NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
Author:
Feng Wei, Beer Joanne, 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 JasperORCID, Buddika Kasun, Kuo Dwight, Fang Lei, Zhang Bingqing, Chen Steve, Latz Eicke, Yin Yiyuan, Luo Yuling, Ma Xiao-JunORCID,
Abstract
AbstractThe blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology – NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) – that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
Publisher
Cold Spring Harbor Laboratory
Cited by
4 articles.
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