计软件和3D打印，向未被充分代表的学生介绍高性价比医疗工具和诊断设备的设计和制造。该职业奖项的目标是开发一种新型的超灵敏便携式免疫分析，称为暂态数字分析(TSDAS)，它结合了磁控旋转纳米机器人和纳米间隙增强的拉曼散射纳米探针，能够在接近患者的情况下同时定量循环中的细胞因子生物标志物，并结合高速、灵敏、准确和多路复用。通过开发考虑旋流、质量传输、结合动力学和单分子数字信号传导的多物理模型，将为TSDAS建立坚实的理论基础。该模型的实验验证将揭示基于纳米蠕动的暂态生物识别背后的基本机制和关键参数。这一基础知识将使TSDA在不同样品介质中对多种分析物进行生物传感的优化指南得以开发，从而显著提高现有微阵列分析的速度和灵敏度。在与快速和便携式激光扫描光学系统兼容的微阵列芯片中实施TSDA将在同一便携式平台中实现前所未有的高分析速度、低检测限(LOD=0.05-1pg/mL)、大动态范围和多重(多达24个生物标志物)。在TSDA过程中，使用紧凑的磁力驱动系统对纳米机器人进行优化控制，将导致检测反应时间缩短至1分钟，比传统的ELISA试剂盒缩短100多倍。补充这项研究的教育计划将支持STEM在学校的参与，为代表不足的群体提供研究机会，并培训学生最先进的纳米机器人、生物学和诊断技术，增强未来的工程工作能力。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。