Microfluidic network-based combinatorial dilution device for high throughput screening and optimization

Lee, Kangsun; Kim, Choong; Jung, Geunhui; Kim, Tae Song; Kang, Ji Yoon; Oh, Kwang W.

doi:10.1007/s10404-009-0500-z

Cited by 33 publications

(42 citation statements)

References 35 publications

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“…This assembly approach allows for the application of network analysis techniques like those used in classical electronic circuit design, facilitating the straightforward design of predictable flow systems. process (9,14,15), the powerful analysis techniques used in electronics design have not been widely adopted by the microfluidics community largely due to the lack of a standardized parts platform for circuit construction, inhibiting the exploration of large-scale designs and the growth of the field in general. In other words, the advent of discrete microfluidic components with standardized interconnects and dimensional freedom naturally fits within the framework of design based on welldefined device terminal characteristics.…”

mentioning

confidence: 99%

Discrete elements for 3D microfluidics

Bhargava¹,

Thompson

Malmstadt³

2014

Proc. Natl. Acad. Sci. U.S.A.

271

235

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Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry. modular microfluidics | microfluidic circuit design | 3D-printed microfluidics

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mentioning

confidence: 99%

Discrete elements for 3D microfluidics

Bhargava¹,

Thompson

Malmstadt³

2014

Proc. Natl. Acad. Sci. U.S.A.

271

235

View full text Add to dashboard Cite

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“…1, in our previous design for combinatorial module (Lee et al 2010a), face-to-face contact of channels between the multiple layers caused contamination of the samples due to leakage at the cross junction (Ismagilov et al 2001). In this study, to prevent the leakage, the channels between the multiple layers are interconnected all the way through via-holes.…”

Section: A Combinatorial Dilution Modulementioning

confidence: 97%

“…The concept of mathematical modeling to design microfluidic network-based devices has been generally overviewed in our previous publications (Lee et al 2010a). Based on the mathematical modeling, we have designed the microfluidic combinatorial device integrated with the initial concentration controller for seven combinations using three samples.…”

Section: The Integrated Concentration-on-demand Combinatorial Dilutiomentioning

confidence: 99%

“…In the design, analogy between microfluidic and electrical circuits is exploited to determine proper hydraulic resistances of the channel segments corresponding to desirable volumetric mixing ratios of the samples (Lee et al , 2010a. We can attain linear equations derived from an equivalent circuit using Ohm's and Kirchhoff's Table 1 Details of flow rates and concentrations for an example using the microfluidic initial concentration control module…”

Section: A Combinatorial Dilution Modulementioning

confidence: 99%

“…Previously, we had reported a microfluidic network-based combinatorial device capable of systematically adjusting the mixing ratio of samples for specific combinations with three layers (Lee et al 2010a). In the previous work, face-to-face contact of channels between the multiple layers caused contamination of the samples due to leakage at the cross junction.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Microfluidic concentration-on-demand combinatorial dilutions

Lee

Kim

et al. 2011

Microfluid Nanofluid

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We present a microfluidic network-based combinatorial dilution device to generate on-demand combinatorial dilutions of all input samples in the range of a 3D simplex-centroid. The device consists of an initial concentration control module and a combinatorial dilution module. In the initial concentration control module, the concept of using a single common channel has been incorporated to generate desirable concentrations of each sample, diluted independently in response to variable input flow. Then, the diluted samples flow into the combinatorial dilution module to generate a full set of seven combinations from the three samples. First, we investigated the performance of the initial concentration controller by computational simulation (CFD-ACE ? ). The simulated output concentrations are extremely close to the expected theoretical values. Further, a PDMS-based initial concentration controller was fabricated, and its linearity and independency were tested with fluorescent dye. Then, we designed, simulated, and tested a combinatorial dilution device integrated with the initial concentration controller. Finally, as proof-of-concept, we performed a simple combinatorial cytotoxicity test with three drugs (Mitomycin C, Doxorubicin, and 5-FU) for MCF-7 cancer cells.

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Arrayed cellular environments for stem cells and regenerative medicine

Titmarsh

Chen

Wolvetang

et al. 2012

Biotechnology Journal

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The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

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Microfluidic network-based combinatorial dilution device for high throughput screening and optimization

Cited by 33 publications

References 35 publications

Discrete elements for 3D microfluidics

Discrete elements for 3D microfluidics

Microfluidic concentration-on-demand combinatorial dilutions

Arrayed cellular environments for stem cells and regenerative medicine

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