Rapid single-molecule digital detection of protein biomarkers for continuous monitoring of systemic immune disorders

Yujing Song, Erin Sandford, Yuzi Tian, Qingtian Yin, Andrew G. Kozminski, Shiuan Haur Su, Tao Cai, Yuxuan Ye, Meng Ting Chung, Ryan Lindstrom, Annika Goicochea, Jenny Barabas, Mary Olesnavich, Michelle Rozwadowski, Yongqing Li, Hasan B. Alam, Benjamin H. Singer, Monalisa Ghosh, Sung Won Choi, Muneesh TewariKatsuo Kurabayashi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Digital protein assays have great potential to advance immunodiagnostics because of their single-molecule sensitivity, high precision, and robust measurements. However, translating digital protein assays to acute clinical care has been challenging because it requires deployment of these assays with a rapid turnaround. Herein, we present a technology platform for ultrafast digital protein biomarker detection by using single-molecule counting of immune-complex formation events at an early, pre-equilibrium state. This method, which we term "pre-equilibrium digital enzyme-linked immunosorbent assay" (PEdELISA), can quantify a multiplexed panel of protein biomarkers in 10 µL of serum within an unprecedented assay incubation time of 15 to 300 seconds over a 104 dynamic range. PEdELISA allowed us to perform rapid monitoring of protein biomarkers in patients manifesting post-chimeric antigen receptor T-cell therapy cytokine release syndrome, with ∼30-minute sample-to-answer time and a sub-picograms per mL limit of detection. The rapid, sensitive, and low-input volume biomarker quantification enabled by PEdELISA is broadly applicable to timely monitoring of acute disease, potentially enabling more personalized treatment.

Original languageEnglish (US)
Pages (from-to)1591-1602
Number of pages12
JournalBlood
Volume137
Issue number12
DOIs
StatePublished - Mar 25 2021
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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