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Rapid generation of spatially and temporally controllable long-range concentration gradients in a microfluidic device.

ABSTRACT: The ability to rapidly generate concentration gradients of diffusible molecules has important applications in many chemical and biological studies. Here we established spatially and temporally controllable concentration gradients of molecules (i.e. proteins or toxins) in a portable microfluidic device in an easy and rapid manner. The formation of the concentration gradients was initiated by a passive-pump-induced forward flow and further optimized during an evaporation-induced backward flow. The centimeter-long gradients along the microfluidic channel were shown to be spatially and temporally controlled by the backward flow. The gradient profile was stabilized by stopping the flow. Computational simulations of this dynamic process illustrated the combined effects of convection and diffusion on the gradient generation, and fit well with the experimental data. To demonstrate the applications of this methodology, a stabilized concentration gradient of a cardiac toxin, alpha-cypermethrin, along the microchannel was used to test the response of HL-1 cardiac cells in the micro-device, which correlated with toxicity data obtained from multi-well plates. The approach presented here may be useful for many biological and chemical processes that require rapid generation of long-range gradients in a portable microfluidic device.

SUBMITTER: Du Y

PROVIDER: S-EPMC2790062 | biostudies-other | 2009 Mar

REPOSITORIES: biostudies-other

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Rapid generation of spatially and temporally controllable long-range concentration gradients in a microfluidic device.

Du Yanan Y Shim Jaesool J Vidula Mahesh M Hancock Matthew J MJ Lo Edward E Chung Bong Geun BG Borenstein Jeffrey T JT Khabiry Masoud M Cropek Donald M DM Khademhosseini Ali A

Lab on a chip 20081210 6

The ability to rapidly generate concentration gradients of diffusible molecules has important applications in many chemical and biological studies. Here we established spatially and temporally controllable concentration gradients of molecules (i.e. proteins or toxins) in a portable microfluidic device in an easy and rapid manner. The formation of the concentration gradients was initiated by a passive-pump-induced forward flow and further optimized during an evaporation-induced backward flow. The ...[more]

PMID: 19255657

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Project description:Generating and maintaining the concentration dilutions of diffusible molecules in microchannels is critical for high-throughput chemical and biological analysis. Conventional serial network microfluidic technologies can generate high orders of arbitrary concentrations by a predefined microchannel network. However, a previous design requires a large occupancy area and is unable to dynamically generate different profiles in the same chip, limiting its applications. This study developed a microfluidic device enabling dynamic variations of both the concentration in the same channel and the concentration distribution in multiple channels by adjusting the flow resistance using programmable pneumatic microvalves. The key component (the pneumatic microvalve) allowed dynamic adjustment of the concentration profile but occupied a tiny space. Additionally, a Matlab program was developed to calculate the flow rates and flow resistance of various sections of the device, which provided theoretical guidance for dimension design. In silico investigations were conducted to evaluate the microvalve deformation with widths from 100 to 300 µm and membrane thicknesses of 20 and 30 µm under the activation pressures between 0 and 2000 mbar. The flow resistance of the deformed valve was studied both numerically and experimentally and an empirical model for valve flow resistance with the form of Rh=aebP was proposed. Afterward, the fluid flow in the valve region was characterized using Micro PIV to further demonstrate the adjustment mechanism of the flow resistance. Then, the herringbone structures were employed for fast mixing to allow both quick variation of concentration and minor space usage of the channel network. Finally, an empirical formula-supported computational program was developed to provide the activation pressures required for the specific concentration profile. Both linear (Ck = -0.2k + 1) and nonlinear (Ck = (110)k) concentration distribution in four channels were varied using the same device by adjusting microvalves. The device demonstrated the capability to control the concentration profile dynamically in a small space, offering superior application potentials in analytical chemistry, drug screening, and cell biology research.

Dataset Information

Rapid generation of spatially and temporally controllable long-range concentration gradients in a microfluidic device.

Publications

Rapid generation of spatially and temporally controllable long-range concentration gradients in a microfluidic device.

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