Ultrasensitive detection of protein targets in plasma for early detection of cancer

项目总结 癌症的早期发现是生物医学领域需要解决的最重要问题之一。 研究是因为癌症发现得越早，治愈或成功的机会就越大 治疗。与目前的DNA液体活组织检查方法不同，我们建议开发一种 超灵敏免疫分析技术，使早期癌症的蛋白质液体活检成为可能 侦测。通过利用我们在改善信号与背景比方面的见解，我们已经 开发了一种名为NULISA的免疫分析原型，即核酸连接免疫... 三明治检测，达到了前所未有的检测灵敏度水平 商业上可用的免疫分析在~20,000分子/毫升(即~30上午)。在这份提案中， 我们的目标是优化NULISA方法，以进一步提高检测的下限和下限 定量(LOD和LOQ)并测试几个候选标记物在早期癌症中的潜力 侦测。此第一阶段SBIR方案的具体目标包括：1)优化单丛 NULISA用于超灵敏地检测血浆中的蛋白质标志物，并至少展示10- 检测灵敏度比市场上最灵敏的免疫分析方法高出一倍；以及2) 展示NULISA用于早期癌症检测的概念的初步证据。在这个结束的时候 项目，我们希望建立一个高性能的NULISA测试和可行性 癌症早期检测的新标记物。该项目的较长期目标是开发 非侵入性单项和/或泛癌筛查测试可以更早地发现癌症 更成功或更有效的治疗。

PROJECT SUMMARY Early detection of cancer is amongst the most important problems to address in biomedical research because the earlier cancer is detected, the better chance of a cure or a successful treatment. In contrast to the current approach of DNA liquid biopsy, we propose to develop an ultra-sensitive immunoassay technology that enables protein liquid biopsy for early cancer detection. By leveraging our insights in improving signal-to-background ratio, we have developed a prototype immunoassay named NULISA, or NUcleic acid-Linked Immuno- Sandwich Assay, that has achieved unprecedented level of detection sensitivity of any commercially available immunoassays at ~20,000 molecules/mL (i.e. ~30 aM). In this proposal, we aim to optimize the NULISA assay to further boost lower limit of detection and limit of quantitation (LOD and LOQ) and test a few candidate markers for their potential in early cancer detection. The specific aims of this Phase 1 SBIR proposal include: 1) Optimize single plex NULISA for ultrasensitive detection of protein markers in plasma and demonstrate minimally 10- fold better detection sensitivity over the most sensitive immunoassay on market; and 2) Demonstrate initial proof of concept of NULISA for early cancer detection. At the end of this project, we expect to have established a high performance NULISA assay and the feasibility of novel markers for early cancer detection. The longer-term goal of the project is to develop noninvasive single- and/or pan-cancer screen tests that could detect cancer much earlier for more successful or curative treatment.