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

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 their deployment with a rapid turnaround. Herein, we present a technology platform for ultra-fast digital protein biomarker detection by employing 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 15-300 sec over a 104 dynamic range. PEdELISA allowed us to perform rapid monitoring of protein biomarkers in patients manifesting post-chimeric antigen receptor T-cell (CAR-T) therapy cytokine release syndrome (CRS), with ~30 min sample-to-answer time and a sub-pg/mL limit of detection (LOD). 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.

journal_name

Blood

journal_title

Blood

authors

Song Y,Sandford E,Tian Y,Yin Q,Kozminski AG,Su SH,Cai T,Ye Y,Chung MT,Lindstrom R,Goicochea A,Barabas J,Olesnavich M,Rozwadowski M,Li Y,Alam HB,Singer BH,Ghosh M,Choi SW,Tewari M,Kurabayashi K

doi

10.1182/blood.2019004399

subject

Has Abstract

pub_date

2020-12-04 00:00:00

eissn

0006-4971

issn

1528-0020

pii

474418

pub_type

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