Journal article
Rapid single-molecule digital detection of protein biomarkers for continuous monitoring of systemic immune disorders
Blood, Vol.137(12), pp.1591-1602
03/25/2021
DOI: 10.1182/blood.2019004399
PMCID: PMC8065241
PMID: 33275650
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 mu L of serum within an unprecedented assay incubation time of 15 to 300 seconds over a 10(4) 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 similar to 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.
Details
- Title: Subtitle
- Rapid single-molecule digital detection of protein biomarkers for continuous monitoring of systemic immune disorders
- Creators
- Yujing Song - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USAErin Sandford - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USAYuzi Tian - Xiangya Hospital Central South UniversityQingtian Yin - University of PennsylvaniaAndrew G. Kozminski - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USAShiuan-Haur Su - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USATao Cai - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USAYuxuan Ye - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USAMeng Ting Chung - Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USARyan Lindstrom - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USAAnnika Goicochea - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USAJenny Barabas - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USAMary Olesnavich - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USAMichelle Rozwadowski - University of Michigan–Ann ArborYongqing Li - University of Michigan–Ann ArborHasan B. Alam - University of Michigan–Ann ArborBenjamin H. Singer - University of Michigan–Ann ArborMonalisa Ghosh - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USASung Won ChoiKatsuo Kurabayashi - University of Michigan–Ann ArborMuneesh Tewari - Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.137(12), pp.1591-1602
- Publisher
- Amer Soc Hematology
- DOI
- 10.1182/blood.2019004399
- PMID
- 33275650
- PMCID
- PMC8065241
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Number of pages
- 12
- Grant note
- University of Michigan Precision Health Scholars Grant U068874 / University of Michigan; University of Michigan System A. Alfred Taubman Medical Research Institute U068874 / Peking University Health Science Center; Peking University ECCS 1708706; CBET 1931905 / National Science Foundation; National Science Foundation (NSF) AWD012546 / Cancer Research Institute
- Language
- English
- Date published
- 03/25/2021
- Academic Unit
- Emergency Medicine
- Record Identifier
- 9984702942402771
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