Dispersible oxygen microsensors map oxygen gradients in three-dimensional cell cultures.

Phase fluorimetry, unlike the more commonly used intensity-based measurement, is not affected by differences in light paths from culture vessels or by optical attenuation through dense 3D cell cultures and hydrogels thereby minimizing dependence on signal intensity for accurate measurements. This work describes the use of phase fluorimetry on oxygen-sensor microbeads to perform oxygen measurements in different microtissue culture environments. In one example, cell spheroids were observed to deplete oxygen from the cell-culture medium filling the bottom of conventional microwells within minutes, whereas oxygen concentrations remained close to ambient levels for several days in hanging-drop cultures.

Microfluidic device capable of medium recirculation for non-adherent cell culture.

We present a microfluidic device designed for maintenance and culture of non-adherent mammalian cells, which enables both recirculation and refreshing of medium, as well as easy harvesting of cells from the device. We demonstrate fabrication of a novel microfluidic device utilizing Braille perfusion for peristaltic fluid flow to enable switching between recirculation and refresh flow modes. Utilizing fluid flow simulations and the human promyelocytic leukemia cell line, HL-60, non-adherent cells, we demonstrate the utility of this RECIR-REFRESH device.

Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates.

Using stereolithography, 20 different structural variations comprised of millimeter diameter holes surrounded by trenches, plateaus, or micro-ring structures were prepared and tested for their ability to stably hold arrays of microliter sized droplets within the structures over an extended period of time. The micro-ring structures were the most effective in stabilizing droplets against mechanical and chemical perturbations. After confirming the importance of micro-ring structures using rapid prototyping, we developed an injection molding tool for mass production of polystyrene 3D cell culture plates with an array of 384 such micro-ring surrounded through-hole structures.

Responses of endothelial cells to extremely slow flows.

The process of blood vessel formation is accompanied by very minimal flow in the beginning, followed by increased flow rates once the vessel develops sufficiently. Many studies have been performed for endothelial cells at shear stress levels of 0.1-60 dyn∕cm(2); however, little is known about the effect of extremely slow flows (shear stress levels of 10(-4)-10(-2) dyn∕cm(2)) that endothelial cells may experience during early blood vessel formation where flow-sensing by indirect mass transport sensing rather than through mechanoreceptor sensing mechanisms would become more important.

Integrated Elastomeric Components for Autonomous Regulation of Sequential and Oscillatory Flow Switching in Microfluidic Devices.

A critical need for enhancing usability and capabilities of microfluidic technologies is the development of standardized, scalable, and versatile control systems1,2. Electronically controlled valves and pumps typically used for dynamic flow regulation, although useful, can limit convenience, scalability, and robustness3-5. This shortcoming has motivated development of device-embedded non-electrical flow-control systems.

Dynamics of liquid plugs of buffer and surfactant solutions in a micro-engineered pulmonary airway model.

We describe a bioinspired microfluidic system that resembles pulmonary airways and enables on-chip generation of airway occluding liquid plugs from a stratified air-liquid two-phase flow. User-defined changes in the air stream pressure facilitated by mechanical components and tuning the wettability of the microchannels enable generation of well-defined liquid plugs. Significant differences are observed in liquid plug generation and propagation when surfactant is added to the buffer.

External compression-induced fracture patterning on the surface of poly(dimethylsiloxane) cubes and microspheres.

This article describes a method for creating submicrometer surface patterns on cubes and microspheres. In this method, PDMS cubes and microspheres are exposed to oxygen plasma, which creates a very thin, hard, surface-modified layer on a compliant substrate. These are then compressed, causing the layer to crack in patterns dictated by the distribution of tensile stresses in the surface layer.