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Abstract Integrated microfluidic cellular phenotyping platforms provide a promising means of studying a variety of inflammatory diseases mediated by cell‐secreted cytokines. However, immunosensors integrated in previous microfluidic platforms lack the sensitivity to detect small signals in the cellular secretion of proinflammatory cytokines with high precision. This limitation prohibits researchers from studying cells secreting cytokines at low abundance or existing at a small population. Herein, the authors present an integrated platform named the “digital Phenoplate (dPP),” which integrates digital immunosensors into a microfluidic chip with on‐chip cell assay chambers, and demonstrates ultrasensitive cellular cytokine secretory profile measurement. The integrated sensors yield a limit of detection as small as 0.25 pg mL−1for mouse tumor necrosis factor alpha (TNF‐α). Each on‐chip cell assay chamber confines cells whose population ranges from ≈20 to 600 in arrayed single‐cell trapping microwells. Together, these microfluidic features of the dPP simultaneously permit precise counting and image‐based cytometry of individual cells while performing parallel measurements of TNF‐α released from rare cells under multiple stimulant conditions for multiple samples. The dPP platform is broadly applicable to the characterization of cellular phenotypes demanding high precision and high throughput.
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Microfluidic Compartmentalization Platforms for Single Cell Analysis
Many cellular analytical technologies measure only the average response from a cell population with an assumption that a clonal population is homogenous. The ensemble measurement often masks the difference among individual cells that can lead to misinterpretation. The advent of microfluidic technology has revolutionized single-cell analysis through precise manipulation of liquid and compartmentalizing single cells in small volumes (pico- to nano-liter). Due to its advantages from miniaturization, microfluidic systems offer an array of capabilities to study genomics, transcriptomics, and proteomics of a large number of individual cells. In this regard, microfluidic systems have emerged as a powerful technology to uncover cellular heterogeneity and expand the depth and breadth of single-cell analysis. This review will focus on recent developments of three microfluidic compartmentalization platforms (microvalve, microwell, and microdroplets) that target single-cell analysis spanning from proteomics to genomics. We also compare and contrast these three microfluidic platforms and discuss their respective advantages and disadvantages in single-cell analysis.
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- PAR ID:
- 10316881
- Date Published:
- Journal Name:
- Biosensors
- Volume:
- 12
- Issue:
- 2
- ISSN:
- 2079-6374
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/bios12020058
