JP2018071980A - Microchannel device and micro fluid feeding method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microchannel device which can ensure feeding and feeding stop of a micro fluid to a branch flow channel.SOLUTION: In a microchannel device 1, y≥-0.013x1+2.3, y≥0.5, x1≤180° and y≤1.5 are satisfied when an angle A is defined as x1 and y≥0.033x2-0.5, y≥0.5, x2≤105° and y≤1.5 are satisfied when an angle B is defined as x2, wherein the ratio of a cross sectional area of a fifth microchannel to a cross section area of a fourth microchannel is defined as a channel cross sectional area ratio y, an angle of the extending direction of the fourth microchannel relative to the extending direction of a third microchannel is defined as the angle A, and an angle of the extending direction of the fifth microchannel relative to the extending direction of the third microchannel is defined as the angle B.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a microchannel device provided with a plurality of microchannels for feeding a plurality of microfluids, and a method of feeding a microfluid using the microchannel device.

  Conventionally, various microchannel devices using microfluids have been proposed for biochemical analysis and the like. In the microchannel device, a microfluid is sent through the microchannel. Various valves and the like have been proposed for on / off and switching of the liquid feeding.

  In Patent Document 1 below, a groove for forming a micro flow path is formed in a substrate made of silicone rubber. This groove is sealed with another sheet to form a microchannel. By pressing this substrate, the microchannel is closed.

  In the following Patent Document 2, a micro flow path is formed between two plate-like members. On this plate-like member, a blade projecting toward the microchannel is provided. The microchannel is closed by moving the blade by the blade actuator and pressing the plate-like member.

JP 2002-219697 A Special table 2000-508058 gazette

  In the microchannel device described in Patent Document 1 or Patent Document 2, the microchannel is closed by pressing a substrate or a plate-like member. With such a structure, even if the liquid feeding of the microfluid is turned on / off, the microfluid may enter an undesired branch channel or the like.

  An object of the present invention is to provide a microfluidic device and a microfluidic liquid feeding method that can reliably perform the feeding of a microfluid to a branching channel and the stopping of the feeding.

  The microchannel device of the present invention is a microchannel device in which a plurality of microchannels are provided in a microchannel chip, wherein the plurality of microchannels are first to fifth microchannels. A downstream end portion of the first microchannel and a downstream end portion of the second microchannel, and the first microchannel and the second microchannel The third micro-channel where the micro-channel is joined is connected, and the downstream end of the third micro-channel branches into the fourth and fifth micro-channels The ratio of the area of the cross section of the fifth microchannel to the area of the cross section of the fourth microchannel is the channel cross-sectional area ratio y, and the direction in which the third microchannel extends With respect to the direction in which the fourth microchannel extends. A, where an angle formed by the extending direction of the fifth microchannel with respect to the extending direction of the third microchannel is an angle B, where the angle A is x1, y ≧ −0.013 × 1 + 2.3 ( However, 60 degrees ≦ x1 ≦ 135 degrees), y ≧ 0.5 (however, 135 degrees ≦ x1 ≦ 180 degrees), x1 ≦ 180 degrees (where 0.5 ≦ y ≦ 1.5) and y ≦ 1. 5 (60 ≦ x1 ≦ 180 degrees), and when angle B is x2, y ≧ 0.033x2-0.5 (30 degrees ≦ x2 ≦ 60 degrees), y ≧ 0.5 ( However, 30 degrees ≦ x2 ≦ 105 degrees), x2 ≦ 105 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 degrees ≦ x2 ≦ 105 degrees).

  In a specific aspect of the microchannel device according to the present invention, the microchannel device further includes first and second on-off valves respectively provided at downstream ends of the fourth and fifth microchannels. ing.

  In another specific aspect of the microchannel device according to the present invention, the first and second microfluids are respectively introduced or included in the first and second microchannels. Two microfluidic supply units are provided.

  In still another specific aspect of the microchannel device according to the present invention, the first and second microchannels are provided on the upstream side of the first and second microfluidic supply units. First and second pumps are further provided.

  In another specific aspect of the microchannel device according to the present invention, in the first and second microchannels, the first and second microchannel devices are located upstream of the first and second microfluid supply units. A pump connection portion to which an external pump is connected is provided in the two micro flow paths.

  The microfluidic feeding method according to the present invention is a first and second microfluidic feeding method in a microchannel device configured according to the present invention, wherein the first microchannel and the first A step of feeding the microfluid to the fourth microchannel so as not to reach the fifth microchannel, and the second microfluid from the second microchannel. And a step of feeding the liquid to the fifth microchannel so as not to reach the fourth microchannel.

  In a specific aspect of the microfluidic liquid feeding method according to the present invention, the microchannel device includes the first and second valves, and the first microchannel is connected to the first microchannel. When the fluid is sent, the second valve is closed, the first valve is opened, and when the second microfluid is sent, the first valve is closed. And the second valve is opened.

  According to the microchannel device and the microfluidic liquid feeding method according to the present invention, the liquid feeding from the third microchannel to the fourth microchannel or the fifth microchannel is turned on / off. At this time, the microfluid can be reliably sent to one of the fourth microchannel and the fifth microchannel, and the intrusion into the other microchannel can be reliably suppressed.

1 is a schematic configuration diagram of a microchannel device according to a first embodiment of the present invention. It is a figure which shows the relationship between the angle A in the microchannel device of 1st Embodiment, and a channel cross-sectional area ratio. It is a figure which shows the relationship between the angle A and flow-path cross-sectional area ratio. It is a figure which shows the relationship between the angle B and flow-path cross-sectional area ratio. It is a figure which shows the relationship between the angle B and flow-path cross-sectional area ratio.

  Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.

  FIG. 1 is a schematic configuration diagram of a microchannel device according to an embodiment of the present invention.

  The microchannel device 1 has a chip body 2. The chip body 2 is not particularly limited, but is made of a synthetic resin in the present embodiment. Specifically, the chip body 2 may be composed of a laminate of a plurality of synthetic resin plates. Or you may use the laminated body formed by laminating | stacking synthetic resin on the at least single side | surface of the injection molded product of a plate-shaped synthetic resin.

  The illustrated microchannel structure is provided in the chip body 2. This microchannel structure has first to fifth microchannels 11 to 15. The downstream end portion of the first microchannel 11 and the downstream end portion of the second microchannel 12 are joined. The third microchannel 13 is connected to this junction. That is, the third microchannel 13 is connected to the downstream end portions of the first and second microchannels 11 and 12. The downstream end of the third microchannel 13 is branched into fourth and fifth microchannels 14 and 15. That is, the fourth and fifth microchannels 14 and 15 are connected to the downstream end of the third microchannel 13. In FIG. 1, the branch portion is indicated as a branch point O.

  The first microchannel 11 and the second microchannel 12 are provided with first and second microfluid supply units 11a and 12a. In the present embodiment, the first and second microfluid supply units 11a and 12a contain the first and second microfluids in advance. But you may be comprised so that the 1st, 2nd microfluid may be introduce | transduced into the 1st, 2nd microfluid supply part 11a, 12a from the outside.

  In the first and second microchannels 11 and 12, pumps 16 and 17 are disposed upstream of the first and second microfluidic supply portions 11a and 12a. The pumps 16 and 17 include a gas generating material that generates a gas for feeding a microfluid. However, the pumps 16 and 17 may be other types of microfluidic liquid feeding pumps. In this embodiment, the pumps 16 and 17 are built in the chip body 2. However, the pump 16 is disposed outside the chip body 2 and connected to the first and second microchannels 11 and 12. May be.

  In the case of a pump arranged outside the chip body 2, an infusion pump using a syringe or other types of pumps may be used in addition to a pump containing a gas generating material.

  Note that the microfluid is a minute droplet having a volume of 1 to 500 μl. The microchannel is a channel through which such a microfluid is sent, and the microfluid is different from a normal liquid, depending on the surface tension of the microfluid and the wall surface of the microchannel, It has a different tolerance than normal liquids.

The cross-sectional areas of the first to fifth microchannels 11 to 15 are not particularly limited. However, since the microfluid is supplied, the area is about 0.01 to 2.0 mm ^2. Yes.

  The angle formed by the direction E in which the fourth microchannel 14 extends with respect to the direction C in which the third microchannel 13 extends is defined as an angle A, the direction C in which the third microchannel 13 extends, and the fifth An angle formed with the direction D in which the microchannel 15 extends is defined as an angle B. The feature of the microchannel device 1 is that the angles A and B are within the following specific ranges.

  That is, when the angle A is x1, y ≧ −0.013 × 1 + 2.3 (provided that 60 degrees ≦ x1 ≦ 135 degrees), y ≧ 0.5 (where 135 degrees ≦ x1 ≦ 180 degrees), x1 ≦ 180 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 ≦ x1 ≦ 180 degrees).

  When angle B is x2, y ≧ 0.03x2-0.5 (provided 30 degrees ≦ x2 ≦ 60 degrees), y ≧ 0.5 (provided 30 degrees ≦ x2 ≦ 105 degrees), x2 ≦ 105 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 degrees ≦ x2 ≦ 105 degrees).

  Thereby, as will be described later, a process of reliably feeding the first microfluidic fluid to the fourth microchannel 14 so as not to reach the fifth microchannel 15 from the first microchannel 11; The second microfluid can be reliably fed from the second microchannel 12 to the fifth microchannel 15 without entering the fourth microchannel 14.

  In order to enable the liquid feeding, a first valve 18 is provided at the downstream end of the fourth microchannel 14. A second valve 19 is provided at the downstream end of the fifth microchannel 15.

  The first and second valves 18 and 19 are open / close valves that open or close the fourth and fifth microchannels 14 and 15. The structure of such an on-off valve is not particularly limited, and a method of sealing the flow path with a push pin can be used.

  The open state of the fourth microchannel 14 and the fifth microchannel 15 means that the microfluid can be sent to the fourth and fifth microchannels 14 and 15. The closed state refers to a state in which it is difficult for liquid supply of the microfluidic fluid to the fourth and fifth microchannels 14 and 15 to proceed.

  Next, a method for feeding a microfluid using the microchannel device 1 will be described.

  Although the first and second microfluids are not particularly limited, in the present embodiment, an aqueous solution containing a surfactant is used as the first microfluid. A cell-containing aqueous solution is used as the second microfluid. Thereby, the surfactant used for PCR and the cell-containing aqueous solution can be fed.

  First, the first valve 18 is opened and the second valve 19 is closed. In this state, the first microfluid contained in the first microfluidic supply section 11a is driven from the first microchannel 11 to the downstream side by driving the first pump 16. The microfluidic reaches the third microchannel 13 and reaches the branch point O. At the branch point O, since the angle A and the angle B are within the specific range, the first microfluid does not enter the fifth microchannel 15, and the fourth microchannel is surely obtained. Proceed to 14.

  Next, the first pump 16 is stopped, the first valve 18 is closed, and the second valve 19 is opened. Then, the second pump 17 is driven, and the second microfluid contained in the second microfluid supply section 12 a is sent from the second microchannel 12 to the third microchannel 13. Since the angle A and the angle B are within the specific range, the second microfluid does not enter the fourth microchannel 14 at the branch point O, and the fifth microfluidity is surely obtained. The liquid is sent to the flow path 15. After that, the second pump 17 is stopped. In this way, the first microfluid can be reliably stored in the fourth microchannel 14 and the second microfluid can be securely stored in the fifth microchannel 15.

  In particular, since the angle A and the angle B are within the specific range, the entry of the first microfluid into the fifth microchannel 15 side is reliably suppressed, and similarly the second Intrusion of the microfluid into the fourth microchannel 14 side is also reliably suppressed. Therefore, contamination of the first microfluid and the second microfluid is unlikely to occur.

  Next, when the angle A and the angle B are within the specific range, the first and second microfluids are fed to the fourth or fifth microchannels 14 and 15 as described above. This will be described with reference to FIGS.

  In this specification, the channel cross-sectional area ratio indicates the ratio of the cross-sectional area of the fifth micro-channel 15 to the cross-sectional area of the fourth micro-channel 14.

Example 1
As shown in Table 1 below, the microchannel device of Example 1 has an angle B of 45 degrees, an angle A of 60 degrees, a channel cross-sectional area ratio of 1.5, and a cross-sectional area of the fifth microchannel. 0.6 mm ² , the cross-sectional area of the fourth microchannel was 0.4 mm ² , the volume of the fifth microchannel was 10 μl, and the volume of the fourth microchannel was 20 μl.

(Examples 2-11 and Comparative Examples 1-11)
In Examples 2 to 11 and Comparative Examples 1 to 11, as shown in Table 1 and Table 2 below, the angle B was fixed at 45 degrees, and the angle A was different from that in Example 1. Further, the cross-sectional area of the fourth microchannel and the cross-sectional area of the fifth microchannel were changed.

  In Tables 1 and 2, the meanings of the evaluation symbols “◯”, “Δ”, and “X” are as follows.

◯: Indicates that no microfluid has entered the microchannel in the closed state.
(Triangle | delta): The state which the microfluid has penetrate | invaded only the length of 0-1 mm in the microchannel in a closed state is shown.
X: Indicates a state in which the microfluid has entered the microchannel in the closed state over a length exceeding 1 mm.

  In addition, when the fifth microchannel is in a closed state and the first microfluid is fed to the fourth microchannel before / in front of the evaluation symbols ○ / ○, Δ / Δ, × / Δ, etc. After /, the result when the fourth microchannel is closed and the second microfluid is sent to the fifth microchannel is shown.

  As is apparent from Tables 1 and 2, in Comparative Examples 1 to 11, when the first microfluid and / or the second microfluid is sent, the microfluid is not limited to the microchannel in the closed state. Can be seen. On the other hand, in Examples 1 to 11, it can be seen that the microfluid does not enter the microchannel in the closed state when supplying either the first microfluid or the second microfluid. .

(Examples 12 to 22)
As shown in Table 3 below, in Examples 12 to 22, the angle B is fixed to 90 degrees, and the angle A, the cross-sectional area of the fourth microchannel, and the cross-sectional area of the fifth microchannel are changed. It was.

  As is clear from Table 3, in Examples 12 to 22, the microfluid intrudes into the microchannel in the closed state when supplying either the first microfluid or the second microfluid. I understand that there is no.

(Examples 23 to 33)
As shown in Table 4 below, in Examples 23 to 33, the angle B is fixed to 105 degrees, and the angle A, the cross-sectional area of the fourth microchannel, and the cross-sectional area of the fifth microchannel are made different. It was.

  As apparent from Table 4, also in Examples 23 to 33, in any of the cases where the first and second microfluids are fed, the intrusion of the microfluid into the microchannel in the closed state is recognized. There wasn't.

(Examples 7, 34, 35 and Comparative Examples 12, 13)
As shown in Table 5 below, the angle B was fixed at 45 degrees and the angle A was fixed at 180 degrees, except that the volumes of the fourth microchannel and the fifth microchannel were changed.

  As is apparent from Table 5, in Comparative Examples 12 and 13, when the second microfluid was fed or when the first and second microfluids were fed, entry into the closed microchannel was recognized. It was. On the other hand, in Examples 7, 34, and 35, infiltration of the microfluid into the microchannel in the closed state was not recognized when any of the first and second microfluids was fed.

  FIG. 2 is a plot of the results shown in Tables 1-5 above. That is, the relationship between the angle A and the channel cross-sectional area ratio when the angle B is fixed is shown.

  In FIG. 2, the embodiment is indicated by black dots. Moreover, about a comparative example, it shall show with a black dot smaller than an Example.

  As is clear from FIG. 2, if the angle A and the channel cross-sectional area ratio are within a specific range, the first and second microfluids enter the microchannel in the closed state as described above. It can be seen that this can be prevented. That is, it can be seen that the first and second microfluids can be prevented from entering the closed microchannel within the region indicated by the solid line F in FIG. A solid line F and a straight line F1 extending in an oblique direction in FIG. 2 correspond to portions where Examples 1, 5, 8, 9, 10, and 11 shown in Table 6 below are located.

  This is shown enlarged in FIG. That is, the straight line F1 is represented by y = −0.013 × 1 + 2.3, where the angle A is x1 and the channel cross-sectional area ratio is y.

  Accordingly, the area indicated by the solid line F in FIG. 2 is, as described above, y ≧ −0.013 × 1 + 2.3 (60 degrees ≦ x1 ≦ 135 degrees), y ≧ 0.5 (however, 135 degrees ≦ x1 ≦ 180 degrees), x1 ≦ 180 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 ≦ x1 ≦ 180 degrees).

(Examples 36 to 44 and Comparative Examples 14 to 23)
As shown in Table 7 and Table 8 below, the angle A was fixed at 180 degrees, and the angle B, the cross-sectional area of the fourth microchannel, and the cross-sectional area of the fifth microchannel were varied.

  As is clear from Tables 7 and 8, in Comparative Examples 14 to 23, when the first microfluid and / or the second microfluid was sent, the intrusion of the microfluid into the microchannel in the closed state occurred. Admitted.

  On the other hand, in Examples 36 to 44, intrusion of the microfluid into the microchannel in the closed state was not observed at the time of feeding any of the first and second microfluids.

(Examples 45-53)
As shown in Table 9 below, the angle A was fixed at 135 degrees, and the angle B, the cross-sectional area of the fourth microchannel, and the cross-sectional area of the fifth microchannel were varied.

  As is clear from Table 9, also in Examples 45 to 53, when the first and second microfluids are fed, the first and second microfluids enter the closed microchannel. I couldn't.

(Examples 54 and 55 and Comparative Examples 24 and 25)
As shown in Table 10 below, the angle B was fixed at 105 degrees and the angle A was fixed at 180 degrees, except that the volumes of the fourth and fifth microchannels were changed.

  As is apparent from Table 10, in Comparative Examples 24 and 25, when at least one of the first and second microfluids was fed, the intrusion of the microfluid into the microchannel in the closed state was observed.

  On the other hand, in Examples 40, 54, and 55, regardless of whether the first microfluid or the second microfluid is fed, the microfluid enters the microchannel in the closed state. Was not recognized.

  The results of Tables 7 to 10 are plotted in FIG. In FIG. 4, an example is shown with large black dots, and a comparative example is shown with small black dots. As is clear from FIG. 4, in the region surrounded by the solid line G, the microfluid to the microchannel in the closed state is sent regardless of whether the first or second microfluid is fed. It can be seen that the intrusion can be prevented.

  Of the solid line G, a straight line G1 extending in the oblique direction is a straight line connecting the positions of the thirty-sixth, thirty-six and thirty-first embodiments.

  When Examples 36, 38, and 41 shown in Table 11 are plotted, they are as shown in FIG. That is, when the angle B is x2, the flow path cross-sectional area ratio y is y = 0.0333x2 + 0.5. That is, the straight line G1 is represented by y = 0.0333x2 + 0.5.

  Therefore, the region surrounded by the straight line G in FIG. 4 has the following specific range when the angle B is x2.

  y ≧ 0.033x2-0.5 (provided 30 degrees ≦ x2 ≦ 60 degrees), y ≧ 0.5 (provided 30 degrees ≦ x2 ≦ 105 degrees), x2 ≦ 105 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 degrees ≦ x2 ≦ 105 degrees).

  Therefore, in the present invention, when the angle A and the angle B are within the specific ranges, the first and second microfluids can be reliably prevented from entering the closed microchannel. Can do.

DESCRIPTION OF SYMBOLS 1 ... Microchannel device 2 ... Chip body 11, 12 ... 1st, 2nd microchannel 11a, 12a ... 1st, 2nd microfluid supply part 13-15 ... 3rd-5th microchannel 16, 17 ... first and second pumps 18, 19 ... first and second valves

Claims (7)

A microchannel device in which a plurality of microchannels are provided in a microchannel chip,
The plurality of microchannels have first to fifth microchannels,
The downstream end of the first microchannel and the downstream end of the second microchannel are joined together,
The third micro-channel of the portion where the first micro-channel and the second micro-channel are merged is connected;
The downstream end portion of the third microchannel is branched into the fourth and fifth microchannels, and the fourth microstream having an area of a cross section of the fifth microchannel. The ratio of the cross-sectional area of the path to the cross-sectional area ratio y is defined as an angle A, the angle formed by the direction in which the fourth microchannel extends with respect to the direction in which the third microchannel extends. When the angle formed by the extending direction of the fifth microchannel with respect to the extending direction of the microchannel is defined as an angle B, the angle A is x1.
y ≧ −0.013 × 1 + 2.3 (provided that 60 degrees ≦ x1 ≦ 135 degrees), y ≧ 0.5 (provided that 135 degrees ≦ x1 ≦ 180 degrees), x1 ≦ 180 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 ≦ x1 ≦ 180 degrees),
When the angle B is x2,
y ≧ 0.033x2-0.5 (provided 30 degrees ≦ x2 ≦ 60 degrees), y ≧ 0.5 (provided 30 degrees ≦ x2 ≦ 105 degrees), x2 ≦ 105 degrees (provided that 0.5 ≦ y ≦ 1.5) and y ≦ 1.5 (provided that 60 degrees ≦ x2 ≦ 105 degrees).   2. The microchannel device according to claim 1, further comprising first and second open / close valves respectively provided at downstream ends of the fourth and fifth microchannels.   2. The first and second microfluidic supply sections are provided in the first and second microfluidic channels, respectively, for introducing or enclosing the first and second microfluids, respectively. 3. The microchannel device according to 2.   The said 1st, 2nd micro flow path is further equipped with the 1st, 2nd pump provided in the upstream rather than the said 1st, 2nd microfluid supply part. Microchannel device.   In the first and second micro-channels, a pump connection part in which an external pump is connected to the first and second micro-channels on the upstream side of the first and second micro-fluid supply units The microchannel device according to claim 1, wherein the microchannel device is provided. It is a liquid feeding method of the 1st, 2nd microfluidic in the microchannel device of any one of Claims 1-5, Comprising: Said 1st microfluidic from said 1st microchannel, Feeding the liquid to the fourth microchannel so as not to reach the fifth microchannel;
Feeding the second microfluidic fluid from the second microfluidic channel to the fifth microfluidic channel so as not to reach the fourth microfluidic channel. Liquid method. The microchannel device has the first and second valves, and when the first microfluid is fed from the first microchannel, the second valve is closed. The first valve is opened,
The liquid feeding method according to claim 6, wherein when the second microfluid is fed, the first valve is closed and the second valve is opened.

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