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Progress in Chemistry 2021, Vol. 33 Issue (4): 543-554 DOI: 10.7536/PC200667 Previous Articles   Next Articles

• Review •

Droplet Microarrays in Biomedical High-Throughput Research

Yifeng Chen1, Cong Wang1, Kefeng Ren1, Jian Ji1()   

  1. 1 Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  • Received: Revised: Online: Published:
  • Contact: Jian Ji
  • Supported by:
    the National Natural Science Foundation of China(51933009); the Key Project of National Key Research and Development Program of China(2017YFB0702500)
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In order to handle a large number of experiment conditions and outputs and further accelerate the material development process, high-throughput screening has become a more and more important experimental method, which has been widely used in many fields to improve experimental efficiency. And the high-throughput platform is the basic condition for carrying out high-throughput experiments. Existing high-throughput platforms, like microtiter plates, still suffer from problems such as high consumption and low experimental throughput when dealing with precious samples and reagents and further optimization is still required. As an emerging miniaturized and integrated high-throughput platform, droplet microarrays have the advantages of low consumption of reagent and sample, short reaction time, high integration and strong operability, and have been widely studied and applied in the field of biomedicine. In this paper, the construction methods of droplet microarrays are summarized and divided into two categories: surface chemistry driving and physical morphology assisted. The advantages and disadvantages of different construction methods are briefly analyzed. Then the applications of droplet microarrays in biomedical high-throughput research are also briefly introduced from the four directions of 2D cell screening, 3D cell culture, single cell analysis and whole organism screening. Finally, the problems existing in the application process of droplet microarrays and its future development direction are also summarized and analyzed.

Contents

1 Introduction

2 Construction methods

2.1 Surface chemistry

2.2 Surface morphology

3 Applications in biomedical high-throughput research

3.1 2D cell screening

3.2 3D cell culture

3.3 Single cell analysis

3.4 Whole organism screening

4 Conclusion and outlook

Key words: droplet microarrays, construction methods, biomedicine, high-throughput
Fig.1 Different types of droplet microarrays. A) The schematic and image of droplet microarray formed on a superhydrophilic-superhydrophobic patterned surface[7]. Copyright 2012, Royal Society of Chemistry B) The schematic and microscopic image of droplet microarray captured by micropillars[8]. Copyright 2019, American Chemical Society
Fig.2 The schematic of fabrication of droplet microarray by wet etching[12]. Copyright 2011, Royal Society of Chemistry
Fig.3 Droplet microarrays formed by A) soft lithography[13], Copyright 2016, John Wiley and Sons and B) photografting[16]. Copyright 2011, John Wiley and Sons
Fig.4 A) Droplet microarray formed by rolling droplet method[7]. Copyright 2012, Royal Society of Chemistry; B) Fabrication of superhydrophilic-superhydrophobic patterned surface by photocatalysis[20]. Copyright 2018, American Chemical Society
Fig.5 Droplet microarray formed among the micropillars by shear force[33]. Copyright 2018, Royal Society of Chemistry
Fig.6 Droplet microarrays formed A) on micropillars[35]. Copyright 2019, John Wiley and Sons and B) by emulsion breaking[36]. Copyright 2019, American Chemical Society
Fig.7 The procedure to create a wettability gradient on the initially superhydrophobic surface by changing the plasma-exposure time[44]. Copyright 2009, John Wiley and Sons
Fig.8 The schematic of a workflow of A) cell based screening using sandwiching technology[48]. Copyright 2015, John Wiley and Sons and B) high-throughput screening of cell transfection enhancers[49]. Copyright 2020, John Wiley and Sons
Fig.9 A) The schematic of cell culture by hanging drop method on superhydrophobic surface with micro-indentations and drug-screening test[29]. Copyright 2014, John Wiley and Sons B) The confocal microscope of the spheroids formed by hanging drop method with different initial cell densities[61]. Copyright 2015, Royal Society of Chemistry
Fig.10 A) Three different positions to be perforated in order to add and remove medium from the drop[26]. Copyright 2014, American Chemical Society B) Schematic of the fabrication of droplet microarray on the superhydrophobic butterfly wing and the formation of the spheroids[28]. Copyright 2019, American Chemical Society
Fig.11 A) Schematic of the fabrication of arrays of hydrogel micropads incorporating cells[7]. Copyright 2012, Royal Society of Chemistry; B) Schematic and confocal florescence image of layer-by-layer assembled cells in a single microgel and C) Schematics of side-by-side assembly of two cell populations in a single microgel[13]. Copyright 2016, John Wiley and Sons
Fig.12 Schematic of the operation procedures of single cell gene expression analysis using droplet microarray system[66]. Copyright 2015, Springer Nature
Fig.13 Schematic of the workflow of single cell droplet microarray formation[68]. Copyright 2016, MDPI
Fig.14 Schematic and images of the formation of droplet microarray containing zebrafish embryos[27]. Copyright 2017, John Wiley and Sons
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