Optofluidic Nanoplasmonic Biosensors for Next Generation Point-of-Care Immunoassays

用于下一代护理点免疫测定的光流控纳米等离子体生物传感器

• 批准号: 10460475
• 负责人: Pengyu Chen
• 金额: $ 37.55万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460475
• 关键词: Achievement; Address; Autoimmune Diseases; Behavior; Biological; Biological Assay; Biology; Biosensing Techniques; Biosensor; Cell Communication; Cells; Clinic; Clinical; Communicable Diseases; Complex; Data; Decentralization; Detection; Diagnosis; Disease; Enzyme-Linked Immunosorbent Assay; Feedback; Fingerprint; Future; Growth; Hour; Hypersensitivity; Immune; Immune System Diseases; Immune response; Immune system; Immunity; Immunoassay; Immunologic Monitoring; Immunologics; Immunology; Immunophenotyping; Ion Transport; Label; Malignant Neoplasms; Measurement; Mediating; Molecular; Outcome; Patients; Phenotype; Physicians; Population; Process; Proteins; Research; Sampling; Series; Serum; Signal Transduction; System; Technology; Testing; Time; Transplantation; Visualization; Whole Blood; base; clinical application; cytokine; diagnostic tool; fundamental research; immune system function; immunological status; immunomodulatory therapies; nanoplasmonic; next generation; patient response; personalized immunotherapy; point of care; predictive modeling; real time monitoring; sensor; tool

Optofluidic Nanoplasmonic Biosensors for Next Generation Point-of-care Immunoassays Abstract: Building predictive models of immunity requires comprehensive understanding of the complex and dynamic functional behavior of immune system. A need for such understanding is obvious with a number of immune related diseases for which viable treatments are not currently available. Cytokines are well-studied proteins secreted by immune cells and essential for intercellular signaling to regulate the maturation, growth, and responsiveness of particular cell populations. Previous studies suggest that quantification of cytokine-based immune fingerprints provides clinically and immunologically useful information related to infectious diseases, cancer, autoimmune diseases, and allergy transplantation. The ongoing revolution in fundamental biology, immunology and clinical discovery critically hinges on the availability of diagnostic tools capable of decentralized point-of-care measurements to provide immediate quantitative information of cytokine levels at the bedside or in the clinic. Current existing clinical technology is mainly based on Enzyme-linked immunosorbent assay (ELISA). The complex labelling and washing processes require a total assay time up to more than a few hours and a sample volume of 0.1- 2 mL per test per patient, which greatly hinders its application for immune monitoring at the point of care. Thus, there is an emerging clinical demand for transformative platforms that can perform multi- parametric cytokine detection to understand the dynamical immune response of the patient in a rapid and accurate manner. This requires collecting time series data that could be on the order of seconds for ion transport, to hours for changes in protein levels, and to days for phenotypic changes in host body with sensor sensitivity from biological relevant concentration to single molecular level using minimum sample volume. To address this need, the central objectives of this MIRA application are to develop integrated optofluidic nanoplasmonic biosensing platforms for rapid, high throughput, sensitive and multiplex cytokine detection from whole blood to single-cell level towards next-generation point-of-care immunoassays. The PI proposes the following three projects: 1) Label free, ultra-sensitive, high throughput nanoplasmonic serum immunoassay for real-time immune monitoring; 2) Multi-parametric cellular functional immunophenotyping assay for personalized immunomodulatory therapy; 3) Nanoplasmon ruler for direct visualization of single-cell cytokine secretion and cell-to-cell communication. The planned multi-scale research both experimentally and theoretically will bridge the gap in fundamental understanding of immune system and enhance the applicability, diagnosis and prediction power for immune system diseases. The proposed platforms would ultimately gear the biologists and clinicians with capability to real-time monitor the immune status in patients, a transformative achievement that has enormous implications to fundamental research and clinical applications.

用于下一代床旁免疫分析的光流体纳米等离子体生物传感器 翻译后摘要：建立免疫预测模型需要全面了解复杂的， 免疫系统的动态功能行为。对这种理解的需要是显而易见的， 免疫相关疾病，目前还没有可行的治疗方法。细胞因子已经被充分研究 由免疫细胞分泌的蛋白质，对于调节成熟，生长， 和特定细胞群的反应性。以前的研究表明，定量基于精氨酸的 免疫指纹提供了与传染病相关的临床和免疫学上有用的信息， 癌症、自身免疫性疾病和过敏移植。基础生物学的革命， 免疫学和临床发现关键取决于能够分散的诊断工具的可用性 床旁测量，以提供床边或体内细胞因子水平的即时定量信息。 诊所目前现有的临床技术主要是基于酶联免疫吸附试验（ELISA）。 复杂的标记和洗涤过程需要高达几个小时以上的总测定时间， 每例患者每次检测的样本量为0.1- 2 mL，这极大地阻碍了其在免疫监测中的应用， 护理要点。因此，对于能够执行多功能的变革性平台存在新兴的临床需求。 参数细胞因子检测，以快速和准确地了解患者的动态免疫应答， 准确的方式。这需要收集时间序列数据，其对于离子传输可以是秒的数量级， 对于蛋白质水平的变化为小时，对于具有传感器灵敏度的宿主体内的表型变化为天 从生物相关浓度到单分子水平，使用最小的样品体积。为了解决这个 需要，这个MIRA应用的中心目标是开发集成的光流体纳米等离子体 生物传感平台，用于快速、高通量、灵敏和多重细胞因子检测，从全血到 单细胞水平的下一代即时免疫测定。PI提出以下三点 项目：1）无标记、超灵敏、高通量纳米等离子体血清免疫分析，用于实时免疫 监测; 2）多参数细胞功能免疫表型分析，用于个性化的免疫检测。 免疫调节治疗; 3）用于直接可视化单细胞细胞因子分泌的纳米等离子体标尺， 细胞间通讯计划中的多尺度实验和理论研究将 弥补免疫系统基本认识上的差距，增强免疫系统的适用性、诊断性和预测性 免疫系统疾病的力量。拟议的平台最终将使生物学家和临床医生 具有实时监测患者免疫状态的能力，这是一项变革性的成就， 对基础研究和临床应用的巨大影响。