Microfluidics for Manipulating Cells

Mu, Xuan; Zheng, Wenfu; Sun, Jiashu; Zhang, Wei; Jiang, Xingyu

doi:10.1002/smll.201200996

Cited by 181 publications

(134 citation statements)

References 221 publications

(227 reference statements)

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“…flow cytometry, capillary electrophoresis) 29 , they still suffer from a poor control over the cellular microenvironment. Conversely, microfluidics has proven to be the leading tool for single cell analysis allowing for precise fluid and cell manipulation while featuring a scale-size comparable to the cellular level 10,30 . In addition, microfluidic assays can be easily parallelized for testing several parameters at a time within the same platform.…”

Section: Discussionmentioning

confidence: 99%

High-throughput microfluidic platform for adherent single cells non-viral gene delivery

et al. 2015

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The widespreading of gene therapy as therapeutic tool relies on the development of DNAcarrying vehicles devoid of safety concerns. Opposite to viral vectors, non-viral gene carriers are promising in this perspective, although their low transfection efficiency leads to the necessity of further optimizations. Aiming at overcoming the limitation of traditional macroscale approaches, mainly consisting in time-consuming and simplified models, a microfluidic strategy was developed for transfection studies on single cells in a highthroughput and deterministic fashion. A single cell trapping mechanism was implemented based on dynamic variation of fluidic resistances. At this purpose, we conceived a roundshaped culture chamber integrated with a bottom trapping junction which modulates the hydraulic resistance. Several layouts of the chamber were designed and computationally validated for the optimization of the single cell trapping efficacy. The optimized chamber layout was integrated in a polydimethylsiloxane (PDMS) microfluidic platform presenting two main functionalities: (i) 288 chambers for trapping single cells, (ii) a serial dilution generator provided with chaotic mixing properties, able to deliver to chambers both soluble factors and non-diffusive particles (i.e. polymer/DNA complexes, polyplexes) under spatio-temporally controlled chemical patterns. Devices were experimentally validated and allowed for trapping individual human glioblastoma-astrocytoma epithelial-like cells (U87-MG) with a trapping efficacy of about 40%. Cells were cultured within the device and underwent preliminary transfection experiments using 25kDa linear polyethylenimine (lPEI)-based polyplexes, confirming the potentiality of the proposed platform for the future high-throughput screening of gene delivery vectors and the optimization of transfection protocols.

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Section: Discussionmentioning

confidence: 99%

High-throughput microfluidic platform for adherent single cells non-viral gene delivery

et al. 2015

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“…mLSI is particularly well suited for single cell analysis and manipulation; several excellent review articles have already summarized recent studies [50][51][52], which generally focus on single cell imaging [24 ,26,31,32 ,53-55] or single cell genomic/ proteomic analysis [19,30,56 ,57 ,58,59]. Another field of application of mLSI is protein synthesis and characterization.…”

Section: Biological and Chemical Applicationsmentioning

confidence: 99%

Recent developments in microfluidic large scale integration

Araci

Brisk

2014

Current Opinion in Biotechnology

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In 2002, Thorsen et al. integrated thousands of micromechanical valves on a single microfluidic chip and demonstrated that the control of the fluidic networks can be simplified through multiplexors [1]. This enabled realization of highly parallel and automated fluidic processes with substantial sample economy advantage. Moreover, the fabrication of these devices by multilayer soft lithography was easy and reliable hence contributed to the power of the technology; microfluidic large scale integration (mLSI). Since then, mLSI has found use in wide variety of applications in biology and chemistry. In the meantime, efforts to improve the technology have been ongoing. These efforts mostly focus on; novel materials, components, micromechanical valve actuation methods, and chip architectures for mLSI. In this review, these technological advances are discussed and, recent examples of the mLSI applications are summarized. Recent advancements in microfluidic technologies have created new opportunities in the fields of biology and chemistry through miniaturization and automation of common processes, including mixing, metering, trapping, reaction, filtering, and separation, among others. Microfluidic large scale integration (mLSI) enables the fabrication of microfluidic chips containing hundreds or more of these functions using well-established lithography techniques, similar in principle to electronic LSI in the semiconductor industry [1]. Small feature dimensions, abundant spatial parallelism, and control over fluid flow provide mLSI technology with advantages such as high throughput, precise metering, automation and low reagent consumption. The implications of mLSI technology can especially be seen in recent advances in single cell, genomic, and protein analysis.

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“…127 Page 2 of 7 Additionally, PDMS is gas permeable which makes it suitable for long-term cell culture in biological studies like cell screening (Kim et al 2015), biochemical assays (El-Ali et al 2006) and single cell analysis (Mu et al 2013). On the other hand, permeability to gases can cause water evaporation during the flow and simultaneous crystallization of the dissolved analytes.…”

mentioning

confidence: 99%

Compatibility of organic solvents for electrochemical measurements in PDMS-based microfluidic devices

Adamiak

Kałuża

Jönsson-Niedziółka

2016

Microfluid Nanofluid

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possesses their drawbacks and advantages. Historically, the first materials for microfluidic device fabrication were glass and silicon, and the chips were made by wet etching and then fusion bonding procedures. Because of the stiffness and chemical resistivity of these materials, processing usually requires the use of dangerous chemicals like hydrofluoric acid (in the wet etching step) and super clean environments together with high temperature and pressure conditions (in the fusion bonding step). These factors increase the overall cost of microfluidic chips fabrication and limit the broader use of these materials.Over the last few years, devices made from paper where the liquid solutions are moved along the chip by capillary forces have become increasingly popular (Martinez et al. 2007). Since the channels are open to air and there is a cellulose matrix in the channel area, the number of analytical methods that can be integrated with these devices is also limited. So far, the most commonly used method is colorimetry, whose application to paper chips seems to be the main strategy for their commercial applications, mainly due to minimum requirements of the equipment needed for analysis (Martinez et al. 2008). Another drawback of the paper chips is that they cannot be integrated with small size valves which are used for precise control and manipulation of the flowing liquids.For laboratory research-where one needs to compromise the ease of fabrication and the performance of the device-the most commonly used materials are elastomers, and among these, poly(dimethylsiloxane) (PDMS) is the most popular one (McDonald and Whitesides 2002). The main advantage of PDMS is the convenience in fabrication-it can be cast with high resolution in a relatively simple and fast photolithography process (Wu et al. 2003). Due to PDMS elasticity, it is possible to fabricate microvalves which can act like on-demand filters (Unger et al. 2000). AbstractWe have investigated the compatibility of some organic solvents commonly used in electrochemistry with microfluidic channels based on poly(dimethylsiloxane) (PDMS) and compared the stability of electrochemical measurements over several hours with how much PDMS swells when immersed in these solvents. Lee et al. (Anal Chem 75: 6544-6554. doi:10.1021/ac0346712, 2003 have shown that there is a good correlation between swelling of PDMS and the solubility parameter (δ H ) of the various solvents and suggested that δ H can function as an indication of PDMS compatibility. We show that solvents with a very high swelling ratio can give stable voltammetry over several hours, and thus, we do not find that swelling is a good measure for compatibility with PDMS in electrochemical experiments.

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Microfluidics for Manipulating Cells

Cited by 181 publications

References 221 publications

High-throughput microfluidic platform for adherent single cells non-viral gene delivery

High-throughput microfluidic platform for adherent single cells non-viral gene delivery

Recent developments in microfluidic large scale integration

Compatibility of organic solvents for electrochemical measurements in PDMS-based microfluidic devices

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