Open AccessSpatial Chemical Stimulation Control in Microenvironment by Microfluidic Probe Integrated Device for Cell-Based Assay
Author(s) -
Masayuki Horayama,
Kenta Shinha,
Kazuya Kabayama,
Teruo Fujii,
Hiroshi Kimura
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0168158
Subject(s) - microfluidics , cell , population , multicellular organism , stimulation , biophysics , nanotechnology , chemistry , biological system , materials science , biology , biochemistry , neuroscience , medicine , environmental health
Cell—cell interactions play an important role in the development and function of multicellular organisms. To investigate these interactions in detail, it is necessary to evaluate the behavior of a cell population when the minimum number of cells in the population is stimulated by some chemical factors. We propose a microfluidic device integrated with microfluidic probe (MFP) functionality; this device is capable of imparting a chemical stimulus to cells within a microenvironment, for cell-based assays. The device contains MFP channels at the walls of the cell culture microchannels, and it can control a localized chemical stimulation area at the scale of a single cell to a few cells using MFP fluid control in a microspace. The results of a finite element method-based simulation indicated that it is possible to control the chemical stimulation area at the scale of a single cell to a few cells by optimizing the MFP channel apex width and the flow ratio. In addition, localized cell staining was demonstrated successfully using a spatial chemical stimulus. We confirmed the device functionality as a novel cell-based assay tool. We succeeded in performing localized cell collection using this method, which suggested that the single cell analysis of a cell monolayer that is subjected to a specific chemical stimulus is possible. The method proposed in this paper can contribute significantly to the fields of cell biology and drug development.