JP4367283B2 - Microfluidic chip - Google Patents

Description

  The present invention is directed to a micro that obtains a processed liquid from a liquid discharge port by guiding the liquid supplied from a plurality of liquid supply ports to a micro flow channel, causing the liquid to be mixed and reacted (chemical reaction) in the micro flow channel. The present invention relates to a fluid chip.

  A microfluidic chip supplies a plurality of liquids to a microchannel with a width and depth of several μm to several hundred μm, and mixes and reacts liquids based on the spontaneous behavior of the molecules and particles that make up the liquid. It is an apparatus that performs in a micro flow path.

  That is, the Reynolds number of the liquid is several hundreds or less in the micro flow path possessed by the microfluidic chip, and it becomes a world of laminar flow control, not turbulent flow control as in the conventional reaction apparatus. The mixing and reaction of liquids under the control of laminar flow is mainly due to molecular diffusion at the contact interface of each liquid, and the thing that defines the speed is the thickness of the liquid in the diffusion direction (different liquids have a uniform concentration) Is the distance to be diffused = diffusion distance).

  Many conventional microfluidic chips are intended for liquid analysis, and a liquid having a flow rate of several μl / min to several tens of μl / min is a narrow flow (= short diffusion distance) of a few hundred μm or less. It is designed to mix and react in the road.

  Specifically, as disclosed in the following Patent Document 1, a plurality of liquids are divided into a large number of laminar flows, and these are alternately arranged, so that the contact area of each liquid occupying the total volume of the liquid Forming a laminate flow with an increased proportion of the liquid, enabling highly efficient liquid mixing, and as disclosed in Patent Document 2 below, the liquid is shaped into a thin film flow, and the flow direction For example, there is known a method in which liquids are mixed in a stirring flow generated by stacking perpendicularly to each other and intermittently narrowing the stacked flow.

JP 2003-1077 A

JP 2002-346355 A

  The above prior art has designed a microfluidic chip on the premise of analyzing a small amount of liquid of about several tens of μl / min, and at high speed to mix and react at a flow rate of about several tens of ml / min. When the liquid is flowed, the flow path is too small, the internal pressure loss becomes excessive, and it is impossible to flow a desired flow rate, and an increase in the processing amount cannot be expected. Further, when the liquid passes through the microchannel at high speed, the diffusion becomes insufficient, and the expected mixing and reaction cannot be obtained.

  In order to increase the amount of processing and to obtain reliable mixing and reaction, it is necessary to perform parallel processing using a plurality of microfluidic chips called numbering up, which increases the size of the entire apparatus.

  Therefore, an object of the present invention is to provide a microfluidic chip that can process a large flow rate of liquid at high speed and does not increase the size of the apparatus.

The microfluidic chip of the present invention that achieves the above object is characterized in that the liquid supplied from a plurality of liquid supply ports is guided to the micro flow channel, and the liquid is mixed and reacted in the micro flow channel. In the microfluidic chip for obtaining the processed liquid from the above, a liquid supply unit that supplies at least two types of liquids so as to be divided into a plurality of flows alternately divided, and downstream of the liquid supply unit The dimensions in the arrangement direction of the liquids arranged alternately in the liquid supply section become smaller as they go downstream, and the dimensions in the direction intersecting the arrangement direction and the flow direction become larger as they go downstream. A flow flattening portion having a flow path shape that is substantially equal to or slightly larger in the direction, and the liquid supply section defines a flow path for one liquid and is formed on both sides of the flow path for the one liquid. A laminate flow forming portion that has a barrier to be formed and starts from the downstream end of the flow path of the barrier and causes another liquid to flow down into the flow path formed between the flow of one liquid to form a laminate flow, It exists in providing between the said liquid supply part and the said flow flattening part .

  Further, the microfluidic chip of the present invention that achieves the above object is characterized in that the cross-sectional area at the connection portion with the flow flattening portion in the direction intersecting the flow downstream of the flow flattening portion is the liquid discharge port as it is. And a processing section having a channel having a length that ensures a residence time until mixing or reaction of each liquid supplied from the liquid supply section is completed.

  When the dimensions in the arrangement direction of the alternately arranged liquids in the liquid supply unit are reduced toward the downstream, the width of each liquid in the arrangement direction of the alternately arranged liquids becomes narrower (the diffusion distance is shortened). However, if the dimensions in the direction intersecting the direction of flow and the direction of flow are maintained in the direction of flow, the cross-sectional area of the flow path becomes smaller in the direction of flow. go. If it does so, pressure loss will become large and will not be able to flow a big flow.

  Therefore, by increasing the dimension in the direction intersecting the direction of flow and the flow direction in the flow direction so that the cross-sectional area of the flow path is approximately equal to or slightly larger than the flow direction, the pressure loss is increased. And a large flow rate of liquid was allowed to flow.

  In addition to reducing the width of each liquid in the arrangement direction of the alternately arranged liquids when the dimension in the arrangement direction of the alternately arranged liquids in the liquid supply unit is reduced as it goes downstream, When the dimension in the direction intersecting the direction of flow and the direction of flow is increased in the direction of flow, the contact area between adjacent liquids per unit length in the direction of flow is expanded.

  If the cross-sectional area at the connection portion with the flow flattening portion in the direction intersecting the flow in the subsequent processing portion is maintained as it is to the liquid discharge port, the adjacent liquid per unit length in the flow direction also in the processing portion Therefore, the residence time until the mixing or reaction of each liquid supplied from the liquid supply unit is completed can be shortened, and the length of the flow path in the processing unit is shortened. Can be miniaturized.

  As a result, the liquid can be flowed at a high speed, and the flow rate that can be processed by one microfluidic chip is improved, so that the number of parallel processes can be reduced and the enlargement of the apparatus can be avoided.

  Hereinafter, embodiments shown in the drawings will be described.

Hereinafter, as an embodiment of the microfluidic chip of the present invention, a microfluidic chip for mixing two kinds of liquids will be illustrated and described, but the present invention is not limited to these examples.
FIG. 1 is a schematic exploded perspective view showing the entire microfluidic chip 1.

  The microfluidic chip 1 includes a microfluidic chip body 10 formed of a plate material having a thickness of several millimeters such as metal, glass, silicon, and resin according to the type of liquid to be processed such as mixing and reaction, and the microfluidic chip body 10. A lid member 30 disposed on one main surface side and constituting a ceiling portion of the flow path in the microfluidic chip body 10, and disposed on the other main surface side of the microfluidic chip body 10 on the opposite side of the lid member 30. It comprises an adapter member 50 that connects a liquid feeding mechanism such as a pump and a chip, and seal members 70 and 90 (see FIG. 3) disposed between these three members, and prevents the liquid from leaking by screw fastening.

  As the sealing member, an adhesive packing material, a metal packing material, or the like may be used. However, the lid member 30 and the adapter member 50 are directly attached to the front and back of the microfluidic chip body 10 using other methods such as laser bonding or adhesive. It may be fixed. In FIG. 1, the ellipses drawn on the microfluidic chip body 10, the lid member 30, and the adapter member 50 are screw holes. Further, although the adapter member 50 and the seal member 90 are provided with openings serving as passages for the raw solution to be supplied and the processing liquid to be discharged, detailed illustration is omitted.

  FIG. 2 is a front view of one main surface side of the microfluidic chip body 10, and includes a first liquid supply unit 11, a first liquid induction channel unit 12, a second liquid supply unit 13, a laminate flow forming unit 14, and a flow flatness. The control unit 15, the processing unit 16, and the liquid discharge unit 17 are provided.

  The microfluidic chip body 10 is provided with grooves of various shapes from the liquid supply unit to the liquid discharge port, which will be described in detail below. Serves as a lid to seal the groove.

  The first liquid supply unit 11 includes a large number of first liquid supply nozzles 11a. The first liquid supply nozzles 11a are arranged from the back surface (main surface on the adapter member 50 side) of the microfluidic chip body 10 to the front surface (the main surface on the adapter member 50 side) so as to be arranged in a line at a certain interval in the width direction of the microfluidic chip body 10. It is composed of openings provided over the main surface.

  FIG. 3 is a cross-sectional view of the microfluidic chip body 10 taken along the line AA shown in FIG. 2, and the lower part of each first liquid supply nozzle 11a (the back surface on the adapter member 50 side) is supplied with the supply liquid. A buffer tank 18 for temporarily storing a first liquid is provided. The buffer tank 18 is formed by a recess provided on the back surface of the microfluidic chip body 10 and an adapter member 50.

  The first liquid supply head 19 is attached to the adapter member 50 at a position corresponding to the buffer tank 18, and the first liquid supplied from the first liquid supply head 19 increases the liquid level after filling the buffer tank 18. Accordingly, it is uniformly supplied to all the first liquid discharge nozzles 11a. As a result, the first liquid is discharged from all the first liquid discharge nozzles 11a, and these liquids move to the laminate flow forming section 14 through the first liquid guide passage section 12 extending from each nozzle.

  The second liquid supply unit 13 includes a first liquid discharge nozzle 11a and a large number of second liquid discharge nozzles 13a whose positions are shifted in the width direction of the microfluidic chip body 10 by one nozzle. It has the same structure as the first liquid supply unit 11 in that it includes a liquid supply head.

  The second liquid is discharged from all the second liquid discharge nozzles 13 a and supplied to the laminate flow forming unit 14.

  As shown in FIG. 4 in an enlarged manner, in the first liquid guiding channel section 12, a number of barriers along the longitudinal direction of the microfluidic chip body 10 (the direction of the first liquid flow) from the position of each first liquid discharge nozzle 11a. There is a first liquid induction channel 12b between 12a, and the first liquid flows down the first liquid induction channel 12b.

  A large number of second liquid discharge nozzles 13a are opened at the downstream end of the barrier 12a, and both liquids discharged from the first liquid discharge nozzles 11a and the second liquid discharge nozzles 13a are the two nozzles 11a, Due to the displacement of the position 13a, the laminate flow forming unit 14 forms a laminate flow 14A in which two kinds of liquids are alternately arranged.

  By forming the laminate flow, the ratio of the contact area to the total volume of the two types of liquid increases, the molecular diffusion generated at the contact surface becomes active, and the amount of molecular diffusion for a certain time increases, so the microfluidic chip High efficiency of processing is realized. For the same volume, the processing efficiency of the microfluidic chip is proportional to the number of layers in the laminate flow.

  The first liquid supply unit 11, the first liquid guide channel unit 12, the second liquid supply unit 13, and the laminate flow forming unit 14 are alternately formed by dividing at least two types of liquids into a plurality of flows. The liquid supply unit is configured to supply the liquid so as to be arranged.

  The laminate flow 14 </ b> A formed by the laminate flow forming unit 14 then moves with the flow flattening unit 15.

  In liquid mixing by molecular diffusion, the time to mixing is affected by the liquid thickness in the direction perpendicular to the contact interface (= diffusion distance of molecules and particles), and time is proportional to the square of the thickness. Have a relationship. For example, in the case of spreading 1 mm in 10 seconds, if the diffusion distance is reduced to 0.5 mm, which is 1/2, the time only takes 1/4 seconds, 2.5 seconds.

  Based on this relationship, the flow flattening section 15 narrows the flow path width in the direction perpendicular to the contact interface of the laminate flow 14A. As a result, the diffusion distance can be shortened and the liquid can be mixed at high speed.

  In addition, when the ratio of the flow path width before and after squeezing is the same value, the position of the first liquid discharge nozzle 11a and one nozzle is shifted in the width direction of the microfluidic chip body 10 by the second liquid discharge nozzle. As the number of alternating arrangements of 13a is increased and the number of layers in the laminate flow is increased, the thickness per layer is reduced, thereby shortening the time until mixing is completed.

  Usually, when the width of the flow path is reduced, the cross-sectional area of the flow path is reduced, whereby the pressure loss per unit length in the flow path increases toward the downstream. In particular, when trying to send liquid to the microfluidic chip at a large flow rate, the pressure loss in the flow path exceeds the performance limit of a pump (not shown) arranged on the upstream side of the first liquid supply head 19 and the like, and the liquid is sent. Liquid becomes impossible.

  Therefore, in the present embodiment, a plate material having a thickness of several millimeters is used for the microfluidic chip body 10 that has been conventionally manufactured with a thin plate of about 0.5 mm, and the flow path width W is increased toward the downstream as shown in FIG. As shown in FIG. 5, which is a partial longitudinal sectional view taken along the line BB shown in FIG. 2, the flow path depth H is increased and the flow path sectional area is kept constant. By providing the flow flattening portion 15 to be maintained, the pressure loss is not increased. The flow flattening portion 15 can be said to be a diffusion distance shortening portion having a pressure loss increase preventing function.

  In this case, even if the depth H of the flow path is increased, the laminar flow is maintained in the flow in the flow path, so that the laminate flow 14A is not disturbed, and the molecular diffusion is not disturbed.

  As shown in FIG. 6, in the flow flattening unit 15, the flow direction is the X direction, the width direction (the arrangement direction of the liquids alternately arranged in the liquid supply unit 11) is the Y direction, and the depth direction (the liquid supply unit 11). In the Z direction, the direction in which the liquids arranged alternately and the direction intersecting the flow direction are expressed in the Z direction, each layer of the laminate flow becomes thinner as the thickness progresses downstream (thickness w1). ⇒ w2), instead, it is flattened to be longer in the depth direction (Z direction) (depth h1 ⇒ h2), and the cross-sectional area in the direction intersecting the flow direction is the upstream laminating flow forming portion 14 side ( The cross-sectional area A1) and the downstream processing unit 16 side (cross-sectional area A2) are almost the same (cross-sectional area A1≈A2), but the cross-sectional area is made slightly wider toward the downstream (cross-sectional area A2 ≧). Good with A1).

  What to do with the cross-sectional shape of the connecting portion 20 with the processing portion 16 may be determined by the thickness of the microfluidic chip body 10 and the length of the processing portion 16 described later.

  In FIG. 2, the flow flattening portion 15 is semicircular when viewed from the front of the microfluidic chip body 10, but the shape is not limited and may be triangular. Further, the shape such as a semicircle or a triangle may be simulated as a step shape with a fine pitch, and a gentle slope may be formed in a step shape in the depth direction according to the shape.

The liquid that has passed through the flow flattening unit 15 moves to the processing unit 16.
The processing unit 16 maintains the cross-sectional area at the connection unit 20 with the flow flattening unit 15 in the direction crossing the flow as it is to the liquid discharge unit (liquid discharge port) 17.

  This is because processing can be facilitated by making the cross-sectional shapes of the channels the same, and calculation for estimating the mixed state of the liquid can be facilitated. However, if there is a margin in the thickness of the microfluidic chip body 10, the flow path depth H of the flow flattening portion 15 can be increased, and the ratio of the interface area / total volume of the laminate flow 14A can be increased. It is also possible to raise.

  In the embodiment, the processing unit 16 has a circular spiral shape. However, if the required residence time until the completion of mixing is obtained by calculation and the necessary flow path length derived therefrom can be secured on the microfluidic chip main body 10, FIG. Other shapes such as a rectangular spiral shape 7, a hexagonal spiral shape not shown, and a meandering shape in FIG. 8 may be used.

  Mixing of the liquid is completely completed while passing through the processing unit 16, and the processing liquid uniformly mixed out of the apparatus is discharged from the liquid discharging unit 17. A treatment liquid discharge head (not shown) is provided at a location corresponding to the liquid discharge portion 17 of the adapter member 50, and a treatment liquid is obtained through this treatment liquid discharge head.

  As long as the liquid is a laminar flow, the mixing performance of the microfluidic chip 1 of the present invention is determined by the ratio of the number of layers of the laminate flow 14A and the flow path width before and after the flow flattened portion 15. Therefore, fine nozzles and grooves as in the conventional microfluidic chip are not necessarily required, and each of them can exhibit performance as a combination of nozzles and grooves of several hundred μm to several mm, so that it is excellent in workability.

  In the embodiment of FIG. 2, the laminate flow 14 </ b> A is arranged horizontally, but the shape arranged in the thickness direction of the microfluidic chip body 10, that is, the axial directions of Y and Z in each axial direction of FIG. 6. A vertical arrangement may be adopted in which the image is rotated 90 degrees around the X axis and the Y axis is in the Z axis direction of FIG.

  In the above-described embodiment, an example in which two liquids are mixed has been described. However, when three or more liquids are to be mixed, a large number of liquid supply units may be provided.

It is a schematic exploded perspective view of a microfluidic chip. It is a front view of the microfluidic chip main body shown in FIG. FIG. 3 is a cross-sectional view of the microfluidic chip body taken along the line AA in FIG. 2. It is the elements on larger scale of the lamination flow formation part in the microfluidic chip main body shown in FIG. FIG. 3 is a partial longitudinal sectional view of the microfluidic chip body taken along the line BB in FIG. 2. It is a figure for demonstrating the flow flat part in the microfluidic chip main body shown in FIG. It is a figure which shows the shape applied as a microchannel of the process part in the microfluidic chip main body shown in FIG. It is a figure which shows the other shape applied as a microchannel of the process part in the microfluidic chip main body shown in FIG. 1 in simulation.

Explanation of symbols

1 ... Microfluidic chip
10 ... Microfluidic chip body
11 ... First liquid supply unit
12 ... First liquid guiding channel section
13 ... Second liquid supply section
14 ... Laminate flow forming part
15 ... Flow flattening part
16 ... processing part
17 ... Liquid discharge part
30 ... Lid member
50 ... Adapter member

Claims (6)

In a microfluidic chip that guides liquid supplied from a plurality of liquid supply ports to a microchannel, mixes and reacts liquids in the microchannel, and obtains processed liquid from the liquid outlet,
A liquid supply unit that supplies a plurality of flows obtained by dividing at least two types of liquids, and an array of liquids arranged alternately in the liquid supply unit downstream of the liquid supply unit The shape of the flow path is such that the dimension in the direction becomes smaller as it goes downstream, the dimension in the direction intersecting the direction of flow and the flow direction becomes larger, and the cross-sectional area becomes almost equal to or slightly larger in the flow direction A flow flattening portion, and the liquid supply portion defines a flow path for one liquid and has barriers formed on both sides of the flow path for the one liquid. A laminating flow forming part for forming a laminating flow by causing another liquid to flow down in a flow path formed between the flow of one liquid is provided between the liquid supply part and the flow flattening part. Microfluidic features -Up.   In the microfluidic chip according to claim 1, the cross-sectional area at the connection portion with the flow flattening portion in the direction intersecting the flow downstream of the flow flattening portion is maintained as it is to the liquid discharge port, and the liquid supply portion A microfluidic chip characterized in that a processing unit having a flow path having a length that ensures a residence time until mixing or reaction of each supplied liquid is completed.   2. The microfluidic chip according to claim 1, wherein the liquid supply unit supplies each of the liquids divided into a plurality of flows so as to be alternately arranged horizontally, and the flow flattening unit is provided downstream. A microfluidic chip characterized by having a flow channel shape in which the width of the flow channel narrows and the flow channel depth increases and the cross-sectional area of the flow channel becomes equal or slightly larger as it goes toward   2. The microfluidic chip according to claim 1, wherein the processing section constituting the microchannel is provided in a spiral shape or a meandering shape.   2. The microfluidic chip according to claim 1, wherein the flow flattened portion has a semicircular or triangular plan shape.   2. The microfluidic chip according to claim 1, wherein the liquid supply unit, the flow flattening unit, and the processing unit each have a groove provided in the microfluidic chip body, and a lid provided on the surface of the microfluidic chip body. A microfluidic chip characterized in that the groove is sealed with a member, each liquid is supplied to the liquid supply part through an adapter member provided on the back surface of the microfluidic chip body, and a processed liquid is obtained from a liquid discharge port.

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