Electric manipulations of hydrogel on a digital microfluidic platform

Chiang, Min-Yu; Fan, Shih-Kang

doi:10.1109/nems.2012.6196805

Cited by 3 publications

(4 citation statements)

References 8 publications

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“…For example, digital microfluidics allows for the interrogation of hanging drops either individually or in parallel, enables handling of very small volumes of liquid (pL-µL), 72,73 allows for magnetic or dielectrophoretic sorting of cells or beads, [74][75][76][77] enables programmable and spatially controlled heating of individual or multiple locations, 78 supports rapidly sequential delivery of reagents to single or multiple locations, 79 allows for in situ electrochemical detections, [80][81][82] and allows for the formation of hydrogels with controllable geometry and orientation. 61,83,84 In addition, a wide range of bioanalytical capabilities including mass spectrometry sample preparation, 85 PCR, 86 qPCR, 87 immunoassays, 88 surface plasmon resonance imaging, 89 and fluorescence imaging 90 have been developed for the DµF platform, providing in situ analytical and multiplexing functionalities that could be challenging to incorporate into a robotic liquid-handling spheroid-culture workflow.…”

Section: Cell Spheroid Culturementioning

confidence: 99%

Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture

Aijian

Garrell

2015

SLAS Technology

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Cell spheroids are multicellular aggregates, grown in vitro, that mimic the three-dimensional morphology of physiological tissues. Although there are numerous benefits to using spheroids in cell-based assays, the adoption of spheroids in routine biomedical research has been limited, in part, by the tedious workflow associated with spheroid formation and analysis. Here we describe a digital microfluidic platform that has been developed to automate liquid-handling protocols for the formation, maintenance, and analysis of multicellular spheroids in hanging drop culture. We show that droplets of liquid can be added to and extracted from through-holes, or "wells," and fabricated in the bottom plate of a digital microfluidic device, enabling the formation and assaying of hanging drops. Using this digital microfluidic platform, spheroids of mouse mesenchymal stem cells were formed and maintained in situ for 72 h, exhibiting good viability (>90%) and size uniformity (% coefficient of variation <10% intraexperiment, <20% interexperiment). A proof-of-principle drug screen was performed on human colorectal adenocarcinoma spheroids to demonstrate the ability to recapitulate physiologically relevant phenomena such as insulin-induced drug resistance. With automatable and flexible liquid handling, and a wide range of in situ sample preparation and analysis capabilities, the digital microfluidic platform provides a viable tool for automating cell spheroid culture and analysis.

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Section: Cell Spheroid Culturementioning

confidence: 99%

Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture

Aijian

Garrell

2015

SLAS Technology

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“…Microfluidic systems have also been used to shape and manipulate hydrogels at the microscale (microgels) . Eydelnant et al utilized electrostatic manipulation of discrete nano- and microliter droplets across open-electrode arrays containing hydrophilic patches to form hydrogels of reconstituted basement membrane, collagen, and agarose.…”

Section: High-throughput Processing Techniques For 3d Cell Culturementioning

confidence: 99%

Synthesis and High-Throughput Processing of Polymeric Hydrogels for 3D Cell Culture

Lowe¹,

Tan²,

Soeriyadi³

et al. 2014

Bioconjugate Chem.

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3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.

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“…A major application of DµF is as a platform for biological assays and cell manipulation [3,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Technological advances that have enabled these applications have included improvements to automated proteomics [9,23,33], DEP-based protein and cell sorting [34][35][36], complete mammalian cell culture on-chip [37], and cell spheroid development [38].…”

Section: Introductionmentioning

confidence: 99%

“…Investigations have demonstrated negligible effects to cell health during low-frequency DµF actuation using small electrodes [39]. Spatiotemporal control of tissue-engineered scaffolds has emerged as a critical tool for controlling cell behavior and directing cell fate [40][41][42][43][44][45], so it is not surprising that hydrogels have also recently been incorporated into DµF devices [18,23,24,33,46]. The mechanical properties of hydrogels, such as their elastic modulus and toughness, have been shown to correlate with cell behaviors such as extracellular matrix protein production, cell adhesion, migration, and stem cell differentiation [40][41][42]44,45,47].…”

Section: Introductionmentioning

confidence: 99%

Digital Microfluidic System with Vertical Functionality

Bender

Garrell

2015

Micromachines

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Digital (droplet) microfluidics (DµF) is a powerful platform for automated lab-on-a-chip procedures, ranging from quantitative bioassays such as RT-qPCR to complete mammalian cell culturing. The simple MEMS processing protocols typically employed to fabricate DµF devices limit their functionality to two dimensions, and hence constrain the applications for which these devices can be used. This paper describes the integration of vertical functionality into a DµF platform by stacking two planar digital microfluidic devices, altering the electrode fabrication process, and incorporating channels for reversibly translating droplets between layers. Vertical droplet movement was modeled to advance the device design, and three applications that were previously unachievable using a conventional format are demonstrated: (1) solutions of calcium dichloride and sodium alginate were vertically mixed to produce a hydrogel with a radially symmetric gradient in crosslink density; (2) a calcium alginate hydrogel was formed within the through-well to create a particle sieve for filtering suspensions passed from one layer to the next; and (3) a cell spheroid formed using an on-chip hanging-drop was retrieved for use in downstream processing. The general capability of vertically delivering droplets between multiple stacked levels represents a processing innovation that increases DµF functionality and has many potential applications.

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Electric manipulations of hydrogel on a digital microfluidic platform

Cited by 3 publications

References 8 publications

Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture

Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture

Synthesis and High-Throughput Processing of Polymeric Hydrogels for 3D Cell Culture

Digital Microfluidic System with Vertical Functionality

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