Quantification of chemical–polymer surface interactions in microfluidic cell culture devices

Xu, Hui; Shuler, Michael L.

doi:10.1002/btpr.135

Cited by 17 publications

(15 citation statements)

References 37 publications

(61 reference statements)

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“…Tradeoffs in microscale systems include drug adsorption and complex operation, and other approaches are continuously being developed to address specific assays such as low clearance compounds and reactive metabolites [93]. Thus, the advantages of microfluidic systems may be greater for more complex applications that require microscale 3D architectures to retain function, or applications where interconnection with other microscale organ mimics provides greatly enhanced information [94–96]. …”

Section: Bioreactorsmentioning

confidence: 99%

“…PDMS is the same material used to deliver the steroid hormones in the implantable drug delivery system Norplant, in which the steroid hormones diffuse through a PDMS barrier in which they are highly soluble compared to their solubility in saline. The drawbacks of working with PDMS when quantitative control of highly lipophilic compounds is needed have been described by several labs, and though the problem can be partially and temporarily mitigated by various surface treatments, the PDMS molecules are highly mobile and the surface rearranges over time [63,187–189]. Other elastomers suitable for microfluidics are now being explored, but no prominent solution has emerged for widespread use, in part as the properties that allow elastomers to work well in microfabrication overlap with those that foster drug partitioning to some degree.…”

Section: Opportunities and Challenges For Use Of Bioreactors In Drmentioning

confidence: 99%

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Bioreactor technologies to support liver function in vitro

Ebrahimkhani

Neiman

Raredon

et al. 2014

Advanced Drug Delivery Reviews

119

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Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drive efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.

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Section: Bioreactorsmentioning

confidence: 99%

Section: Opportunities and Challenges For Use Of Bioreactors In Drmentioning

confidence: 99%

Bioreactor technologies to support liver function in vitro

Ebrahimkhani

Neiman

Raredon

et al. 2014

Advanced Drug Delivery Reviews

119

View full text Add to dashboard Cite

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“…A tight seal between the housing, the silicon chip and tubing connections is essential while cells can be damaged by device assembly. Chemical cross contamination is another potential problem when housing pieces are reused, as plastic is prone to hydrophobic chemical surface adsorption (Xu and Shuler 2009). As an alternative, disposable PDMS microCCA devices are lower in material cost, less expensive to fabricate, easier to seal by plasma and need no extra housing pieces.…”

Section: Construction Of Microcca Devicesmentioning

confidence: 99%

Development of disposable PDMS micro cell culture analog devices with photopolymerizable hydrogel encapsulating living cells

Chu

et al. 2011

Biomed Microdevices

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Microscale cell culture devices with two or more cell types, such as the micro cell culture analog (microCCA), are promising devices to predict mammalian response to toxic drug and chemical exposure. A polydimethylsiloxane (PDMS) version of such microfluidic devices has been challenging to construct due to the difficulty of patterning multi cell types directly into designated individual cell culture chambers in an oxygen plasma bonded PDMS device. Approaches with micro-valves for flow control are complex, expensive and inconvenient to use. In this study, an alternative approach using polyethylene glycol diacrylate (PEG-DA) for spatially controlled multi-cell type patterning inside a bonded microCCA device is described. We constructed a three-cell type PDMS microCCA following a human physiologically based pharmacokinetic (PBPK) modeling, and applied continuous cell culture medium recirculation within the device as a blood surrogate. A fluorescence microscope based direct pattern writing method was used to form cell/hydrogel microstructures with higher cell viability than the traditional UV lamp based method. The positive effect of mixed molecular weight PDG-DA on hydrogel-encapsulated cell membrane integrity was also studied. This prototype PDMS microCCA device was then tested with Triton X-100 as a model toxicant. The combination of hydrogel photo-patterning and the microfluidic cell culture platform enables the fabrication of simple and low cost multi-cell type biosensors for drug development, toxicity study and clinical diagnosis.

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“…Most prototype devices reviewed here were operated with relatively large equipment such as incubators, syringe pumps, or peristaltic pumps. Peristaltic pumps often are operated with flexible polymer tubing that can absorb compounds (especially hydrophobic ones), leading to significant chemical loss when the fluid is recirculated (95). Possible solutions to this problem include the development of nonabsorbent tubing (96), on-chip micropumps (97), or pumpless systems such as that developed by Sung et al (93).…”

Section: Increasing the Potential Impact Of Microfluidic In Vitro Sysmentioning

confidence: 99%

The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies

Esch

King

Shuler

2011

Annu. Rev. Biomed. Eng.

298

254

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High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.

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Quantification of chemical–polymer surface interactions in microfluidic cell culture devices

Cited by 17 publications

References 37 publications

Bioreactor technologies to support liver function in vitro

Bioreactor technologies to support liver function in vitro

Development of disposable PDMS micro cell culture analog devices with photopolymerizable hydrogel encapsulating living cells

The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies

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