SBIR Phase II: Development of an ultrasensitive, high-throughput autoantibody discovery platform using agglutination-PCR

SBIR 第二阶段：使用凝集 PCR 开发超灵敏、高通量自身抗体发现平台

• 批准号: 1758698
• 负责人: David Seftel
• 金额: $ 75万
• 依托单位: Enable Biosciences Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1758698&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Development; ultrasensitive

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to develop a platform technology for detecting autoantibody markers for research and clinical diagnostics. Precision medicine requires the development of more powerful bioanalytic technologies to diagnose disease and direct targeted therapies. This platform uses a ligation-based DNA barcoding technology for improved antibody detection with increased analytical sensitivity and multiplex power to detect more at the most clinically useful time. Additionally, as a solution-phase assay, it is able to detect numerous clinically-relevant autoantibodies that are refractory to common techniques like ELISA. This platform has the potential to accelerate the development of lifesaving diagnostics across a broad spectrum of human diseases. This Small Business Innovation Research Phase II project aims to develop the first solution-phase, ultrasensitive and multiplex antibody assay platform for the early detection, monitoring and treatment of human diseases. The Antibody Detection by Agglutination-PCR (ADAP) platform represents a major advancement in multiplex immunoassay testing. Many current multiplex technologies, such as microarrays and bead-based arrays, scale poorly due to cross-analyte interference, and lack the analytical sensitivity to detect crippling diseases at the most favorable time. The Phase I results showed the expanded and validated ADAP technology for the ultrasensitive and multiplex detection of antibody biomarkers. The Phase II objectives are: 1) Validation of the multiplex ADAP assay for clinical diagnostics serving autoimmune connective tissue diseases, thyroid disorders and celiac diseases; 2) High-throughput automation of multiplex ADAP assay technology for clinical diagnostics; 3) Manufacturing of assay reagents and establishment of quality control standards; and 4) Demonstration of the applicability of multiplex ADAP for a broader set of antibodies. The intellectual merit of this project resides in the achievement of 10,000x increased sensitivity, and 20-30% increased specificity at multiplex while having the option to use existing PCR reader platforms to help keep lab capital costs low.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.

这项小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力将是开发一种平台技术，用于检测用于研究和临床诊断的自身抗体标记。精密医学需要开发更强大的生物分析技术来诊断疾病和直接靶向疗法。该平台使用基于连接的DNA条形码技术来改进抗体检测，并提高分析灵敏度和多重功率，以在最有用的时间内检测更多。此外，作为一种溶液相测定，它能够检测出许多与ELISA这样常见技术难治性的临床自身抗体。 该平台有可能加快各种人类疾病范围内救生诊断的发展。这项小型企业创新研究阶段项目旨在开发第一个溶液相，超敏感和多重抗体测定平台，用于早期发现，监测和治疗人类疾病。通过凝集-PCR（ADAP）平台检测的抗体检测代表了多重免疫测定测试的主要进步。许多当前的多重技术，例如微阵列和基于珠子的阵列，由于交叉分析的干扰，并且缺乏在最有利的时间检测残酷疾病的分析敏感性。 第一阶段的结果显示了抗体生物标志物的超敏和多重检测的扩展和验证的ADAP技术。 II期目标是：1）对临床诊断的多重ADAP分析的验证，用于临床诊断，可为自身免疫结缔组织疾病，甲状腺疾病和腹腔疾病验证； 2）用于临床诊断的多重ADAP测定技术的高通量自动化； 3）制定试剂制造和建立质量控制标准； 4）演示多路复用器适用于一组更广泛的抗体。该项目的智力优点在于实现10,000倍的提高敏感性，而在多重方面的特异性提高了20-30％，同时可以选择使用现有的PCR读取器平台来帮助保持实验室资本成本较低。该奖项反映了NSF的法定任务和使用基金会的知识分子优点和更广泛的审查标准，通过评估被认为值得支持。