Cells on chips

El-Ali, Jamil; Sorger, Peter K.; Jensen, Klavs F.

doi:10.1038/nature05063

Cited by 1,987 publications

(1,525 citation statements)

References 97 publications

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“…In particular, they provide very tightly controlled and tailored environments for the culture of cells [1,2], tissues [3], and small organisms [4]. In principle, NMR spectroscopy would complement such systems very well, enabling non-destructive and non-invasive observation of metabolic processes over a period of time.…”

Section: Introductionmentioning

confidence: 99%

An optimised detector for in-situ high-resolution NMR in microfluidic devices

Finch

Yılmaz

Utz

2016

Journal of Magnetic Resonance

109

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Integration of high-resolution nuclear magnetic resonance (NMR) spectroscopy with microfluidic lab-on-a-chip devices is challenging due to limited sensitivity and line broadening caused by magnetic susceptibility inhomogeneities. We present a novel double-stripline NMR probe head that accommodates planar microfluidic devices, and obtains the NMR spectrum from a rectangular sample chamber on the chip with a volume of 2 l. Finite element analysis is used to jointly optimise the detector and sample volume geometry for sensitivity and RF homogeneity. A prototype of the optimised design has been built, and its properties have been characterised experimentally. The performance in terms of sensitivity and RF homogeneity closely agrees with the numerical predictions. The system reaches a mass limit of detection of 1.57 nMol p s, comparing very favourably with other micro-NMR systems. The spectral resolution of this chipGprobe system is better than 1.75 Hz at a magnetic field of 7 T, with excellent line shape.

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Section: Introductionmentioning

confidence: 99%

An optimised detector for in-situ high-resolution NMR in microfluidic devices

Finch

Yılmaz

Utz

2016

Journal of Magnetic Resonance

109

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“…Microfluidics has sparked increasing interests in cellbased biological and medical analysis, due to its miniaturization, low consumption of reagents, and capabilities to integrate various experimental operation units onto a single device [15][16][17]. Recently, several work has been reported to perform co-culture on microfluidic platform, including capillary morphogenesis [14]; macrophage cells invasion [18], HeLa and HUVECs cells movements [13].…”

Section: Introductionmentioning

confidence: 99%

“…However, these assays are limited by the tedious manual operations which require several procedures, and they are all typical end-point assays, which are difficult to realize real-time observation. In addition, they still require large consumption of cells and reagents that are expensive in amount.Microfluidics has sparked increasing interests in cellbased biological and medical analysis, due to its miniaturization, low consumption of reagents, and capabilities to integrate various experimental operation units onto a single device [15][16][17]. Recently, several work has been reported to perform co-culture on microfluidic platform, including capillary morphogenesis [14]; macrophage cells invasion Abbreviations: ACC, adenoid cystic carcinoma; GES-1, gastric mucosa epithelia cell line; HepG-2, human liver carcinoma cell line; HFL-I, human embryonic lung fibroblast; PI, propidium iodide; a-SMA, a-smooth muscle actin…”

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confidence: 99%

Characterization of the interaction between fibroblasts and tumor cells on a microfluidic co‐culture device

Liu

Qin

et al. 2010

Electrophoresis

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Fibroblasts and tumor cells have been involved in the process of cancer development, progression and therapy. Here, we present a simple microfluidic device which enables to study the interaction between fibroblasts and tumor cells by indirect contact co-culture. The device is composed of multiple cell culture chambers which are connected by a parallel of cell migration regions, and it enables to realize different types of cells to communicate each other on the single device. In this work, human embryonic lung fibroblasts cells were observed to exhibit obvious migration towards tumor cells instead of normal epithelial cells on the co-culture device. Moreover, transdifferentiation of human embryonic lung fibroblast cells was recognized by the specific expression of a-smooth musle actin, indicating the effect of tumor cells on the behavior of fibroblasts. Furthermore, multiple types of cell co-culture can be demonstrated on the single device which enables to mimic the complicated microenviroment in vivo. The device is simple and easy to operate, which enables to realize real-time observation of cell migration after external stimulus. This microfluidic device allows for the characterization of various cellular events on a single device sequentially, faciliating the better understanding of interaction between heterotypic cells in a more complex microenvironment. Keywords:Co-culture / Microfluidic / Migration / Transdifferentiation DOI 10.1002/elps.200900776 IntroductionGrowing evidences demonstrate that tumor microenvironment including stromal cells, inflammatory cells, extracellular matrix and vessels plays an important role in the development, progression and therapy of cancer [1][2][3][4][5].Fibroblasts make up the largest number of stromal cells, which are continuously influenced by soluble factors secreted by tumor cells and their migration abilities can be enhanced by tumor cells. When fibroblasts are transdifferentiated, they become activated and were termed cancerassociated fibroblasts or myofibroblasts, which will have a significant effect on the proliferation, invasion and metastasis of tumor cells [6][7][8]. Therefore, it is of great importance to investigate the heterotypic cell interactions between tumor cells and fibroblasts. At present, co-culture is often used to investigate the interactions between heterotypic cells by using Transwell assay [9,10], in which two types of cells are separated into upper and lower chambers by a semi-permeable membrane, or by bathing cells in conditioned medium [11][12][13][14]. However, these assays are limited by the tedious manual operations which require several procedures, and they are all typical end-point assays, which are difficult to realize real-time observation. In addition, they still require large consumption of cells and reagents that are expensive in amount.Microfluidics has sparked increasing interests in cellbased biological and medical analysis, due to its miniaturization, low consumption of reagents, and capabilities to integrate various experimental op...

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“…OEGMA was chosen for its demonstrated ability in improving the biocompatibility of PDMS, which was the key for the success of many bioMEMS devices. 1,3 FMA was commonly used to create surfaces with ultralow surface energy. 13 In Figure 2A, the characteristic F 1s peak at 690 eV clearly indicated the success of polymerization and film deposition (∼28 nm after 1 h SIP, θ ≈ 128°).…”

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confidence: 99%

A Facile Method for Permanent and Functional Surface Modification of Poly(dimethylsiloxane)

2007

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Poly(dimethylsiloxane) (PDMS) is the choice of material for a wide range of applications, 1-3 because PDMS has many advantageous properties such as chemical inertness, nontoxicity, ease of handling, and commercial availability. It is impossible, however, to have one material that meets all the individual needs of microfluidic systems, 1 micro-electromechanical systems (MEMS), 2 and cellular study. 3 New materials have been developed to replace PDMS. For example, a photocurable perfluoropolyether (PFPE) was synthesized to fabricate microfludic devices that were organic solvent compatible. 4,5 In a consensus, it is costly to develop a new elastomer for each individual need. And we believe surface modification of PDMS will be a cost-effective and time-saving strategy, if a facile method for surface modification can be developed, since surface modification retains the desired bulk properties of PDMS and reveals the need for new material development.A number of strategies have been developed for PDMS surface modification, which can be divided into two categories, namely physisorption and chemical coupling. Physisorption of materials to PDMS surface, such as surfactants 6 and polyelectrolytes 7 are driven by hydrophobic force and electrostatic force, respectively. This simple method ensures PDMS based devices after modification perform well in situations that only require moderate density and thickness of coatings, and only to sustain low shear force.Chemical coupling is stable but is difficult to achieve because PDMS is chemically inert, which is ironically one of its merits. Common for this approach, the first step is to apply high-energy bombardment (i.e., plasma) to PDMS surface, which results in a silicate layer with functional groups on the surface, such as -OH and -NH 2 . Those functional groups not only render the surface hydrophilicity but also allow further modification via chemical coupling. 8 Chemical coupling has two problems: (1) Plasma treatment is easy but not sustainable; recovery of hydrophobicity of treated PDMS is well documented. 9 High-energy bombardment also has the tendency to damage PDMS. Furthermore, this strategy is only applicable to planar structure because of its limited penetration depth. (2) Concentration gradient in "grafting to" strategy prevents the preparation of thick and dense films. 10 We reported herein a facile method for permanent and functional surface modification of PDMS based on a commercial material. First, a vinyl-terminated initiator (v-initiator, part C in Scheme 1) was mixed with the viscous base and curing agent of Sylgard 184, resulting in an initiator integrated PDMS (iPDMS). The base is a poly(dimethyl-methylvinylsiloxane) prepolymer with small amount of platinum (Pt) catalyst (part A in Scheme 1) and the curing agent is a mixture of vinyl-endcapped PDMS precursors and poly-(dimethyl-methylhydrogenosiloxane) precursors as cross-linkers (part B in Scheme 1). Upon mixing together (the so-called curing process), the vinyl groups and the hydrosilane hydrogens undergo ...

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Cells on chips

Cited by 1,987 publications

References 97 publications

An optimised detector for in-situ high-resolution NMR in microfluidic devices

An optimised detector for in-situ high-resolution NMR in microfluidic devices

Characterization of the interaction between fibroblasts and tumor cells on a microfluidic co‐culture device

A Facile Method for Permanent and Functional Surface Modification of Poly(dimethylsiloxane)

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