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Progress in Chemistry 2021, Vol. 33 Issue (7): 1138-1151 DOI: 10.7536/PC200717 Previous Articles   Next Articles

• Review •

Concentration-Gradient Microfluidic Chips for Drug Screening

Fangjuan Zhang, Haibing Liu, Mengqi Gao, Defu Wang, Yanbing Niu, Shaofei Shen*()   

  1. College of Life Sciences,Shanxi Agricultural University, Jinzhong 030801, China
  • Received: Revised: Online: Published:
  • Contact: Shaofei Shen
  • About author:
    * Corresponding author e-mail:
  • Supported by:
    National Natural Science Foundation of China(31700749); Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2019L0362); Science and Technology Innovation Funds of Shanxi Agricultural University(2016YJ02)
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Microfluidic chip is one of the most representative technologies of micro-analysis platform in this century. It has many advantages such as low reagent consumption, analytical miniaturization, easy control and integration, high automation and good biological compatibility. It has outstanding performances in many fields such as biology, medicine, food and environment, especially in the field of drug screening which has achieved a series of achievements with its own advantages. This article summarizes the research progress of concentration gradient microfluidic chips for drug screening in recent years, including paper chip, hydrogel chip, droplet chip and polydimethylsiloxane (PDMS) chip. Furthermore, the advantages and disadvantages of concentration gradient microfluidic chip in single cell analysis, combination drug screening, three-dimensional (3D) cell culture, cell microenvironment simulation are described. Finally, we provide a perspective for its application prospects.

Contents

1 Introduction

2 Characteristics of concentration-gradient microfluidic chip

3 Type of concentration-gradient microfluidic chip

3.1 Paper chip

3.2 Hydrogel chip

3.3 Droplet chip

3.4 PDMS chip

4 Application of concentration-gradient microfluidic chip

4.1 Single cell analysis

4.2 Combination drug screening

4.3 3D cell cultures

4.4 Simulated cell microenvironment

5 Conclusion and outlook

Key words: microfluidic chip, concentration gradient, drug screening
Fig. 1 Microfluidic paper chip. (A) The hybrid 3D-printed and paper-based microfluidic platform[25]; (B) A paper-based multichannel microfluidic chip for drug screening[26]
Fig. 2 Hydrogel microfluidic chip: (a) Schematic diagram of 2D and 3D surface gradients of hydrogel[34]; (b) Convection-diffusion based gradient drug fluid generating microfluidic system[37]; (c) Multi-concentration gradient hydrogel device[38]; (d) Microfluidic platform with multi-gradient biochemical concentration and hydrogel barrier[39]
Fig. 3 Droplet microfluidic chip. (a) Droplets microreactor formed by microfluidic channels[42]; (b) Schematic diagram of a microfluidic device for generating an array of moving droplets[44]; (c) Schematic diagram of droplet array chip with concentration gradient[45]
Fig. 4 PPDMS microfluidic chip. (a) Schematic diagram of PDMS chip of double concentration gradient construction[16]; (b) PDMS chip platform of automated cell culture[51]; (c) A PDMS chip platform for the study of bronchial epithelial injury caused by environmental pollutants[52]
Fig. 5 Microfluidic platform for single cell analysis. (a) Microfluidic array platform for single cell tracking and cloning[58]; (b) Multi-concentration gradient microfluidic device for single cell research[59]; (c) Microfluidic platform for real-time monitoring and analysis of single cell reaction[60]; (d) Microfluidic gradient device containing single cell capture array[61]; (e) Schematics showing the workflow for phenotype-related drug sensitivity analysis of single CTCs using the DS-Chip[62]
Fig. 6 Combination drug Screening. (a) Comparison between monotherapy and combination therapy[70]; (b) Schematic diagram of a microfluidic array for generating different drug combinations[71]; (c) Microfluidic platform of combined antibiotic testing[72]; (d) Schematic diagram of microfluidic device for generating triple concentration gradient[15]
Fig. 7 3D cell culture. (a) Graphical representation of a growing cell on a 2D and 3D substrate[74]; (b) The 3D chip is used for simultaneous delivery of multiple drug concentrations[75]; (c) Droplet-microfluidic platform for the culture of spheroids[76]
Fig. 8 Simulated cell microenvironment. (a) The microfluidic chip simulates the tumor microenvironment[81]; (b) Microfluidic model of bionic tumor micro-tissue in vitro for drug screening research[83]; (c) Microtumor model for cell capture and sphere formation[84]
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