The present invention relates to a liquid handling device.
In recent years, microchannel chips (flow cells) have been used to accurately and speedily analyze a trace substance such as protein and nucleic acid. Microchannel chips can advantageously handle a small amount of reagents or samples, and are expected to be used for various uses such as laboratory tests, food tests, and environment tests.
The microchannel chip disclosed in PTL 1 includes a supply part for supplying liquid, and a plurality of discharging parts for discharging the provided liquid, and a channel connecting the supply part and the discharging parts. The microchannel chip is composed of an upper substrate and a lower substrate. In the upper substrate, a through hole that serves as the supply part and a plurality of through holes that serve as discharging parts are formed. In the lower substrate, a groove that serves as the channel is formed.
In the microchannel chip disclosed in PTL 1, when liquid is provided to the supply part, the channel is filled with the liquid by capillarity. Next, the liquid filling the channel flows into the discharging part.
As described above, in microchannel chips used for various inspections, the capacity of each discharging part may be reduced and the distance between each discharging part may be reduced so as to reduce the size of the microchannel chip in some situation. In such microchannel chips, however, the liquid may flow out of the discharging part after the inspection, and the liquid may be mixed with liquid that flows out from another discharging part.
In view of this, an object of the present invention is to provide a liquid handling device that can prevent liquids retained in discharging parts from making contact with each other between the discharging parts.
A liquid handling device of an embodiment of the present invention includes one introduction part that opens at a first surface of a substrate, the one introduction part being configured to introduce liquid; a plurality of discharging parts that open at the first surface of the substrate, the plurality of discharging parts being configured to discharge the liquid introduced from the one introduction part; a channel configured to connect the one introduction part and the plurality of discharging parts in the substrate; and a plurality of outflow preventing parts disposed to surround respective openings of the plurality of discharging parts, the plurality of outflow preventing parts being configured to prevent advancement of outflow of the liquid from the plurality of discharging parts by using surface tension. Two or more of the plurality of outflow preventing parts are disposed for each opening so as to surround each opening.
According to the present invention, it is possible to provide a liquid handling device that can prevent liquids retained in discharging parts from making contact with each other between the discharging parts.
Embodiments of the present invention are elaborated below with reference to the accompanying drawings. In the following description, a microchannel chip (flow cell) is described as a typical example of the liquid handling device of the present invention.
As illustrated in
Introduction part 110 is an inlet for introducing liquid to channel 130 and discharging part 120. Introduction part 110 includes retainer 112 and inlet 114.
The type of the liquid to be introduced to channel 130 may be appropriately selected. Examples of the liquid include reagent and liquid sample. In addition, the viscosity of the liquid to be introduced to channel 130 may be appropriately selected. In the present embodiment, the viscosity of the liquid is set to a viscosity at which the liquid can advance in channel 130 by capillarity.
Retainer 112 temporarily retains the liquid to be introduced to channel 130. Retainer 112 is disposed on the side same as top surface 152 of substrate 150 on which the plurality of outflow preventing parts 140 are disposed. The shape of retainer 112 may be appropriately set as long as liquid can be temporarily retained. In the present embodiment, retainer 112 is a substantially cylindrical space disposed above inlet 114. Retainer 112 is surrounded by a side wall. Since the liquid inside retainer 112 is finally housed in the plurality of discharging parts 120, the volume of retainer 112 is normally greater than the volume of each discharging part 120. As such, it is preferable that the distance between the opening of introduction part 110 and the top surface 152 (first surface) of substrate 150 is greater than the distance between the opening of discharging part 120 and the top surface 152.
Inlet 114 guides the liquid retained in retainer 112 to channel 130. The upper opening of inlet 114 is communicated with retainer 112, and the side opening of introduction part 110 is communicated with channel 130. The shape of inlet 114 may be appropriately set as long as the liquid retained in retainer 112 can be guided to channel 130. In the present embodiment, the shape of inlet 114 is a bottomed recess whose diameter gradually decreases from retainer 112 toward channel 130.
Channel 130 is a channel through which liquid can move by capillarity, and channel 130 has a branch. The upstream end of channel 130 is connected with introduction part 110 (inlet 114), and a plurality of downstream ends of channel 130 are connected with respective discharging parts 120.
The plurality of discharging parts 120 are housing parts that retain liquid incoming from channel 130, and cause a desired reaction as necessary. In addition, the liquid in discharging part 120 is discharged to the outside from the opening of discharging part 120. Discharging part 120 functions also as an air hole for introducing liquid to channel 130. The plurality of discharging parts 120 are communicated with the downstream ends of channel 130. The shape of discharging part 120 may be appropriately set as long as the liquid from channel 130 can be retained. The shape of discharging part 120 may be a shape whose diameter gradually increases from the bottom toward the opening, a shape whose diameter gradually decreases from the bottom toward the opening, or a shape whose diameter is identical between the bottom and the opening.
In the present embodiment, discharging part 120 has a shape of a bottomed recess whose diameter is identical between the bottom and the opening.
The plurality of outflow preventing parts 140 are disposed so as to surround the openings of respective discharging parts 120, and prevent advancement of outflow of the liquid from the openings of discharging part 120 by using the surface tension of the liquid.
In microchannel chip 100 according to the present embodiment, two or more outflow preventing parts 140 are disposed for each opening so as to surround the opening. The configuration of outflow preventing part 140 may be appropriately set as long as advancement of the liquid from the opening of discharging part 120 can be prevented by using the surface tension of the liquid. For example, outflow preventing part 140 is (A) an opening edge of discharging part 120, (B) a step that is disposed in the inner surface of discharging part 120 so as to surround the opening and is formed to extend toward the outside from the center side of discharging part 120, (C) an annular groove that is disposed outside the opening so as to surround the opening, or (D) eaves part 142 extending from the inner surface of the discharging part toward the opening. In the present embodiment, outflow preventing part 140 is (D) eaves part 142 extending from the inner surface of discharging part 120 toward the center of the opening, and (A) the opening edge of discharging part 120. More specifically, as illustrated in
Eaves part 142 is an annular plate-shaped member disposed at the inner surface of discharging part 120. The internal diameter of eaves part 142 in plan view of eaves part 142 may be appropriately set as long as it is smaller than the diameter of the opening of discharging part 120. In addition, the thickness of eaves part 142 may be appropriately set.
In the above-mentioned manner, microchannel chip 100 is composed of substrate 150 and film 160. Substrate 150 is a substantially rectangular transparent resin substrate. Substrate 150 includes channel groove 155, first through hole 156, and a plurality of second through holes 157.
Of two surfaces of substrate 150, channel groove 155 is formed in bottom surface 154 (second surface) on the side opposite to top surface 152 (first surface) where retainer 112 and outflow preventing part 140 are disposed. One end of channel groove 155 is communicated with first through hole 156. The other end of channel groove 155 has a branch, and is communicated with respective second through holes 157. When the opening of channel groove 155 is covered with film 160, channel groove 155 serves as channel 130.
First through hole 156 is a through hole that opens at the top surface 152 and bottom surface 154 of substrate 150. First through hole 156 is communicated with the upstream end of channel groove 155. The shape of first through hole 156 may be appropriately set. In the present embodiment, first through hole 156 has a shape whose diameter gradually decreases from top surface 152 toward bottom surface 154. When the opening on bottom surface 154 side is covered with film 160, first through hole 156 serves as inlet 114.
In addition, a side wall extending in the thickness direction of substrate 150 is disposed so as to surround the upper opening of first through hole 156. This side wall defines retainer 112.
The plurality of second through holes 157 are through holes that open at the top surface 152 and bottom surface 154 of substrate 150. The plurality of second through holes 157 are communicated with respective downstream ends of channel groove 155. The shape of second through hole 157 may be appropriately set. In the present embodiment, second through hole 157 has a shape whose diameter is identical from the opening of bottom surface 154 side to the opening of top surface 152 side. When the opening on bottom surface 154 side is covered with film 160, each second through hole 157 serves as discharging part 120.
In addition, eaves part 142 is disposed so as to close a part of the opening of second through hole 157 on top surface 152 side. As described above, each of the lower opening edge and the upper opening edge (the opening edge of discharging part 120) of the opening of eaves part 142 functions as the outflow preventing part 140.
The kind of the resin of substrate 150 is not limited and may be appropriately selected from publicly known resins as long as the surface (the surface serving as the internal wall of the channel) that allows liquid to advance channel 130 by capillarity, the adhesion strength to film 160, and the resistance to thermal hysteresis and reagent during various processes can be ensured. The examples of the resin of substrate 150 include polyethylene terephthalate, polycarbonate, polymethylmethacrylate, vinyl chloride, polypropylene, polyether, polyethylene, polystyrene, silicone resin and the like. Substrate 150 has a thickness of 1 to 10 mm for example.
Film 160 is a transparent resin film joined to bottom surface 154 of substrate 150. For example, film 160 and substrate 150 are joined together by thermal compression bonding. Film 160 covers the opening of first through hole 156 on the bottom surface 154 side, the opening of channel groove 155, and the openings of the plurality of second through holes 157 on bottom surface 154 side. The type of the resin of film 160 may be selected from the resin for substrate 150. The resin of film 160 may be identical to that of substrate 150. The thickness of film 160 may be appropriately set in accordance with the resin type (rigidity) as long as the above-described function can be ensured. In the present embodiment, film 160 has a thickness of about 20 μm.
Next, an operation of microchannel chip 100 is described.
As illustrated in
With the above-mentioned configuration, with the lower opening edge (outflow preventing part 140 of the first stage) of the opening of eaves part 142 and the upper opening edge (outflow preventing part 140 of the second stage) of the opening of eaves part 142, microchannel chip 100 according to the present embodiment can reduce outflow of the liquid from discharging part 120. Thus, even if an excessive amount of liquid is introduced into introduction part 110, the possibility of a situation where the liquids retained in discharging parts 120 make contact with each other between discharging parts 120 can be further reduced.
Microchannel chip 200 according to Embodiment 2 differs from microchannel chip 100 according to Embodiment 1 only in the structure of outflow preventing part 240. In view of this, in the present embodiment, outflow preventing part 240 is mainly described. Note that the components similar to those of microchannel chip 100 according to Embodiment 1 are denoted with the same reference numerals, and the description thereof will be omitted.
As illustrated in
Substrate 250 includes channel groove 155, first through hole 156, and second through hole 357. In addition, eaves part 142 is disposed at top surface 152 of substrate 250, and annular groove 244 opens at top surface 152 of substrate 250.
In the present embodiment, as outflow preventing part 240, (C) annular groove 244 that is disposed outside the opening so as to surround the opening also functions in addition to (D) eaves part 142 extending from the inner surface of discharging part 120 toward the center of the opening and (A) the opening edge of discharging part 120.
Annular groove 244 is an annular groove that is disposed outside the opening of discharging part 120 so as to surround the opening of discharging part 120. In the present embodiment, annular groove 244 is disposed in the top surface of eaves part 142. The width and depth of annular groove 244 are not limited as long as movement of liquid passing over annular groove 244 can be reduced, and may be appropriately set in accordance with the location where annular groove 244 is disposed. While one annular groove 244 is provided for each discharging part 120 in microchannel chip 200 in the present embodiment, a plurality of annular grooves 244 may be provided for each discharging part 120. In this case, annular grooves 244 are concentrically disposed about the center of the opening of discharging part 120.
Next, an operation of microchannel chip 200 is described.
As illustrated in
In the above-mentioned manner, with eaves part 142 extending from the inner surface of discharging part 120 toward the center of the opening (outflow preventing part 240 of the first stage), the opening edge of discharging part 120 (outflow preventing part 240 of the second stage), and annular groove 244 that is disposed outside the opening so as to surround the opening (outflow preventing part 240 of the third stage), microchannel chip 200 according to the present embodiment can reduce outflow of the liquid from discharging part 120, and can limit expansion of the liquid that has flown out from liquid discharging part 120. Thus, the possibility of a situation where the liquids retained in discharging parts 120 make contact with each other between discharging parts 120 can be further reduced.
Microchannel chip 300 according to Embodiment 3 differs from microchannel chip 100 according to Embodiment 1 only in the structure of outflow preventing part 340. In view of this, in the present embodiment, outflow preventing part 340 is mainly described.
Note that the components similar to those of microchannel chip 100 according to Embodiment 1 are denoted with the same reference numerals, and the description thereof will be omitted.
As illustrated in
The plurality of discharging parts 320 are housing parts that retain liquid coming from channel 130, and cause a desired reaction as necessary. The liquid in discharging part 320 is discharged to the outside from the opening of discharging part 320. Discharging part 320 functions also as an air hole for introducing liquid to channel 130.
The plurality of discharging parts 320 are communicated with the downstream end of channel 130. In the present embodiment, discharging part 320 is a bottomed recess whose diameter gradually increases from the bottom toward the opening.
In the present embodiment, (A) the opening edge of discharging part 320, and (C) annular groove 244 that is disposed outside the opening so as to surround the opening function as outflow preventing part 340. Annular groove 244 is disposed outside the opening of discharging part 320 so as to surround the opening in top surface 152.
Substrate 350 includes channel groove 155, first through hole 156 and second through hole 357. In addition, annular groove 244 is open at top surface 152 of substrate 350. Second through hole 357 is a through hole that opens at top surface 152 and bottom surface 154, and is a bottomed recess whose diameter gradually increases from bottom surface 154 toward top surface 152. When the openings of the plurality of second through holes 357 on bottom surface 154 side is covered with film 160, each through holes 357 serves as discharging part 320.
Next, an operation of microchannel chip 300 is described.
As illustrated in
Effect
In the above-mentioned manner, with the opening edge of discharging part 320 (outflow preventing part 340 of the first stage), and annular groove 244 that is disposed outside the opening so as to surround the opening (outflow preventing part 240 of the second stage), microchannel chip 300 according to the present embodiment can reduce outflow of the liquid from discharging part 320, and can limit expansion of the liquid that has flown out from liquid discharging part 320. Thus, even if an excessive amount of liquid is introduced into introduction part 110, the possibility of a situation where the liquids retained in discharging parts 320 make contact with each other between discharging parts 320 can be further reduced.
Microchannel chip 400 according to Embodiment 4 differs from microchannel chip 100 according to Embodiment 1 only in the structure of outflow preventing part 440. In view of this, in the present embodiment, outflow preventing part 440 is mainly described.
Note that the components similar to those of microchannel chip 100 according to Embodiment 1 are denoted with the same reference numerals, and the description thereof will be omitted.
As illustrated in
In the present embodiment, (B) step 442 that is formed so as to extend toward the outside from the center side of discharging part 120, (A) the opening edge of discharging part 420, and (C) annular groove 244 that is disposed outside the opening so as to surround the opening function as outflow preventing part 440.
Step 424 is disposed in the inner surface of discharging part 420 so as to extend away from the center side of the opening toward the outside. In the present embodiment, step 424 is a step portion formed between a cylindrical part whose opening area is greater than that of discharging part 420 and the inner surface of discharging part 120.
Substrate 450 includes channel groove 155, first through hole 156, and second through hole 457. In addition, step 424 is formed in top surface 152 of substrate 450 and annular groove 244 is open at top surface 152 of substrate 450.
Next, an operation of microchannel chip 400 is described.
As illustrated in
In the above-mentioned manner, with step 424 that is formed in the inner surface of discharging part 420 so as to surround the opening and to extend toward the outside from the center side of discharging part 420 (outflow preventing part 440 of the first stage), the opening edge of discharging part 420 (outflow preventing part 440 of the second stage), and annular groove 244 that is disposed outside the opening so as to surround the opening, microchannel chip 400 according to the present embodiment can reduce outflow of the liquid from discharging part 420, and can limit the expansion of the liquid that has flown out from liquid discharging part 420. Thus, even if an excessive amount of liquid is introduced into introduction part 110, the possibility of a situation where the liquids retained in discharging parts 420 make contact with each other between discharging parts 420 can be further reduced.
Note that the combinations and number of outflow preventing parts (A), (B), (C) and (D) may not be those described in Embodiment 1 to 4.
Microchannel chip 500 according to Embodiment 5 is different from microchannel chip 100 according to Embodiment 1 only in that hydrophilic treatment is provided in at least a part of a region. Note that the components similar to those of microchannel chip 100 according to Embodiment 1 are denoted with the same reference numerals, and the description thereof will be omitted.
Microchannel chip 500 includes one introduction part 110, a plurality of discharging parts 120, channel 130, and a plurality of outflow preventing parts 140.
Microchannel chip 500 is composed of substrate 150 and film 160. As illustrated in
Microchannel chip 500 may be manufactured by the following method, for example.
Next, as illustrated in
The method of providing the hydrophilic treatment may be appropriately selected. Examples of the method of providing the hydrophilic treatment include a plasma treatment and an atomic layer deposition (ALD) method. Examples of the thin film formed by the atomic layer deposition (ALD) method include a layer including silicon oxide, a layer including aluminum oxide, and a layer including titanium oxide. With this configuration, hydrophilicity is provided to the regions other than the region masked with mask member 570. In addition, the regions other than the region masked with mask member 570 become hydrophobic in comparison with the region masked with mask member 570. Note that, normally, the surface of an injection-molded article using a commonly used resin has hydrophobicity.
Next, film 160 is joined to bottom surface 154 of substrate 150 after mask member 570 is removed, and thus microchannel chip 500 illustrated in
With the above-mentioned configuration, microchannel chip 500 according to the present embodiment can easily carry the liquid since the hydrophilicity is provided at the interior of channel 130 and discharging part 120 with the hydrophilic region and the hydrophobic region while achieving the effect of Embodiment 1.
Microchannel chip 600 according to Embodiment 6 is different from microchannel chip 200 according to Embodiment 2 only in that hydrophilic treatment is provided in at least a part of a region. Note that the components similar to those of microchannel chip 200 according to Embodiment 2 are denoted with the same reference numerals, and the description thereof will be omitted.
Microchannel chip 600 includes introduction part 110, channel 130, a plurality of discharging parts 120, and a plurality of outflow preventing parts 240. Microchannel chip 600 is composed of substrate 250 and film 160. As illustrated in
Microchannel chip 600 may be manufactured by the following method, for example. As illustrated in
Effect With the above-mentioned configuration, microchannel chip 600 according to the present embodiment can easily carry the liquid since the hydrophilicity is provided at the interior of channel 130 and discharging part 120 with the hydrophilic region and the hydrophobic region while achieving the effect of Embodiment 2.
Microchannel chip 700 according to Embodiment 7 is different from microchannel chip 300 according to Embodiment 3 only in that hydrophilic treatment is provided in at least a part of a region. Note that the components similar to those of microchannel chip 300 according to Embodiment 3 are denoted with the same reference numerals, and the description thereof will be omitted.
Note that, in
Microchannel chip 700 includes one introduction part 110, a plurality of discharging parts 320, channel 130 and a plurality of outflow preventing parts 340. In the present embodiment, at the surface of microchannel chip 700, outflow preventing part 340 where the liquid first reaches when the liquid is continuously introduced into discharging part 320 from channel 130 is the opening edge of discharging part 320. In addition, outflow preventing part 340 where the liquid reaches last is annular groove 244. The hydrophilic treatment is provided in at least a part of the region other than the region between the opening edge of discharging part 320 and annular groove 244. In the present embodiment, the hydrophilic treatment is provided in all regions except for the region between the opening edge of discharging part 320 and annular groove 244. The region between the opening edge of discharging part 320 and annular groove 244 is the hydrophobic region.
Microchannel chip 700 may be manufactured by the following method, for example.
With the above-mentioned configuration, microchannel chip 700 according to the present embodiment can easily carry the liquid since the hydrophilicity is provided at the interior of channel 130 and discharging part 320 with the hydrophilic region and the hydrophobic region while achieving the effect of Embodiment 3.
Microchannel chip 800 according to Embodiment 8 is different from microchannel chip 400 according to Embodiment 4 only in that hydrophilic treatment is provided in at least a part of a region. Note that the components similar to those of microchannel chip 400 according to Embodiment 4 are denoted with the same reference numerals, and the description thereof will be omitted.
Microchannel chip 800 includes one introduction part 110, a plurality of discharging parts 420, channel 130 and a plurality of outflow preventing parts 440. Microchannel chip 800 is composed of substrate 450 and film 160. In the present embodiment, at the surface of microchannel chip 800, outflow preventing part 440 where the liquid first reaches when the liquid is continuously introduced into discharging part 420 from channel 130 is the opening edge of discharging part 420. In addition, outflow preventing part 440 where the liquid reaches last is annular groove 244. The hydrophilic treatment is provided in at least a part of the region other than the region between the opening edge of discharging part 420 and annular groove 244. In the present embodiment, the hydrophilic treatment is provided in all regions other than the region between the opening edge of discharging part 420 and annular groove 244.
Microchannel chip 800 may be manufactured by the following method, for example.
With the above-mentioned configuration, microchannel chip 800 according to the present embodiment can easily carry the liquid since the hydrophilicity is provided at the interior of channel 130 and discharging part 420 with the hydrophilic region and the hydrophobic region while achieving the effect of Embodiment 4.
This application is entitled to and claims the benefit of Japanese Patent Application No. 2017-071235 filed on Mar. 31, 2017, and Japanese Patent Application No. 2017-167630 filed on Aug. 31, 2017, the disclosure each of which including the specification, drawings and abstract is incorporated herein by reference in its entirety.
The microchannel chip of embodiments of the present invention is useful as a microchannel chip used in the scientific fields, the medical fields and the like, for example.
Number | Date | Country | Kind |
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2017-071235 | Mar 2017 | JP | national |
2017-167630 | Aug 2017 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2018/009115 | 3/9/2018 | WO | 00 |