Concentration Gradient Chip Customization and Processing
Compared with other in vitro research systems, the concentration gradient microfluidic chip has many unique advantages.
First of all, the concentration gradient microfluidic chip can form an accurate concentration gradient, and a series of complex concentration gradients can be obtained by changing the configuration design of the network channel and the concentration and combination order of the initial liquid flow. This is difficult for other systems to achieve.
Secondly, compared with the traditional research system, the concentration gradient microfluidic chip has microchannels similar to the size of microvessels in vivo and adopts perfusion culture, which is closer to the complex microenvironment in vivo. It can carry out cell growth and differentiation, cell chemotaxis, and intracellular substance analysis.
In addition, the fluid in this micro-size channel has laminar flow characteristics. When two or more different reagents flow into the same channel, each reagent flow can keep its own flow pattern unchanged, but only the reaction or molecular diffusion occurs at the phase-to-phase contact interface, which has high stability and reproducibility.
Finally, according to the characteristics of flexible design and processing of concentration gradient microfluidic chips, a variety of unit operation technologies can be flexibly combined and integrated on an overall controllable micro platform. For example, it can be combined with resistors, valves, and other modules to obtain the desired arbitrary concentration gradient, and the resulting gradient has real-time variability.
Design and Fabrication
The design principle of the concentration gradient microfluidic chip is to rely on different concentrations of parallel inlets, control the flow rate and flow through the fluid drive device, so that the liquid flows in a laminar flow; and gradually mix through multi-level diversion and confluence by diffusion, flowing through different chip networks to form a complex concentration gradient. It can maintain stability for a long time. The design of the chip network has significant flexibility and can have different shapes and spatial configurations. By changing the length of the channel and the configuration of the network, various concentration gradients can be obtained.
The traditional fabrication materials of concentration gradient microfluidic chips are mainly monocrystalline silicon, glass, quartz, and so on. High precision microfluidic chips can be obtained by lithography and etching technology. However, this method has some defects, such as high processing conditions, long processing cycle, high processing cost and so on.
Polymer materials such as polydimethylsiloxane (PDMS) and polymethyl methacrylate (PMMA) have been widely used because of their excellent optical properties, high biocompatibility and gas permeability, cheap raw materials, short manufacturing cycle, good durability and flexible packaging methods. PDMS or PMMA devices are fabricated by casting, and then sealed with other materials such as glass to make microfluidic chips. This chip micromachining method has low requirements for processing equipment, short processing cycle, and low cost, so it is a good rapid processing technology for microfluidic chips.
Microfluidic concentration gradient chips can be used to simulate the external environment, establish chemical substance concentration gradients, and study the response of organisms to changes in the external environment at the cell and individual levels. This technology has been widely used in drug screening, simulated biological chemotaxis, toxicity evaluation, and other research fields.
- Drug Screening
With the development of new drug development technology, the activity test for newly developed drug compounds has gradually changed from the early confirmatory test to the screening test. When the microfluidic concentration gradient chip is used for drug screening experiments, compared with the traditional multi-well plate technology, it saves the complicated operation of configuring and distributing solutions of different concentrations of various drugs and greatly simplifies the operations of cell plating, drug application, washing, labeling, etc. The process enables high-throughput screening while significantly reducing cell and reagent consumption.
- Simulated Biological Chemotaxis
Simulated organisms can react to chemicals in liquids and air and feel water-soluble initiators and volatile substances in the range of micro-molar concentrations, resulting in tendency or avoidance behavior. A controllable concentration gradient becomes the key to studying chemotaxis in model organisms. Microfluidic concentration gradient chip has the characteristics of free control and creation of chemical concentration gradients, short time to form concentration gradient, and high repeatability of experimental conditions. Therefore, it has become a powerful tool to study model biochemotactic behavior.
- Toxicity Evaluation
The microfluidic concentration gradient chip can generate different concentration gradients of chemical factors to act on marine microalgae, zebrafish, and other subjects under the stimulation of different concentrations of chemical factors. The biochemical reaction was used as a feedback signal to evaluate the toxicity of chemical factors.
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- Yin, B.S.; et al. An integrated microfluidic device for screening the effective concentration of locally applied tacrolimus for peripheral nerve regeneration. Experimental and therapeutic medicine. 2015 Jan 1;9(1):154-8.
- Fangjuan, Z.; et al. Concentration-gradient microfluidic chips for drug screening. Progress in Chemistry. 2021 Jul 20;33(7):1138.
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