The present invention relates to a liquid handling system.
In recent years, microwell plates, channel chips, and the like are used to analyze, for example, cells, proteins, and nucleic acids. Microwell plates and channel chips are advantageous such that only a small amount of reagents and samples is required for analysis, thus are expected to be used in a variety of applications such as clinical tests, food tests, and environment tests.
Patent Literature (hereinafter, referred to as PTL) 1, for example, discloses a reaction container including a sample container for housing a sample, a sample container housing part for housing the sample container, and a sample channel connected to the sample container housed in the sample container housing part. The sample container includes a plurality of locking grooves on the surface thereof, and the sample container housing part includes a plurality of locking claws. By engaging the locking claws with the locking grooves, the sample container is held in the sample container housing part at a predetermined position.
PTL 1
WO2009/072332
Regarding the reaction container described in PTL 1, the sample container is not configured to be detached from the sample container housing part. Once the sample container is housed in the sample container housing part, it is difficult to remove the sample container.
An object of the present invention is to provide a liquid handling system including a channel chip and a cartridge containing a liquid to be introduced into the channel chip, and in the liquid handling system, the cartridge can be fixed to or removed from the channel chip.
A liquid handling system of the present invention includes the following: a channel chip including an introduction port for introducing a liquid and a channel for allowing a liquid introduced from the introduction port to flow therethrough; a chip holder for housing the channel chip; a cartridge housing a liquid to be introduced into the introduction port; and a liquid handling device for supporting the chip holder and for controlling a flow of a liquid in the channel chip housed in the chip holder, in which the channel chip, the chip holder, or the liquid handling device includes a first engagement part, and the cartridge includes: a housing part housing a liquid; a communication pipe configured to allow the housing part and the introduction port to communicate with each other; packing disposed at the communication pipe, and a second engagement part configured to detachably engage with the first engagement part, in which the first engagement part and the second engagement part are configured in such a way that when the first engagement part and the second engagement part detachably engage with each other, the communication pipe is connected to the introduction port while the packing is pressed by the introduction port.
The present invention is capable of providing a liquid handling system including a channel chip and a cartridge containing a liquid to be introduced into the channel chip, and in the liquid handling system, the cartridge can be fixed to or removed from the channel chip.
Hereinafter, a liquid handling system according to an embodiment of the present invention will be described.
Configuration of Liquid Handling System
As illustrated in
Configuration of Chip Holder
As illustrated in
As illustrated in
Through hole 111 is formed in the top surface of chip holder 110, and allows thereto insertion of communication pipes 121 of cartridge 120. In the present embodiment, the number of through holes 111 is two. In the present embodiment, through hole 111 has a size in plan view such that five introduction ports 240 can be housed therein.
First opening 112 is formed in the front surface of chip holder 110 and is used for placing or removing channel chip 200.
Recesses 114 are formed in the top surface, front surface and rear surface of chip holder 110 and each configured to house corresponding one of two second engagement parts 124 of cartridge 120. In the present embodiment, the number of second engagement parts 124 is two; thus the number of recesses 114 is two (a pair).
Second opening 115 is formed in the bottom surface of chip holder 110 (the surface to contact film 220 of channel chip 200). First rotary member 300 and second rotary member 320 contact the bottom surface (the surface to which film 220 is bonded) of channel chip 200 through second opening 115 (see
The shapes of chip holder 110, through hole 111, first opening 112, second opening 115, and recess 114 are not limited as long as the components can exhibit their respective functions.
Configuration of Cartridge
Cartridge 120 houses a liquid to be introduced into introduction port 240 of channel chip 200. As illustrated in
The material for cartridge 120 can be appropriately selected from known resins or metals. In the present embodiment, cartridge 120 is preferably made of a material that allows bending part 125 of second engagement part 124 to have elasticity. Examples of the material for cartridge 120 include polyethylene terephthalate, polycarbonate, polymethyl methacrylate, polyvinyl chloride, polypropylene, polyether, polyethylene, polystyrene, cyclo-olefine resins, silicone resins, and elastomers.
Communication pipe 121 allows housing part 123 and introduction port 240 to communicate with each other when cartridge 120 is fixed to chip holder 110. Communication pipe 121 may have any diameter as long as the communication pipe can exhibit the above function.
Packing 122 is disposed at the tip of communication pipe 121 of cartridge 120. The material for packing 122 is not limited as long as the packing can exhibit elasticity such that the packing collapses when pressed, thereby sealing the internal space of communication pipe 121 and introduction port 240 from the outside. Examples of the material for packing 122 include known rubbers or elastomers.
Housing part 123 temporarily stores a liquid. The number of housing parts 123 is not limited, that is, any number can be selected depending on the types of reagents, liquid samples, washing liquids, and the like desired to be housed. In the present embodiment, the number of housing parts 123 is 10. The shape and volume of housing part 123 are not limited, either. For example, the volume of each housing part 123 is such that the housing part can contain approximately 20 to 200 μL of liquid.
In addition, it is preferable that housing part 123 is sealed by, for example, heat sealing. Such a configuration can prevent foreign substances from entering housing part 123.
Second engagement part 124 engages with first engagement part 132 described below. Second engagement part 124 may have any configuration as long as the second engagement part can exhibit the above functions. In the present embodiment, first engagement part 132 and second engagement part 124 are detachably engaged with each other by a snap fit mechanism. More specifically, second engagement part 124 includes bending part 125 and claw 126. Bending part 125 extends along the extending direction of communication pipe 121, and claw 126 protrudes toward the side opposite to housing part 123 and located at the end portion of bending part 125, the end portion on the channel chip 200 side (the side closer to first engagement part 132). In the present embodiment, second engagement part 124 is configured in such a way that length W1 thereof is longer than length W2 of housing part 123 in the depth direction, and length W1 is shorter than the total length W3 of length W2 of housing part 123 and the length of communication pipe 121, and second engagement part 124 is disposed so as to be separated from communication pipe 121 and housing part 123 (see
When cartridge 120 is installed at the position surrounded by the dashed line in
Configuration of Liquid Handling Device
Liquid handling device 130 is configured to support chip holder 110 and control the flow of the liquid in channel chip 200 housed in chip holder 110. As illustrated in
Disposition part 131 supports chip holder 110. Disposition part 131 may have any configuration as long as the disposition part can exhibit the above function. In the present embodiment, the shape of disposition part 131 in plan view is substantially similar to the shape of chip holder 110 in plan view. Disposition part 131 is formed to have a shape slightly larger than that of chip holder 110 in plan view. In the present embodiment, disposition part 131 is a recess in which at least part of chip holder 110 is disposed.
First engagement part 132 is a portion configured to be engaged with second engagement part 124. Disposing first engagement part 132 at an appropriate position can fix cartridge 120 to channel chip 200 at the optimum position when first engagement part 132 and second engagement part 124 are engaged with each other. In the present embodiment, first engagement part 132 is disposed in liquid handling device 130. More specifically, first engagement part 132 is the edge of the opening of the casing of liquid handling device 130. First engagement part 132 may be disposed in, for example, chip holder 110 or channel chip 200. The configuration of first engagement part 132 is not limited as long as the first engagement part can exhibit the above function and is appropriately set according to the configuration of second engagement part 124. As described above, in the present embodiment, first engagement part 132 and second engagement part 124 are detachably engaged with each other by a snap fit mechanism.
As illustrated in
First rotary member 300 includes cylindrical first main body 310 and first protrusion 311 disposed on the top surface of first main body 310, and is rotated about first central axis CA1 by a drive mechanism (not illustrated).
The upper portion of first main body 310 is provided with first protrusion 311 configured to close valve 250 by pressing the diaphragm of valve 250 and first recess 312 configured to open the valve by not pressing the diaphragm. First protrusion 311 and first recess 312 are disposed on the circumference of a circle whose center is first central axis CA2. In the present embodiment, first protrusion 311 in plan view has a shape of an arc (“C” shape) corresponding to a portion of the circle whose center is first central axis CA2. The region, on the circumference, where first protrusion 311 is not present is first recess 312.
Second rotary member 320 includes cylindrical second main body 330 and second protrusion 331 disposed on the top surface of second main body 330, and is rotated about second central axis CA2 by a drive mechanism (not illustrated).
The upper portion of second main body 330 is provided with second protrusion 331 configured to operate rotary membrane pump 260 by pressing diaphragm 261 of rotary membrane pump 260 while second protrusion 331 is sliding along diaphragm 261. Second protrusion 331 is disposed on the circumference of a circle whose center is second central axis CA2. Second protrusion 331 may have any shape as long as rotary membrane pump 260 can be operated appropriately. In the present embodiment, second protrusion 331 in plan view has a shape of an arc corresponding to a portion of the circle whose center is second central axis CA2.
In liquid handling system 100 according to the present embodiment, first protrusion 311 of first rotary member 300 controls opening and closing of the plurality of valves 250 of channel chip 200. For achieving such control, plurality of valves 250 of channel chip 200 and first protrusion 311 of first rotary member 300 are disposed on the circumference of the first circle whose center is first central axis CA2.
In a similar manner, in liquid handling system 100 according to the present embodiment, second protrusion 331 of second rotary member 320 controls the operation of rotary membrane pump 260 of channel chip 200. For achieving such control, rotary membrane pump 260 of channel chip 200 and second protrusion 331 of second rotary member 320 are disposed on the circumference of the second circle whose center is second central axis CA2.
Configuration of Channel Chip
Channel chip 200 is configured to be housed in chip holder 110 and disposed at a predetermined location of liquid handling device 130 for supporting chip holder 110 (see
Channel chip 200 includes substrate 210 and film 220. In substrate 210, grooves to serve as channels, a recess to serve as a chamber, and through holes to serve as introduction ports or discharge ports are formed. Film 220 is joined to one of the surfaces of substrate 210 so as to block the openings of the recesses and through holes formed in substrate 210 (see
The thickness of substrate 210 is not limited. For example, the thickness of substrate 210 is 1 mm or more and 10 mm or less. In addition, the material for substrate 210 is not limited. For example, the material for substrate 210 may be appropriately selected from known resins and glass. Examples of the material for substrate 210 include polyethylene terephthalate, polycarbonate, polymethyl methacrylate, polyvinyl chloride, polypropylene, polyether, polyethylene, polystyrene, cyclo-olefine resins, silicone resins, and elastomers.
The thickness of film 220 is not limited as long as the film can function as a diaphragm. For example, the thickness of film 220 is 30 μm or more and 300 μm or less. The material for film 220 is not limited either as long as the film can function as a diaphragm. For example, the material for film 220 may be appropriately selected from known resins. Examples of the material for film 220 include polyethylene terephthalate, polycarbonate, polymethyl methacrylate, polyvinyl chloride, polypropylene, polyether, polyethylene, polystyrene, cyclo-olefine resins, silicone resins, and elastomers. Film 220 is joined to substrate 210 by, for example, heat welding, laser welding, or an adhesive.
In the present embodiment, channel chip 200 includes a plurality of first channels 230, a plurality of introduction ports (wells) 240 each connected to first channel 230, and a plurality of valves 250 each disposed between introduction port 240 and first channel 230. The numbers of introduction ports 240 and valves 250 are not limited, and are appropriately set according to the application of the channel chip 200.
Introduction port 240 is a bottomed recess for introducing a sample such as blood, a washing liquid, or the like. As described above, communication pipe 121 of cartridge 120 is inserted into introduction port 240. In the present embodiment, each of these recesses is composed of a through hole formed in substrate 210 and film 220 blocking one of the openings of the through hole. The shape and size of each recesses are not limited, and can be appropriately set according to the shape of communication pipe 121. The shape of these recesses is, for example, substantially cylindrical. The width of these recesses is, for example, approximately 2 mm.
First channel 230 is a channel through which liquid can move. In the upstream end thereof, first channel 230 is connected to introduction ports 240 at different positions. The downstream end of first channel 230 is connected to rotary membrane pump 260. First channel 230 is composed of a groove formed in substrate 210 and film 220 blocking the opening of the groove. The cross-sectional area and cross-sectional shape of first channel 230 are not limited. Herein, a “cross section of a channel” means a cross section—orthogonal to the direction in which a liquid flows—of a channel. The cross-sectional shape of each channel is, for example, a substantially rectangular shape with a side length (width and depth) of about several tens of μm. The cross-sectional area of each channel may or may not be constant in the direction of fluid flow. In the present embodiment, the cross-sectional area of each channel is constant.
Each valve 250 is a membrane valve (diaphragm valve) disposed between first channel 230 and corresponding one of introduction ports 240, and configured to control the flow of liquid between the first channel and the introduction port. In the present embodiment, each valve is a rotary membrane valve whose opening and closing are controlled by the rotation of first rotary member 300. In the present embodiment, these valves are disposed on the circumference of one circle whose center is first central axis CA1.
Rotary membrane pump 260 is a space which has a substantially arc shape (“C” shape) in plan view and is formed between substrate 210 and film 220. The upstream end of rotary membrane pump 260 is connected to first channel 230, and the downstream end of rotary membrane pump 260 is connected to second channel 270. Second channel 270 is composed of a groove formed in substrate 210 and film 220 blocking the opening of the groove. In the present embodiment, rotary membrane pump 260 is composed of the bottom surface of substrate 210 and diaphragm 261 facing the bottom surface while being separated from the bottom surface. Diaphragm 261 is a portion of flexible film 220 (see
Diaphragm 261 of rotary membrane pump 260 bends and contacts substrate 210 when pressed by second protrusion 331 of second rotary member 320. For example, when second protrusion 331 slides along and presses diaphragm 261 from the connection part with first channel 230 toward the connection part with second channel 270 (counterclockwise in
Operation of Liquid Handling System
Hereinafter, a method for using liquid handling system 100 according to the present embodiment will be described.
First, channel chip 200 is inserted into chip holder 110 together with spacer 116 to dispose chip holder 110 in disposition part 131 of liquid handling device 130. Chip holder 110 is fixed by fixing parts 134 located on the upper portion of liquid handling device 130.
Next, cartridge 120 is installed at a predetermined position on chip holder 110 (the position indicated by the dashed line in
With cartridge 120 fixed, button 133 disposed on liquid handling device 130 is pressed, thereby performing various processes, such as rotating first rotary member 300 to open and close the valves or rotating second rotary member 320 to drive the rotary membrane pump to move the liquid from introduction port 240 as illustrated in
After various processes are completed, the engaged state between first engagement part 132 and second engagement part 124 can be easily released by pressing bending part 125 inward (toward the housing part 123).
Effects
As described above, in liquid handling system 100 according to the present embodiment, cartridge 120 can be easily fixed to or removed from channel chip 200.
In the above-described embodiment, second engagement part 124 of cartridge 120 is pressed to be bent, thereby releasing the engaged state between first engagement part 132 and second engagement part 124; however, the present invention is not limited thereto. For example, second engagement part 124 may include, at an appropriate position, a protrusion for releasing the engaged state between first engagement part 132 and second engagement part 124. Alternatively, first engagement part 132 may be a groove included in chip holder 110 and second engagement part 124 may be a projection configured to engage the groove. Furthermore, first engagement part 132 may include a first groove extending along the extending direction of communication pipe 121 and a second groove connected to the first groove and extending in a direction orthogonal to the extending direction of communication pipe 121 (see Embodiment 2).
Hereinafter, liquid handling system 500 according to Embodiment 2 will be described. Liquid handling system 500 according to the present embodiment differs from liquid handling system 100 according to Embodiment 1 in the shapes of chip holder 510, cartridge 520, and liquid handling device 530. Therefore, in the present embodiment, the same components as those of liquid handling system 100 according to Embodiment 1 are denoted by the same reference numerals, and descriptions thereof are omitted.
Configuration of Liquid Handling System
As illustrated in
The configuration of channel chip 200 is the same as that of channel chip 200 in Embodiment 1; thus, the description thereof is omitted.
Through holes 511, first opening 112, and second opening 115 are formed in chip holder 510. That is, chip holder 510 according to the present embodiment does not include recess 114 of Embodiment 1.
Through hole 511 is formed in the top surface of chip holder 510, and functions to allow insertion of communication pipes 121 of cartridge 120. In the present embodiment, the number of through holes 511 is two. In the present embodiment, through hole 511 has a size in plan view such that five introduction ports 240 can be housed therein. First engagement parts 532 are formed in each of the two through holes 511.
First engagement part 532 may have any configuration as long as the first engagement part can be engaged with second engagement part 524 and can be detachably engaged with second engagement part 524. In the present embodiment, first engagement part 532 includes first groove 532a and second groove 532b (see
First engagement part 532 includes first groove 532a and second groove 532b. First groove 532a is formed along the extending direction of communication pipe 521. Second groove 532b is formed along a direction orthogonal to the extending direction of communication pipe 521 (longitudinal axis direction of chip holder 510). First groove 532a and second groove 532b may have any width as long as the grooves are large enough for the projection of second engagement part 524 to fit therein. The width of first groove 532a may be the same as or different from the width of second groove 532b. In the present embodiment, width of first groove 532a is the same as the width of second groove 532b. The side walls of first grooves 532a may or may not be continuous. Similarly, the side walls of second grooves 532b may or may not be continuous.
Configuration of Cartridge
As illustrated in
Cartridge main body 520a is configured to be slidable with respect to slide part 520b. Cartridge main body 520a includes housing parts 123, second engagement parts 524, and first communication pipes 521a—each first communication pipe is a portion of communication pipe 521 on the housing part 123 side.
Second engagement part 524 is included in cartridge main body 520a or in slide part 520b. In the present embodiment, second engagement part 524 is formed on the outer side surface of cartridge main body 520a. The number of second engagement parts 524 is not limited as long as cartridge 520 can be fixed to chip holder 510 by engaging second engagement parts 524 with first engagement parts 532. In the present embodiment, the number of second engagement parts 524 is four. Second engagement part 524 may have any shape as long as the second engagement part can engage with first engagement part 532 and slide with respect to first engagement part 532. In the present embodiment, second engagement part 524 has a shape of a substantially cylindrical projection.
First communication pipe 521a is a portion of communication pipe 521 on the upstream side. The upstream end of first communication pipe 521a is connected to housing part 123, and the downstream end of first communication pipe 521a is connected to second communication pipe 521b.
Slide part 520b includes pieces of packing 122 and second communication pipes 521b (each located on the downstream side of communication pipe 521), and is configured to be slidable with respect to cartridge main body 520a.
Second communication pipe 521b is a portion of communication pipe 521 on the packing 122 side. The upstream end of second communication pipe 521b is connected to first communication pipe 521a, and the packing 122 is disposed at the downstream end of second communication pipe 521b.
Communication pipe 521 connects housing part 123 with packing 122 regardless of whether the channel between housing part 123 and packing 122 is in a communicating state or the channel between housing part 123 and packing 122 is in a blocked state. The material for communication pipe 521 is not limited as long as the connection between housing part 123 and packing 122 can be maintained. Examples of the material for communication pipe 521 include silicone, urethane, polytetrafluoroethylene (PTFE), and Tygon (registered trademark) of polyvinyl chloride resin.
In the following, a mechanism for opening and closing the channel between housing part 123 and packing 122 will be described.
As illustrated in
As illustrated in
Sliding cartridge main body 520a with respect to slide part 520b thus can open and close the channel between housing part 123 and packing 122.
Operation of Liquid Handling System
Hereinafter, a method for using liquid handling system 500 according to the present embodiment will be described.
First, channel chip 200 is inserted into chip holder 510 together with spacer 116 to dispose chip holder 510 in disposition part 131 of liquid handling device 530. Chip holder 510 is fixed by fixing parts 134 located on the upper portion of liquid handling device 530 (both not illustrated).
Next, cartridge 520 is installed at a predetermined position on chip holder 510. Specifically, communication pipes 521 are inserted into through holes 511 (see
Next, cartridge main body 520a is slid with respect to slide part 520b. Cartridge main body 520a moves while being guided by second groove 532b of first engagement part 532 at this time. As a result, the channel between housing part 123 and packing 122 is “opened,” and housing part 123 and introduction port 240 communicate with each other (see
With cartridge 520 fixed, button 133 disposed on liquid handling device 130 is pressed, thereby performing various processes, such as rotating first rotary member 300 to open and close the valves or rotating second rotary member 320 to drive the rotary membrane pump to move the liquid from introduction port 240 as illustrated in
After various processes are completed, the engaged state between first engagement part 532 and second engagement part 524 can be easily released by bringing cartridge main body 520a into a state of being displaced with respect to slide part 520b to “close” the channel, and removing cartridge 520 from through hole 521.
Liquid handling device 530 according to the present embodiment includes disposition part 131, a plurality of buttons 133, and fixing parts 134. In addition, liquid handling device 530 includes jack 135, connector 136, first rotary member 300, and second rotary member 320. That is, liquid handling device 530 according to the present embodiment does not include first engagement part 132 of Embodiment 1.
Effects
As described above, in liquid handling system 500 according to the present embodiment, cartridge 520 can be easily fixed to or removed from channel chip 200. In addition, the channel between housing part 123 and packing 122 can be opened and closed; thus, cartridge 520 can be attached and removed without spilling a liquid from cartridge 520.
In liquid handling system 500 according to Embodiment 2, first engagement part 532 has a groove shape, and second engagement part 524 has a projection shape; however, first engagement part 523 may have a shape of recess 114, and second engagement part 524 may have a shape of bending part 125 and claw 126 as in Embodiment 1, for example. In this case, second engagement part 524 (having a shape of, for example, bending part 125 and claw 126) is formed on slide part 520b.
The above-described embodiments are no more than specific examples in carrying out the present invention, and the technical scope of the present invention is not to be construed in a limitative sense due to the above-described embodiments. The present invention can be carried out in various forms without departing from the spirit and the main features thereof.
This application is entitled to and claims the benefit of PCT/JP2021/2207 filed on Jan. 22, 2021, the disclosure of which including the specification and drawings is incorporated herein by reference in its entirety.
Liquid handling devices and liquid handling systems according to the present embodiments are particularly advantageous, for example, in a variety of applications such as clinical, food, and environmental testing.
Number | Date | Country | Kind |
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PCT/JP2021/002207 | Jan 2021 | WO | international |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2021/007051 | 2/25/2021 | WO |
Number | Date | Country | |
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Parent | PCT/JP2021/002207 | Jan 2021 | US |
Child | 18273314 | US |