Digital microfluidics with impedance sensing for integrated cell culture andanalysis

Shih, Steve C. C.; Barbulovic-Nad, Irena; Yang, Xuning; Fobel, Ryan; Wheeler, Aaron R.

doi:10.1016/j.bios.2012.10.035

Cited by 104 publications

(74 citation statements)

References 62 publications

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“…The ability to impart electric fields to actuate and sense cellular characteristics, for example, requires the sample to be positioned near electrodes [69][70][71]. We hypothesized that using a second plane below the hanging drop would provide a path for a delivering a new droplet to the hanging drop that could be used to retrieve the EB.…”

Section: Embryoid Body (Eb) Sample Retrievalmentioning

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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Section: Embryoid Body (Eb) Sample Retrievalmentioning

confidence: 99%

Digital Microfluidic System with Vertical Functionality

Bender

Garrell

2015

Micromachines

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“…3). Recent advances in sensor integration [4,8,16,17,22,[25][26][27]30] provide the ability to execute intelligent computer-controlled assays that obtain feedback and make decisions in real-time based on sensor readings (Fig. 4).…”

Section: Introductionmentioning

confidence: 99%

Simulation of feedback-driven PCR assays on a 2D electrowetting array using a domain-specific high-level biological programming language

Curtis

Brisk

2015

Microelectronic Engineering

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a b s t r a c t a r t i c l e i n f oThe motivation of our work is to demonstrate that scientists can describe biochemical assays using a high-level domain-specific programming language and can execute them automatically on a two-dimensional electrowetting array featuring integrated sensors that provide feedback in real-time to the host PC that controls the integrated system. The fundamental research problem that this paper addresses is how to express, at a high level of abstraction, the acquisition of sensory information from the device, and the computation on that data, which is required to perform real-time decision making in response. The approach that we have taken is first, to create a new version of BioCoder, a programming language for automated biology, which we have specialized for electrowetting arrays featuring integrated sensors, and second, to use this language to specify two feedbackdriven Polymerase Chain Reaction (PCR) assays at the desired level of abstraction. Our methodology is to evaluate the performance of these assays using a custom-build runtime system to control the execution of feedbackdriven assays on a cycle-accurate software simulator that accurately characterizes the behavior of the electrowetting platform during assay execution. The result of this experiment is successful simulation of these non-trivial feedback-driven assays, starting from a high-level specification, which allows us to conclude that high-level programming language design and implementation targeting electrowetting (or other competing laboratory-on-a-chip technologies) is feasible.

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“…In general, potential applications for microchips have been demonstrated through various analytes, including viruses, 10,11 disease biomarkers, [12][13][14] environmental pollutants, [15][16][17] proteins and enzymes, [18][19][20][21][22] mammalian cells, [23][24][25] and antibiotics. 26 These involve various bioanalytical assays such as hybridization, immunoassay, and cell/viral analysis.…”

mentioning

confidence: 99%