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

超灵敏检测血浆中的蛋白质靶标以早期发现癌症

• 批准号: 10080139
• 负责人: YULING LUO
• 金额: $ 32.19万
• 依托单位: ALAMAR BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080139
• 关键词: Address; Biological; Biological Assay; Biomedical Research; Blood; Blood Cells; Cancer Patient; Cells; Colon Carcinoma; DNA; Detection; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Face; Goals; HIV; Human; Immunoassay; In Situ; Link; Malignant Neoplasms; Methods; Modeling; Mutation; Names; Noise; Nucleic Acids; Performance; Phase; Plasma; Population; Proteins; RNA; Sampling; Screening for cancer; Signal Transduction; Signaling Protein; Small Business Innovation Research Grant; Technology; Testing; Tumor Markers; assay development; base; candidate marker; clinical development; colon cancer screening; curative treatments; improved; insight; liquid biopsy; methylation pattern; milliliter; neoplastic cell; next generation sequencing; novel; novel marker; protein biomarkers; protein expression; prototype; single molecule; tumor; tumor DNA

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.

项目摘要 癌症的早期检测是生物医学领域需要解决的最重要的问题之一。 因为癌症被发现得越早，治愈或成功治疗的机会就越大。 治疗与目前的DNA液体活检方法相比，我们建议开发一种 超灵敏的免疫分析技术，可对早期癌症进行蛋白质液体活检 侦测通过利用我们在提高信号与背景比方面的见解， 开发了一种名为NULISA的原型免疫测定法，或核酸连接免疫测定法， 夹心检测，已达到前所未有的检测灵敏度水平的任何 在约20，000分子/mL（即约30 aM）下使用市售免疫测定。在这项提案中， 我们的目标是优化NULISA测定，以进一步提高检测下限和 定量（LOD和LOQ），并测试一些候选标记物在早期癌症中的潜力 侦测第一阶段SBIR提案的具体目标包括：1）优化单丛 NULISA用于超灵敏检测血浆中的蛋白质标志物，并显示至少10- 与市场上最灵敏的免疫测定相比，检测灵敏度提高一倍;以及2） 展示NULISA用于早期癌症检测的初步概念证明。于年底 项目，我们期望已经建立了一个高性能的NULISA检测和可行性， 用于早期癌症检测的新标记物。该项目的长期目标是开发 非侵入性的单一和/或泛癌症筛查测试，可以更早地检测癌症， 更成功或更有效的治疗。

项目成果

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

• DOI: 10.1038/s41467-023-42834-x
• 发表时间: 2023-11-09
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Feng, Wei;Beer, Joanne C.;Hao, Qinyu;Ariyapala, Ishara S.;Sahajan, Aparna;Komarov, Andrei;Cha, Katie;Moua, Mason;Qiu, Xiaolei;Xu, Xiaomei;Iyengar, Shweta;Yoshimura, Thu;Nagaraj, Rajini;Wang, Li;Yu, Ming;Engel, Kate;Zhen, Lucas;Xue, Wen;Lee, Chen-jung;Park, Chan Ho;Peng, Cheng;Zhang, Kaiyuan;Grzybowski, Adrian;Hahm, Johnnie;Schmidt, Susanne V.;Odainic, Alexandru;Spitzer, Jasper;Buddika, Kasun;Kuo, Dwight;Fang, Lei;Zhang, Bingqing;Chen, Steve;Latz, Eicke;Yin, Yiyuan;Luo, Yuling;Ma, Xiao-Jun
• 通讯作者: Ma, Xiao-Jun