I-Corps: A diagnostic platform for the analysis of biomarkers in multiplexed immunoassays

I-Corps：用于在多重免疫分析中分析生物标志物的诊断平台

• 批准号: 2139567
• 负责人: Katsuo Kurabayashi
• 金额: $ 5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2139567&HistoricalAwards=false
• 关键词: Corps; diagnostic; platform; analysis; biomarkers

The broader impact/commercial potential of this I-Corps project is to enable a rapid, high-sensitivity, multiplex, digital immunoassay diagnostic platform. With a short turnaround, the platform is able to test blood samples of critically ill patients suffering from life-threatening conditions. If successfully commercialized, the technology is expected to provide immediate guidance for caregivers to make timely clinical decisions and proactively intervene before disease conditions worsen. The platform can potentially reduce the current mortality rate of infection-related acute illnesses in intensive care units. Additionally, the platform allows for the simultaneous detection of multiple biomarkers in a highly reliable and accurate manner. The I-Corps project will explore the commercialization potential of the digital immunoassay platform, exploring the use by diagnostic companies having clients in clinical laboratory medicine, hospital procurement managers and doctors of pathology, and researchers in biopharmaceutical companies as potential customers.This I-Corps project is based on the development of a prototype digital immunoassay platform using a pre-equilibrium digital enzyme-linked immunosorbent assay microarray. The microarray has been demonstrated to allow real-time profiling of multiple biomarker molecules (proteins and metabolites) for critically ill patients suffering from the side effects of cancer immune therapy and COVID-19 infections. The platform confines antibody-conjugated beads into an array of a large number of femtoliter-sized microwells on a microfluidic chip, each forming a fluorescent pixel turned on when the target analyte is bound. The highly localized confinement of antibody-antigen immune complex formation within such a small volume enables single-molecule detection of individual analyte binding events. The technique counts the number of fluorescence signal-activated pixels from a snapshot image of the entire microwell array taken for highly pre-equilibrated analyte binding events. As a result, the platform achieves high testing speed, high sensitivity, and potentially lower instrumentation cost than current systems.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.

该 I-Corps 项目更广泛的影响/商业潜力是实现快速、高灵敏度、多重数字免疫分析诊断平台。 该平台能够在短时间内检测危及生命的危重患者的血液样本。如果成功商业化，该技术预计将为护理人员提供即时指导，以便他们及时做出临床决策，并在病情恶化之前主动进行干预。 该平台有可能降低目前重症监护室感染相关急性疾病的死亡率。此外，该平台允许以高度可靠和准确的方式同时检测多个生物标志物。 I-Corps项目将探索数字免疫分析平台的商业化潜力，探索拥有临床检验医学客户的诊断公司、医院采购经理和病理医生以及生物制药公司的研究人员作为潜在客户的使用。该I-Corps项目基于使用预平衡数字酶联免疫吸附分析开发原型数字免疫分析平台 微阵列。该微阵列已被证明可以对遭受癌症免疫治疗和 COVID-19 感染副作用的危重患者进行多种生物标志物分子（蛋白质和代谢物）的实时分析。该平台将抗体缀合的珠子限制在微流体芯片上的大量飞升大小的微孔阵列中，每个微孔形成一个荧光像素，当目标分析物结合时打开。将抗体-抗原免疫复合物形成高度局部限制在如此小的体积内，使得能够对单个分析物结合事件进行单分子检测。该技术从针对高度预平衡的分析物结合事件拍摄的整个微孔阵列的快照图像中计算荧光信号激活像素的数量。因此，该平台实现了高测试速度、高灵敏度，并且比当前系统可能更低的仪器成本。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。