Rapid single-molecule digital detection of protein biomarkers for continuous monitoring of systemic immune disorders
| Autor: | Qingtian Yin, Monalisa Ghosh, Michelle Rozwadowski, Yujing Song, Hasan B. Alam, Katsuo Kurabayashi, Sung Won Choi, Jenny Barabas, Yuxuan Ye, Muneesh Tewari, Ryan Lindstrom, Meng Ting Chung, Yuzi Tian, Benjamin H. Singer, Mary Olesnavich, Shiuan-Haur Su, Tao Cai, Yongqing Li, Andrew G. Kozminski, Annika J. Goicochea, Erin Sandford |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Protein biomarkers Immunobiology and Immunotherapy Immunology Enzyme-Linked Immunosorbent Assay 02 engineering and technology Computational biology Immune complex formation Biochemistry 03 medical and health sciences Immune system medicine Humans In patient Immunodiagnostics business.industry Continuous monitoring Blood Proteins Equipment Design Cell Biology Hematology 021001 nanoscience & nanotechnology medicine.disease Biomarker (cell) Cytokine release syndrome 030104 developmental biology Immune System Diseases Point-of-Care Testing Cytokines 0210 nano-technology business Biomarkers |
| Zdroj: | Blood |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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