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

具有高灵敏度和选择性的多种生物标志物的检测对于指导疾病（例如呼吸道感染、免疫反应或癌症）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才能完成，这阻碍了治疗。该学院早期职业发展（CAREER）资助支持研究调查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。这些平台将增强测试能力，并使拯救生命的个性化治疗的快速发展成为可能，支持NSF推进国民健康的使命。这个CAREER项目支持一个名为“医疗诊断革命”的新教育项目，该项目利用易于使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成本效益高的医疗工具和诊断设备的设计和制造。这个CAREER奖项的目标是开发一种新型的超灵敏便携式免疫测定，称为瞬态数字测定（TSDA），其结合了联合收割机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，使得能够以高速、灵敏度、准确度和多重性的组合在患者附近同时定量循环血液细胞因子生物标志物。TSDA的坚实的理论基础将建立通过一个多物理模型会计旋流，质量传输，结合动力学，和单分子数字信号转导的发展。该模型的实验验证将揭示基于纳米漩涡的瞬态生物识别背后的基本机制和关键参数。这一基础知识将允许在不同的样品介质中的多种分析物的TSDA生物传感的优化准则的发展，显着提高现有的微阵列检测的速度和灵敏度。在与快速和便携式激光扫描光学器件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测定速度、低检测限（LOD=0.05- 1 pg/mL）、大动态范围和多重性（多达24种生物标志物）。在TSDA期间使用紧凑的磁致动系统对纳米机器人进行最佳控制将导致检测反应时间短至1分钟，这比常规ELISA试剂盒短100倍以上。该研究的教育计划将支持学校的STEM参与，为代表性不足的群体提供研究机会，并在最先进的纳米机器人，生物学和诊断技术方面培训学生，增强未来的工程劳动力。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.