CN112473758A

CN112473758A - Equivalent circuit micro-fluidic concentration gradient chip of simplified channel

Info

Publication number: CN112473758A
Application number: CN202011314734.9A
Authority: CN
Inventors: 石环环; 周亚诺; 张嘉豪; 袁霖; 余月华; 陶林节
Original assignee: Nanchang Hangkong University
Current assignee: Nanchang Hangkong University
Priority date: 2020-11-20
Filing date: 2020-11-20
Publication date: 2021-03-12

Abstract

The invention discloses an equivalent circuit micro-fluidic concentration gradient chip of a simplified channel, which comprises at least two liquid inlet holes, wherein the liquid inlet holes are used for being connected with a connecting channel, a flow resistance channel, a mixing channel and an outlet channel, and the mixing channel replaces a traditional linear mixing channel by a novel mixing channel with a transverse elliptical bulge structure, so that the mixing effect superior to that of the traditional method can be realized by only adopting the mixing length of one mixing period, and the structure of the whole micro-fluidic concentration gradient chip is simplified.

Description

Equivalent circuit micro-fluidic concentration gradient chip of simplified channel

Technical Field

The invention belongs to the technical field of microfluidic chips, and particularly relates to an equivalent circuit microfluidic concentration gradient chip with a simplified channel.

Background

Concentration gradients are widely used in high throughput drug screening, chemotaxis assays, and toxicity evaluation, and in macroscopic devices it is difficult to maintain a stable concentration gradient over time due to the fluid flow characteristics making it difficult to maintain stability over time. The micro-fluidic chip technology well solves the problem, and a stable concentration gradient can be formed in a micro-channel of dozens to hundreds of micrometers based on the mixing and diffusion principle of laminar flow liquid in the micro-fluidic channel. The most classical microfluidic concentration gradient chip design is the christmas tree model proposed by the teachings of Whitesides of harvard university, which achieves concentration gradients step by layer through the layer-by-layer diffusion and mixing of samples and diluents within microchannels. The type of the obtained concentration gradient, such as linear, power index and the like, can be adjusted by controlling the inlet flow rate ratio so as to meet the application requirements of different types. However, since the liquid mixing in the microchannel is based on mixing diffusion, it is known from the calculation formula of peclet number that the distance of fluid flow in the time required for the components to diffuse to the entire width of the microchannel is very long, which means that a very lengthy microchannel network is required for the formation of a concentration gradient. This undoubtedly increases the pressure drop in the microchannel, reduces the liquid inlet speed, and limits the application scenarios.

Therefore, in order to reasonably design a microfluidic micro-channel network, in the years, other various methods (a node analysis method, an equivalent circuit method, a bonding graph method, a Petri network method and a neural network method) are adopted for designing a microfluidic chip system. The equivalent circuit method is most widely applied to the design of a concentration gradient chip, flow resistance in a micro-channel is equivalent to resistance in a circuit, flow is equivalent to current, a series of equation sets are obtained based on kirchhoff current and a voltage law, resistance values in the equation sets are finally solved, and therefore the flow resistance values are obtained in an equivalent mode, and the length of the needed micro-channel is calculated. However, the resulting hybrid diffusion channel is still long, as calculated by conventional methods, which greatly increases the difficulty of chip processing and limits its degree of integration. However, the length of the mixed diffusion channel has a direct relationship with the lengths of the mixed channel and the connecting channel in the concentration gradient chip network, and if the length of the mixed channel can be reduced, the length of the mixed diffusion channel calculated according to a corresponding formula is also greatly reduced.

The patent ZL201621081990.7 granted by the applicant proposes that the laminar mixing efficiency under the condition of low reynolds number can be improved by adding a semicircular convex structure on the side wall of the square wave type micro mixer, and further inducing the secondary flow phenomenon by the structure. Compared with a common square wave mixing channel, the mixing device realizes the same mixing efficiency, and the mixing length of the mixing device is only one third of the original mixing length. Therefore, if the mixing channel is introduced into the equivalent circuit microfluidic network, the length of the mixing diffusion channel is greatly shortened, and the original microfluidic channel network is simplified.

Disclosure of Invention

The invention aims to solve the technical problem of providing a simplified and effective concentration gradient chip aiming at the defect of long channel of the existing equivalent circuit microfluidic concentration gradient chip.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows: the liquid inlet comprises at least two liquid inlets, a first inlet channel and a second inlet channel, wherein the first inlet channel and the first outlet are communicated directly through a first flow resistance channel, the second inlet channel and the outlet channel are communicated directly through a second flow resistance channel, the first inlet channel is connected with a first connecting channel and a second inlet channel through a first channel, the first channel is divided into a first flow resistance channel, a second flow resistance channel and a third flow resistance channel, the first channel is led out of a fourth flow resistance channel through a second connecting channel, the first flow resistance channel, the second flow resistance channel, the third flow resistance channel and the fourth flow resistance channel are connected in pairs through the first connecting channel to realize that the four channels are communicated, and the first flow resistance channel, the second flow resistance channel, the third flow resistance channel and the fourth flow resistance channel are communicated with the second outlet through a mixing channel, The third outlet, the fourth outlet and the fifth outlet are connected in sequence, and outwards convex ellipses are distributed on two sides of the mixing channel in a staggered mode to form a micro-mixing channel.

Preferably, the micro-mixing channel has at least one square wave period.

Preferably, at least one protrusion is disposed on both sides of each mixing channel, and the protrusions are distributed in a staggered manner.

Preferably, the width of each mixing channel is 50-200 microns, and the radius of each semicircular bulge is 50-100 microns, so that the overall mixing efficiency is further improved.

Preferably, the etching depth of the mixing channel is 50-200 microns, so that the micro-mixing channel can be etched by a simple etching process.

Preferably, the number of the liquid inlets is two, the two liquid inlets are respectively arranged on two sides of the inlet channel and are respectively communicated with the first inlet channel and the second inlet channel.

Preferably, the first outlet, the outlet channel, the second outlet, the third outlet, the fourth outlet and the fifth outlet are all communicated with other connecting channels.

Compared with the prior art, the invention has the following beneficial effects: because the two sides of the mixing channel are provided with the semicircular bulges to generate dean vortex, change the direction of liquid and further generate secondary flow to disturb laminar flow liquid, promote diffusion between laminar flows and further promote mixing, the invention can obviously shorten the length of the mixing diffusion channel in the concentration gradient chip, especially can simplify the cost in the design and preparation of the concentration gradient, reduce the pressure drop and further reduce the problem of liquid loss.

Drawings

FIG. 1 is a schematic plan view of a simplified equivalent circuit concentration gradient chip according to the present invention;

FIG. 2 is a schematic diagram of a simplified equivalent circuit concentration gradient chip according to the present invention;

FIG. 3 is the outlet concentration distribution of the un-simplified equivalent circuit concentration gradient chip at different inlet speeds;

FIG. 4 is the outlet concentration distribution of the simplified equivalent circuit concentration gradient chip of the present invention at different inlet velocities;

FIG. 5 is an equivalent circuit diagram of an equivalent circuit concentration gradient chip design;

FIG. 6 is a cloud of concentration profiles under optimized conditions for an unreduced equivalent circuit concentration gradient chip;

FIG. 7 is a simplified cloud diagram of the concentration profile of an equivalent circuit concentration gradient chip under optimized conditions;

FIG. 8 is a cloud diagram (in pascal) of the feed pressure drop distribution of the simplified equivalent circuit concentration gradient chip of the present invention.

Description of reference numerals: the first flow resistance channel comprises a first inlet channel 1, a second inlet channel 2, a mixing channel 3, a first connecting channel 4, a first outlet 5, a second outlet 6, a third outlet 7, a fourth outlet 8, a fifth outlet 9, an outlet channel 10, a first flow resistance channel 11, a third flow resistance channel 12, a fourth flow resistance channel 13, a fifth flow resistance channel 14, a second flow resistance channel 15, a first channel 16, a second connecting channel 17 and a sixth flow resistance channel 18.

Detailed Description

The first embodiment is as follows:

design for simplifying equivalent circuit concentration gradient to form micro-channel network (taking double concentration gradient as an example)

Firstly, the two times concentration gradient chip designed in the traditional mode is realized by adopting an equivalent circuit method to verify the effectiveness of the method, as shown in fig. 5, according to the principle of the equivalent circuit method design, the chip is provided with two inlets which are respectively a sample inlet and a diluent inlet (the flow of the sample inlet is named as Q)_SampleThe inlet flow of the diluent is named as Q_Buffer) Six outlets (named as C according to the concentration from low to high in sequence)₀-C₅) The flow resistance of the liquid mixing channel is named R_MixingThe flow resistance of the connecting channel is named R_connect. Known as R_Mixing＝x，R_connectY, R needs to be solved₀-R₈Expression of (2), double concentration gradient outlet concentration C₀＝0,C₁＝0.0625,C₂＝0.125,C₃＝0.25,C₄＝0.5,C₅＝1,Q₀＝Q₁＝Q₂＝Q₃＝Q₄＝Q₅A. Q represents the flow rate of each channel, as shown in FIG. 3.

According to Kirchhoff's Current Law (KCL):

the entrance node satisfies:

Q_Buffer＝Q_R,0+Q_L,0

Q_Sample＝Q_R,4+Q₅

Q_Buffer+Q_Sample＝Q₀+Q₁+Q₂+Q₃+Q₄+Q₅

Q₀＝Q_L,0＝Q_Buffer-Q_R,0

Q₁＝Q_L,1+Q_R,1

Q₂＝Q_L,2+Q_R,2-Q_R,1

Q₃＝Q_L,3+Q_R,3-Q_R,2

Q₄＝Q_L,4+Q_R,3-Q_R,3

Q₅＝Q_Sample-Q_R,4

Q_R,0＝Q_L,1+Q_L,2+Q_L,3+Q_L,4

due to the two-fold dilution, C₀＝0,C₁＝1/2C₂,C2＝1/2C₃,C₃＝1/2C₄,C₄＝1/2C₅,C ₅1 is as follows

Q_L,1＝Q_R,1＝0.5Q₁

Q_L,2＝Q_R,2＝0.5(Q_R,1+Q₂)＝0.75Q₁

Q_L,3＝Q_R,3＝0.5(Q_R,2+Q₃)＝0.875Q₁

Q_L,4＝Q_R,4＝0.5(Q_R,3+Q₄)＝0.9375Q₁

According to Kirchhoff's Voltage Law (KVL):

1.R₀*Q_L,0＝Q_R,0*R_c+Q_R,1*R₆+Q₁*R₁

2.R₆*Q_L,1＝Q_L,2*R₇+(Q_L,2+Q_R,2)*R_m+Q_R,1*R_c

3.R₇*Q_L,2＝Q_L,3*R₈+(Q_L,3+Q_R,3)*R_m+Q_R,2*R_c

4.R₈*Q_L,3＝Q_L,4*R₉+(Q_L,4+Q_R,4)*R_m+Q_R,3*R_c

5.R₂*Q₂＝Q₁*R_m+Q_R,1*R_c＝x+0.5y

6.R₃*Q₃＝Q_R,2*R_c+(Q_L,2+Q_R,2)R_m+Q₂*R₂＝2.5x+1.25y

7.R₄*Q₄＝Q_R,3*R_c+(Q_L,3+Q_R,3)R_m+Q₃*R₃＝4.25x+2.125y

8.R₅*Q₅＝Q_R,4*R_c+(Q_L,4+Q_R,4)R_m+Q₄*R₄＝6.125x+3.0625y

Q_Buffer＝4.0625Q₁,Q_Sample＝1.9375Q₁

from the above equation, the ratio of the diluent to the sample inlet flow is about 2. As can be seen from a number of numerical simulations, the length of the mixing channel is typically set at 12mm, the length of the connecting channel at 4mm, and R₉By combining the kirchhoff current and voltage equations described above, the expression for each flow resistance can be solved as shown in the following table. The patent ZL201621081990.7 granted by the applicant proposes that the laminar mixing efficiency under the condition of low reynolds number can be improved by adding a semicircular convex structure on the side wall of the square wave type micro mixer, and further inducing the secondary flow phenomenon by the structure. Compared with a common square wave mixing channel, the mixing device realizes the same mixing efficiency, and the mixing length of the mixing device is only one third of the original mixing length. Therefore, if the mixing channel is introduced into the equivalent circuit microfluidic network, the length of the mixing diffusion channel is greatly shortened, and the original microfluidic channel network is simplified.

Example two: comparison of concentration gradient formation before and after simplification and stability optimization condition analysis

In order to verify the effectiveness of the designed equivalent circuit microfluidic network before and after simplification, the present example aims at twice dilution, and tests the effect of twice concentration gradient. As shown in fig. 4, the concentration ratios produced at the six outlets were 0,0.0625,0.125,0.25,0.5,1, in that order. The microfluidic network was designed in example 1 without simplification. According to the results obtained in the examples, the ratio of the inlet flow rates of the diluent and the sample was about 2, therefore, FIG. 3 selects a plurality of sets of the ratio of the double flow rate (120-60,60-30,30-15, 15-7.5. mu.l/min), and it can be seen from the computational fluid dynamics simulation results that the concentration output results obtained when the inlet flow rates of the diluent and the sample are 60-30. mu.l/min, respectively, are closest to the target concentration (the simulated concentration distribution cloud is shown in FIG. 6). Therefore, as can be seen from this embodiment, the chip designed in embodiment 1 conforms to the design principle of the equivalent circuit, and the validity of the method is verified.

Subsequently, a computational fluid dynamics simulation (shown in fig. 4) was performed under the same conditions using a simplified microfluidic network, and the concentration output results obtained were closest to the target concentrations when the inlet flow rates of the diluent and the sample were 60-30 μ l/min, respectively. 0,0.0625,0.125,0.25,0.5,1, the concentration obtained is very close to the dilution concentration twice of the target output, therefore, the simplified chip designed by the method is proved to be consistent with the design result, and the concentration distribution output with the same effect can be realized on the basis of the simplified network (the concentration distribution cloud graph obtained by simulation is shown in figure 7).

It can be known by comparing the distribution of the concentration cloud charts before and after simplification (fig. 6 and 7), laminar flow liquid is still difficult to mix in the mixing channel in the model which is not simplified, the laminar flow phenomenon is obvious, however, after the simplified mixing channel is adopted, sufficient liquid mixing can be realized only by 1/3 with the original length, which is undoubtedly significant for simplifying the channel network, and the pressure drop of the inlet liquid can be controlled under a reasonable condition, as shown in fig. 8 (unit is pascal).

Claims

1. The utility model provides a simplify micro-fluidic concentration gradient chip of equivalent circuit of passageway which characterized in that: the invention comprises at least two liquid inlets, a first inlet channel (1) and a second inlet channel (2) which are communicated with the liquid inlets, wherein the first inlet channel (1) and a first outlet (5) are directly communicated through a first flow resistance channel (11), the second inlet channel (2) and an outlet channel (10) are directly communicated through a second flow resistance channel (15), the first inlet channel (1) is connected with a first connecting channel (4) and a second inlet channel (2) through a first channel (16), the first channel (16) is divided into a third flow resistance channel (12), a fourth flow resistance channel (13) and a fifth flow resistance channel (14), the first channel (16) is led out of the fourth flow resistance channel (18) through a second connecting flow resistance channel (17), the third flow resistance channel (12), the fourth flow resistance channel (13), the fifth flow resistance channel (14) and the sixth flow resistance channel (18) are connected in pairs through the first connecting channel (4), the third flow resistance channel (12), the fourth flow resistance channel (13), the fifth flow resistance channel (14) and the sixth flow resistance channel (18) are sequentially connected with the second outlet (6), the third outlet (7), the fourth outlet (8) and the fifth outlet (9) through a mixing channel (3), outwards-convex ellipses are distributed on two sides of the mixing channel (3) in a staggered mode to form a micro-mixing channel, and the micro-mixing channel is provided with at least one square wave period.

2. The equivalent circuit microfluidic concentration gradient chip of claim 1, wherein: at least one bulge is arranged on each of the two sides of the mixing channel (3), and the bulges are distributed in a staggered manner.

3. The equivalent circuit microfluidic concentration gradient chip of claim 1, wherein: the width of each mixing channel (3) is 50-200 microns, and the radius of the semicircular bulge is 50-100 microns.

4. The equivalent circuit microfluidic concentration gradient chip of claim 1, wherein: the etching depth of the mixing channel (3) is 50-200 microns.

5. The simplified-channel equivalent-circuit microfluidic concentration gradient chip according to any one of claims 1-4, wherein: the mixing channel (3) can shorten the mixing distance so as to simplify the design of the whole equivalent circuit microfluidic concentration gradient chip.

6. The simplified-channel equivalent-circuit microfluidic concentration gradient chip according to any one of claims 1-4, wherein: the equivalent circuit microfluidic concentration gradient chip is suitable for simplified application of a plurality of concentration dilution chips with at least double concentration dilution and cross-order dilution.