Microtiter plate-sized standalone chip holder for microenvironmental physiological control in gas-impermeable microfluidic devices

Harink, Björn; Gac, Séverine Le; Barata, David; Blitterswijk, Clemens A. van; Habibović, Pamela

doi:10.1039/c4lc00190g

Cited by 18 publications

(21 citation statements)

References 13 publications

(14 reference statements)

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“…Microtiter plate (MTP) is a flat plate with multiple "wells" used as small test tubes, which has become a standard tool in analytical research and clinical diagnostic testing laboratories (Duetz, 2007). Since the high-binding MTP is usually modified using an oxygen plasma discharge to make their surfaces more hydrophilic, it is easier for adherent proteins, e.g., antibody, cell and streptavidin (Harink et al, 2014;Wilming et al, 2014;Sabaeifard et al, 2014). Through modifying nucleic acids with the proteins, the oligonucleotides can be immobilized onto the MTP.…”

Section: Introductionmentioning

confidence: 99%

Low-cost and highly efficient DNA biosensor for heavy metal ion using specific DNAzyme-modified microplate and portable glucometer-based detection mode

Zhang

Tang

Teng

et al. 2015

Biosensors and Bioelectronics

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Section: Introductionmentioning

confidence: 99%

Low-cost and highly efficient DNA biosensor for heavy metal ion using specific DNAzyme-modified microplate and portable glucometer-based detection mode

Zhang

Tang

Teng

et al. 2015

Biosensors and Bioelectronics

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“…These platforms broadly follow a few working principles: (i) the gas exchange through the chip material is blocked or limited; (ii) oxygen is delivered or eliminated from a fluid source; and (iii) oxygen gradients develop from an oxygen source to the core of the tissue model due to the cell consumption. One first and straightforward approach consists of fabricating the devices from gas-impermeable materials such as glass [28], SU-8 [29] or polystyrene [16]. Alternatively, polymer films with low oxygen permeability were embedded in PDMS devices to induce hypoxic conditions on 2D [30] or 3D cell cultures [31].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

et al. 2020

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Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas.

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“…Furthermore, a routine was developed to analyze fluorescent images to retrieve information at the single‐cell level in an automated way. Using a standalone chip holder, which also functions as an incubator, we performed live imaging and thereby visualized in situ cell interactions with the gradients of overlapping compounds . As a proof of principle, the screening method was applied to test the effects of phenanthroline, a small hypoxia‐mimicking molecule with direct applications in regenerative medicine, on the behavior of an osteoblastic cell line .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic platform with four orthogonal and overlapping gradients for soluble compound screening in regenerative medicine research

et al. 2014

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We present here a screening method based on a microfluidic platform, which can generate four orthogonal and overlapping concentration gradients of soluble compounds over a monolayer of cells, in combination with automated and in situ image analysis, for use in regenerative medicine research. The device includes a square chamber in which cells are grown, and four independent supply channels along the sides of the chamber, which are connected through an array of small diffusion channels. Compounds flown through the supply channels diffuse through diffusion channels into the chamber to create a gradient over the cell culture area. Further, the chamber is connected to two channels intended for introduction of cells and in situ staining. In this study, the dimensions of the different channels were optimized through finite element modeling to yield stable gradients, and two designs were used with gradients spanning 2.9-2.4 μM and 3.4-2.0 μM. Next, overlapping gradients were generated using four rhodamine-derived fluorescent dyes, and imaged using confocal microscopy. Finally, the platform was applied to assess the concentration-dependent response of an osteoblastic cell line exposed to a hypoxia-mimicking molecule phenanthroline, using an in situ fluorescent staining assay in combination with image analysis, applicable to closed microfluidic devices. The on-chip assay yielded results comparable to those observed in conventional culture, where a range of concentrations was tested in independent microwells. In the future, we intend to use this method to complement or replace current research approaches in screening soluble compounds for regenerative medicine, which are often based on one-sample-for-one-experiment principle.

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Microtiter plate-sized standalone chip holder for microenvironmental physiological control in gas-impermeable microfluidic devices

Cited by 18 publications

References 13 publications

Low-cost and highly efficient DNA biosensor for heavy metal ion using specific DNAzyme-modified microplate and portable glucometer-based detection mode

Low-cost and highly efficient DNA biosensor for heavy metal ion using specific DNAzyme-modified microplate and portable glucometer-based detection mode

Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

Microfluidic platform with four orthogonal and overlapping gradients for soluble compound screening in regenerative medicine research

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