JP2009229240A - Microchip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip for searching the characteristics of a specimen while preventing gas from getting mixed in a mixing part, with the gas used for separating a reagent from the specimen so as to prevent them from getting mixed with each other in the middle of a flow path. <P>SOLUTION: Assuming that V1 is the volume of the gas used for separating the reagent from the specimen, S1 a cross section of the mixing part for mixing the reagent with the specimen, with the cross section viewed from a flow-path direction of the mixing part, W1 the width of the flow path, and V2 the total volume of the reagent and the specimen, if the following relations hold, (2/π)×S1×W1 <V1 and (2/π)×S1×W1 <V2, then the reagent and the specimen are trapped on a wall surface of the flow path while the gas outruns the reagent and specimen. Accordingly, a mixed fluid of the reagent and the specimen remains in the flow path after the gas has passed therethrough, allowing the characteristics of the specimen to be investigated in a next process. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a microchip.

  In recent years, by making full use of micromachine technology and ultrafine processing technology, conventional chips, devices, means (for example, pumps, valves, flow paths, etc.) for sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized to one chip. A system using a microchip integrated on top attracts attention. This is also referred to as μ-TAS (Micro Total Analysis System), and a DNA-treated extraction solution extracted from a microchip by processing a reagent and a sample (for example, urine, saliva, blood, and sample of a subject to be tested) Etc.) and the characteristics of the specimen are examined by detecting the reaction.

  Microchips use a photolithographic process (a method of creating a groove by etching a pattern image with a chemical) or a groove using a laser beam on a substrate made of a resin material or glass material, and flow a reagent or specimen. A fine channel and a liquid reservoir for storing reagents have been provided, and various patterns have been proposed.

  However, when mixing the reagent and the sample, if the sample is mixed in the microchip flow path other than the mixing part, it is impossible to check the characteristics of the sample accurately. Therefore, in order to prevent the reagent and the sample from mixing and reacting at a place other than the mixing part in the middle of the flow path, for example, Patent Document 1 discloses a liquid that does not react with the reagent or the sample between the reagent and the sample. A technique for separating using the method is disclosed.

Furthermore, Patent Document 2 describes a method of separating a reagent and a sample using a gas, and the gas generated at this time is a flow path so that it does not flow out to the next flow path such as a reaction section. A technique for trapping droplets by forming a step in the groove is disclosed.
JP 2005-274199 A JP 2006-266924 A

  However, in the technical means that uses a liquid as disclosed in Patent Document 1, a new flow path must be provided in order to supply the liquid between the reagent and the specimen. Therefore, the flow pattern of the microchip becomes complicated, and there arises a problem that the control for supplying the liquid in a timely manner and a new problem that the cost increases for performing the accurate control occur.

  Further, the technical means disclosed in Patent Document 2 has a problem that the liquid feeding pressure of a pump or the like for feeding a reagent or the like must be controlled in order to trap gas.

  It is an object of the present invention to provide a microchip capable of examining the characteristics of a sample so that a gas to be separated so that the reagent and the sample are not mixed in the middle of a flow path is not mixed in a mixing part.

The above object can be achieved by the following configuration.
1. A flow path for sending at least one kind of reagent and a specimen to be reacted with the reagent via a gas therebetween;
A mixing section for mixing the reagent and the specimen provided in the flow path;
A microchip having
When the volume of the gas is V1, the cross-sectional area of the mixing unit viewed from the liquid feeding direction is S1, the width is W1, and the total volume of the reagent and the specimen is V2, the following relational expression (1): (2) The microchip characterized by satisfy | filling.
(2 / π) × S1 × W1 <V1 (1)
(2 / π) × S1 × W1 <V2 (2)
2. The contact angle between the reagent or the sample and the wall surface of the flow path is 90 ° or more, and the contact angle between the reagent or the sample and the wall surface of the mixing unit is 90 ° or more, 2. The microchip according to 1.
3. 1 or 2 satisfying the following relational expression (3), where S2 is the cross-sectional area of the flow path upstream of the mixing unit in the liquid feeding direction, and W2 is the width. Microchip.
(2 / π) × S2 × W2> V1 (3)

According to the present invention, the volume V1 of the gas that separates the reagent and the sample is S1, the cross-sectional area of the mixing unit that mixes the reagent and the sample viewed from the flow direction, the width of the flow channel is W1, and the reagent and the sample When the total volume of V2 is V2,
(2 / π) × S1 × W1 <V1 (1)
(2 / π) × S1 × W1 <V2 (2)
When the relations (1) and (2) are established, the reagent and the sample are trapped on the channel wall surface in the mixing unit, and the gas passes through the reagent and the sample, so that the gas is not mixed.

  An embodiment of the present invention will be described. In addition, although this invention is demonstrated based on embodiment of illustration, this invention is not restricted to this embodiment. In addition, the following assertive description in the embodiment of the present invention shows the best mode, and does not limit the meaning or technical scope of the terms of the present invention.

  FIG. 1 shows a microchip according to the present embodiment. The microchip 1 has a substantially rectangular card shape, and a series of flow paths are formed. The base material BP constituting the wall surface of the microchip 1 is composed of a single chip made of, for example, silicon, glass, ceramics, quartz or the like. These base materials BP desirably have excellent water repellency in order to prevent the liquid from moving due to external pressure and mixing of other reagents. Specifically, water repellent treatment is performed so that the contact angles ψ between the base material BP, the reagent L, and the specimen Q are each 90 ° or more (see FIG. 3).

  Of course, the microchip 1 is not limited to the shape shown in FIG. 1, and its arrangement, shape, size, size, and the like can be changed according to the type of specimen, examination items, and the like.

  In FIG. 1, P1 and P2 are injection ports for injecting the driving liquid D. The driving liquid D is a liquid for sending the liquid reagent L and the specimen Q in the microchip 1 along the flow path, and a liquid such as pure water that does not react with the reagent L and the specimen Q is used. The driving liquid D is fed by a liquid driving pump (not shown) that feeds the liquid.

  Reference numeral 2 denotes a sample storage unit for storing the sample Q, and the sample Q is injected from the injection port P3 using a liquid drive pump. Reference numerals 3 and 4 are flow paths for storing the gas E and the reagent L, and are injected from the injection port P5 using a liquid drive pump. In addition, the liquid drive pump is prepared for each of the plurality of injection ports.

  Reference numeral 5 denotes a mixing unit that mixes the reagent L and the sample Q. Reference numeral RB denotes a hydrophobic valve (referred to as valve RB), which is provided to temporarily stop the liquid fed into the microchip 1 at a predetermined position. The valve RB has a short channel shape in which the cross-sectional area is smaller than that of the liquid-feed channel and the width and depth are reduced. When the liquid-driven pump sends the liquid such as the reagent L or the specimen Q in the microchip 1 at a pressure lower than a predetermined pressure, when the liquid is about to flow out from the valve RB to the wide channel, the liquid Since the liquid feeding is hindered by the surface tension acting on the surface, the liquid feeding is stopped. When the liquid is sent at a predetermined pressure or higher, this surface tension is overcome, and the liquid passes through the valve RB and is sent downstream. As described above, by providing the valve RB, the position of each liquid does not move against an impact such as a drop when the reagent is stored, while a pressure capable of passing through the high resistance channel is applied when the liquid is sent. This makes it possible to send liquids.

In this example, the cross-sectional area of the flow path 6 was 50000 μm ² (width 200 μm × depth 250 μm), and the cross-sectional area of the valve RB was 625 μm ² (width 25 μm × depth 25 μm).

  Reference numeral 7 denotes a pre-mixing section flow path connecting the flow path 4 and the mixing section 5.

  FIG. 2 is a view showing a state where the reagent L and the specimen Q stored in the microchip 1 are sequentially sent by the driving liquid D. In the figure, the net pattern portion indicates the specimen Q, the fine hatching portion indicates the gas E, and the rough hatching portion indicates the reagent L1.

  In FIG. 2A, gas is injected into the flow path 3 from the injection port P4, and the reagent L1 is stored in the flow path 4. In addition, the sample Q is stored in the sample storage unit 2, and the liquid is prevented from flowing out by the valves RB1 and RB2, respectively.

  Next, as shown in FIG. 2B, the driving liquid D is injected at a predetermined pressure from the injection port P1, and the sample Q stored in the sample storage unit 2 is pushed downstream against the valve RB1 and flows. Stored in path 6.

  Next, as shown in FIG. 2C, the driving liquid D is injected at a predetermined pressure from the injection port P2, and the specimen Q is pushed out to the flow path 3 through the valve RB2. As the sample Q is stored in the flow path 3, the gas E and the reagent L 1 sequentially move to the flow path 4 and the pre-mixing section flow path 7.

  Further, as shown in FIG. 2D, the driving liquid D injected from the injection port P2 is further injected, and the gas E moves to the pre-mixing section flow path 7. As a result, as shown in FIG. 2 (e), the specimen Q is also fed to the pre-mixing section flow path 7.

  FIG. 6 is an enlarged view of FIG. 2 (e) showing the reagent L and the sample Q trapped on the wall surface in the pre-mixing section flow path 7.

  Here, the gas E is mixed in the pre-mixing section flow path 7 at the same time. For example, when the mixed liquid in which the gas E is mixed is heated in a subsequent process such as a reaction section, there is a problem that an accurate inspection cannot be performed due to the expansion of the gas E.

  In the present invention, a liquid such as a reagent or a specimen (simply referred to as a liquid) is attached (referred to as a trap) to the wall surface of the flow path, and the gas E is passed through the flow path during that time, so that the gas E does not enter the next process. This is a microchip. Details will be described below.

  In general, liquids in the air (referred to as droplets) become spherical because they attempt to minimize the surface area of the droplets due to surface tension. Here, when the liquid droplet flows through the flow path, when the liquid droplet passes through the wall surface of the flow path subjected to the surface treatment such that the contact angle ψ between the liquid droplet and the wall surface of the flow path is 90 ° or more, Whether to maintain a spherical shape or adhere to the wall surface to become a hemisphere depends on the surface area of the droplet, and the smaller surface area adheres to the wall surface. According to the calculation, when the droplets have the same volume, the surface area when the droplets are hemispherical is smaller than the spherical surface area, so that they continue to adhere to the wall surface.

The droplet continues to adhere to the wall when it touches all the walls (it is said to be stable). However, when the distance from the wall is increased to some extent, the surface area increases and the adhesion force decreases and moves. The distance from the wall at this time is called the critical width. Whether the droplet adheres to the wall side and the droplet overtakes the side 1) The width of the flow path is not less than the critical width.
2) The droplet continues to adhere to the wall against the pressure of the gas flowing next to the droplet.
Is satisfied.
(Determine critical width)
When the cross-sectional shape of the flow channel when the liquid droplet is in contact with the entire circumferential surface of the flow channel is rectangular, the shape of the liquid droplet is a prism (see FIG. 4). When the width viewed from the liquid feeding direction is w (referred to as critical width), the height is h, and the droplet length is l,
Droplet volume v = whl (4)
Droplet area s1 = 2wh (5)
Droplet adhesion force f1 = 2σ (w + h) (6)
It is. Here, σ is the surface tension of the liquid.

Next, when it becomes hemispherical (see FIG. 5),
If the radius of the droplet is r and the height is h,
Droplet volume sv = (1/2) πr ² h (7)
Droplet area s2 = πrh (8)
Droplet adhesion force fv = 2σ (πr + h) (9)
Because the smaller the droplet area, the more stable
2wh> πrh ... (10)
Therefore, the critical width w is w = (1/2) πr (11)
And the liquid droplet is stabilized when it is more than that.
(Relationship with channel cross-sectional shape)
(11) is transformed to (2 / π) w = r (12)
If the cross-sectional area of the flow path is s1, s1 = wh, so h = s1 / w (13)
Substituting (12) into (7), sv = (1/2) π × ((2 / π) w) ² × s1 / w
= (2 / π) × S1 × w (14)
It becomes.
In order for the droplet to be trapped on the wall surface, sv <(2 / π) × S1 × w (15)
It becomes.

Here, when the volume of the gas E provided for separating the reagent and the specimen in the flow path is V1, a droplet is trapped on the flow wall and the gas E passes through the liquid.
V1> sv (16)
And, moreover,
V1> (2 / π) × S1 × w (1)
Need to hold.

Further, the mixing unit needs to have a volume smaller than the total volume V2 of the reagent and the specimen so that the liquid droplets do not flow backward. That is, (2 / π) × S1 × W1 <V2 (2)
It becomes.

The channel 7 before the mixing unit is a channel for temporarily trapping the reagent L and the specimen Q and allowing the liquid droplets to pass therethrough. The gas volume V1 and the cross-sectional area of the channel 7 before the mixing unit are represented by S2. If the width of the flow path 7 on the near side is W2,
(2 / π) × S2 × W2> V1 (3)
In this case, the droplet V1 passes through the flow path 7 before the mixing unit, and the liquid is trapped on the wall surface.

  If a microchip channel having a shape satisfying the above (1), (2), and (3) is used, the droplet is trapped on the wall surface of the channel, so that the droplet V1 overtakes the liquid and mixes. The liquid can be fed to the downstream side of the part 5 in the liquid feeding direction. In the subsequent steps, the characteristics of the specimen can be examined.

It is a figure which shows the microchip which concerns on this Embodiment. FIG. 2A is a diagram illustrating a state where different reagents are stored in two flow paths and a sample is stored in the sample storage unit. FIG. 2B is a diagram illustrating a state where the driving liquid is injected from the injection port and the specimen is stored in the flow path. FIG. 2C is a diagram showing a state where the specimen is pushed out into the flow path by the injection of the driving liquid. FIG. 2D is a diagram showing a state where the driving liquid is further injected and the reagent is sent to the mixing unit. FIG. 2E is a diagram showing a state where the specimen is also sent to the mixing unit. It is a figure which shows the contact angle (psi) of the base material BP, the reagent L, and the sample Q. It is a figure which shows when the shape of a liquid is a prism. It is a figure which shows the case where a liquid becomes hemispherical. It is the figure which expanded the vicinity of the flow path before a mixing part of FIG.2 (e).

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 2 Sample storage part 5 Mixing part 7 Flow path before mixing part P1-P5 Inlet S1 Cross section of mixing part W1 Channel width V1 Gas volume D Driving liquid L Reagent Q Sample

Claims (3)

A flow path for sending at least one kind of reagent and a specimen to be reacted with the reagent via a gas therebetween;
A mixing section for mixing the reagent and the specimen provided in the flow path;
A microchip having
When the volume of the gas is V1, the cross-sectional area of the mixing unit viewed from the liquid feeding direction is S1, the width is W1, and the total volume of the reagent and the specimen is V2, the following relational expression (1): (2) The microchip characterized by satisfy | filling.
(2 / π) × S1 × W1 <V1 (1)
(2 / π) × S1 × W1 <V2 (2) The contact angle between the reagent or the sample and the wall surface of the flow path is 90 ° or more, and the contact angle between the reagent or the sample and the wall surface of the mixing unit is 90 ° or more, The microchip according to claim 1. The following relational expression (3) is satisfied, where S2 is a cross-sectional area of the flow path upstream of the mixing section in the liquid feeding direction as viewed from the liquid feeding direction, and W2 is a width thereof. A microchip according to claim 1.
(2 / π) × S2 × W2> V1 (3)

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