Citation: Yiran Guo, Peng Chen, Zhaolong Gao, Yiwei Li, Shunji Li, Xiaojun Feng, Bi-Feng Liu. A time-coded multi-concentration microfluidic chemical waveform generator for high-throughput probing suspension single-cell signaling[J]. Chinese Chemical Letters, ;2022, 33(6): 3091-3096. doi: 10.1016/j.cclet.2021.09.080 shu

A time-coded multi-concentration microfluidic chemical waveform generator for high-throughput probing suspension single-cell signaling

Yiran Guo ^{a, 1} ,
Peng Chen ^{a, 1} ,
Zhaolong Gao ^b ,
Yiwei Li ^a ,
Shunji Li ^a ,
Xiaojun Feng ^a ,
Bi-Feng Liu ^{a, *,}

a.
The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and 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
b.
The Key Laboratory of Ministry of Education for Image Processing and Intelligent Control, School of Artificial Intelligence and Automation, Huazhong University of Science and Technology, Wuhan 430074, China

bfliu@mail.hust.edu.cn

Received Date: 31 May 2021
Revised Date: 14 September 2021
Accepted Date: 22 September 2021
Available Online: 30 September 2021

Figures(6)

The cellular response to the complex extracellular microenvironment is highly dynamic in time and type of extracellular matrix. Accurately reconstructing this process and analyzing the changes in receptor conformation on the cell membrane surface and intracellular or intercellular signaling has been a major challenge in analytical chemistry and biophysical methodology. In this paper, a time-coded multi-concentration microfluidic chemical waveform generator was developed for the dynamic signaling probing with single-cell array of high temporal resolution, high throughput, and multi-concentration combination stimulation. Based on innovative microchannel structure, sophisticated external control methods and multiplexing technology, the system not only allowed for temporally sequential permutations of the four concentrations of stimuli (time code), but also generated pulsed and continuous waveforms at different frequencies in a highly controllable manner. Furthermore, the single-cell trap array was set up to efficiently capture cells in suspension, dramatically increasing throughput and reducing experiment preparation time. The maximum frequency of the platform was 1 Hz, and one cell could be stimulated at multiple frequencies. To show the ability of the system to investigate rapid biochemical events in high throughput, pulse stimulation and continuous stimulation of different frequencies and different time codes, combined with four concentrations of histamine (HA), were generated for probing G protein-coupled receptor (GPCR) signaling in HeLa cells. Then, statistical analysis was performed for the mean peak height and mean peak area of the cellular response. We believe that the time-coded multi-concentration microfluidic chemical waveform generator will provide a novel strategy for analytical chemistry, biophysics, cell signaling, and individualized medicine applications.
- Microfluidics,
- Dynamic stimulation,
- Time code,
- High-throughput,
- Single-cell array
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