Microstructure-based techniques for single-cell manipulation and analysis

Pang, Long; Ding, Jing; Liu, Xi-Xian; Yuan, Haoyue; Ge, Y.X.; Fan, Jianglin; Fan, Shih-Kang

doi:10.1016/j.trac.2020.115940

Cited by 25 publications

(17 citation statements)

References 122 publications

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“…Also, any changes in the solution or external electric field may affect cells, especially neural cells. In order to minimize the external influences on cells, microstructure-based cell manipulation, which does not require any electrical field or adjustment of conductivity, has become great interest to researchers ( Carlo et al, 2006 ; Frimat et al, 2011 ; Pang et al, 2020 ). Such microstructures include cup-shaped traps ( Di Carlo et al, 2006 ), micropillars ( Tan et al, 2009 ), and pneumatic valves ( Kim and Kim, 2014 ).…”

Section: Advanced Techniques For Ex Vivo Non Studiesmentioning

confidence: 99%

Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review

Zhang

Rong

Bian

2022

Front. Bioeng. Biotechnol.

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Increasing population is suffering from neurological disorders nowadays, with no effective therapy available to treat them. Explicit knowledge of network of neurons (NoN) in the human brain is key to understanding the pathology of neurological diseases. Research in NoN developed slower than expected due to the complexity of the human brain and the ethical considerations for in vivo studies. However, advances in nanomaterials and micro-/nano-microfabrication have opened up the chances for a deeper understanding of NoN ex vivo, one step closer to in vivo studies. This review therefore summarizes the latest advances in lab-on-chip microsystems for ex vivo NoN studies by focusing on the advanced materials, techniques, and models for ex vivo NoN studies. The essential methods for constructing lab-on-chip models are microfluidics and microelectrode arrays. Through combination with functional biomaterials and biocompatible materials, the microfluidics and microelectrode arrays enable the development of various models for ex vivo NoN studies. This review also includes the state-of-the-art brain slide and organoid-on-chip models. The end of this review discusses the previous issues and future perspectives for NoN studies.

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Section: Advanced Techniques For Ex Vivo Non Studiesmentioning

confidence: 99%

Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review

Zhang

Rong

Bian

2022

Front. Bioeng. Biotechnol.

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“…Cell-cell and cell-ECM interaction at the single-cell level provide a simple and easy solution. Some tumorigenesis (e.g., breast cancer and glioma) is also closely related to single tumor stem cells and tumor microenvironment interaction (Pang et al, 2020). The single-cell intercellular interaction plays a key role in organ-on-a-chip.…”

Section: Organ-on-a-chipmentioning

confidence: 99%

“…In contrast to a group of cells, single-cell microfluidics-based systems exhibit numerous advantages. For instance, as cells are heterogeneous and varied in numerous aspects like mechanical characterization and protein expression, microfluidics-based systems can isolate and study individual cells, including circulating tumor cells (CTCs) and stem cells (Gupta et al, 2010;Cheng et al, 2018;Pang et al, 2020). Intercellular interaction at a single-cell level is valuable in understanding communication pathways and commutating behaviors of special subpopulations of cells, which could be employed for the studies of secretion, differentiation, and migration (Lu et al, 2017;Alonso et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Microfluidics-Based Single-Cell Research for Intercellular Interaction

Pang

Ding

Liu

et al. 2021

Front. Cell Dev. Biol.

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Intercellular interaction between cell–cell and cell–ECM is critical to numerous biology and medical studies, such as stem cell differentiation, immunotherapy and tissue engineering. Traditional methods employed for delving into intercellular interaction are limited by expensive equipment and sophisticated procedures. Microfluidics technique is considered as one of the powerful measures capable of precisely capturing and manipulating cells and achieving low reagent consumption and high throughput with decidedly integrated functional components. Over the past few years, microfluidics-based systems for intercellular interaction study at a single-cell level have become frequently adopted. This review focuses on microfluidic single-cell studies for intercellular interaction in a 2D or 3D environment with a variety of cell manipulating techniques and applications. The challenges to be overcome are highlighted.

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“…The microscale channel or chamber inside the chips has similar dimensions to those of most cells, allowing excellent performance in single-cell manipulations and guaranteeing the precision of single-cell analysis [ 10 ]. Furthermore, the use of multiple parallel micro-units (e.g., microtraps, droplets, and micropatterns) allows high-throughput single-cell analysis [ 11 , 12 ]. Notably, the feasibility of integration with functional on-chip modules (e.g., a chemical gradient generator) or surrounding equipment (e.g., microscope, and mass spectrometer) enables the construction of a microenvironment close to physiological conditions and the application of dynamic spatiotemporal analysis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening

Wang

Ruan

et al. 2022

Military Med Res

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Background Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions. Methods We developed a new microfluidics-based “SMART” platform that is Simple to operate, able to generate a Massive single-cell array and Multiplex drug concentrations, capable of keeping cells Alive, Retainable and Trackable in the microchambers. These features are achieved by integrating a Microfluidic chamber Array (4320 units) and a six-Concentration gradient generator (MAC), which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way. Results A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity. The statistic results reveal that Imatinib (Ima) and Resveratrol (Res) combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment, indicated by the markedly reduced half maximal inhibitory concentration (IC50). Additionally, single-cell derived clones demonstrate a higher IC50 in each drug treatment compared to single cells. Moreover, primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC. Conclusion This microfluidics-based “SMART” platform allows high-throughput single-cell capture and culture, dynamic drug-gradient treatment and cell response monitoring, which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers.

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Microstructure-based techniques for single-cell manipulation and analysis

Cited by 25 publications

References 122 publications

Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review

Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review

Microfluidics-Based Single-Cell Research for Intercellular Interaction

An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening

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