Microfluidic single-cell analysis for systems immunology

作者:Junkin Michael; Tay Savas*
来源:Lab on a Chip, 2014, 14(7): 1246-1260.
DOI:10.1039/c3lc51182k

摘要

The immune system constantly battles infection and tissue damage, but exaggerated immune responses lead to allergies, autoimmunity and cancer. Discrimination of self from foreign and the fine-tuning of immunity are achieved by information processing pathways, whose regulatory mechanisms are little understood. Cell-to-cell variability and stochastic molecular interactions result in diverse cellular responses to identical signaling inputs, casting doubt on the reliability of traditional population-averaged analyses. Furthermore, dynamic molecular and cellular interactions create emergent properties that change over multiple time scales. Understanding immunity in the face of complexity and noisy dynamics requires time-dependent analysis of single-cells in a proper context. Microfluidic systems create precisely defined microenvironments by controlling fluidic and surface chemistries, feature sizes, geometries and signal input timing, and thus enable quantitative multi-parameter analysis of single cells. Such qualities allow observable dynamic environments approaching in vivo levels of biological complexity. Seamless parallelization of functional units in microfluidic devices allows high-throughput measurements, an essential feature for statistically meaningful analysis of naturally variable biological systems. These abilities recapitulate diverse scenarios such as cell-cell signaling, migration, differentiation, antibody and cytokine production, clonal selection, and cell lysis, thereby enabling accurate and meaningful study of immune behaviors in vitro.

  • 出版日期2014