Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays.

Microfluidic cell-based systems have enabled the study of cellular phenomena with improved spatiotemporal control of the microenvironment and at increased throughput. While poly(dimethylsiloxane) (PDMS) has emerged as the most popular material in microfluidics research, it has specific limitations that prevent microfluidic platforms from achieving their full potential. We present here a complete process, ranging from mold design to embossing and bonding, that describes the fabrication of polystyrene (PS) microfluidic devices with similar cost and time expenditures as PDMS-based devices.

Image-based analysis of primary human neutrophil chemotaxis in an automated direct-viewing assay.

Multi-well assays based on the Boyden chamber have enabled highly parallel studies of chemotaxis-the directional migration of cells in response to molecular gradients-while direct-viewing approaches have allowed more detailed questions to be asked at low throughput. Boyden-based plates provide a count of cells that pass through a membrane, but no information about cell appearance. In contrast, direct-viewing devices enable the observation of cells during chemotaxis, which allows measurement of many parameters including area, shape, and location.

An automated high-content assay for tumor cell migration through 3-dimensional matrices.

High-content tumor cell migration assays in 3-dimensional (3D) extracellular matrix are a powerful tool for modeling and understanding the biology of this critical step in the process of metastasis. Currently available methods offer very limited throughput and are not amenable to studies of comparative pharmacology or small-scale screening. The authors present an automated approach to high-content tumor cell migration assays.

Cellular observations enabled by microculture: paracrine signaling and population demographics.

The cellular microenvironment plays a critical role in shaping and directing the process of communication between the cells. Soluble signals are responsible for many cellular behaviors such as cell survival, proliferation and differentiation. Despite the importance of soluble signals, canonical methods are not well suited to the study of soluble factor interactions between multiple cell types.

Cell culture models in microfluidic systems.

Microfluidic technology holds great promise for the creation of advanced cell culture models. In this review, we discuss the characterization of cell culture in microfluidic systems, describe important biochemical and physical features of the cell microenvironment, and review studies of microfluidic cell manipulation in the context of these features. Finally, we consider the integration of analytical elements, ways to achieve high throughput, and the design constraints imposed by cell biology applications.

Automated cell culture in high density tubeless microfluidic device arrays.

Microfluidics is poised to have an impact on life sciences research. However, current microfluidic methods are not compatible with existing laboratory liquid dispensing and detection infrastructure. This incompatibility is a barrier to adoption of microfluidic systems and calls for improved approaches that will enhance performance and promote acceptance of microfluidic systems in the life sciences.

High-throughput microfluidics: improved sample treatment and washing over standard wells.

Fluid flow in microchannels is used to treat or wash samples and can be incorporated into high-throughput applications such as drug screening, which currently use standard microtiter wells for performing assays. This paper provides theoretical and experimental data comparing microchannels and standard wells on the metrics of sample washing and experimental error in treatment concentrations. It is shown numerically and experimentally that microchannel concentration can be approximated with an inverse linear relationship to input volume.

Diffusion dependent cell behavior in microenvironments.

Understanding the interaction between soluble factors and cells in the cellular microenvironment is critical to understanding a wide range of diseases. Microchannel culture systems provide a tool for separating diffusion and convection based transport making possible controlled studies of the effects of soluble factors in the cellular microenvironment. In this paper we compare the proliferation kinetics of cells in traditional culture flasks to those in microfluidic channels, and explore the relationship between microchannel geometry and cell proliferation.