HOMOGENEOUS ASSAY PLATFORM FOR CLINICAL DIAGNOSTICS

用于临床诊断的均质检测平台

• 批准号: 7482522
• 负责人: ROBERT F BALINT
• 金额: $ 14.95万
• 依托单位: CYTODESIGN, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-15 至 2009-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482522
• 关键词: Acute myocardial infarction; Address; Adsorption; Antibody Affinity; Appearance; Biological; Biological Assay; Biological Markers; Blood Circulation; Cardiac; Cardiovascular system; Chest Pain; Clinical; Clinical Medicine; Collaborations; Communicable Diseases; Detection; Diagnostic; Diagnostics Research; Disease; Early Diagnosis; Endocrine; Enzyme Reactivation; Enzyme-Linked Immunosorbent Assay; Equipment; Evaluation; Eye; Generations; Goals; Human; Immunoglobulin Fragments; Immunosorbents; Industry; Inflammatory; Injury; Investigational Therapies; Ischemia; Kinetics; Laboratories; Lactamase; Liquid substance; Malignant Neoplasms; Measurement; Mediating; Microfluidics; Modeling; Myocardial Infarction; Neurologic; Patients; Pharmacodynamics; Pharmacologic Substance; Phase; Process; Quantitative Evaluations; Radioimmunoassay; Reagent; Reporter; Reproducibility; Risk; Sampling; Serum; Specialist; Specimen; Speed; Standards of Weights and Measures; Stream; Stroke; System; Testing; Time; Trauma; Troponin I; United States Food and Drug Administration; Upper arm; Validation; assay development; base; disorder risk; point of care; pre-clinical; reproductive; response; sensor; therapeutic target

DESCRIPTION (provided by applicant): A major challenge facing the clinical diagnostics industry in the years ahead is the need for new assay platforms capable of rapid, accurate evaluation of low-abundance biomarkers for early detection of disease and risk for diseases such as cancer, cardiovascular, and infectious diseases, as well as rapid evaluation of traumas, such as heart attack, stroke, and injury. Thus, new assay platforms are urgently needed which permit real-time quantitative evaluation of low-abundance therapeutic targets and biomarkers in clinical specimens with minimal sample processing. Ideally, such new assay platforms should be endowed with: (1) superior sensitivity to permit early detection and evaluation of risk, (2) suitability for kits for rapid analysis at points of care by non-specialists using simple equipment, (3) adaptability to standard automated high-throughput microfluidic systems. For many years immunosorbent assay platforms, such as RIA, and ELISA, have formed the basis of most biomarker assays, but as clinical medicine has evolved, increasing demand for sensitivity, accuracy, speed, and versatility have rendered these platforms sub-optimal for many important applications. To address the need for a quantitative clinical assay platform that overcomes the limitations of the immunosorbent platforms, and meets the requirements listed above for the ideal assay platform, a proprietary target recognition-mediated enzyme reactivation sensor based on the reactivation of an auto-inhibited 2- lactamase has been developed, called TRAIL. The TRAIL system is completely homogeneous, and has the potential for rapid, accurate measurement of any macromolecular species at picomolar concentrations in most biological fluids in standard laboratory settings with minimal sample processing and standard detection equipment. In addition, the system permits sensitive detection in minutes at points of care by non- professionals. The system utilizes universal reporter activation components that can be readily combined with standard target-binders such as antibody fragments for rapid generation of new assays. In Phase I, human cardiac Troponin I (cTnI) will be used as a model biomarker for validation and optimization of the TRAIL assay platform. The appearance of cTnI in the circulation has become a preferred indicator of heart attack in patients presenting with chest pain in the ER. A TRAIL assay for cTnI could allow rapid confirmation of acute myocardial infarction (AMI) sooner after onset of ischemia than is possible with current immunosorbent tests. The Phase I goal is to optimize a TRAIL assay which can quantify cTnI in human serum down to 1.0 picomolar or less in less than 30 minutes. In Phase II, the TRAIL cTnI assay will be validated for accuracy, sensitivity, and reproducibility on pre-clinical and clinical samples, and compared to standard commercial assays. FDA approval will be sought, and a corporate partner will be engaged for commercial development of the assay. Additional assays will be developed and validated for other biomarkers of disease and trauma in collaboration with corporate partners in the pharmaceutical and diagnostics industries.

描述（由申请人提供）：未来几年临床诊断行业面临的主要挑战是需要新的检测平台能够快速、准确地评估低丰度生物标志物，以早期检测疾病和癌症、心血管和传染病等疾病的风险，以及快速评估心脏病、中风和损伤等创伤。因此，迫切需要新的检测平台，能够以最少的样品处理对临床样本中的低丰度治疗靶点和生物标志物进行实时定量评估。理想情况下，此类新的检测平台应具有：（1）卓越的灵敏度，以允许早期检测和评估风险，（2）适合非专业人员使用简单设备在护理点进行快速分析的试剂盒，（3）对标准自动化高通量微流体系统的适应性。多年来，RIA 和 ELISA 等免疫吸附测定平台已成为大多数生物标志物测定的基础，但随着临床医学的发展，对灵敏度、准确性、速度和多功能性的需求不断增加，使得这些平台对于许多重要应用而言并不是最佳选择。为了满足定量临床检测平台的需求，该平台克服了免疫吸附平台的局限性，并满足上述理想检测平台的要求，开发了一种基于自动抑制 2-内酰胺酶重新激活的专有目标识别介导的酶重新激活传感器，称为 TRAIL。 TRAIL 系统是完全均质的，并且具有在标准实验室环境中以最少的样品处理和标准检测设备快速、准确地测量大多数生物液体中皮摩尔浓度的任何大分子物质的潜力。此外，该系统允许非专业人员在几分钟内在护理点进行灵敏检测。该系统利用通用报告激活组件，可以轻松与标准靶标结合物（例如抗体片段）结合，以快速生成新的检测方法。在第一阶段，人心脏肌钙蛋白 I (cTnI) 将用作模型生物标志物，用于验证和优化 TRAIL 检测平台。循环中 cTnI 的出现已成为急诊室出现胸痛的患者心脏病发作的首选指标。与目前的免疫吸附测试相比，cTnI 的 TRAIL 检测可以在缺血发作后更快地快速确认急性心肌梗塞 (AMI)。第一阶段的目标是优化 TRAIL 测定，该测定可以在 30 分钟内将人血清中的 cTnI 定量至 1.0 皮摩尔或更低。在第二阶段，将验证 TRAIL cTnI 检测的准确性、灵敏度和可重复性，并在临床前和临床样本上进行验证，并与标准商业检测进行比较。将寻求 FDA 批准，并将聘请企业合作伙伴进行该检测的商业开发。将与制药和诊断行业的企业合作伙伴合作，开发和验证其他疾病和创伤生物标志物的检测方法。