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

检测具有高灵敏度和选择性的多种生物标志物对于指导疾病的个性化治疗至关重要，例如呼吸道感染，免疫反应或癌症。不幸的是，目前的临床检测技术需要几天到几周才能完成，这阻碍了治疗。这项教师早期职业发展（Career）资助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能够快速发展，支持NSF推进国民健康的使命。这个职业项目支持一个名为“革命性医疗诊断”的新教育计划，该计划利用易于使用的计算机辅助设计软件和3D打印向代表性不足的学生介绍具有成本效益的医疗工具和诊断设备的设计和制造。该职业奖的目标是开发一种新型的超灵敏便携式免疫分析，称为瞬态数字分析（TSDAs），它结合了磁控制的旋转纳米机器人和纳米间隙增强的拉曼散射纳米探针，使循环血液细胞因子生物标志物的快速、敏感、准确和多样性的结合，能够在患者附近同步定量。通过建立多物理场模型，计算旋流、质量输运、结合动力学和单分子数字信号转导，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涡旋的瞬态生物识别的基本机制和关键参数。这些基础知识将允许开发TSDA生物传感在不同样品介质中多种分析物的优化指南，显着提高现有微阵列分析的速度和灵敏度。在与快速便携式激光扫描光学器件兼容的微阵列芯片中实施TSDA，将在同一个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）、大动态范围和多样性（多达24个生物标志物）。在TSDA过程中，利用紧凑的磁驱动系统对纳米机器人进行最优控制，将使检测反应时间缩短至1分钟，比传统ELISA试剂盒缩短100倍以上。补充这项研究的教育计划将支持STEM在学校的参与，为代表性不足的群体提供研究机会，并培训学生掌握最先进的纳米机器人、生物学和诊断技术，增强未来的工程劳动力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识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.