Microfluidics-enabled directed affinity reagent engineering for fast, sensitive diagnostics

支持微流体的定向亲和试剂工程可实现快速、灵敏的诊断

• 批准号: 10527811
• 负责人: HADLEY D SIKES
• 金额: $ 21.66万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527811
• 关键词: Affinity; Autoimmune Diseases; Binding; Biological; Biological Assay; Biological Products; Biology; Caring; Cell Separation; Chemical Engineering; Chemicals; Chronic; Detection; Development; Devices; Diagnostic; Diagnostic tests; Dissociation; Electrical Engineering; Elements; Engineering; Enzyme-Linked Immunosorbent Assay; Equilibrium; Faculty; Future; Generations; Goals; Gold; Health; Healthcare; Home; Hour; Inflammatory; Interleukin-1 beta; Interleukin-17; Interleukin-6; Investigation; Kinetics; Laboratories; Libraries; Liquid substance; Medical; Medicine; Methods; Microfluidic Microchips; Microfluidics; Modeling; Monitor; Monoclonal Antibodies; Patients; Penetration; Performance; Process; Protein Analysis; Protein Engineering; Proteins; Rapid diagnostics; Reagent; Receptor Signaling; Reproducibility; Rheumatoid Arthritis; Scheme; Science; Site; Specificity; Speed; Surface; System; TNF gene; Testing; Therapeutic; Time; Tissues; Translating; Yeasts; base; biomarker panel; chronic autoimmune disease; clinically relevant; combinatorial; computer science; cytokine; design; design-build-test; effective intervention; improved; improved outcome; mathematical model; monitoring device; novel; pathogen; personalized care; point of care; point-of-care diagnostics; predictive test; protein biomarkers; screening; tumor

PROJECT SUMMARY/ABSTRACT Near-patient detection and quantification of specific proteins in bodily fluids can enable medical professionals to offer timely and effective care that improves outcomes. In protein biomarker detection, a tradeoff exists between assay sensitivity and time to result. Affinity reagents are key components of microfluidic devices that enable protein analysis at the point of care. At present, affinity reagents are selected on the basis of equilibrium binding constants, which are most predictive of assay performance on hours-long timescales. The proposed project will develop transformative kinetic screening methods and devices that allow engineering of affinity reagents that can offer sensitive detection on the timescales of seconds to minutes, and use the reagents to enable frequent, convenient monitoring of cytokine panels to improve care for rheumatoid arthritis patients. This project leverages the collective cross-disciplinary expertise of faculty at MIT from the Departments of Chemical Engineering and Electrical Engineering and Computer Science. The team's synergistic expertise in protein engineering for diagnostics (Sikes) and design, fabrication and application of microfluidics and BioMEMS for point-of-care diagnostic tests (Voldman) will be collectively focused on developing new kinetic screening devices for engineering superior affinity reagents, and translating the new capability into an impactful on-site assay for inflammatory cytokines. Specific Aim 1 is to create novel microfluidic devices that can be used to select for fast-binding affinity reagents. Specific Aim 2 is to establish and validate new library screening processes uniquely enabled by the devices. Specific Aim 3 uses fast- binding affinity reagents to create a near-patient cytokine assay that maintains the required sensitivity without requiring a laboratory, which can enable more frequent testing and more individualized care for rheumatoid arthritis.

项目摘要/摘要 体液中特定蛋白质的近乎检测和定量可以实现医疗 专业人士提供及时有效的护理，以改善结果。在蛋白质生物标志物中 检测，在测定敏感性与结果时间之间存在权衡。亲和力试剂是关键 在护理点上实现蛋白质分析的微流体设备的组件。现在， 亲和力试剂是根据平衡结合常数选择的，这是最多的 预测长时间时间尺度上的测定性能。拟议的项目将开发 变革性的动力学筛选方法和设备，允许工程的亲和力试剂 可以在几秒钟到几分钟的时间尺度上提供敏感的检测，并使用试剂 为了频繁，方便地监测细胞因子面板以改善类风湿的护理 关节炎患者。该项目利用了麻省理工学院教师的集体跨学科专业知识 来自化学工程，电气工程和计算机的部门 科学。该团队在诊断蛋白工程方面的协同专业知识（Sikes）和 用于护理点诊断测试的微流体和生物元的设计，制造和应用 （沃尔德曼）将集体专注于开发新的动力学筛选设备 工程高级亲和力试剂，并将新能力转化为有影响力的现场 炎性细胞因子的测定。特定目的1是创建新颖的微流体设备 用于选择快速结合亲和力试剂。具体目标2是建立和验证 设备唯一启用了新的库筛选过程。特定的目标3使用快速使用 - 结合亲和力试剂以创建近乎病人的细胞因子测定法，以维持所需的 灵敏度而无需实验室，这可以实现更频繁的测试和更多 类风湿关节炎的个性化护理。