Generation of microfluidic gradients and their effects on cells behaviours
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Generation of microfluidic gradients and their effects on cells behaviours Qiangqiang Tang1,2 · Xiran Yang2,3,4 · Chengkai Xuan2,3,4 · Kai Wu3 · Chen Lai1 · Xuetao Shi1,2,3,4 Received: 30 March 2020 / Accepted: 4 August 2020 © Zhejiang University Press 2020
Introduction The concept of “gradients” has been widely demonstrated and applicated in biology. For example, concentration gradients and potential gradients in the body can regulate the homeostasis as well as the balance of physiological environment; oxygen gradients play a vital role in cellular gene expression and migration. Moreover, biomolecular gradient guidance is also very important in biological processes such as embryonic development, cancer spread, immune response, wound healing and osteogenesis [1]. These biological processes have been studied in vitro to explore various cellular behaviours under molecular gradients, such as cell proliferation, migration, differentiation and adsorption [2]. The importance of biomolecular gradients in regulating cells behaviours leads to the development of multiple methods for the generation of chemical gradients in vitro by performing them in vivo studies. It has been revealed that gradient signal transmission is a complex and highly regulated process since the cellular response depends on the gradient concentration and its temporal and spatial characteristics [3]. As early as 1977, Sally Zigmond proposed the “Zigmond chamber”. In this traditional chemotaxis assay system, it can Qiangqiang Tang and Xiran Yang are contributed equally to this work. * Xuetao Shi [email protected] 1
Peking University Shenzhen Institute, Peking University, Shenzhen, People’s Republic of China
School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, People’s Republic of China
2
3
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, People’s Republic of China
4
Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China
be observed that cells tend to migrate towards a source chemoattractant at a narrow constriction (3–10 micrometres). Based on this research, biologists subsequently developed the “Dunn chamber” and “Insall chamber”. These advances had greatly improved the stable gradient, high resolution and longterm imaging capabilities of the traditional visual chemotaxis assays [4]. However, compared with microfluidic technology, the traditional methods of gradient-generating in vitro are laborious and limited. Besides, it is difficult to accurately control the diffusion of molecules and maintain it in a relatively stable state in time and space by traditional methods. Microfluidic technology has offered great potential for next generation of chemotaxis assays, it can generate highly dynamic, controllable and micron-level gradients in a small integrated chip which exposes cells into one or more custom-made spatial–temporal biomolecular gradients. This
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