JP2010085281A - Container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reaction container with a flow path and a reservoir communicated with the flow path and storing liquid to be introduced into the flow path, and capable of easily preventing the liquid in the reservoir from creeping up to an opening by capillarity without applying a surface treatment for water repellence. <P>SOLUTION: The reaction container 1 including the flow path 3 and the reservoir 2 storing the liquid F to be introduced into the flow path 3 forms a large-diameter section 24 in the upper part of the reservoir 2 by means of a step 22. The step 22 has a size which prevents the liquid F stored in the reservoir 2 below the step 22 from creeping up above the step 22 by capillarity. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a reaction container that stores a minute amount of liquid, and more specifically, a reaction container that includes a flow path and a storage section that communicates with the flow path and stores liquid introduced into the flow path. It is about.

  In recent years, in the fields of chemistry, biotechnology, and the like, an analysis method called microfluidics is known in which analysis is performed using a microchip in which microchannels are formed on a substrate by applying microfabrication technology.

  The microchip accommodates a liquid sample to be analyzed by the microfluidics. On this microchip, extraction of components to be analyzed from samples (extraction process), analysis of components to be analyzed using chemical and biochemical reactions (analysis process), separation (separation process), detection (detection process), etc. A series of analysis steps are integrated, and this integrated system is also called μ-TAS (microtas), Lab-on-a-Chip (lab-on-chip) or the like.

  The microchip is a reaction vessel that is formed of a resin material such as acrylic and includes a storage section called a well that communicates with the microchannel and stores a sample and the like. The sample or the like is introduced into the micro flow path by injecting the sample or the like into a fine hole opened on the upper surface of the well by a probe. After that, a high voltage is applied to the microchip, and by applying this high voltage, each component of the sample in the microchannel is electrophoresed, and the measurement target substance in the sample is separated by the difference in the migration degree. . The separated measurement target substance is identified and detected by the reagent.

  Since a sample or the like supplied to such a reaction vessel, that is, a microchip, wets the wall surface of the micropores and crawls up the micropore wall surface of the well by capillary action, and may reach the upper surface of the well. The container is formed of a hydrophilic material, and the upper region of the container including the opening is subjected to surface treatment with a hydrophobic material, and the contact angle in the upper region is defined as the contact angle of the lower region where the surface treatment is not performed. A technique for preventing the liquid from creeping up from the lower region by making it larger than that has been proposed.

  However, in the technique proposed in Patent Document 1, it is necessary to consider the chemical influence that the surface treatment agent for the surface treatment gives to the liquid contained therein. In addition, since accurate surface treatment of the reservoir is technically difficult, the surface treatment becomes insufficient, and the supplied liquid crawls up to the upper surface of the reservoir due to capillary action, causing carryover and contamination. May occur.

In view of the above circumstances, an object of the present invention is to provide a surface treatment for water repellency in a reaction vessel provided with a flow channel and a reservoir that communicates with the flow channel and stores liquid introduced into the flow channel. It is an object of the present invention to provide a reaction container that can easily prevent the liquid from rising up to the upper surface due to capillary action (interfacial tension, surface tension) or the like.
JP 2008-2850 A

  In order to solve the above problems, a reaction container of the present invention is a reaction container provided with a flow path and a reservoir that communicates with the flow path and stores a liquid introduced into the flow path. The reservoir has a large-diameter portion above the step, and the liquid stored in the reservoir below the step is moved upward from the step by capillarity or the wall of the reservoir and the surface of the liquid. It is characterized by having a size that does not crawl up due to interaction with tension (hereinafter collectively referred to as capillary action).

  Here, the “reservoir” means a part of the reaction vessel that has an inner diameter sufficient to cause capillary action. The above “via a step upward” means that there is a step extending in the radial direction of the reservoir in the middle of the reservoir. The above "does not crawl up due to the capillary phenomenon" means that the capillary phenomenon does not crawl up to the upper part of the reservoir due to the capillary phenomenon. Including the case of going up. The above-mentioned “climbing up” means that the liquid in a wet state moves upward.

  In the reaction vessel of the present invention, the step may have a size of 0.05 mm or more in the horizontal direction.

  Here, the “size” means a value obtained by dividing the difference between the large diameter and the internal diameter of the storage portion into two. The “horizontal direction” is not limited to a strictly horizontal direction, but includes substantially horizontal.

  The reaction container of the present invention may be provided with a plurality of reservoirs.

  The reaction container of the present invention may be a micro flow channel in which the liquid is a sample or a reagent and the liquid into which the flow channel is introduced flows.

  As described above, the reaction container of the present invention includes a flow path and a storage section that communicates with the flow path and stores the liquid introduced into the flow path. Since there is a large-diameter portion through the liquid, the liquid stored in the storage portion below the step does not crawl upward due to the capillary phenomenon. Therefore, the reaction container according to the present invention does not perform surface treatment for water repellency, and simply forms a step in the storage part, so that the liquid in the storage part can crawl up to the upper surface of the storage part by capillary action. Can be easily prevented.

  Embodiments of the reaction container of the present invention will be described with reference to the drawings. Hereinafter, the reaction container of the present invention will be described as a microchip 1 as an example of an embodiment. FIG. 1 is a schematic configuration diagram of a dispensing process of an analyzer to which the microchip 1 is applied. Here, the dispensing step is a step of dispensing a predetermined amount of liquid F, such as a sample or a reagent, to the microchip 1 by the dispensing device 100 built in the analyzer.

  The dispensing apparatus 100 will be described. A dispensing apparatus 100 includes a dispensing nozzle 101 connected to a pump unit (not shown), a nozzle driving unit 102 for driving the dispensing nozzle 101, a liquid level detecting unit 103 for detecting the liquid level of the liquid F, and the liquid level. It is mainly comprised by the control part 104 which controls the nozzle drive part 102 based on the signal from the detection part 103. FIG. The dispensing nozzle 101 is connected to a syringe pump (not shown) that supplies suction pressure and discharge pressure, and this syringe pump is controlled by the control unit 104.

  The dispensing apparatus 100 sucks the liquid F from a test tube or the like from the nozzle tip 101a, and discharges the liquid F from the nozzle tip 101a to the microchip 1 positioned in the analyzer. The liquid F includes a clinical test reagent and the like.

  The microchip 1 will be described. FIG. 2 is a front view of the microchip 1, and FIG. 3 is a side view of the microchip 1.

  The microchip 1 will be described. The microchip 1 is manufactured by injection molding of a thermoplastic polymer. The polymer to be used is not particularly limited, but a polymer that can be easily injection-molded is preferable, and COP (cycloolefin polymer), PMMA (methyl methacrylate resin), and the like are desirable.

  As shown in the figure, the microchip 1 is formed with twelve protruding wells 2 and a microchannel 3 indicated by a broken line in the drawing. Each well 2 communicates with the microchannel 3. In the present embodiment, eleven wells 3 have the same shape, and one well 3 has a smaller shape than the others. The microchannel 3 is formed with dimensions of about 30 to 100 μm in width and about 15 to 50 μm in depth, for example, by a fine processing technique such as etching or photolithography.

  The microchip 1 contains the liquid F in the microchannel 3.

  The well 2 will be described in detail. FIG. 4 shows a cross-sectional view of the well 2. In the present embodiment, the well 2 will be described as a reservoir. Each well 2 is formed with a fine hole 21 communicating with a microchannel 3 (not shown).

  The fine hole 21 has a small diameter portion 23 below the step 22 and a large diameter portion 24 above the step 22 through the step 22 in the middle. The small-diameter portion 23 has an inner diameter D that allows the liquid F contained in the microchip 1 to wet the wall surface and crawl up toward the upper surface 2a by capillary action. Specifically, the inner diameter D of the fine hole 21 has a lower limit of 0.01 mm or more, desirably 0.05 mm or more, more desirably 0.5 mm or more, more desirably 1 mm or more, and an upper limit of 5 mm or less. Is in the range of 3 mm or less. The outer edge of the well 2 in which the fine holes 21 are formed is not particularly limited, but it is desirable that the width be 0.05 mm or more in consideration of strength.

  Further, the step 22 has a predetermined width W in the radial direction and is horizontal. The width W of the step 22 is appropriately set according to the state (nature) of the liquid F and the wall surface 23a of the small diameter portion 23, but the lower limit is 0.05 mm or more, preferably 0.13 mm or more, More desirably, it is 0.23 mm or more, and the upper limit is 5 mm or less, desirably 3 mm or less, and more desirably 1 mm or less. Here, the width W of the step 22 is a value obtained by dividing the difference between the inner diameter of the large diameter portion 24 and the inner diameter of the small diameter portion 23 into two. Both the small diameter portion 23 and the large diameter portion 24 are formed with a taper for convenience of manufacture.

  The dispensing operation to the microchip 1 will be described. As shown in the central view of FIG. 3, the dispensing nozzle 101 sucks a predetermined amount of the liquid F, descends to a predetermined depth in the micro hole 21 of the well 2, and discharges the sucked liquid F. Dispensing nozzle 101 is filled with liquid F to a predetermined depth in microchannel 3 and small diameter portion 23 of well 2. The liquid F is preferably filled to a depth of half or more of the small-diameter portion 23 of the fine hole. After filling, the dispensing nozzle 101 rises and moves out of the micropores 21. Thereafter, the liquid F is pressurized by injecting air through a vent passing through the lid body R in contact with the upper surface 2 a of the well 2. The lid body R may be a hard body such as plastic or an elastic body such as rubber. When an elastic body is used as the lid body R, it is not necessary to have a vent as described above, and the liquid F may be pressurized by directly pressing the lid body R. In order to avoid contact between the lid body R and the liquid F, the step 22 is usually formed at a position about 0.5 to 3 mm, preferably about 1 mm away from the upper surface 2a.

  FIG. 5 is a diagram showing the transition of the liquid F after dispensing. The liquid F in the microchip 1 crawls up in the micropore 21 toward the upper surface 2a of the well 2 by capillary action as shown in the left diagram of FIG. As described above, since the upper surface 2a of the well 2 is pressurized by the lid body R, contamination or the like may occur when the liquid F rises up to the upper surface 2a. Therefore, the volume of the liquid F is 90% or less of the volume of the small diameter part 23, desirably 80% or less.

  Here, when the wall surface 23a of the small diameter portion 23 is a hydrophilic material, the liquid F is in a wet state on the wall surface 23a. The liquid F in the vicinity of the wall surface 23a becomes high at both ends with an angle γ with respect to the wall surface 23a, and a force acts in a direction in which the liquid surface contracts due to surface tension. As a result, the liquid F crawls up to the height at which the weight of the liquid F that crawls up the wall surface 23a and the surface tension is balanced. Accordingly, the smaller the inner diameter D of the small diameter portion 23, the more liquid F scoops up the wall surface 23a.

  Here, whether the liquid F is in a wet state or a water-repellent state on the contact surface is determined by the contact angle B. The contact angle B is determined by physical properties such as the density of the liquid F and the characteristics of the contacting surface. FIG. 6 is a schematic diagram showing the contact angle B of the liquid F. As shown in FIG.

  As shown in the figure, when the contact angle B is greater than 0 degree and less than 90 degrees, the liquid F is wet on the contact surface, and when the contact angle B exceeds 90 degrees, the liquid F Is a water-repellent state on the contact surface.

  The operation of the step 22 will be described. Refer to FIG. 5 again. The right diagram in FIG. 5 is a diagram showing a state where the liquid F has reached just before the step 22. As shown by the arrow in the figure, the liquid F that rises by capillary action at an angle γ on the wall surface 23a exceeds the edge 22a on the small diameter portion 23 side of the step 22 having a predetermined width W in the horizontal direction. In order to be in a wet state at the step 22, approximately 90 degrees indicated by the angle α in the drawing of the step 22 is added to the angle γ of the liquid F. For this reason, the angle γ of the liquid F needs to exceed 90 degrees, and the liquid F is in a water-repellent state at the step 22, so that the scooping up of the liquid F stops at the step 22. Therefore, regardless of the angle between the step 22 and the wall surface 23a of the small diameter portion 23, α + γ is more than 90 degrees at the angle α formed by the extension line of the wall surface 23a and the surface of the step 22 and the contact angle γ of the liquid F. (Provided that γ <90 degrees). More specifically, when the step 22 has a downward slope toward the inside of the horizontal or fine hole 21, if the α + γ is set so as to exceed 90 degrees, the rising of the liquid F causes the step 22 to rise. Stop at. Further, even when the step 22 has a downward slope toward the outside of the fine hole 21, α + γ may be set to exceed 90 degrees, but α is preferably set to 90 degrees or more. . The angle α is not particularly limited, but is about 80 to 100 degrees, desirably 85 to 95 degrees, and more desirably 85 to 87 degrees.

  FIG. 7 shows the rising of the liquid F in the micro hole 21 having the horizontal step 22 having the inner diameter D of the small diameter portion 23 of 1.7 mm and the width W of 0.13 mm. The dispensing amount of the liquid F is 14 μL.

  The left figure shows the change with time of the liquid F after 10 seconds have elapsed after dispensing, and the right figure shows the change with time of the liquid F after 120 seconds have elapsed after dispensing. As shown in the figure, in any case, the liquid F is prevented from scooping up before the step 22.

  As described above, the size of the step 22 is determined by the density of the liquid F and the state of the wall surface 23a. There is no particular limitation. The said dimension is suitably determined according to the liquid F and the wall surface 23a.

  Since the well 2 of the microchip 1 has the large-diameter portion 24 through the step 22 at the upper side, the wet liquid F filling the small-diameter portion 23 and scooping up the wall surface 23a of the small-diameter portion 23 by capillary action. Since it is necessary to be in a water-repellent state to cross the step 22, the liquid F scooping up the wall surface 23 a stops at the step 22. That is, it is possible to easily prevent the liquid F from climbing up to the upper surface 2a by simply forming the step 22 without subjecting the well 2 to surface treatment.

  In the present embodiment, the container according to the present invention has been described as the microchip 1 as an example, but is not limited thereto. For example, instead of the well 2, a material in which a fine hole having a shape like the fine hole 21 described above is formed on an appropriate plate-like material used for forming a microchip as described above is also included.

Schematic configuration diagram in dispensing process to microchip 1 Front view of microchip 1 Side view of microchip 1 Cross section of well 4 Schematic showing the transition of liquid F Schematic diagram of contact angle B of liquid F The figure which shows the effect of the level | step difference 22

Explanation of symbols

B Contact angle F Liquid, sample, reagent R Lid body 1 Microchip 2 Residing part, Well 3 Flow path, Micro flow path 21 Fine hole 22 Step 23 Wall surface 24 Large diameter part

Claims (4)

A reaction vessel comprising a flow channel and a reservoir communicating with the flow channel and storing a liquid introduced into the flow channel;
The storage part has a large diameter part through a step above,
The step is a reaction vessel having a size such that the liquid stored in the storage part below the step does not crawl up the storage part above the step by capillary action. .   The reaction vessel according to claim 1, wherein the step has a size of 0.05 mm or more in the horizontal direction.   The reaction container according to claim 1, wherein a plurality of the storage units are provided. The liquid is a sample or a reagent;
The reaction vessel according to any one of claims 1 to 3, wherein the flow channel is a micro flow channel for allowing the introduced liquid to flow.