Rapid Prototyping of Arrayed Microfluidic Systems in Polystyrene for Cell-Based Assays

Young, Elton T.; Berthier, Jean; Guckenberger, David J.; Sackmann, Eric K.; Lamers, Casey; Meyvantsson, Ivar; Huttenlocher, Anna; Beebe, David J.

doi:10.1021/ac102897h

Cited by 151 publications

(157 citation statements)

References 57 publications

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“…However, the plasma treatment can significantly affect the thermopress bonding strength because of surface reaction due to the plasma [22]. Moreover, it is noticed during our experiments that washing the PS films using DI water after oxygen plasma treatment can affect the bonding strength.…”

Section: Ps Thermopress Bonding Strength Testmentioning

confidence: 79%

A 3D microfluidic device fabrication method using thermopress bonding with multiple layers of polystyrene film

Cao

Bontrager-Singer

Zhu

2015

J. Micromech. Microeng.

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In this paper, we present a fabrication method that is capable of making three dimensional (3D) microfluidic devices with multiple layers of homogeneous polystyrene (PS) film. PS film was chosen as primary device material due to its advantageous features for microfluidics applications. Thermopress is used as bonding method because it provides sufficient bonding strength while requires no heterogeneous bonding materials. By aligning and sequentially stacking multiple layers (3 to 20) of patterned PS film which were achieved by a craft cutter, complicated 3D structured microfluidic devices can be fabricated by multiple steps of thermopress bonding. The smallest feature can be achieved in this method is around 100 μm, which is limited by the resolution of the cutter (25μm) as well as the thickness of the PS films.Bonding characteristics of PS films are given in this paper, including PS film bonding strength test, bonding precision assessment, and PS surface wettability manipulation. To demonstrate the capability of this method, the design, fabrication and testing results of a 3D interacting L-shaped passive mixer are presented in the paper.

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Section: Ps Thermopress Bonding Strength Testmentioning

confidence: 79%

A 3D microfluidic device fabrication method using thermopress bonding with multiple layers of polystyrene film

Cao

Bontrager-Singer

Zhu

2015

J. Micromech. Microeng.

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“…Although devices in the current work were fabricated in PDMS and glass, our platform can also be fabricated in polystyrene, 41 a thermoplastic widely used in common cell culture labware and useful for studies involving small hydrophobic molecules (eg, estrogen, fluoxetine) that are known to absorb into bulk PDMS. [42][43][44] We validated the platform in the context of MM and showed that other suspension cell types (CLL) can also be studied.…”

Section: Discussionmentioning

confidence: 99%

Microscale functional cytomics for studying hematologic cancers

Young

Pak

Kahl

et al. 2012

Blood

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An important problem in translational cancer research is our limited ability to functionally characterize behaviors of primary patient cancer cells and associated stromal cell types, and relate mechanistic understanding to therapy selection. Functional analyses of primary samples face at least 3 major challenges: limited availability of primary samples for testing, paucity of functional information extracted from samples, and lack of functional methods accessible to many researchers. We developed a microscale cell culture platform that overcomes these limitations, especially for hematologic cancers. A key feature of the platform is the ability to compartmentalize small populations of adherent and nonadherent cells in controlled microenvironments that can better reflect physiological conditions and enable cell-cell interaction studies. Custom image analysis was developed to measure cell viability and protein subcellular localizations in single cells to provide insights into heterogeneity of cellular responses. We validated our platform by assessing viability and nuclear translocations of NF-B and STAT3 in multiple myeloma cells exposed to different conditions, including cocultured bone marrow stromal cells. We further assessed its utility by analyzing NF-B activation in a primary chronic lymphocytic leukemia patient sample. Our platform can be applied to myriad biological questions, enabling high-content functional cytomics of primary hematologic malignancies. (Blood. 2012;119(10):e76-e85) IntroductionOne challenging area of translational cancer research is the difficulty of performing functional analyses of primary patient samples to increase our understanding of human cancer biology. Highly sensitive genomic and proteomic methods, approaches that primarily evaluate the state of cancer samples, have significantly added to, and continue to increase, our understanding of the biology and the stratification of human malignancies. [1][2][3][4] In contrast, functional analyses, assessing biological responses to various experimental conditions, with primary patient samples are challenging for two reasons: (1) standard in vitro models and cell culture platforms (eg, Petri dishes, well plates, Transwell inserts) do not accurately reflect the complex spatiotemporal dynamics of the physiological microenvironment 5,6 ; and (2) current laboratory techniques often require more biological starting material than can be adequately obtained from patients. For example, electrophoretic mobility shift assays (EMSAs) to detect transcription factor-DNA interactions typically require a minimum of 10 5 to 10 6 cultured cells per condition (ie, per lane). 7,8 This quantity, in some cases, may not be obtainable from patient samples with particularly low cell counts. EMSAs also belong to a broad class of populationaverage cellular assays that provide only a single readout for the entire cultured cell population. Such population-average approaches not only restrict experimentation to samples with abundant populations and limit the number of...

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“…Polymers such as polydimethylsiloxane (PDMS) [5,6], polymethylmethacrylate (PMMA) [7,8], polystyrene (PS) [9], polycarbonate (PC) [10,11] and cyclin olefin copolymer (COC) [12] are fabricated using methods such as soft lithography, hot embossing, micromolding and laser micromachining techniques. Despite their widespread use, functional integration of components including electronics, heaters, electrodes, optoelectronics, and sensing elements remains a challenge [13].…”

Section: Page 2 Ofmentioning

confidence: 99%

Long-lasting FR-4 surface hydrophilisation towards commercial PCB passive microfluidics

Vasilakis

Moschou

Carta

et al. 2016

Applied Surface Science

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Highlights oxygen plasma treatment on FR-4 laminates  effect of power and exposure time studied to achieve long-lasting hydrophilic properties  super-hydrophilic surface for 13 days demonstrated  surface remains weakly hydrophilic between 13 th and 26 th day after the treatment  hydrophilic behaviour is retained for 26 days in total  oxygen plasma treatment was used on a commercially manufactured PCB microfluidic chip to enable passive filling of a microfluidic network AbstractPrinted circuit boards (PCB) technologies are an attractive system for simple sensing and microfluidic systems. Controlling the surface properties of PCB material is an important part of this technology and to date there has been no study on long-term hydrophilisation stability of these materials. In this work, the effect of different oxygen plasma input power and treatment duration times on the wetting properties of FR-4 surfaces was investigated by sessile droplet contact angle measurements. Super and weakly hydrophilic behaviour was achieved and the retention time of these properties was studied, with the hydrophilic nature being retained for at least 26 days. To demonstrate the applicability of this treatment method, a commercially manufactured microfluidic structure made from a multilayer PCB (3-layer FR-4 stack) was exposed to oxygen plasma at the optimum conditions. The structures could be filled with deionised (DI) water under capillary flow unlike the virgin devices.

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Rapid Prototyping of Arrayed Microfluidic Systems in Polystyrene for Cell-Based Assays

Cited by 151 publications

References 57 publications

A 3D microfluidic device fabrication method using thermopress bonding with multiple layers of polystyrene film

A 3D microfluidic device fabrication method using thermopress bonding with multiple layers of polystyrene film

Microscale functional cytomics for studying hematologic cancers

Long-lasting FR-4 surface hydrophilisation towards commercial PCB passive microfluidics

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