A fluorescent microbead-based microfluidic immunoassay chip for immune cell cytokine secretion quantification

Xin Cui, Ya Liu, Dinglong Hu, Weiyi Qian, Chung Tin, Dong Sun, Weiqiang Chen, Raymond H.W. Lam

Research output: Contribution to journalArticle

Abstract

Quantitative and dynamic analyses of immune cell secretory cytokines are essential for precise determination and characterization of the "immune phenotype" of patients for clinical diagnosis and treatment of immune-related diseases. Although multiple methods including the enzyme-linked immunosorbent assay (ELISA) have been applied for cytokine detection, such measurements remain very challenging in real-time, high-throughput, and high-sensitivity immune cell analysis. In this paper, we report a highly integrated microfluidic device that allows for on-chip isolation, culture, and stimulation, as well as sensitive and dynamic cytokine profiling of immune cells. Such a microfluidic sensing chip is integrated with cytometric fluorescent microbeads for real-time and multiplexed monitoring of immune cell cytokine secretion dynamics, consuming a relatively small extracted sample volume (160 nl) without interrupting the immune cell culture. Furthermore, it is integrated with a Taylor dispersion-based mixing unit in each detection chamber that shortens the immunoassay period down to less than 30 minutes. We demonstrate the profiling of multiple pro-inflammatory cytokine secretions (e.g. interleukin-6, interleukin-8, and tumor necrosis factors) of human peripheral blood mononuclear cells (PBMCs) with a sensitivity of 20 pg ml-1 and a sample volume of 160 nl per detection. Further applications of this automated, rapid, and high-throughput microfluidic immunophenotyping platform can help unleash the mechanisms of systemic immune responses, and enable efficient assessments of the pathologic immune status for clinical diagnosis and immune therapy.

Original languageEnglish (US)
Pages (from-to)522-531
Number of pages10
JournalLab on a Chip
Volume18
Issue number3
DOIs
StatePublished - Jan 1 2018

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Microfluidics
Microspheres
Immunoassay
Cytokines
Lab-On-A-Chip Devices
Throughput
Immunologic Monitoring
Immunophenotyping
Immunosorbents
Immune System Diseases
Interleukin-8
Cell culture
Tumors
Interleukin-6
Assays
Blood Cells
Blood
Enzymes
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

Cite this

A fluorescent microbead-based microfluidic immunoassay chip for immune cell cytokine secretion quantification. / Cui, Xin; Liu, Ya; Hu, Dinglong; Qian, Weiyi; Tin, Chung; Sun, Dong; Chen, Weiqiang; Lam, Raymond H.W.

In: Lab on a Chip, Vol. 18, No. 3, 01.01.2018, p. 522-531.

Research output: Contribution to journalArticle

Cui, Xin ; Liu, Ya ; Hu, Dinglong ; Qian, Weiyi ; Tin, Chung ; Sun, Dong ; Chen, Weiqiang ; Lam, Raymond H.W. / A fluorescent microbead-based microfluidic immunoassay chip for immune cell cytokine secretion quantification. In: Lab on a Chip. 2018 ; Vol. 18, No. 3. pp. 522-531.
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