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Solution gradient dilution device with microfluidic chip

A microfluidic chip and gradient dilution technology, which is applied in the field of chemical analysis, can solve the problems of combined dilution, increased chip area, difficult to different substances, etc., and achieve the effects of fast and stable concentration, fine concentration differentiation, and various concentration types

Inactive Publication Date: 2014-03-05
NORTHEASTERN UNIV LIAONING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the channel of the microfluidic chip, the two solutions can form a concentration gradient in the main channel after confluence by repeating the flow-mixing-splitting process (Jeon N L, Dertinger S K W, Chiu D T, Choi I ​​S, Stroock A D, Whitesides G M.Langmuir, 2000, 16, 8311-8316.), if the above solutions do not merge into one main channel in the last step, but disperse into multiple branch channels, a series of gradient dilution solutions are formed (Ye N N, Qin J H, Shi W W, Liu X, Lin B C.Lab Chip, 2007, 7, 1696-1704), this gradient dilution method can easily dilute a drug solution into a series of concentrations, and can be integrated with cell culture devices in Together, it is used for drug screening research, but if this method is to form a wider concentration range, the chip area is required to be significantly increased, and it is difficult to realize the combined dilution solution of multiple drugs, and the operation process becomes more complicated.
Through different flow resistance ratios, the gradient dilution operation of the solution can also be realized on the microfluidic chip, and a gradient with a concentration range spanning 6 orders of magnitude can be generated (Sugiura S, Hattori K, Kanamori T.Anal.Chem., 2010, 82,8278-8282), but this gradient dilution method also has the problem that increasing the concentration gradient branch channel will significantly increase the chip area, it is difficult to perform combined dilution of different solutions, and the concentration gradient distribution is not fine enough
The existing microfluidic gradient dilution method that has been reported so far, because the concentration distribution range of the diluted solution is not wide enough, it is difficult to dilute the combination of different substances, and cannot meet the needs of large-scale dilution of one solution and combined dilution of multiple solutions. There are many limitations in practical application

Method used

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  • Solution gradient dilution device with microfluidic chip
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  • Solution gradient dilution device with microfluidic chip

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] The structure of the microfluidic chip solution gradient dilution device of this embodiment is as follows: figure 1 As shown, it is a microfluidic chip with an upper and lower two-layer structure, the upper layer is made of polydimethylsiloxane, one side has a microchannel network structure, and the lower layer 2 is a transparent flat glass substrate without a channel structure.

[0032] The disk-shaped radial microchannel network of the upper substrate is as figure 2 As shown, according to the standard manufacturing process of the SU-8 photoresist male mold, a male mold of the microchannel network is formed on the silicon wafer, and the thickness of the male mold is 40mm, and then polydimethylsiloxane prepolymer is cast on it. , after heating and polymerization, curing and molding, after curing and turning over the mold, 7 concentric circular channels and 7 levels of meandering channels are obtained. Around the first circular channel, two holes with a diameter of 0.45...

Embodiment 2

[0037] For the microfluidic chip with 3 inlets and 6 channels as the dilution device, the manufacturing process and concentration gradient formation method are the same as the 2 inlet chip in Example 1, the difference lies in the concentration gradient formation process of the chip with 3 inlets. First, it is necessary to introduce three solutions A, B and C at the same time, and then flow through the microchannel network. The microchannel network includes 5 levels of meandering channels, and the number of meandering channels is 6, 12, 24, and 48 respectively. lines, 96 lines, 1 group of 192 linear channels and 6 concentrically arranged circular channels, the final concentration gradient is divided into two cases: first, if the initial concentration is 0 (blank solution), 1 B (B solution) and 1 C (C solution), then generate a set of diluted gradient dilutions of solution B from 0 to 1, a total of 64 kinds, a set of diluted gradient dilutions of solution C from 0 to 1', a total...

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Abstract

The invention belongs to the field of chemical analysis, and in particular relates to a solution gradient dilution device with a microfluidic chip. The device consists of the microfluidic chip with a structure comprising an upper layer and a lower layer, wherein the upper layer of the microfluidic chip is a disk-shaped substrate with a radial micro-channel network; the lower layer of the microfluidic chip is a flat substrate; the disk-shaped substrate is packaged with the flat substrate relatively to form a micro-channel network on a bottom layer; the micro-channel network is provided with N concentric circular channels, N stages of zigzag channels and M holes used as inlets; and the last stage of zigzag channel is a linear channel. According to the solution gradient dilution device, fluid is distributed averagely by using the symmetric micro-channel network; complete mixing based on molecule diffusion is realized in the zigzag channels; and through a repeated dividing-mixing process, an initial solution is diluted into a solution with gradient distributed concentration. According to the dilution device, the using amount of test samples is small, the space is saved, and series concentration is generated quickly and stably.

Description

technical field [0001] The invention belongs to the field of chemical analysis, and in particular relates to a solution gradient dilution device for a microfluidic chip. Background technique [0002] In chemical and biochemical experiments, gradient dilution is one of the most commonly used operations, especially in cytotoxicity analysis, gradient dilution operation is more important, in drug dose response experiments, it is necessary to prepare a series of linear dilution or logarithmic dilution The drug concentration generally needs to span 3-6 orders of magnitude. The conventional gradient dilution method requires precise metering and mixing of solutions. The operation is time-consuming and laborious, and it is easy to cause experimental errors and affect the accuracy of experimental results. [0003] The emergence of microfluidic technology provides a powerful means for gradient dilution operation. In the channel of the microfluidic chip, the two solutions can form a co...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): B01L3/00
Inventor 徐章润杨春光
Owner NORTHEASTERN UNIV LIAONING