Parallel mixing of photolithographically defined nanoliter volumes using elastomeric microvalve arrays

Abstract

Portable microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed a monolithic polydimethylsiloxane (PDMS) microdevice that allows for storing and mixing subnanoliter volumes of aqueous solutions at various mixing ratios. Filling and mixing is controlled via two integrated PDMS microvalve arrays. The volumes of the microchambers are entirely defined by photolithography, hence volumes from picoliter to nanoliter can be fabricated with high precision. Because the microvalves do not require an energy input to stay closed, fluid can be stored in a highly portable fashion for several days. We have confirmed the mixing precision and predictability using fluorescence microscopy. We also demonstrate the application of the device for calibrating fluorescent calcium indicators. Due to the biocompatibility of PDMS, the device will have broad applications in miniaturized diagnostic assays as well as basic biological studies.

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

“…Poly-dimethylsiloxane (PDMS) molds were fabricated as described previously [71], with a patterned parallel stripes of 80 µm width separated by 120 µm gaps. Briefly, PDMS molds were inversely pressed onto poly-d-lysine-coated glass coverslips, and microchannels formed between the PDMS molds and coverslips were used for microfluidic patterning of individual substrates (0.1 mg/ml collagen, fibronectin or 0.05 mg/ml laminin, mixed with 5 µg/ml of fluorescence-conjugated BSA, respectively), which were driven through the microchannels by a vacuum.…”

Cell handling using microstructured membranes

“…12,16,17 In contrast, most of the other elastomeric mechanical valves would seal upon the application of pressure through a thin membrane, and may introduce the challenge of maintaining the homeostasis of a cell suspension in the controlled channel. Gasses can diffuse easily through the membrane under the actuation pressure 18 and either diffuse in the cell suspension or, worse, form gas bubbles that can damage the cells.…”

“…Precise metering volumes are possible using valves in channels with vertical walls. 16 In our design, the use of microstructured membranes for the implementation of four valves, in a chromatography T-junction-like design, allowed the precise metering of 30 nL of blood. Chambers with volumes from few nanoliters to several microliters were designed by changing the position of the barriers or by altering the height of the chamber.…”

Microvalves and Micropumps for BioMEMS

“…These bonding prevention strategies present a unique challenge to the fabrication process that adds to its complexity. Alternately, one may choose to forgo bonding of the fluidic layer to the membrane, a strategy applied by Hosokawa et al [7] and Li et al [44], and instead control the valves and fluid flow by negative pressure only. However, the limitation on positive pressures can act as a significant design restriction on certain types of microfluidic devices.…”