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Anal Chem. 2017 Sep 5;89(17):9209-9217. doi: 10.1021/acs.analchem.7b01967. Epub 2017 Aug 22.

Microfluidic Chemical Function Generator for Probing Dynamic Cell Signaling.

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The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, China.


Cellular environments are inherently dynamic and generally involve complex, temporally varying signals. Reconstruction of these environments with high spatial and temporal fidelity and simultaneous imaging of intracellular dynamics in live cells remains a major challenge. In this paper, a microfluidic chemical function generator (μCFG) was proposed for probing cell dynamic signaling with high temporal resolution. By combining a hydrodynamic gating module with a chaotic advection mixing module, the μCFG was able to generate a variety of chemical waveforms, such as digital pulsatile chemical waveforms with a frequency higher than 10 Hz and analog chemical waveforms with a frequency higher than 0.2 Hz. The shape, frequency, amplitude, and duty cycle of the waveforms could be also conveniently modulated. To demonstrate the capability of μCFG of probing fast biological processes and elucidate signal transduction pathways in complex signaling networks, a variety of temporal responses of Ca2+ signaling to ATP-induced activation of the P2Y receptor, a prototypical G-protein coupled receptor (GPCR), were investigated in live cells by precisely and dynamically controlling their microenvironment.

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