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Annu Rev Anal Chem (Palo Alto Calif). 2019 Jun 12;12(1):431-449. doi: 10.1146/annurev-anchem-061318-115055. Epub 2019 Apr 12.

Single-Cell Protein Secretion Detection and Profiling.

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Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, USA; email:
Yale Cancer Center, Yale Stem Cell Center, Human and Translational Immunology Program, Yale School of Medicine, New Haven, Connecticut 06520, USA.


Secreted proteins play important roles in mediating various biological processes such as cell-cell communication, differentiation, migration, and homeostasis at the population or tissue level. Here, we review bioanalytical technologies and devices for detecting protein secretions from single cells. We begin by discussing conventional approaches followed by detailing the latest advances in microengineered systems for detecting single-cell protein secretions with an emphasis on multiplex measurement. These platforms include droplet microfluidics, micro-/nanowell-based assays, and microchamber-based assays, among which the advantages and limitations are compared. Microscale systems also enable the tracking of protein secretion dynamics in single cells, further empowering the study of the cell-cell communication network. Looking forward, we discuss the remaining challenges and future opportunities that will transform basic research of cellular secretion functions at the systems level and the clinical applications for immune monitoring and cancer treatment.


multiplex assay; protein secretion; secretion dynamics; single-cell analysis

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