JP6554077B2 - Microfluidic merging method - Google Patents

Description

  The present invention relates to a microchannel chip in which a microchannel and a merging portion are provided, and a microfluidic merging method using the microchannel chip.

  Conventionally, various microchannel chips provided with microchannels have been proposed. For example, in the microchannel chip described in Patent Document 1 below, a plurality of microchannels are connected to the junction. In order to align the timing for sending the microfluid from the plurality of microchannels to the junction, the inner surface of the microchannel is surface-treated before the junction.

Japanese Patent No. 3793433

  In the case of combining a plurality of microfluidics in a microchannel chip, it is required that the contact timings of the tips in the liquid transfer direction of the plurality of microfluidics coincide with each other. If this timing deviates even slightly, there is a risk that air bubbles may be caught. When bubbles are involved, there is a risk of adverse effects on liquid feeding timing, diffusion and mixing between a plurality of microfluids, and reactions generated by merging.

  In the microchannel chip described in Patent Document 1, the timing of arrival at the junction is matched by applying surface treatment to a plurality of microchannels. However, it has been difficult to accurately adjust the timing. Further, in order to accurately match the timing, the surface treatment has to be performed with high accuracy, and the accuracy has to be improved when forming a plurality of microchannels. Therefore, there is a problem that the manufacturing cost of the microchannel chip becomes high.

  An object of the present invention is to provide a microfluidic chip and a microfluidic merging method using the microfluidic chip, in which a plurality of microfluids can be merged and the manufacturing cost can be reduced.

  The microchannel chip according to the present invention includes a chip body having a microchannel, a first microfluid, and a merging portion where the second microfluid merges, and the microchannel includes the merging portion. An inlet-side microchannel for feeding the first microfluid and the second microfluid, and an outlet-side microchannel for feeding the microfluid joined at the junction, The one side and the other side of the merging portion are asymmetric in at least one of the space shape and the state with a virtual line extending in the direction in which the first microfluid flows into the merging portion as a boundary.

  In a specific aspect of the microchannel chip according to the present invention, the one side of the merging portion and the other side of the merging portion are asymmetric in the shape of the space.

  In another specific aspect of the microchannel chip according to the present invention, the size of the space between the one side of the junction and the other side of the junction is different. In this case, it is possible to easily stop the first microfluidic at the junction simply by varying the size of the space.

  In still another specific aspect of the microchannel chip according to the present invention, angles formed by an end edge of the confluence portion where the virtual line intersects and the virtual line are on one side and the other side of the virtual line. Is different. In this case, the first microfluid can be surely stopped at the joining portion only by setting the angle formed between the edge of the joining portion and the virtual line as described above.

  In still another specific aspect of the microchannel chip according to the present invention, an angle formed between an edge of the merging portion and the virtual line is an acute angle on one side of the virtual line and an obtuse angle on the other side. .

  In still another specific aspect of the microchannel chip according to the present invention, in the merging portion, the liquid transfer of the microfluidic is inhibited on at least one of the one side of the virtual line and the other side of the merging portion. Spacers are provided.

  In another specific aspect of the microchannel chip according to the present invention, the roughness of the inner surface of the merging portion is different between the one side of the merging portion and the other side of the merging portion. That is, the first microfluid can be surely stopped first at the junction by simply varying the roughness as the state at the junction.

  In another specific aspect of the microchannel chip according to the present invention, the temperature is different between the one side of the merging portion and the other side of the merging portion. Thus, the state of being asymmetric at the junction may be temperature.

  In another specific aspect of the microchannel chip according to the present invention, the contact angle with respect to water is different between the one side of the merging portion and the other side of the merging portion.

  In yet another specific aspect of the microchannel chip according to the present invention, the inlet-side microchannel is a first inlet-side microchannel for transferring the first microfluidic fluid; and the second inlet-side microchannel And a second inlet-side microchannel for feeding the microfluidic fluid.

  In the microchannel chip according to the present invention, the inlet-side microchannel is the same, and the first microfluid and the second microfluid are fed from a single inlet-side microchannel to the junction. May be.

  In still another specific aspect of the microchannel chip according to the present invention, the inlet-side microchannel includes a first upstream microchannel portion and a second upstream microchannel portion; One end is connected to the downstream end of 2 upstream microchannel parts, and the other end has a confluence | merging microchannel part connected to the said junction part.

  In still another particular aspect of the micro-channel chip according to the present invention, the temperature control is performed to adjust the temperature of at least one of the one side and the other side of the virtual line, which is fixed to the chip body A device is further provided.

  A method of combining microfluidics according to the present invention is a method of combining microfluidics using a microchannel chip configured according to the present invention, wherein the first microfluidic fluid is joined to the junction from the inlet-side microchannel Transferring the second micro fluid to the merging portion and combining the second micro fluid with the first micro fluid; Prepare.

  In a specific aspect of the method for combining microfluidics according to the present invention, the first micro fluid is transported to the side of the merging portion by using a gas in the inlet-side microchannel, thereby forming the first micro Fluid is sent to the junction, and the gas is overtaken by the first microfluid at the junction to stop the first microfluid.

  According to the micro-channel chip and the method for combining microfluidics according to the present invention, in the merging portion, the first micro fluid is first sent and stopped, and in this state, the second micro fluid is merged in the merging portion Can be made. Thus, the first microfluidic and the second microfluidic can be merged. In addition, since it is only necessary to have an asymmetric structure in at least one of the space shape and the state at the junction, the cost of the microchannel chip can be reduced.

It is a sectional view for explaining a microchannel chip concerning a 1st embodiment of the present invention. The microchannel chip of 1st Embodiment, It is sectional drawing which shows the state which liquid-fed the 1st microfluidic to a confluence | merging part, and stopped. In the microchannel chip of the first embodiment, it is a cross-sectional view showing a state in which a second microfluid is joined to a first microfluid and mixed. It is a schematic diagram for demonstrating the structure of the microchannel chip which concerns on 2nd Embodiment. It is a schematic diagram for demonstrating the structure of the microchannel chip which concerns on 3rd Embodiment. It is a schematic diagram for demonstrating the structure of the microchannel chip which concerns on 4th Embodiment. It is a schematic diagram for demonstrating the structure of the microchannel chip which concerns on 5th Embodiment. It is a schematic diagram for demonstrating the structure of the microchannel chip which concerns on 6th Embodiment. It is a schematic diagram which shows the microchannel chip which concerns on the 7th Embodiment of this invention.

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

  FIG. 1 is a cross-sectional view for explaining a microchannel chip according to a first embodiment of the present invention. The microchannel chip 1 has a chip body 2. The chip body 2 is made of, but not limited to, a synthetic resin. As the synthetic resin, various resins such as polyolefin such as polypropylene, (meth) acrylic resin, and cycloolefin resin can be used. Preferably, it is desirable to use a translucent resin. In that case, by the light irradiation, a reaction by optical measurement or light irradiation can be generated in the microchannel or the junction.

  Preferably, the chip body 2 is made of a synthetic resin injection-molded product. In that case, the mass productivity can be enhanced and the cost can be further reduced.

  In the chip body 2, a microchannel and a merging portion 4 are provided. As the micro channel, a first upstream micro channel unit 3a, a second upstream micro channel unit 3b, and an outlet side micro channel 3c are provided. The inlet-side microchannel is configured by the first upstream microchannel portion 3 a and the second upstream microchannel portion 3 b.

  The first upstream microchannel portion 3a and the second upstream microchannel portion 3b are provided for feeding the first and second microfluids, respectively. The planar shape of the merging portion 4 is rectangular. The junction 4 has a pair of inner walls 4a, 4b on the long side of the rectangle and a pair of inner walls 4c, 4d on the short side. The first upstream microchannel portion 3a is connected to the inner wall 4a. The second upstream microchannel portion 3b is connected to the inner wall 4c.

  The outlet-side microchannel 3c is connected to the inner wall 4d. The second upstream microchannel portion 3b and the outlet side microchannel 3c are connected in a straight line. The second upstream microchannel 3b and the outlet microchannel 3c are not necessarily in a straight line, but are preferably in a straight line. As a result, the mixed fluid after the merging can be quickly sent to the outlet-side microchannel 3c. As indicated by an arrow A from the first upstream microchannel portion 3a, the first microfluid is sent to the merging portion 4. On the other hand, in the second upstream microchannel portion 3b, as indicated by the arrow B, the second microfluid is sent toward the merging portion 4. A feature of the microchannel chip 1 is that when a virtual line extending in a direction in which the first microfluid flows into the merge part 4 is defined as a virtual line X, one side of the merge part 4 with the virtual line X as a boundary And the other side are asymmetric in the space shape. Thereby, the second microfluidic can be reliably joined to the first microfluidic without entraining air bubbles. This will be described with reference to FIGS. 2 and 3.

  In the method of combining microfluidics using the microchannel chip 1 of the present embodiment, as shown in FIG. 2, first, the first microfluidics 5 are joined from the first upstream microchannel portion 3 a to the merging portion. The liquid is fed toward 4. This liquid feeding is preferably performed by applying a gas from behind the first microfluid 5. A micropump that generates such gas is connected to the first upstream microchannel portion 3a. However, not only the micro pump, but using an appropriate device for pressing the first microfluidic 5 from the rear of the first microfluidic 5 in the first upstream microchannel portion 3 a as described above Can do.

  By being pushed by the gas, as shown in FIG. 2, the first microfluid 5 is fed into the merging portion 4 and accommodated in the merging portion 4. At this time, gas enters the junction 4 from behind the first microfluid 5. Therefore, as shown by arrow C in FIG. 2, the gas passes the first microfluidic fluid 5 and is discharged from the outlet-side microchannel 3c. As the gas overtakes the first microfluidic fluid 5, the movement of the first microfluidic fluid 5 is completed, and the first microfluidic fluid 5 stops. At this time, since one side and the other side of the merging portion 4 are asymmetric with respect to the imaginary line X, the first microfluid 5 is arranged so as to be biased toward one side with respect to the imaginary line X as described above. Will be stopped. Therefore, the gas overtakes and the position of the first microfluid 5 can be determined as described above.

  Next, in the method for merging microfluidics of the present embodiment, the second microfluid 6 is fed from the second upstream microchannel portion 3b. There is no particular limitation on the method of sending the second microfluidic 6. Preferably, a gas is used as well as the first microfluidic 5. In that case, the cost can be further reduced by using the same liquid feeding means for the first and second microfluids 5 and 6.

  In this case, as shown in FIG. 2, since the first micro fluid 5 is stopped in the merging portion 4, when the second micro fluid 6 is sent to the merging portion 4, air bubbles are generated when both are in contact with each other. It is difficult to involve. Therefore, as shown in FIG. 3, the mixed fluid 7 of the first and second microfluidics 5 and 6 is formed in the merging portion 4. Next, by supplying further gas from at least one of the first and second upstream microchannel portions 3a and 3b, the mixed fluid 7 can be discharged from the outlet microchannel 3c and collected. it can.

  Prior to recovery, the mixed fluid 7 may be heated in the junction 4 or a reaction may be caused in the mixed fluid 7. In addition, the characteristic etc. of the mixed fluid 7 may be measured at the merging portion 4. That is, the merging portion 4 can be used as a reaction cell or a measurement cell as described above.

  In the microchannel chip 1, as described above, the first microfluidic fluid 5 is first stopped in the merging portion 4, and in this state, the second microfluidic fluid 6 is fed to the merging portion 4. Contact with microfluidic 5. Therefore, it is not necessary to match the timings of liquid transfer of the first microfluidic 5 and the second microfluidic 6 with high accuracy. Therefore, the microchannel chip 1 can be manufactured inexpensively. Even in such a case, since one of the first microfluids 5 is stopped, it is difficult for bubbles to be involved at the time of merging.

  It is preferable that the volume of the confluence part 4 is 200% or more of the first microfluidic fluid 5 to be fed first. When it is 200% or more, the first microfluidic can be reliably stopped at the biased position. Also, the liquid transfer rate of the first microfluidic is not particularly limited, but is preferably 1 to 50 μL / s. In that case, it is possible to more reliably stop the first microfluidic at an asymmetric position.

  In the first embodiment, the shape of the space on one side and the other side of the merging portion 4 is different with the virtual line X as a boundary. That is, in the rectangular planar confluence 4, the direction formed by the first upstream microchannel portion 3 a intersecting the inner wall 4 a, that is, the angle between the virtual line X and the inner wall 4 a is an acute angle on the other side. The side was obtuse.

  Furthermore, the difference between the obtuse angle and the acute angle is preferably in the range of 10 ° to 170 °. However, in the present invention, the configuration in which one side and the other side of the merging portion are asymmetric is not limited to this.

  In the merging portion 4, one side and the other side may be different in the planar shape, but one side and the other side may be different in the height direction. For example, the height of the space may be different on one side of the merging portion 4.

  When the height of the space is made different between one side and the other side of the imaginary line X, the difference is preferably in the range of 0.1 to 5.0 mm. In addition, in the rectangular planar shape, when the depths are different on one side and the other side, the difference is preferably in the range of 1 to 20 mm.

  Hereinafter, second to seventh embodiments of the present invention will be described with reference to FIGS. 4 to 9. FIG. 4 is a schematic diagram of a microchannel and a merging portion in the microchannel chip according to the second embodiment. As shown in FIG. 4, in the second embodiment, the planar shape of the merging portion 11 is an L-shape. The merging portion 11 has an inner wall 11a to which the first upstream microchannel portion 3a is connected. The inner walls 11b and 11c are provided to face the inner wall 11a. The inner wall 11b and the inner wall 11c are parallel to each other and connected by the inner wall 11d. A pair of opposing inner walls 11e and 11f are provided. The inner wall 11 e connects the inner wall 11 a and the inner wall 11 c. The inner wall 11 f connects the inner wall 11 b and the inner wall 11 a. The second upstream microchannel portion 3b is connected to the inner wall 11f. The outlet-side microchannel 3c is connected to the inner wall 11e. Also in the present embodiment, the shapes of the space on one side and the other side of the merging portion 11 are different with the virtual line X described above as a boundary. Therefore, similarly to the first embodiment, after the first microfluid is sent to the junction 11 and stopped, the second microfluid can be sent to the junction 11 to be joined.

  In the third embodiment shown in FIG. 5, the surface of the merging portion 12 is roughened so that one side of the merging portion 12 is hatched with the virtual line X as a boundary. On the other hand, on the other side of the merging portion 12, the hatching is not applied, and the inner surface is a smooth surface. As described above, the surface state may be different between the one side and the other side of the merging portion 12 with the virtual line X as a boundary. Also in this case, the first micro fluid first introduced to the junction 12 is stopped at a position deviated with respect to the imaginary line X. Accordingly, the second microfluid can be fed to the merging section 12 and the first and second microfluids can be easily merged without including bubbles.

  The difference in surface smoothness is preferably in the range of 0.1 to 10 μm as the difference in surface roughness Ra in JIS B 0601-2001.

  In FIG. 5, the smoothness of the inner surface is different on one side and the other side of the merging portion 12, but the contact angles with respect to water may be different.

  The difference in the contact angle is not particularly limited, but is preferably in the range of 10 ° to 130 °.

  FIG. 6 is a schematic diagram illustrating a confluence portion and a microchannel of a microchannel chip according to the fourth embodiment of the present invention. In the merging portion 13, the shape of the space on one side and the other side of the merging portion 13 is symmetric with respect to the virtual line X. However, the temperature control device 14 is provided in the microchannel chip. The temperature control device 14 is located on one side of the merging portion 13 with respect to the virtual line X. One side is heated with respect to the virtual line X of the junction part 13 by the temperature control apparatus 14, and the temperature of the one side of the junction part 13 is made higher than the temperature of the other side. As described above, the temperature may be made different between one side and the other side of the imaginary line X, and both states may be made asymmetric.

  In addition, not only when raising temperature with the temperature control apparatus 14, you may lower temperature relatively conversely. As such a temperature control device 14, a thermistor or the like is preferably used for heating. Moreover, if a Peltier device is used, both heating and cooling can be performed.

  Further, the temperature control device 14 is not necessarily provided in the chip body in the microchannel chip, and may be fixed to the chip body.

  As mentioned above, when giving a temperature difference in one side and the other side of junction part 13, it is preferred that a temperature difference is the range of 0 ° C-140 ° C.

  FIG. 7 is a schematic view for explaining the merging portion and the microchannel in the microchannel chip according to the fifth embodiment of the present invention.

  The planar shape of the merging portion 16 is a rectangular shape with rounded corners. Thus, in the planar shape of the merging portion 16, the corner portion may be rounded.

  Further, the first upstream microchannel portion 3a and the second upstream microchannel portion 3b are joined before the joining portion 16 and are connected to the joining microchannel portion 3d. The merging microchannel portion 3 d is connected to the merging portion 16. In the present embodiment, the entrance-side microchannel includes the first upstream microchannel unit 3a, the second upstream microchannel unit 3b, and the merging microchannel unit 3d. Here, the first microfluid is first fed to the merging section 16 via the first upstream microchannel section 3a and the merging microchannel section 3d. Also in this embodiment, the shape of the space of the merging portion 16 is asymmetric between one side and the other side of the virtual line X. Therefore, as in the case of the first embodiment, the first micro fluid is stopped at the biased position at the junction 16. Next, the second microfluid is fed from the second upstream microchannel portion 3b to the merging portion 16 via the merging microchannel portion 3d. Therefore, similarly to the first embodiment, the first and second microfluids can be merged without involving bubbles.

  As in the present embodiment, the entrance-side microchannel connected to the junction 16 may be single. In addition, although the first and second upstream microchannel portions 3a and 3b are used in FIG. 7, the first micro fluid and the second micro fluid are used by using only the confluent microchannel portion 3d. It may be sent in order. That is, you may comprise the entrance side microchannel in this invention only by the confluence | merging microchannel part 3d.

  FIG. 8 is a schematic view showing the merging portion and the microchannel of the microchannel chip according to the sixth embodiment. As in the present embodiment, the planar shape of the merging portion 17 may be elliptical. That is, the planar shape of the merging portion 17 is not particularly limited, and may be another shape such as a triangle or a trapezoid in addition to an oval.

  FIG. 9 is a schematic view showing the merging portion and the microchannel of the microchannel chip according to the seventh embodiment. Here, the spacers 19 a and 19 b are provided in the rectangular merging portion 18. The spacers 19a and 19b have a columnar shape and are provided only on one side of the virtual line X. Therefore, the space is asymmetric on one side and the other side of the merging portion 18 with the virtual line X as a boundary. Thus, the asymmetric structure in the present invention may be achieved by providing the spacers 19a, 19b and the like.

  Next, specific examples and comparative examples will be described. The present invention is not limited to the following examples.

Example 1
The microchannel chip 1 of the first embodiment was produced. The chip body 2 was obtained as an injection-molded article of cycloolefin resin. In the chip body 2, the volume of the merging portion 4 is 60 μL. The dimensions of the cross sections of the first and second upstream microchannel portions 3a and 3b and the outlet microchannel 3c were as follows.

  1st upstream microchannel part 3a: It has the rectangular cross-sectional shape, The dimension was 0.8 mm x 0.7 mm.

  Second upstream microchannel portion 3b: The cross-sectional shape was rectangular, and the dimensions were 0.8 mm × 0.7 mm.

  Outlet-side microchannel 3c: A rectangular cross-sectional shape with a size of 0.8 mm × 0.7 mm.

  In the merging portion 4, the incident angle θ of the first upstream microchannel portion 3a with respect to the inner wall 4a, that is, the incident angle θ shown in FIG.

  As a first microfluidic, water was sent to the merging portion 4 at a rate of 5 μL / s using a gas, and was stopped in the merging portion 4. Next, water was fed as a second microfluid at a rate of 5 μL / s, and merged with the first microfluid in the junction 4. As a result, the first and second microfluids could be merged without entraining bubbles.

(Example 2)
The first and second microfluidics were merged in the same manner as in Example 1 except that the incident angle θ was changed to 10 °. Also in Example 2, the first and second microfluids could be merged with almost no bubbles involved.

(Example 3)
The first and second microfluidics were merged in the same manner as in Example 1 except that the incident angle θ was 70 °. As a result, the first and second microfluids could be merged with almost no bubbles.

(Comparative example)
In the comparative example, the incident angle θ is 90 °, and the portion where the first upstream microchannel portion 3a is connected to the inner wall 4a is the center of the first inner wall 4a. Thus, one side and the other side of the merging portion 4 are symmetrical with respect to the virtual line X as a boundary. The other configuration is the same as that of the first embodiment.

  In the comparative example, when the first micro fluid was sent to the merging portion 4, the outlet of the first upstream micro flow path portion 3a was blocked by the first micro fluid, and it was difficult for the gas to escape. For this reason, when the second microfluid is merged with the first microfluidic, bubbles are involved between the two.

  In the present invention, the first microfluid and the second microfluid are merged at the merge portion, but one or more other microfluids may be merged at the merge portion.

DESCRIPTION OF SYMBOLS 1 ... Microchannel chip 2 ... Chip body 3a, 3b ... 1st, 2nd upstream microchannel part 3c ... Outlet side microchannel 3d ... Merged microchannel part 4 ... Merged part 4a-4d ... Inner wall 5 , 6 ... 1st and 2nd microfluids 7 ... Mixed fluid 11 ... Merge parts 11a to 11f ... Inner walls 12, 13 ... Merge parts 14 ... Temperature control devices 16 to 18 ... Merge parts 19a and 19b ... Spacers

Claims (13)

A chip body having a microchannel and a first microfluidic and a merging portion where the second microfluidic merging,
The microchannel has an inlet-side microchannel for feeding the first microfluid and the second microfluid to the junction, and an outlet for feeding the microfluid joined at the junction Side microchannels,
A micro that has one side and the other side of the merging portion asymmetric in at least one of a space shape and a state with a virtual line extending in a direction in which the first microfluid flows into the merging portion as a boundary. A method of combining microfluidics using a flow path chip, comprising:
Feeding a first microfluid from the inlet-side microchannel to the junction;
A step of stopping the first microfluid in the merging portion after feeding the first microfluid to the merging portion ;
A step of stopping the first microfluid in the merging portion, then feeding a second microfluid to the merging portion and merging with the first microfluid ;
The gas is supplied from the rear of the first microfluidic in the inlet-side microchannel and the first microfluidic is transported to the merging portion side, whereby the first microfluidic is transferred to the merging portion feeding and, by the gas to overtake the first microfluidic at the merging section, by removing the pressing force by the gas, the first microfluidic Ru was stopped and merging method of microfluidic. And the one side of the merging portion, and the other side of the merging section is asymmetrical in shape space, merging method of microfluidic of Claim 1. And the one side of the merging portion, the size of the space between the other side of the merging portion are different, the merging process of microfluidic of Claim 2. The angle which the edge of the said confluence part which the said imaginary line crosses, and the said imaginary line make differs in one side and the other side of the said imaginary line, as described in any one of Claims 1-3. confluence method of micro-flow body. The edge and an angle between the virtual line merging section is a sharp one side of the imaginary line, is an obtuse angle on the other side, joins a method of microfluidic of Claim 4. The said junction part WHEREIN: The spacer which inhibits the liquid feeding of microfluidic is provided in at least one of the one side of the said virtual line, and the other side of the said junction part. merging method of microfluidic described. In the other side of the one side of the merging portion and the merging section, the roughness of the inner surface of the merging portion are different, the merging process of microfluidic according to any one of claims 1 to 6. And the one side of the merging section, at said other side of the merging portion, the temperature is different, the merging process of microfluidic according to any one of claims 1 to 7. And the one side of the merging section, at said other side of the merging portion, the contact angle to water are different, the merging process of microfluidic according to any one of claims 1-8. The inlet-side microchannel is a first inlet-side microchannel for delivering the first microfluidic fluid, and a second inlet-side microchannel for delivering the second microfluidic fluid with the door, merging method of microfluidic according to any one of claims 1-9. The inlet-side microchannel is single, the first micro-fluid and the second micro-fluid is fed to the merging section from the single inlet-side microchannel claims 1 to 10 merging method of microfluidic according to any one of. One end of the inlet-side microchannel is connected to the first upstream microchannel unit and the second upstream microchannel unit, and to the downstream ends of the first and second upstream microchannel units. cage and the other end has a confluent micro flow path portion connected to the merging portion, merging method of microfluidic according to any one of claims 1 to 11. The temperature control apparatus which is fixed to the said chip | tip main body, and further adjusts the temperature of at least one of the one side and the other side of the said imaginary line in the said junction part is provided as described in any one of Claims 1-12. confluence method of micro-flow body.

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