WO2020178947A1

WO2020178947A1 - Fluid handling device

Info

Publication number: WO2020178947A1
Application number: PCT/JP2019/008397
Authority: WO
Inventors: Ashok Sinha; Ben Whiteley; Koichi Ono
Original assignee: Enplas Corp
Current assignee: Enplas Corp
Priority date: 2019-03-04
Filing date: 2019-03-04
Publication date: 2020-09-10
Anticipated expiration: 2021-09-04

Abstract

A fluid handling device that can house microparticles such as droplets while increasing the concentration of the microparticles is provided. A fluid handling device includes: a chamber including a first opening and a second opening in a wall surface; a first channel whose one end is connected with the first opening; and a second channel whose one end is connected with the second opening. The chamber includes a first region on the first opening side and a second region on the second opening side. A height of an interior of the chamber is smaller in the second region than in the first region. The second region includes a plurality of grooves in a bottom, the plurality of grooves extending in a direction from the first region toward the second opening, the plurality of grooves opening at the bottom of the second region and opening toward the first region.

Description

FLUID HANDLING DEVICE

The present invention relates to a fluid handling device.

In laboratory tests, food tests, environment tests and the like, highly accurate analysis of a trace analysis object such as cell, protein and nucleic acid is required in some situation. In a known method for analyzing a trace analysis object, micro liquid droplets (hereinafter referred to also as “droplet”) having a diameter of 0.1 to 1000 um are generated from liquid containing the analysis object so as to observe and analyze the droplets.

Typically, the generated droplets are collected in a micro tube or the like. Then, typically, a required amount of the droplet is separated from the micro tube for an observation and/or analysis. An apparatus provided with a needle is proposed as an apparatus for separation of the droplets collected in the micro tube or the like (e.g. PTL 1).

United States Patent No. 9126160

However, in the case where droplets are separated with the apparatus disclosed in PTL 1 and the like, a member for sucking the droplets, a member for controlling the position of the needle and the like are required, and consequently the apparatus is disadvantageously enlarged.

In view of this, it is conceivable to connect the droplet manufacturing apparatus and various chips to house the droplets in the chips. However, the droplets are typically dispersed in solvent. In the case where the droplets are introduced into the chip with a large amount of solvent, the number of droplets to be housed is small. When the concentration of the droplets is increased before housing the droplets in the chip, the fluidity is reduced and the housing of the droplets becomes difficult. In addition, when only solvent is discharged from the chip after the solvent and the droplets are housed, the droplets are also discharged and/or clogging of the outlet with the droplets results. That is, in the conventional methods, it is difficult to house droplets having a high concentration in a chip.

To solve the above-mentioned problems, an object of the present invention is to provide a fluid handling device that can house microparticles such as droplets while increasing the concentration of the microparticles.

The present invention provides a fluid handling device including: a chamber including a first opening and a second opening in a wall surface of the chamber; a first channel whose one end is connected with the first opening of the chamber; and a second channel whose one end is connected with the second opening of the chamber. The chamber includes a first region and a second region, the first region being closer to the first opening than the second region, the second region being closer to the second opening than the first region. A height of an interior of the chamber is smaller in the second region than in the first region. The second region includes a plurality of grooves in a bottom, the plurality of grooves extending in a direction from the first region toward the second opening, the plurality of grooves opening at the bottom of the second region and opening toward the first region.

According to the present invention, a fluid handling device that can house microparticles such as droplets while increasing the concentration of the microparticles is provided.

FIG. 1A is a plan view illustrating a configuration of a fluid handling device according to an embodiment of the present invention, and FIG. 1B is a sectional view of the fluid handling device along line A-A of FIG. 1A; FIG. 2A is a bottom view of the fluid handling device illustrated in FIG. 1A, and FIG. 2B is a plan view of a main body part of the fluid handling device illustrated in FIG. 1A; FIG. 3 is a partially enlarged view of a broken-line portion in the main body part illustrated in FIG. 2B; and FIG. 4 is a sectional view illustrating a configuration of a fluid handling device according to another embodiment of the present invention.

An embodiment of the present invention is elaborated below with reference to the accompanying drawings. For simplicity and clarity, elements in the figures may not be drawn to scale.

The fluid handling device of an embodiment of the present invention houses microparticles of fluid containing the microparticles and solvent while increasing the concentration of the microparticles. The fluid handling device can be used for storing a large amount of microparticles and for observing microparticles.

In the specification, the term “microparticles” means solid microparticles or liquid droplets (hereinafter referred to also as “droplets”), and the type of microparticles is not limited. The microparticles may have a microparticle size of 0.1 um to 1000 um. Preferably, the microparticle size is 5 um to 200 um.

The solid microparticles that can be housed in the fluid handling device of the present invention may be any microparticles of organic or inorganic materials. Typically, the liquid droplets (droplets) contain various components (e.g. cells, DNAs, and proteins such as enzymes) and a dispersion solvent for dissolving and/or dispersing the components. Each droplet may be a liquid droplet having a substantially spherical shape, and may be produced by a publicly known method. In addition, the solvent for dispersing the above-mentioned microparticles is not limited. The solvent may be appropriately selected in accordance with the type of microparticles, and in the case where the microparticles are droplets, it is possible to use a solvent (hereinafter referred to also as “host solvent”) having a poor compatibility with the components and/or the dispersion solvent included in the droplet.

FIG. 1A is a plan view of fluid handling device 100 according to an embodiment of the present invention, and FIG. 1B is a sectional view taken along line A-A of FIG. 1A. FIG. 2A is a bottom view of fluid handling device 100, and FIG. 2B is a plan view of main body part 101 in the state where cover 102 is dismounted from fluid handling device 100.

As illustrated in FIG. 1B, fluid handling device 100 according to the present embodiment includes main body part 101 including a groove, a recess, a through hole and/or the like, and plate-shaped cover 102 that is bonded on the main body part 101 so as to cover the groove, the recess, the through hole and/or the like. Fluid handling device 100 includes chamber 120 including first opening 122 and second opening 123 in the wall surface, first channel 110 connected with first opening 122 of the chamber 120, and second channel 130 connected with second opening 123 of chamber 120. For convenience of description, in an exemplary configuration described below, cover 102 is disposed on the upper side of main body part 101 in the gravity direction. It should be noted that the orientation of fluid handling device 100 is not limited to the above-mentioned orientation. For example, main body part 101 may be disposed on the upper side of cover 102 in the gravity direction. Further, in chamber 120, first opening 122 may be disposed on the upper side or the lower side with respect to second opening 123 in the gravity direction.

Here, chamber 120 of the present embodiment includes a hollow part defined, in a substantially hexagonal prism shape, by the wall surface and the bottom surface of chamber recess 120a disposed in main body part 101, and cover 102. In addition, first opening 122 and second opening 123 are provided in the upper portion of the wall of chamber recess 120a. Chamber 120 is communicated with first channel 110 described later through first opening 122, and is communicated with second channel 130 described later through second opening 123.

While the positions of first opening 122 and second opening 123 are not limited, it is preferable that first opening 122 and second opening 123 be sufficiently separated from each other in view of housing a large amount of microparticles. In the present embodiment, the openings are disposed at opposite corners in chamber recess 120a having a hexagonal shape in plan view.

It is to be noted that, the shape of the hollow part of chamber 120 is not limited to the substantially hexagonal prism shape, and may be appropriately set in accordance with the use of fluid handling device 100 and/or the number of microparticles to be used. For example, the shape may be a substantially square columnar shape, a substantially columnar shape, a substantially ellipsoidal columnar shape or the like.

Here, chamber 120 includes two regions differing in the height of the interior (the hollow part) thereof. To be more specific, chamber 120 includes first region 121a located on first opening 122 side and second region 122b located on second opening 123 side, and second region 122b has a height smaller than that of the first region 121a. In the present embodiment, the height of the interior of chamber 120 is the length from the bottom surface of chamber recess 120a to cover 102 in each region. Second region 121b includes grooves 124 as described later; however, in the specification, a plane obtained by connecting upper ends of grooves 124 is regarded as the bottom surface, and accordingly the depths of grooves 124 are not included in the height. In addition, the area ratio of first region 121a and second region 121b in chamber 120 in plan view is not limited.

First region 121a need only be a region having height h1 larger than the diameter of the microparticles to be introduced into chamber 120 and can allow the fluid to freely flow. While height h1 of first region 121a is constant in the present embodiment, height h1 may vary from first opening 122 side to second region 121b side so that the flow of the fluid is facilitated. In addition, a groove, a guide and/or the like (not illustrated) may be provided in a part of the region for the purpose of controlling the flow of the fluid.

On the other hand, second region 121b is a region having a height h2 smaller than the diameter of the microparticles to be introduced into chamber 120. By setting height h2 of second region 121b to a value smaller than the height of microparticles, it is possible to suppress the movement of the microparticles to second opening 123 side through second region 121b.

In the bottom portion of second region 121b, a plurality of grooves 124 extending from the first region 121a side to second opening 123 side are formed. Grooves 124 are provided for the purpose of housing the microparticles, and grooves 124 open not only to cover 102 side, but also to first region 121a side. FIG. 3 is a partially enlarged view of the region surrounded with broken line in FIG. 2B. FIG. 3 also illustrates microparticles 140 to illustrate how microparticles are housed in grooves 124.

In the present embodiment, as illustrated in FIG. 3, linear grooves 124 are disposed in parallel to one another in second region 121b. Grooves 124 need only be disposed along the flowing direction of the fluid from first region 121a side toward second opening 123 (second channel 130), and may not be formed in straight-line shapes. In addition, grooves 124 may not be parallel to one another, and may be radially disposed to match the shape of chamber 120, for example.

In addition, the depth of groove 124 is not limited as long as housed microparticles 140 can be prevented from escaping from groove 124. In the present embodiment, the depth of groove 124 is greater than height h2 of second region 121b. This configuration increases the ease of stemming of the microparticles with groove 124. In addition, in the present embodiment, the depth of groove 124 is substantially equal to the diameter of microparticle 140 such that the microparticles do not overlap in the height direction. It should be noted that groove 124 may have a depth that allows housed microparticles 140 to overlap in the height direction. While the depth of groove 124 is constant in the present embodiment, the depth of groove 124 may vary intermittently or continuously. Further, while the bottom surface of groove 124 is flush with the bottom surface of first region 121a, a step may be disposed therebetween as long as flow of microparticles 140 is not blocked.

Further, in the present embodiment, the width of groove 124 is substantially equal to the diameter of microparticle 140 so that microparticles 140 are housed in one line in each groove 124. It should be noted that the width of groove 124 need only be greater than the diameter of housed microparticle 140 and may be set to a width that can house a plurality of lines of microparticles 140, for example. In addition, the width of groove 124 may not be constant.

The number and lengths of grooves 124 may be appropriately set in accordance with the number of the microparticles 140 to be housed. It is to be noted that all microparticles 140 may be housed in grooves 124, or only a part of microparticles 140 may be housed in groove 124. In the case where all microparticles 140 are housed in grooves 124, microparticles 140 are easily observed and analyzed from cover 102 side or main body part 101 side.

In addition, in the present embodiment, the width of opening 124a of groove 124 on first region 121a side is wider than other region of groove 124 for the purpose of facilitating intake of microparticles 140, the width of the opening 124a may be equal to that of other regions of groove 124.

First channel 110 of fluid handling device 100 of the present embodiment is an channel whose one end is connected with first opening 122 of chamber 120, and the other end is connected with fluid inlet 111 and microparticle outlet 112. In the present embodiment, first channel 110 is a region surrounded by first channel groove 110a disposed in main body part 101 and cover 102. In addition, in the present embodiment, first channel 110 is divided into two channels such that one channel is connected with fluid inlet 111 for introducing fluid, and the other channel is connected with microparticle outlet 112 for removing microparticles as necessary. It is to be noted that first channel 110 may be connected with two or more fluid inlets 111. For example, in the case where first channel 110 is connected with a plurality of fluid inlets 111, different fluids can be introduced from respective fluid inlets 111, and the fluids thus introduced can be mixed in first channel 110, for example.

The depth (height) of first channel 110 is not limited as long as the fluid can be kept flowing, and in the present embodiment, the depth of first channel 110 is substantially equal to height h1 of first region 121a of chamber 120. Also, the width thereof is not limited as long as the width is greater than the diameter of the microparticle.

Fluid inlet 111 and microparticle outlet 112 communicated with first channel 110 are through holes disposed in main body part 101, and their diameters are not limited as long as the fluid can be introduced into fluid handling device 100 and the microparticles can be output as necessary after microparticles are housed in chamber 120. For example, fluid inlet 111 and/or microparticle outlet 112 may be connected with a syringe, a tube and the like for introducing fluid.

In addition, second channel 130 is a channel whose one end is connected with second opening 123 of chamber 120 and the other end is connected with solvent outlet 131 for the fluid. In the present embodiment, second channel 130 is a region surrounded by second channel groove 130a disposed in main body part 101 and cover 102. The depth (height) of second channel 130 is not limited as long as the solvent can be discharged from solvent outlet 131 at a desired velocity. While the height of the second channel is substantially equal to height h2 of second region 121b of chamber 120 in the present embodiment, the second channel 130 may be higher or lower than second region 121b. Also, the width of second channel 130 is not limited, and may be appropriately set in accordance with the amount of the solvent to be discharged.

Also, solvent outlet 131 communicated with second channel 130 is a through hole disposed in main body part 101, and the diameter thereof is not limited as long as the solvent can be discharged out of fluid handling device 100.

Here, cover 102 of fluid handling device 100 may be a flat film or a plate-shaped member that covers the openings of chamber recess 120a, first channel groove 110a, second channel groove 130a, fluid inlet 111, microparticle outlet 112, solvent outlet 131 and the like of main body part 101. The thickness and the like of the cover 102 may be appropriately set as long as the cover 102 is composed of a material that is not eroded by the fluid (in particular, the host solvent) introduced to fluid handling device 100. The material of the cover may be an inorganic material such as glass; or a resin material such as polyester such as polyethylene terephthalate; polycarbonate; acrylic resin such as polymethylmethacrylate; polyvinyl chloride; polyolefin such as polyethylene, polypropylene, and cycloolefin resin; polyether; polystyrene; silicone resin; and elastomers.

In addition, cover 102 may be or may not be optically transparent. For example, in the case where microparticles housed in chamber 120 are observed and/or analyzed from cover 102 side, it is preferable that cover 102 be optically transparent. On the other hand, in the case where such an observation is not performed, and the case where observation or the like of the microparticles are performed from main body part 101 side, cover 102 need not have optical transparency.

Main body part 101 need only include the above-described fluid inlet 111, first channel groove 110a, chamber recess 120a, second channel groove 130a, and solvent outlet 131. Examples of the material of main body part 101 include resin materials such as polyester such as polyethylene terephthalate; polycarbonate; acrylic resins such as polymethylmethacrylate; polyvinyl chloride; polyolefin such as polyethylene, polypropylene, and cycloolefin resin; polyether; polystyrene; silicone resins such as polydimethyl siloxane; and elastomers. In addition, the main body part having the above-mentioned configuration may be formed by injection molding and the like, for example. In addition, main body part 101 may be integrally formed, or may be composed of a combination of a plurality of members.

Here, main body part 101 may be or may not be optically transparent. In the case where microparticles 140 housed in chamber 120 are observed and/or analyzed from main body part 101 side, the material of main body part 101 is selected such that main body part 101 is optically transparent.

In addition, main body part 101 and cover 102 may be joined by heat fusing, bonding with an adhesive agent and the like, and may be joined by publicly known methods.

Fluid Handling Method
A fluid handling method using fluid handling device 100 is described below. First, a microparticle manufacturing apparatus (not illustrated) or the like and fluid inlet 111 of fluid handling device 100 are connected with each other with a tube (not illustrated) or the like. Meanwhile, solvent outlet 131 of fluid handling device 100 and a container (not illustrated) or the like for collecting the solvent are connected with each other with a tube (not illustrated) or the like. In addition, first channel 110, chamber 120, and second channel 130 are preliminarily filled with solvent that does not contain microparticles. It is to be noted that “solvent that does not contain microparticles”need only be a solvent having poor compatibility with microparticles. The solvent may be identical to or different from the above-described host solvent.

Then, the fluid is introduced into chamber 120 through fluid inlet 111 and first channel 110. At this time, as necessary, a pressure application from fluid inlet 111 side and/or suction from solvent outlet 131 side may be performed to facilitate the flow of the fluid. Then, the fluid flowing into chamber 120 moves from first region 121a side toward second region 121b side. At this time, since the height of second region 121b is smaller than the diameter of the microparticle, the microparticles are housed in grooves 124 installed in second region 121b without moving between the bottom surface of second region 121b and cover 102. Meanwhile, the solvent in the fluid moves between the bottom surface of second region 121b and cover 102 toward second opening 123 side (second channel 130 side). As a result, only the solvent is discharged from solvent outlet 131, and the microparticles are predominantly housed in chamber 120.

Further, the microparticles housed in chamber 120 of fluid handling device 100 can be output from chamber 120 as necessary by suction from microparticle outlet 112, for example.

Other Configurations
If the velocity of introducing fluid is significantly high, the microparticles might be deformed and discharged from second opening 123 together with the solvent. To reduce such a movement of microparticles, a columnar structure (not illustrated) or the like may be provided between second opening 123 and the end portion groove 124 on second opening 123 side in second region 121b. When such a columnar structure is provided, the movement of the microparticles toward second opening 123 side is reduced even when the velocity of the flow of the fluid is high. It is to be noted that the diameter, shape and the like of the columnar structure may be appropriately set as long as the columnar structure does not block the flow of the solvent.

While first channel 110 is connected with fluid inlet 111 and second channel 130 is connected with solvent outlet 131 in fluid handling device 100 of the embodiment, first channel 110 and/or second channel 130 may be connected with other chambers (not illustrated) provided in fluid handling device 100 or the like.

Further, chamber 120 includes only first region 121a and second region 121b in fluid handling device 100 of the embodiment. It should be noted that chamber 220 may further include third region 221c on second opening 123 side of second region 121b as in fluid handling device 200 of another embodiment illustrated in FIG. 4. Height h3 of third region 221c may be higher or lower than the height of second region 121b. It is to be noted that fluid handling device 200 of the embodiment is identical to fluid handling device 100 of the embodiment except that chamber 220 includes third region 221c. The configurations similar to those of the above-mentioned embodiment are denoted with the same reference numerals, and the description thereof is omitted.

Also in the fluid handling device 200, when fluid is introduced into chamber 220, the fluid moves from first region 121a side toward second region 121b side. Microparticles of the fluid moved to second region 121b side are housed in grooves 124 in second region 121b. Meanwhile, the solvent moves to second region 121b and third region 221c side so as to be discharged from second channel 130.

Effect
According to the fluid handling device of the embodiment of the present invention, microparticles can be collected and the concentration thereof can be increased without using a large-scale apparatus such as a suction member and a control member for needles. In addition, since the microparticles are housed in the groove in the second region in the chamber, the microparticles do not close the opening (second opening) for discharging the solvent. Thus, the solvent can be surely discharged out of the chamber. Further, even when the velocity of the flow of the fluid is increased, the microparticles are not easily discharged from the chamber, and thus the microparticles can be efficiently housed. Further, with the fluid handling device, the microparticles housed in the groove of the chamber can be observed and/or analyzed.

The fluid handling device and the fluid handling method of the present invention are applicable to laboratory tests, food tests, environment tests and the like, for example.

100, 200 Fluid handling device
101 Main body part
102 Cover
110 First channel
110a First channel groove
111 Fluid inlet
112 Microparticle outlet
120, 220 Chamber
120a Chamber recess
121a First region
121b Second region
221c Third region
122 First opening
123 Second opening
124 Groove
124a Opening
130 Second channel
130a Second channel groove
131 Solvent outlet

Claims

A fluid handling device, comprising:
a chamber including a first opening and a second opening in a wall surface of the chamber;
a first channel whose one end is connected with the first opening of the chamber; and
a second channel whose one end is connected with the second opening of the chamber,
wherein the chamber includes a first region and a second region, the first region being closer to the first opening than the second region, the second region being closer to the second opening than the first region,
wherein a height of an interior of the chamber is smaller in the second region than in the first region, and
wherein the second region includes a plurality of grooves in a bottom, the plurality of grooves extending in a direction from the first region toward the second opening, the plurality of grooves opening at the bottom of the second region and opening toward the first region.
The fluid handling device according to claim 1, wherein a depth of each of the plurality of grooves is larger than the height of an interior of the chamber in the second region.
The fluid handling device according to claim 1 or 2,
wherein, when a fluid containing microparticles and a solvent is introduced from the first channel to the chamber, the microparticles are housed in the plurality of grooves and the solvent is discharged from the second channel; and
wherein the height of the interior of the chamber is smaller than a diameter of each microparticle in the second region.
The fluid handling device according to any one of claims 1 to 3, wherein bottom surfaces of the plurality of grooves in the second region and a bottom surface in the first region are flush with one another.
The fluid handling device according to any one of claims 1 to 4, wherein the plurality of grooves in the second region are parallel to one another.
The fluid handling device according to any one of claims 1 to 5,
wherein a main body part and a cover are stacked;
wherein the main body part includes:
a recess forming a part of the chamber,
a first channel groove connected with the recess, the first channel groove forming a part of the first channel, and
a second channel groove connected with the recess, the second channel groove forming a part of the second channel; and
wherein the cover covers an opening of the recess, an opening of the first channel groove, and an opening of the second channel groove.