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

Wei Feng, Joanne C. Beer, Qinyu Hao, Ishara S. Ariyapala, Aparna Sahajan, Andrei Komarov, Katie Cha, Mason Moua, Xiaolei Qiu, Xiaomei Xu, Shweta Iyengar, Thu Yoshimura, Rajini Nagaraj, Li Wang, Ming Yu, Kate Engel, Lucas Zhen, Wen Xue, Chen-jung Lee, Chan Ho Park, Cheng Peng, Kaiyuan Zhang, Adrian Grzybowski, Johnnie Hahm, Susanne V. Schmidt, Alexandru Odainic, Jasper Spitzer, Kasun Buddika, Dwight Kuo, Lei Fang, Bingqing Zhang, Steve Chen, Eicke Latz, Yiyuan Yin, Yuling Luo () and Xiao-Jun Ma ()
Additional contact information
Wei Feng: Alamar Biosciences, Inc
Joanne C. Beer: Alamar Biosciences, Inc
Qinyu Hao: Alamar Biosciences, Inc
Ishara S. Ariyapala: Alamar Biosciences, Inc
Aparna Sahajan: Alamar Biosciences, Inc
Andrei Komarov: Alamar Biosciences, Inc
Katie Cha: Alamar Biosciences, Inc
Mason Moua: Alamar Biosciences, Inc
Xiaolei Qiu: Alamar Biosciences, Inc
Xiaomei Xu: Alamar Biosciences, Inc
Shweta Iyengar: Alamar Biosciences, Inc
Thu Yoshimura: Alamar Biosciences, Inc
Rajini Nagaraj: Alamar Biosciences, Inc
Li Wang: Alamar Biosciences, Inc
Ming Yu: Alamar Biosciences, Inc
Kate Engel: Alamar Biosciences, Inc
Lucas Zhen: Alamar Biosciences, Inc
Wen Xue: Alamar Biosciences, Inc
Chen-jung Lee: Alamar Biosciences, Inc
Chan Ho Park: Alamar Biosciences, Inc
Cheng Peng: Alamar Biosciences, Inc
Kaiyuan Zhang: Alamar Biosciences, Inc
Adrian Grzybowski: Alamar Biosciences, Inc
Johnnie Hahm: Alamar Biosciences, Inc
Susanne V. Schmidt: University of Bonn
Alexandru Odainic: University of Bonn
Jasper Spitzer: University of Bonn
Kasun Buddika: Alamar Biosciences, Inc
Dwight Kuo: Alamar Biosciences, Inc
Lei Fang: Alamar Biosciences, Inc
Bingqing Zhang: Alamar Biosciences, Inc
Steve Chen: Alamar Biosciences, Inc
Eicke Latz: University of Bonn
Yiyuan Yin: Alamar Biosciences, Inc
Yuling Luo: Alamar Biosciences, Inc
Xiao-Jun Ma: Alamar Biosciences, Inc

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract The 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 of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Date: 2023
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DOI: 10.1038/s41467-023-42834-x

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