A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array

Hung, Paul J.; Lee, Philip J.; Sabounchi, Poorya; Aghdam, Nima; Lin, Robert; Lee, Luke P.

doi:10.1039/b410743h

Cited by 248 publications

(205 citation statements)

References 19 publications

(15 reference statements)

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“…In these devices, a highthroughput cell-culture array can be fabricated out of PDMS by a two-step lithography process (9). The array is composed of large, circular chambers where the cells are cultured and two types of channels that define fluid flow.…”

Section: On-chip Cell Culturementioning

confidence: 99%

Chemical Analysis of Single Mammalian Cells with Microfluidics

Price¹,

Culbertson²

2007

Anal. Chem.

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of Single Mammalian Cells with Microfluidics C ells are the fundamental building blocks of life. All basic physiological functions of multicellular organisms reside ultimately in the cell. The misregulation of cellular physiology results in disease at the organism level. Thus, comprehending cell physiology is key to understanding and curing diseases. Many physiological processes can be studied using populations of cells. Others occur either on short timescales (e.g., kinase signaling cascades) or nonsynchronously (e.g., response to an external chemical gradient), so that taking a population average will not lead to an understanding of how the cellular chemistry occurs. These types of processes require single-cell analysis, and thus discretion must be exercised when deciding under which circumstances bulk versus singlecell analyses are more appropriate (1). In addition, many diseases like cancer start with a single cell; therefore, if one would like to find the rare mutations in populations of cells that herald the inception of a disease, then cells must be examined individually.Probing behavior at the single-cell level, however, is a very challenging task, primarily because of the small sample volume, the low abundance of material, and the fragile nature of the cell itself. Analyzing the contents of a single cell requires sensitive detection techniques and handling procedures that do not stress or damage it. Additionally, no proper blank exists that can be used, so truly quantitative studies are difficult. Intense interest in single-cell physiology, however, is driving the analytical and biomedical engineering fields to improve the technology for examining cells. One of the most popular and promising areas is lab-on-a-chip devices to manipulate and analyze single cells.Since Jorgenson's groundbreaking work in 1989, CE has been used to examine the contents of single cells (2-4). However, many procedures for cell injection and lysis are time-consuming, and accuracy and reproducibility rely heavily on the skill of the researcher. Furthermore, the limited number of architectures provided by microbore tubing and its relatively large volume restrict the types of processes that can be investigated. Conversely, microfluidics, or lab-on-a-chip technology, offers a versatile format in which biological cells can be analyzed.These miniaturized devices provide several analytical and operational advantages over conventional macroscale systems (5, 6). Microfluidic architectures provide precise spatial control over reagents and samples, are capable of fast analysis times, can be automated, and can precisely manipulate picoliter volumes of material without dilution. In addition, microfluidic systems are amenable to many different detection schemes, can be manufactured from many different materials at relatively low cost, allow flexibility of design, and provide the capability of integrating a series of multiple tasks (sample preparation, mixing, separation, etc.) in both serial and parallel schemes. Portable versions of these sys...

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Section: On-chip Cell Culturementioning

confidence: 99%

Chemical Analysis of Single Mammalian Cells with Microfluidics

Price¹,

Culbertson²

2007

Anal. Chem.

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“…To reduce the risk of culture medium evaporation, encapsulation of microchannels is considered an essential requirement. A microfluidic device with a high aspect ratio (HAR) provides a suitable environment for cell growth, as claimed by Hung et al [6]. Therefore, production of three-dimensional high aspect ratio microchannels with straight and smooth walls is in high demand.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of three-dimensional SU-8 microchannels by proton beam writing for microfluidics applications: Fluid flow characterisation

Alshehri¹,

Palitsin²,

Webb³

et al. 2015

Nuclear Instruments and Methods in Physics Research Section B:

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“…In order to scale to larger arrays, it is necessary to selectively control fluid transport through the system while maintaining a favorable cell culture environment. Our previous work introduced the concept of a microfluidic cell culture array (Hung et al, 2005a(Hung et al, , 2005b, but was limited by the inability to reliably perform cell-based experiments in a multiplexed manner. In this study, we addressed these issues by implementing a novel design to mechanically decouple cellular compartments from fluid flow.…”

Section: Introductionmentioning

confidence: 99%

Nanoliter scale microbioreactor array for quantitative cell biology

Lee

Hung

Rao

et al. 2005

Biotech & Bioengineering

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203

183

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A nanoliter scale microbioreactor array was designed for multiplexed quantitative cell biology. An addressable 8 Â 8 array of three nanoliter chambers was demonstrated for observing the serum response of HeLa human cancer cells in 64 parallel cultures. The individual culture unit was designed with a ''C'' shaped ring that effectively decoupled the central cell growth regions from the outer fluid transport channels. The chamber layout mimics physiological tissue conditions by implementing an outer channel for convective ''blood'' flow that feeds cells through diffusion into the low shear ''interstitial'' space. The 2 mm opening at the base of the ''C'' ring established a differential fluidic resistance up to 3 orders of magnitude greater than the fluid transport channel within a single mold microfluidic device. Three-dimensional (3D) finite element simulation were used to predict fluid transport properties based on chamber dimensions and verified experimentally. The microbioreactor array provided a continuous flow culture environment with a Peclet number (0.02) and shear stress (0.01 Pa) that approximated in vivo tissue conditions without limiting mass transport (10 s nutrient turnover). This microfluidic design overcomes the major problems encountered in multiplexing nanoliter culture environments by enabling uniform cell loading, eliminating shear, and pressure stresses on cultured cells, providing stable control of fluidic addressing, and permitting continuous on-chip optical monitoring. ß 2005 Wiley Periodicals, Inc.

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A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array

Cited by 248 publications

References 19 publications

Chemical Analysis of Single Mammalian Cells with Microfluidics

Chemical Analysis of Single Mammalian Cells with Microfluidics

Fabrication of three-dimensional SU-8 microchannels by proton beam writing for microfluidics applications: Fluid flow characterisation

Nanoliter scale microbioreactor array for quantitative cell biology

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