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.

具有高灵敏度和选择性的多种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，当前的临床检测技术需要数天至数周才能完成，这阻碍了早期治疗。职业发展 (CAREER) 拨款支持研究利用数百万个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，并促进快速开发挽救生命的个性化治疗，支持 NSF 促进国民健康的使命。 。这CAREER 项目支持一项名为“革新医疗诊断”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。该职业奖旨在开发一种新型超灵敏便携式免疫测定法，称为瞬态数字测定法 (TSDA)，它结合了磁控旋转纳米机器人和纳米间隙增强拉曼散射纳米探针能够在患者附近同时定量循环血液细胞因子生物标志物，兼具高速、灵敏、准确和多重性，通过开发计算旋流、质量的多物理场模型，将为 TSDA 奠定坚实的理论基础。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。制定不同样品介质中多种分析物的 TSDA 生物传感优化指南，显着提高现有微阵列检测的速度和灵敏度。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 将实现前所未有的高检测速度、低检测速度。同一便携式平台中的检测限（LOD=0.05-1pg/mL）、大动态范围和多重性（最多 24 个生物标志物）的最佳控制。 TSDA 期间使用紧凑型磁驱动系统的纳米机器人将导致检测反应时间短至 1 分钟，比传统 ELISA 试剂盒短 100 倍以上。补充这项研究的教育计划将支持学校的 STEM 参与，提供研究。为代表性不足的群体提供机会，并培训学生最先进的纳米机器人、生物学和诊断技术，增强未来的工程劳动力。该奖项反映了 NSF 的法定使命，并被认为值得通过以下方式获得支持：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。