Individually programmable cell stretching microwell arrays actuated by a Braille display.

Cell culture systems are often static and are therefore nonphysiological. In vivo, many cells are exposed to dynamic surroundings that stimulate cellular responses in a process known as mechanotransduction. To recreate this environment, stretchable cell culture substrate systems have been developed, however, these systems are limited by being macroscopic and low throughput. We have developed a device consisting of 24 miniature cell stretching chambers with flexible bottom membranes that are deformed using the computer-controlled, piezoelectrically actuated pins of a Braille display. We have also developed efficient image capture and analysis protocols to quantify morphological responses of the cells to applied strain. Human dermal microvascular endothelial cells (HDMECs) were found to show increasing degrees of alignment and elongation perpendicular to the radial strain in response to cyclic stretch at increasing frequencies of 0.2, 1, and 5 Hz, after 2, 4, and 12h. Mouse myogenic C2C12 cells were also found to align in response to the stretch, while A549 human lung adenocarcinoma epithelial cells did not respond to stretch.

Microfluidics for flow cytometric analysis of cells and particles.

This review describes recent developments in microfabricated flow cytometers and related microfluidic devices that can detect, analyze, and sort cells or particles. The high-speed analytical capabilities of flow cytometry depend on the cooperative use of microfluidics, optics and electronics. Along with the improvement of other components, replacement of conventional glass capillary-based fluidics with microfluidic sample handling systems operating in microfabricated structures enables volume- and power-efficient, inexpensive and flexible analysis of particulate samples. In this review, we present various efforts that take advantage of novel microscale flow phenomena and microfabrication techniques to build microfluidic cell analysis systems.

Multigated contrast-enhanced power Doppler to measure blood flow in mice tumors.

This study evaluated an image-gating method using contrast-enhanced power Doppler ultrasound (US) to estimate blood perfusion in mice tumors. A mathematical model that compensates for the effect of bubble destruction by US pulses was used to determine contrast flow through an image plane. Multigated power Doppler images were obtained following contrast injection. Contrast flow index (CFI) was determined by measuring the area under the color level vs. time curve for each gating frequency. CFI was compared with true flow. The method was first evaluated using a flow phantom with variable flow rates, and then verified in a mouse model with implanted tumors. Color levels in Doppler images were modulated with gating frequency due to variable destruction of microbubbles by US pulses. CFI measured from the images correlated strongly with true flow in the flow phantom (r(2) = 0.87). The proposed method yielded reproducible CFI for mice tumors, suggesting that multigated contrast-enhanced power Doppler imaging may provide noninvasive measurement of tumor perfusion in mice.

Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method.

This paper describes a direct write laser technology, which is fast and flexible, for fabricating multiple-level microfluidic channels. A high brightness diode-pumped Nd-YAG laser with slab geometry was used for its excellent beam quality. Channels with flat walls and staggered herringbone ridges on the floor have been successfully fabricated and their ability to perform passive mixing of liquid is discussed. Also, a multi-width multi-depth microchannel has been fabricated to generate biomimetic vasculatures whose channel diameters change according to Murray's law, which states that the cube of the radius of a parent vessel equals the sum of the cubes of the radii of the daughters. The multi-depth architecture allows for flow patterns to resemble physiological vascular systems with lower overall resistance and more uniform flow velocities throughout the network compared to planar patterning techniques which generate uniformly thin channels. The ability to directly fabricate multiple level structures using relatively straightforward laser technology enhances our ability to rapidly prototype complex lab-on-a-chip systems and to develop physiological microfluidic structures for tissue engineering and investigations in biomedical fluidics problems.