Microfluidic device, connection device, and liquid chromatograph

Abstract

This microfluidic device comprises a body portion composed of one or a plurality of members. The body portion includes a connection portion that is connectable to the separation column, and a plurality of flow passages. The plurality of flow passages include a sample holding portion for holding a sample, and an introduction flow passage capable of introducing a sample into a separation column for separating the sample. The microfluidic device further comprises a switching member slidably connected to the body portion and capable of selectively connecting by switching connection of the plurality of flow passages by sliding with respect to the body portion.

Description

Microfluidic device, connection device and liquid chromatograph

[0001] The present invention relates to a microfluidic device, a connection apparatus, and a liquid chromatograph.

[0002] In a typical liquid chromatograph, piping is used to connect modules. Piping has internal volume. If the internal volume of the piping from the feed pump to the separation column is large, gradient lag (the delay between the change in the composition of the mobile phase generated by the feed pump and its arrival at the separation column) occurs. Furthermore, if the internal volume of the piping from the autosampler to the detector is large, the sample diffuses within the mobile phase (hereinafter referred to as extra-column diffusion). Excessive sample diffusion within the mobile phase reduces the separation accuracy of the compounds in the sample in the separation column. Extra-column diffusion, particularly in analyses at nano- and micro-flow rates, significantly affects the analysis results. Patent Document 1 describes a microfluidic device in which the increase in internal volume is suppressed by integrally forming the autosampler sample holder, column, and detector connections on a chip.

[0003] U.S. Patent No. 6,958,119

[0004] In microfluidic devices, depending on the analytical conditions, parts may need to be replaced to meet those conditions. In the microfluidic device described in Patent Document 1, the autosampler sample holder, column, and detector connection are integrally formed, making it impossible to replace each part independently. Therefore, if any of the integrally formed parts within the microfluidic device does not meet the analytical conditions, the microfluidic device itself must be replaced. For example, because the separation column packing is fixed on the chip, the separation mode and column length are limited. To change the separation mode or column length, it is necessary to change to a microfluidic device that includes a separation column with the desired separation mode and column length. Furthermore, because the connection shape of detectors varies depending on the type, the microfluidic device must be changed depending on the detector being used.

[0005] An object of the present invention is to provide a microfluidic device, a connection apparatus, and a liquid chromatograph that can improve convenience while improving the accuracy of sample analysis.

[0006] A first aspect of the present invention relates to a microfluidic device comprising a main body portion composed of one or more members, the main body portion including a connection portion connectable to the separation column and a plurality of flow paths, the plurality of flow paths including a sample holder portion for holding a sample and an introduction flow path capable of introducing the sample into the separation column which separates the sample, and further comprising a switching member slidably connected to the main body portion and capable of switching the connection of the plurality of flow paths to selectively connect them by sliding relative to the main body portion.

[0007] A second aspect of the present invention relates to a connection device that connects the above-mentioned microfluidic device, the separation column, and a detector, comprising: a first fixing member that can fix the microfluidic device and can connect the connection portion of the microfluidic device to the inlet port of the separation column; a second fixing member that can fix the detector and can connect the inlet port of the detector and the outlet port of the separation column; a guide rail configured to allow at least one of the first fixing member and the second fixing member to move relative to the other; and a clamp mechanism that can shorten the distance between the first fixing member and the second fixing member arranged on the guide rail.

[0008] A third aspect of the present invention relates to a liquid chromatograph comprising the above-mentioned microfluidic device, wherein the plurality of flow paths further include a first port connected to a pump that delivers a mobile phase and a second port connected to a sample filling section that fills with a sample, and the switching member is switchable between a first state in which the second port and the sample holding section are connected and a second state in which the first port, the sample holding section, and the introduction flow path are connected, the microfluidic device also comprising the pump, the sample filling section, the separation column, and a detection section that detects components that have passed through the separation column.

[0009] A fourth aspect of the present invention relates to a microfluidic device comprising: a main body having a plurality of flow paths; and a switching member slidably connected to the main body and capable of switching and selectively connecting the plurality of flow paths of the main body by sliding relative to the main body, wherein the main body includes a first plate-like member and a second plate-like member, and the plurality of flow paths include a sample holding flow path formed in the first plate-like member and holding a sample, and a column flow path formed in the second plate-like member and capable of separating the sample into components.

[0010] A fifth aspect of the present invention relates to a liquid chromatograph comprising the above-mentioned microfluidic device, the pump, the sample filling section, and the detection section, wherein the main body further includes a third plate-like member, the third plate-like member including a connection section connectable to a detection section that detects components that have passed through the column flow path, the plurality of flow paths including a first port connected to a pump that delivers a mobile phase, a second port connected to a sample filling section that fills with a sample, and a discharge port formed in the connection section that discharges the components that have passed through the column flow path to the detection section, and the switching member is switchable between a first state in which the second port and the sample holding flow path are connected, and a second state in which the first port, the sample holding flow path, the column flow path, and the discharge port are connected.

[0011] According to the present invention, it is possible to improve the accuracy of sample analysis while also improving convenience.

[0012] FIG. 1 is an exploded view illustrating the configuration of a microfluidic device according to one embodiment of the present invention. FIG. 2 is a plan view illustrating an example of connecting a microfluidic device. FIG. 3 is a plan view illustrating an example of connecting a microfluidic device. FIG. 4 is an exploded perspective view showing a state before the microfluidic device is attached to a separation column. FIG. 5 is a cross-sectional view showing a state before the microfluidic device is attached to a separation column. FIG. 6 is a cross-sectional view showing a microfluidic device attached to a separation column. FIG. 7 is an exploded perspective view of a microfluidic device according to another embodiment. FIG. 8 is an exploded perspective view of a microfluidic device according to another embodiment. FIG. 9 is an exploded perspective view of a microfluidic device according to another embodiment. FIG. 10 is a cross-sectional view of a microfluidic device according to another embodiment. FIG. 11 is a cross-sectional view showing a microfluidic device attached to a separation column. FIG. 12 is an exploded view illustrating the configuration of a detector used in a fifth installation example. FIG. 13 is a view illustrating the configuration of a column mounting apparatus. FIG. 14 is a view illustrating the configuration of a column mounting apparatus. FIG. 15 is a view illustrating the configuration of a column mounting apparatus. FIG. 16 is an exploded view illustrating the configuration of a microfluidic device according to another embodiment. FIG. 17 is a plan view illustrating an example of connecting a microfluidic device. FIG. 18 is a plan view illustrating an example of connecting a microfluidic device.

[0013] Microfluidic devices and connection devices according to embodiments of the present invention will be described in detail below with reference to the drawings.

[0014] (1) Configuration of Microfluidic Device FIG. 1 is an exploded view illustrating the configuration of a microfluidic device according to one embodiment of the present invention. In the following description, an axis extending linearly in the vertical direction will be referred to as a first axis AX1. As shown in the figure, an axis extending linearly and intersecting the first axis AX1 will be referred to as a second axis AX2. One of the second axes AX2 will be referred to as one direction DA, and the other will be referred to as the other direction DB. In the following description, arrow U will be referred to as the upward direction of the microfluidic device 1, and arrow D will be referred to as the downward direction of the microfluidic device 1.

[0015] The microfluidic device 1 includes a main body 100 and a switching member 200. In this embodiment, the main body 100 is composed of two plate-shaped members 110 and 120. The plate-shaped members 110 and 120 are formed of, for example, resin. The resin used for the plate-shaped members 110 and 120 is, for example, PEEK (polyether ether ketone). The material of the plate-shaped members 110 and 120 may be selected from metal, ceramic, glass, and resin. Furthermore, different materials may be selected for the plate-shaped members 110 and 120.

[0016] The plate-like member 110 is a flat plate having an upper surface 110a and a lower surface 110b. A connecting portion 130 is provided on a side surface of the plate-like member 110 in one direction DA. In this embodiment, the connecting portion 130 is a prismatic member protruding in the one direction DA. The connecting portion 130 can be connected to a separation column (not shown) outside the microfluidic device 1. An example of connecting the connecting portion 130 to a separation column will be described later. In this embodiment, the connecting portion 130 is formed integrally with the plate-like member 110. The plate-like member 110 includes a plurality of flow channels separated from one another. The plurality of flow channels include flow channels 111 to 116, a sample holder 117, and a discharge flow channel 118. The flow channels 111 to 116 are holes penetrating the upper surface 110a and the lower surface 110b. The sample holder 117 is a groove formed in the upper surface 110a and connects the flow channel 113 and the flow channel 116. 1, the sample holder 117 is formed in a straight line, but may also be curved, for example. The shape of the sample holder 117 may be determined appropriately depending on, for example, the amount of sample to be held. The discharge flow path 118 is a groove formed in the upper surface 110a, and extends from the flow path 112 in one direction DA.

[0017] The connection part 130 includes a connection flow path 131. The connection flow path 131 is a groove extending in one direction DA, and is connected to the discharge flow path 118 of the plate-like member 110. A discharge port 132 is provided on the side surface of the connection part 130 in the one direction DA. The connection flow path 131 is connected to the discharge port 132. The discharge port 132 opens the connection flow path 131 to the outside. In the example of FIG. 1 , the connection flow path 131 is formed by a groove in the shape of a rectangular pillar, but it may also be formed by a groove in the shape of a semicircle.

[0018] The plate-shaped member 120 is a flat plate having an upper surface 120a and a lower surface 120b. The plate-shaped member 120 has a shape that overlaps the plate-shaped member 110 and the connection portion 130 when viewed from above. The plate-shaped member 120 functions as a lid for the upper surface 110a of the plate-shaped member 110. If the connecting flow path 131 is formed as a semicircular groove, a semicircular groove may be formed in the lower surface 120b at a position corresponding to the connecting flow path 131 so that the discharge port 132 has a circular shape. When assembling the main body 100, the plate-shaped member 110 and the plate-shaped member 120 are fixed together with bolts or the like (not shown) while the lower surface 120b and the upper surface 110a of the plate-shaped member 110 are abutted against each other. Alternatively, the plate-shaped member 110 and the plate-shaped member 120 are integrated together by joining or adhesive technology.

[0019] The plate-shaped member 120 includes flow paths 121, 124, and 125. The flow paths 121, 124, and 125 are holes that penetrate the upper surface 120a and the lower surface 120b. Hereinafter, the portion of the upper surface 120a where the flow path 121 is formed will be referred to as port A, the portion of the upper surface 120a where the flow path 124 is formed will be referred to as port B, and the portion of the upper surface 120a where the flow path 125 is formed will be referred to as port C. In a top view, the flow path 121 of the plate-shaped member 120 overlaps with the flow path 111 of the plate-shaped member 110, the flow path 124 overlaps with the flow path 114, and the flow path 125 overlaps with the flow path 115.

[0020] In this embodiment, the switching member 200 is a rotor. The switching member 200 is made of, for example, resin. The resin used for the switching member 200 is, for example, PEEK (polyether ether ketone). The switching member 200 may also be made of metal. The switching member 200 is a flat plate having an upper surface 200a. Flow paths 210 to 230 are formed in the upper surface 200a of the switching member 200. The flow paths 210 to 230 are arc-shaped grooves formed at different positions on the upper surface 200a. The switching member 200 also includes a motor and is rotatable around a first axis AX.

[0021] When assembling the microfluidic device 1, the switching member 200 slidably contacts the lower surface 110b of the plate-like member 110 of the main body 100. As a result, by rotating the switching member 200 relative to the main body 100, it becomes possible to selectively connect by switching between a plurality of flow paths in the main body 100. In this embodiment, the switching member 200 can switch the state of the microfluidic device 1 between a first state and a second state. The states of the microfluidic device 1 will be described later.

[0022] 2 and 3 are plan views illustrating connection examples of the microfluidic device 1. Here, the configuration of the microfluidic device 1 is illustrated in a simplified manner in order to explain the connection relationships of the flow paths within the main body 100. As shown in FIGS. 2 and 3, a pump 2 is connected to port A of the microfluidic device 1 via a flow path P2. The pump 2 sends a mobile phase contained in a container (not shown) to the flow path P2. A sample filling unit 3 is connected to port B via a flow path P3. The sample filling unit 3 is, for example, a needle that can be inserted into a container containing a sample. A syringe 4 is connected to port C via a flow path P4. The syringe 4 is capable of aspirating and discharging liquid.

[0023] FIG. 2 shows the microfluidic device 1 in a first state. In the microfluidic device 1 in the first state, port B and the sample holding section 117 are connected by the flow path 220 of the switching member 200, and the sample holding section 117 and port C are connected by the flow path 230. This connects the sample filling section 3 and the syringe 4 via the sample holding section 117. The sample filling section 3 is, for example, a needle capable of piercing a container. With the sample filling section 3 positioned inside a container containing a sample, the syringe 4 aspirates the sample from the container. This allows the sample aspirated from the sample filling section 3 to be held in the sample holding section 117. Furthermore, if an injection port for inserting a needle is provided in port C and a drain is connected to port B, the sample can be aspirated with the needle and inserted into the injection port to fill the sample holding section 117 from port C.

[0024] 3 shows the microfluidic device 1 in a second state. In the microfluidic device 1 in the second state, port A and the sample holder 117 are connected by a flow path 230, and the sample holder 117 and the discharge flow path 118 are connected by a flow path 210. When the pump 2 is operated in this state, the mobile phase is introduced into the sample holder 117. Furthermore, the sample and the mobile phase held in the sample holder 117 are discharged from the discharge port 132 through the discharge flow path 118. The mobile phase and the sample discharged from the discharge port 132 are introduced into a separation column connected to the connection part 130 (not shown).

[0025] With this configuration, the microfluidic device filled with a sample is directly connected to the separation column, eliminating the need for piping connecting the sample injection unit and the separation column compared to conventional systems, thereby shortening the flow path to the separation column through which the sample passes. This reduces the internal volume of the flow path from the sample holder to the separation column, thereby suppressing sample diffusion within the mobile phase. Furthermore, because the connections to the separation column and the detector are separate components in the microfluidic device 1, it is possible to replace only the separation column or detector that does not meet the analytical conditions without replacing the microfluidic device 1 itself. Similarly, even if a defect occurs in one of the components, it is not necessary to replace the microfluidic device 1 itself. As a result, it is possible to improve the accuracy of sample analysis while also improving convenience.

[0026] (2) Mounting on a Separation Column (2-1) First Mounting Example FIG. 4 is an exploded perspective view showing the state before the microfluidic device 1 is mounted on a separation column. FIG. 5 is a cross-sectional view showing the state before the microfluidic device 1 is mounted on a separation column. FIG. 6 is a cross-sectional view showing the microfluidic device 1 mounted on a separation column. First, the separation column to which the microfluidic device 1 is connected will be described. Referring to FIG. 5, the separation column CL includes a port CZ. The port CZ includes a first recess Ca, a second recess Cb, and a third recess Cc. The first recess Ca includes a cylindrical inner circumferential surface Ca1 and a step portion Ca2. A female thread is formed on the inner circumferential surface Ca1 of the first recess Ca. The second recess Cb includes a cylindrical inner circumferential surface Cb1, a step portion Cb2, and a truncated conical inner circumferential surface Cb3. The third recess Cc includes a cylindrical inner circumferential surface Cc1 and a bottom surface Cc2. A column channel CP connected to the port CZ is formed on the one direction DA side of the bottom surface Cc2 of the third recess Cc.

[0027] 4 and 5, the microfluidic device 1 further includes a sleeve 300, a nut 400, and a ferrule 500. The sleeve 300, the nut 400, and the ferrule 500 are members for connecting the connection part 130 of the main body part 100 to the separation column CL.

[0028] The sleeve 300 is a cylindrical member extending along the second axis AX2. The sleeve 300 is formed of a resin such as PEEK (polyether ether ketone). The sleeve 300 is provided with an insertion hole 301 that extends along the second axis AX2 and into which the connection part 130 can be attached. In this embodiment, the length of the sleeve 300 is the same as the length of the connection part 130 along the second axis AX2, but the lengths of the sleeve 300 and the connection part 130 may be different. When connecting the microfluidic device 1 to the separation column CL, the connection part 130 is fixed in the insertion hole 301 of the sleeve 300 as shown in FIG. 5 . An abutment surface 302 is formed on the end face of the sleeve 300 in one direction DA.

[0029] The nut 400 includes a male thread portion 410 and a fastening portion 420. The nut 400 is formed of a metal such as SUS. The nut 400 may also be formed of a resin such as PEEK (polyether ether ketone). The male thread portion 410 is a cylindrical member extending along the second axis AX2 and has a male thread corresponding to the female thread formed on the inner circumferential surface Ca1 of the first recess Ca of the separation column CL. The fastening portion 420 has a generally hexagonal prism shape. The male thread portion 410 and the fastening portion 420 are provided with through-holes 401 that penetrate the male thread portion 410 and the fastening portion 420, respectively. The through-holes 401 have a diameter that allows the sleeve 300 to be inserted therein. When connecting the microfluidic device 1 to the separation column CL, the sleeve 300 is inserted into the through-hole 401 as shown in FIG. 5 .

[0030] The ferrule 500 includes a tapered portion 510 and a circular member 530. The ferrule 500 is formed of a metal such as SUS. The ferrule 500 may also be formed of a resin such as PEEK (polyether ether ketone). The tapered portion 510 is a truncated cone-shaped member and has an outer circumferential surface corresponding to the inner circumferential surface Cb3 of the second recess Cb of the separation column CL. The circular member 530 is a cylindrical member and has an outer circumferential surface corresponding to the inner circumferential surface Cb1 of the second recess Cb of the separation column CL. The tapered portion 510 and the circular member 530 each have a through-hole 501 that penetrates the tapered portion 510 and the circular member 530. The through-hole 501 has a diameter that allows the sleeve 300 to be attached. When connecting the microfluidic device 1 to the separation column CL, the sleeve 300 is fixed in the through-hole 501 as shown in FIG. 5 .

[0031] When the tightening portion 420 is tightened with a tool such as a wrench while the male thread portion 410 is threadedly engaged with the female thread formed on the inner circumferential surface Ca1 of the first recess Ca, the nut 400 advances in the one direction DA. This presses the ferrule 500 in the one direction DA. In this case, the sleeve 300 is fixed in the through hole 501 of the ferrule 500, and the connection portion 130 is fixed in the insertion hole 301 of the sleeve 300. Therefore, the sleeve 300 and the connection portion 130 are pressed in the one direction DA by the nut 400. This presses the abutment surface 302 against the bottom surface Cc2 of the third recess Cc. In this state, when the tightening portion 420 is further tightened, the connection channel 131 of the connection portion 130 can be connected to the column channel CP of the separation column CL, as shown in FIG. 6 .

[0032] (2-2) Second Mounting Example In the above-described embodiment, the connecting portion 130 is a rectangular column-shaped member protruding in one direction DA, but the present invention is not limited to this. FIG. 7 is an exploded perspective view of a microfluidic device 1A according to another embodiment. The microfluidic devices 1 in FIGS. 1 to 6 differ from the microfluidic device 1A in FIG. 7 in the following respects. The connecting portion 130A of the microfluidic device 1A is a cylindrical member protruding in one direction DA. The diameter r of the end face of the connecting portion 130A, on which the discharge port 132 is formed, is set to a size that allows it to be inserted into the through-hole 401 of the nut 400 and attached to the ferrule 500. In this case, there is no need to provide a sleeve 300 for attaching the connecting portion 130 to the ferrule 500, thereby reducing the number of parts required for connecting to the separation column CL.

[0033] (2-3) Third Mounting Example In the microfluidic device 1A of FIG. 7, the connection portion 130A is formed from a single cylindrical member, but the present invention is not limited to this. FIGS. 8 and 9 are exploded perspective views of a microfluidic device 1B according to another embodiment. The microfluidic device 1A of FIG. 7 differs from the microfluidic device 1B of FIGS. 8 and 9 in the following respects. The microfluidic device 1B further includes a face seal member 600. The face seal member 600 is a cylindrical member having an abutment surface 602 and a pressing surface 604, and a through-hole 601 penetrating the abutment surface 602 and the pressing surface 604. The face seal member 600 is formed from resin. The through-hole 601 is a hole connectable to the column flow path CP of the separation column CL. The abutment surface 602 of the face seal member 600 corresponds to the bottom surface Cc2 of the third recess Cc of the separation column CL. An outer peripheral surface 603 of the face seal member 600 corresponds to an inner peripheral surface Cc1 of the third recess Cc of the separation column CL.

[0034] The microfluidic device 1B includes a connecting portion 130B and a nut 400B. As shown in FIG. 8 , the connecting portion 130B includes a first member 133 and a second member 134 extending along a second axis AX2. The first member 133 is cylindrical and has a diameter r1. The second member 134 is cylindrical and has a diameter r2 that is larger than the diameter r1. As a result, a step portion 134a is formed on the end face of the second member 134 on the other direction DB side. Furthermore, an end face 134b including a discharge port 132 is formed on the end face of the second member 134 on the one direction DA side. The first member 133 and the second member 134 are formed with a connecting flow path 131, similar to the connecting portion 130 in FIGS. 1 to 6 .

[0035] As shown in FIG. 9 , the nut 400B has a slot SL extending from its end face on the other direction DB side to its end face on the one direction DA side along the second axis AX2. The width W1 of the slot SL is set to be larger than the diameter r1 of the first member 133 but smaller than the diameter r2 of the second member 134. The diameter r3 of the through hole 401 of the nut 400B is set to be larger than the diameter r1 of the first member 133 but smaller than the diameter r2 of the second member 134. The first member 133 of the connection portion 130b of the nut 400B is fitted into the through hole 401 through the slot SL. When connecting the microfluidic device 1 to the separation column CL, the end face 411 of the nut 400B on the one direction DA side and the stepped portion 134a of the second member 134 are abutted against each other, and the tightening portion 420 is tightened with a tool such as a wrench. In this case, the pressing surface 604 of the face seal member 600 is pressed against the end surface 134b of the second member 134 of the connecting portion 130b. This makes it possible to connect the microfluidic device 1B to the separation column CL. This microfluidic device 1B can be attached to the separation column CL without providing a ferrule 500, so the sample and mobile phase flowing through the flow path do not reach the ferrule, thereby suppressing sample diffusion and carryover.

[0036] (2-4) Fourth Mounting Example In the above embodiment, an example is described in which the main body 100 is connected to the separation column CL using a nut or a nut and a ferrule, but the present invention is not limited to this. FIG. 10 is a cross-sectional view of a microfluidic device 1C according to another embodiment. FIG. 11 is a cross-sectional view showing the microfluidic device 1C mounted on a separation column. The microfluidic device 1C differs from the microfluidic devices 1 in FIGS. 1 to 6 in the following respects. The microfluidic device 1C further includes a column mounting mechanism 700 instead of a nut or a nut and a ferrule.

[0037] The column mount mechanism 700 includes a storage member 710, a spring 720, and a fixing member 730. The storage member 710 includes a covering member 711 and a plate member 712. The plate member 712 has a through-hole 712a formed therein through which the sleeve 300 can pass. A space SP is formed inside the covering member 711 and the plate member 712, capable of accommodating a protrusion PA that protrudes outward around the port CZ of the separation column CL. An insertion hole 711a is formed on the end face of the covering member 711 on the one direction DA side. An engagement portion 713 that protrudes inward toward the second axis AX2 is engageable with a step portion PB of the protrusion PA. The storage member 710 is provided with a cam clamp 714 that can adjust the position of the engagement portion 713 relative to the plate member 712 between an open state and a closed state. When the cam clamp 714 is in the open state, the size of the insertion hole 711a is large enough to insert the protrusion PA of the separation column CL into the space SP. When the cam clamp 714 is in a closed state, the size of the insertion hole 711a is such that the protrusion PA of the separation column CL cannot be inserted into the space SP.

[0038] The fixing member 730 is a cylindrical member fixed around the second axis AX2 of the sleeve 300, and has an abutment surface 731 that can abut against an end surface PC on the other direction DB side of the separation column CL. One end of a spring 720 is connected to an end surface 732 on the other direction DB side of the fixing member 730. The other end of the spring 720 is connected to the plate member 712. The spring 720 is a compression spring, and when the spring 720 contracts, a force acts in the direction in which the spring 720 expands. As a result, when a force is applied to the fixing member 730 in the other direction DB, the spring 720 exerts a force that presses the fixing member 730 in one direction DA.

[0039] When mounting the microfluidic device 1C, the protrusion PA of the separation column CL is inserted into the space SP when the cam clamp 714 is in the open state. In this state, the fixing member 730 is pressed against the protrusion PA of the separation column CL in the other direction DB. This causes the spring 720 to contract. In this state, the cam clamp 714 is switched to the closed state. In this case, as shown in FIG. 11 , the spring 720 presses the fixing member 730 in the one direction DA, so that the protrusion PA of the separation column CL is pressed against the engagement portion 713. This fixes the separation column CL within the space SP of the column mount mechanism 700, making it possible to connect the connection portion 130 and the separation column CL.

[0040] (2-5) Fifth Installation Example In the fifth installation example, a column mounting device capable of connecting the microfluidic device 1, a separation column, and a detector is used. First, the detector will be described. The detector used here is a chip having the functionality of a general photodetector. Figure 12 is an exploded view illustrating the configuration of the detector used in this example.

[0041] The detector Z includes plate-shaped members 100Z and 200Z. The plate-shaped member 100Z includes through holes ZA, ZB, ZC, and ZD. The through hole ZA is connected to one end of a first flow path hole (not shown) formed in the plate-shaped member 100Z, and the other end of the first flow path hole is connected to the through hole ZB. As a result, the through hole ZA is connected to the through hole ZB. The through hole ZC is connected to one end of a second flow path hole (not shown) formed in the plate-shaped member 100Z, and the other end of the second flow path hole is connected to the through hole ZD. As a result, the through hole ZC is connected to the through hole ZD.

[0042] Separate flow paths Z1, Z2, and Z3 are formed on the upper surface of the plate-shaped member 100Z. Flow path Z1 is a groove extending along a second axis AX2 between a port ZZ, which opens on the side surface of the plate-shaped member 100Z in one direction DA, and a through-hole ZA. Flow path Z2 is a groove extending along a third axis AX3, which intersects the second axis AX2, between through-holes ZB and ZC. Flow path Z3 is a groove extending along the second axis AX2 between through-hole ZD and a port ZY, which opens on the side surface of the plate-shaped member 100Z in the other direction DB. In this example, port ZZ is connected to a separation column CL, and port ZY is connected to a drainage mechanism (not shown). During sample analysis, the mobile phase and sample from the separation column CL are introduced into the detector Z from port ZZ. The mobile phase and sample pass through flow paths Z1, Z2, and Z3 in this order and are introduced from port ZY to a drainage mechanism (not shown). The flow channel Z2 of the detector Z functions as a flow cell. Both end surfaces of the flow channel Z2 are made of a light-transmitting material, such as glass.

[0043] A light source unit 10Z, an absorbance detection unit 20Z, and a fluorescence detection unit 30Z are disposed outside the plate-shaped member 100Z. The light source unit 10Z and the absorbance detection unit 20Z are disposed opposite each other on the third axis AX3, sandwiching the flow path Z2 therebetween. The fluorescence detection unit 30Z is disposed between the light source unit 10Z and the absorbance detection unit 20Z. The light source unit 10Z includes a light source such as a deuterium lamp and a diffraction grating capable of dispersing light from the light source. The absorbance detection unit 20Z is, for example, an ultraviolet-visible absorbance detector (UV-VIS) and measures changes in absorbance of the sample passing through the flow path Z2 using light emitted from the light source unit 10Z. The fluorescence detection unit 30Z includes, for example, a photomultiplier tube and converts light emitted from a fluorescent substance contained in the sample in the flow path Z2 into an electrical signal. When assembling the detector Z, the plate-shaped members 100Z and 200Z are fixed together with bolts or the like (not shown) in a state where the plate-shaped members 100Z and 200Z are in contact with each other. Alternatively, the plate-shaped members 110Z and 120Z are integrated together by joining or adhesive technology.

[0044] 13 to 15 are diagrams illustrating the configuration of the column mounting device 800. As shown in FIG. 13, the microfluidic device 1 used in this example does not have a protruding connection portion 130 (see FIG. 1). Instead, a portion of the side surface of the main body 100 serves as the connection portion 130E, and the connection portion 130E is provided with a hole-shaped discharge port 132. As shown in FIG. 14, the column mounting device 800 includes a main body aligner 810, a detector chip aligner 820, a guide rail 830, a clamp mechanism 840, a first seal adapter 850, and a second seal adapter 860. The main body aligner 810 includes a mounting portion 811, an outer frame 812, and a partition wall portion 813. The mounting portion 811 is a flat-plate-shaped member having an upper surface 811a. The mounting portion 811 is provided with a protrusion 811b that protrudes downward. An outer frame 812 and a partition wall 813 are provided on an upper surface 811a of the mounting portion 811. The outer frame 812 and the partition wall 813 are arranged on the upper surface 811a so as to be able to accommodate the microfluidic device 1 therein. The partition wall 813 is provided with a through-hole 813a extending along the fourth axis AX4.

[0045] The detector chip aligner 820 includes a mounting portion 821, an outer frame 822, and a partition wall portion 823. The mounting portion 821 is a flat plate-shaped member having an upper surface 821a. The mounting portion 821 is provided with a protrusion portion (not shown, but having a configuration similar to that of the protrusion portion 811b) that protrudes downward. The upper surface 821a of the mounting portion 821 is provided with an outer frame 822 and a partition wall portion 823. The outer frame 822 and the partition wall portion 823 are arranged on the upper surface 821a so as to be able to accommodate the detector Z therein. The partition wall portion 823 is provided with a through-hole 823a extending along the fourth axis AX4.

[0046] The main body aligner 810 and the detector chip aligner 820 are installed so as to be movable on guide rails 830. Specifically, at least one of the main body aligner 810 and the detector chip aligner 820 is provided so as to be movable relative to the other. In this embodiment, the detector chip aligner 820 is fixed on the guide rails 830, and the main body aligner 810 is arranged so as to be movable on the guide rails 830 relative to the fixed detector chip aligner 820.

[0047] The main body aligner 810 and the detector chip aligner 820 are connected via a clamp mechanism 840. Specifically, the protrusion 811b of the main body aligner 810 and a protrusion (not shown) of the detector chip aligner 820 are connected by the clamp mechanism 840. The clamp mechanism 840 is, for example, a tension spring. Therefore, for example, when the main body aligner 810 is moved away from the detector chip aligner 820, a force is applied in a direction that moves the main body aligner 810 toward the detector chip aligner 820.

[0048] As shown in FIG. 15 , the first seal adapter 850 includes a ferrule portion 851, a shaft member 852, and a face seal member 853. The ferrule portion 851 has a configuration similar to that of the ferrule 500 shown in FIGS. 4 to 6 . The shaft member 852 is a rod-shaped member extending along the fourth axis AX4. The ferrule portion 851 and the shaft member 852 each have a through-hole 850a formed therethrough. The face seal member 853 is a flat seal member extending along the fourth axis AX4. The face seal member 853 has a through-hole 850b formed therethrough along the fourth axis AX4. The shaft member 852 and the face seal member 853 are insertable into the through-hole 813a of the partition wall portion 813.

[0049] The second seal adapter 860 includes a ferrule portion 861, a shaft member 862, and a face seal member 863. The ferrule portion 861 has a configuration similar to that of the ferrule 500 in FIGS. 4 to 6. The shaft member 862 is a rod-shaped member extending along the fourth axis AX4. The ferrule portion 861 and the shaft member 862 each have a through-hole 860a formed therethrough. The face seal member 863 is a flat seal member extending along the fourth axis AX4. The face seal member 863 has a through-hole 860b formed therethrough along the fourth axis AX4. The shaft member 862 and the face seal member 863 are insertable into the through-hole 823a of the partition portion 823.

[0050] 13 to 15 , in assembling the column mounting apparatus 800, first, the microfluidic device 1 is fixed within the outer frame 812 on the upper surface 811a of the mounting portion 811. At this time, the microfluidic device 1 may be further fixed to the upper surface 811a of the mounting portion 811 with bolts or the like. When the microfluidic device 1 is fixed within the outer frame 812, the centers of the discharge ports 132 of the microfluidic device 1, the centers of the through-holes 813a of the partition wall 813, and the fourth axis AX4 coincide. The detector Z is fixed within the outer frame 822 on the upper surface 821a of the mounting portion 821. At this time, the detector Z may be further fixed to the upper surface 821a of the mounting portion 821 with bolts or the like. When the detector Z is fixed within the outer frame 822, the centers of the ports ZY of the detector Z, the centers of the through-holes 823a of the partition wall 823, and the fourth axis AX4 coincide.

[0051] Next, with the main body aligner 810 moved away from the detector chip aligner 820, a face seal member 853 and a shaft member 852 are inserted into the through-hole 813a, thereby fixing the first seal adapter 850 to the main body aligner 810. Furthermore, a face seal member 863 and a shaft member 862 are inserted into the through-hole 823a, thereby fixing the second seal adapter 860 to the detector chip aligner 820. In this state, the ferrule portion 851 of the first seal adapter 850 and the ferrule portion 861 of the second seal adapter 860 are inserted into the ports CZ at both ends of the separation column CL, respectively.

[0052] In this state, the main body aligner 810 is brought closer to the detector chip aligner 820. The contracting force of the clamp mechanism 840 makes it possible to clamp the separation column CL between the main body aligner 810 and the detector chip aligner 820. This makes it possible to connect the microfluidic device 1, separation column CL, and detector Z using only one column mount mechanism 700.

[0053] (3) Other Embodiments In the above embodiment, an example is described in which the main body 100 is composed of two plate-like members 110 and 120, but the present invention is not limited to this. The main body 100 may be composed of one plate-like member, or two or more plate-like members. Figure 16 is an exploded view for explaining the configuration of a microfluidic device 1D according to another embodiment.

[0054] 16 , a main body 100D of a microfluidic device 1D includes plate-like members 140, 150, 160, 170, 180, and 190. The plate-like members 140, 150, 160, 170, 180, and 190 are formed of, for example, resin. The resin used for the plate-like members 110 and 120 is, for example, PEEK (polyether ether ketone). The material of the plate-like members 140, 150, 160, 170, 180, and 190 may be selected from metal, ceramic, glass, and resin.

[0055] Plate-shaped member 150 is a flat plate having upper surface 150a and lower surface 150b. Plate-shaped member 150 includes a plurality of flow paths that are separated from one another. The plurality of flow paths include flow paths 151, 152, 154, and 159. Flow paths 151, 152, 154, and 159 are holes that penetrate upper surface 150a and lower surface 150b.

[0056] The plate-shaped member 160 is a flat plate having an upper surface 160a and a lower surface 160b. The plate-shaped member 160 includes a plurality of flow paths separated from one another. The plurality of flow paths include flow paths 161, 162, 164, 165, and 169 and a column flow path CP. The flow paths 161, 162, 164, 165, and 169 are holes penetrating the upper surface 160a and the lower surface 160b. The column flow path CP is a groove formed in the upper surface 160a and connects the flow path 165 and the flow path 169. The column flow path CP has a curved shape, but may also be linear. The shape of the column flow path CP may be determined appropriately depending on the analysis conditions. A top cover (not shown) is provided on the upper surface of the column flow path CP, and the column flow path CP is filled with a packing material used in a general separation column.

[0057] Plate-shaped member 170 is a flat plate having upper surface 170a and lower surface 170b. Plate-shaped member 170 includes a plurality of flow paths that are separated from one another. The plurality of flow paths include flow paths 171, 172, 174, and 175. Flow paths 171, 172, 174, and 175 are holes that penetrate upper surface 170a and lower surface 170b.

[0058] The plate-shaped member 180 is a flat plate having an upper surface 180a and a lower surface 180b. The plate-shaped member 180 includes multiple flow channels separated from one another. The multiple flow channels include flow channels 181, 182, 183, 184, 185, and 186 and a sample holder SH. The flow channels 181, 182, 183, 184, 185, and 186 are holes penetrating the upper surface 180a and the lower surface 180b. The sample holder SH is a groove formed in the upper surface 180a and connects the flow channel 183 and the flow channel 186. The sample holder SH functions similarly to the sample holder 117 of the microfluidic device 1 in FIG. 1. The sample holder SH has a curved shape, but may also be linear. The shape of the sample holder SH may be determined appropriately depending on the amount of sample to be held.

[0059] The plate-shaped member 140 is a flat plate having an upper surface 140a and a lower surface 140b. A connecting portion 130D is provided on a side surface of the plate-shaped member 140 in the direction DA, protruding along a second axis AX2 in the direction DA. A connecting flow path 131 extending along the second axis AX2 is formed in the connecting portion 130D. The connecting flow path 131 may include an atomization flow path 131D. A gas supply unit GS capable of supplying atomization gas (nebulizer gas) into the atomization flow path 131D is connected to the connecting portion 130D. The connecting portion 130D is also provided with a voltage application unit 133D surrounding the atomization flow path 131D. The voltage application unit 133D is connected to a power supply device (not shown). The voltage application unit 133D applies a high voltage of approximately 3 to 5 kV to the sample flowing through the atomization flow path 131D. These configurations enable the connection part 130D to realize the ESI (Electrospray Ionization) method. As a result, it becomes possible to discharge a mist of sample from the discharge port 132 of the connection part 130D. The connection part 130D is connected to an external detector (not shown). The detector is, for example, a quadrupole mass detector.

[0060] The plate-like member 140 includes a plurality of flow channels that are separated from one another. The plurality of flow channels include flow channels 141, 142, 144, and 149 and a discharge flow channel 118D. The flow channels 141, 142, 144, and 149 are holes that penetrate the upper surface 140a and the lower surface 140b. The structure and function of the discharge flow channel 118D are similar to those of the discharge flow channel 118 of the microfluidic device 1 in FIG. 1.

[0061] Plate-shaped member 190 is a flat plate having an upper surface 190a and a lower surface 190b. Plate-shaped member 190 has a shape that overlaps with plate-shaped member 140 and connecting portion 130D when viewed from above. Plate-shaped member 190 functions as a lid for upper surface 140a of plate-shaped member 140. Plate-shaped member 190 includes flow paths 191, 192, and 194. Flow paths 191, 192, and 194 are holes that penetrate upper surface 190a and lower surface 190b. Hereinafter, the portion of upper surface 120a where flow path 121 is formed will be referred to as port AA, the portion of upper surface 120a where flow path 124 is formed will be referred to as port BB, and the portion of upper surface 120a where flow path 125 is formed will be referred to as port CC.

[0062] The switching member 200 is similar to the switching member 200 in Fig. 1. When assembling the main body 100D, the plate-like members 140, 150, 160, 170, 180, and 190 are stacked vertically and fixed in place with bolts or the like (not shown). In this state, in a top view, the flow paths 191, 141, 151, 161, 171, and 181 overlap with each other, and the flow paths 192, 142, 152, 162, 172, and 182 overlap with each other. The flow paths 194, 144, 154, 164, 174, and 184 overlap with each other, and the flow paths 165, 175, and 185 overlap with each other. Therefore, when assembling main body 100D, flow paths 191, 141, 151, 161, 171, and 181 are connected to each other, and flow paths 192, 142, 152, 162, 172, and 182 are connected to each other. In addition, flow paths 194, 144, 154, 164, 174, and 184 are connected to each other, and flow paths 165, 175, and 185 are connected to each other.

[0063] When assembling the microfluidic device 1D, the switching member 200 slidably contacts the lower surface 180b of the plate-like member 180 of the main body 100D. As a result, by rotating the switching member 200 relative to the main body 100D, the switching member 200 can selectively connect multiple flow paths of the main body 100 by switching between them.

[0064] 17 and 18 are plan views illustrating an example of connections in the microfluidic device 1D. Here, the configuration of the microfluidic device 1 is simplified to illustrate the connection relationships of the flow paths, and plan views of each plate-like member are shown side by side. As shown in FIGS. 17 and 18, a sample filling unit 3 is connected to port AA via a flow path P11. The sample filling unit 3 is, for example, a needle that can be inserted into a container containing a sample. A syringe 4 is connected to port BB via a flow path P12. The syringe 4 is capable of aspirating and discharging liquid. A pump 2 is connected to port CC via a flow path P13. The pump 2 sends a mobile phase contained in a container (not shown) to flow path P2.

[0065] 17 shows microfluidic device 1D in a first state. In microfluidic device 1D in the first state, flow path 210 of switching member 200 connects flow path 182 and flow path 183, flow path 220 of switching member 200 connects flow path 184 and flow path 185, and flow path 230 of switching member 200 connects flow path 186 and flow path 181. As a result, syringe 4 is connected to sample loading unit 3 via flow paths 192, 142, 152, 162, 172, and 182, flow path 210 of switching member 200, flow path 183, sample holder SH, flow path 186, flow path 230 of switching member 200, and flow paths 181, 171, 161, 151, 141, and 191. With sample loading unit 3 positioned in a container containing a sample, the syringe 4 aspirates the sample from the container. As a result, the sample sucked from the sample loading section 3 is held in the sample holding section SH.

[0066] 18 shows microfluidic device 1D in the second state. In microfluidic device 1D in the second state, flow path 210 of switching member 200 connects flow path 181 and flow path 182, flow path 220 of switching member 200 connects flow path 183 and flow path 184, and flow path 230 of switching member 200 connects flow path 185 and flow path 186. In this case, flow paths 194, 144, 154, 164, 174, and 184, flow path 220 of switching member 200, flow path 183, sample holder SH, flow path 186, flow path 230 of switching member 200, flow paths 185, 175, and 165, column flow path CP, flow paths 169, 159, and 149, and connecting flow path 131 of connection portion 130D are connected. Therefore, pump 2 is connected to discharge port 132 via sample holder SH and column flow path CP. As a result, in the first state, the sample held in the sample holder SH can be guided to the column channel CP. Furthermore, the sample separated into individual substances by the column channel CP is guided to the atomization channel 131D of the connection channel 131, and the atomized sample is guided to an external detector connected to the connection section 130D.

[0067] With this configuration, the flow paths and separation columns are formed on multiple plate-like members (chips), shortening the flow path to the separation column compared to when the flow path is formed using piping or the like. This reduces the internal volume of the flow path through which the mobile phase flows to the separation column, thereby suppressing sample diffusion within the mobile phase. Furthermore, even if the separation capability of the column flow path does not meet the analytical requirements, replacing only the plate-like member 160 without replacing the entire microfluidic device allows for a microfluidic device suited to the analytical conditions. As a result, sample analysis accuracy can be improved while convenience can be enhanced. Furthermore, by replacing the plate-like members 180 and 140 depending on the capacity of the sample holder and the connection shape of the detector to be used, a microfluidic device suited to the analytical conditions can be easily adapted.

[0068] (4) Correspondence between each component of the claims and each part of the embodiment: An example of the correspondence between each component of the claims and each part of the embodiment will be described below. In the above embodiment, the connection channel 131 is an example of an introduction channel, ports A and CC are examples of first ports, ports B and AA are examples of second ports, the sample holder SH is an example of a sample loop, and the spring 720 and fixing member 730 are examples of a pressing part. Furthermore, the main body aligner 810 is an example of a first fixing member, and the detector chip aligner 820 is an example of a second fixing member. Furthermore, the plate-shaped member 140 is an example of a first plate-shaped member, the plate-shaped member 160 is an example of a second plate-shaped member, and the plate-shaped member 180 is an example of a third plate-shaped member.

[0069] (5) Aspects It will be understood by those skilled in the art that the exemplary embodiments described above are specific examples of the following aspects.

[0070] (Item 1) A microfluidic device according to one embodiment comprises a main body portion made up of one or more members, the main body portion comprising a connection portion connectable to a separation column and a plurality of flow paths, the plurality of flow paths comprising a sample holding portion for holding a sample and an introduction flow path capable of introducing the sample into the separation column which separates the sample, and further comprising a switching member slidably connected to the main body portion and capable of selectively connecting the plurality of flow paths by sliding relative to the main body portion to switch the connections.

[0071] According to the microfluidic device described in paragraph 1, the microfluidic device filled with a sample is directly connected to the separation column, eliminating the need for piping connecting the sample injection unit and the separation column compared to conventional devices, thereby shortening the flow path to the separation column through which the sample passes. This allows the internal volume of the flow path from the sample holder to the separation column to be reduced, thereby suppressing sample diffusion within the mobile phase. Furthermore, because the microfluidic device and the separation column are separate components, if the separation column needs to be replaced for a different analysis, it is possible to replace only the separation column. As a result, it is possible to improve the accuracy of sample analysis while also improving convenience.

[0072] (Item 2) In the microfluidic device described in item 1, the connecting portion may be in the shape of a rectangular column extending in one direction, and may further include a sleeve that can pass through the connecting portion, has an inner circumferential surface that can engage with the connecting portion, and has a cylindrical outer circumferential surface; a nut that has a first through hole that can pass through the sleeve and a first thread groove that can be threaded into a main thread groove formed in an inlet port of the separation column; and a ferrule that has a second through hole that can pass through the sleeve and can seal a flow path in the separation column.

[0073] According to the microfluidic device described in paragraph 2, the connector and sleeve are engaged by inserting the connector into the sleeve. Furthermore, the main thread groove of the separation column is threadedly engaged with the first thread groove of the nut while the nut and ferrule are inserted through the sleeve. In this case, the ferrule and connector are pressed against the separation column. This connects the flow path in the separation column to the flow path in the main body, while sealing the separation column. This makes it possible to connect the microfluidic device to the separation column with a simple configuration.

[0074] (Item 3) In the microfluidic device described in Item 1, the connecting portion may be cylindrical and extend in one direction, and may further include a nut having a first through-hole that can pass through the connecting portion and a first thread groove that can be threaded into a main thread groove formed in an inlet port of the separation column, and a ferrule that has a second through-hole that can pass through the connecting portion and can seal a flow path in the separation column.

[0075] According to the microfluidic device described in paragraph 3, the main thread groove of the separation column is threaded into the first thread groove of the nut with the connecting portion passing through the nut and ferrule. In this case, the ferrule and the connecting portion are pressed against the separation column. This connects the flow path in the separation column to the flow path in the main body. This configuration eliminates the need for a sleeve to connect the connecting portion to the separation column. This makes it possible to connect the microfluidic device to the separation column with a simpler configuration.

[0076] (Item 4) The microfluidic device described in Item 1 may further include a nut having a first screw groove that can be threaded onto a main screw groove formed in an inlet port of the separation column, and the connecting portion may include a first cylindrical member extending in one direction, and a second cylindrical member that extends further in the one direction from the first cylindrical member, has a diameter larger than that of the first cylindrical member, and has a sealing surface that intersects with the one direction, and the nut may be formed with a first through hole that can pass through the first cylindrical member, and a slot that extends in the one direction and allows the first cylindrical member to be attached to the first through hole.

[0077] According to the microfluidic device described in paragraph 4, with the first cylindrical member positioned in the first through-hole through the slot, the second cylindrical member is pressed in one direction by threading the main thread groove of the separation column into the first thread groove of the nut. This presses the sealing surface against the separation column. This connects the flow path in the separation column to the second flow path, while sealing the separation column. This allows connection to the separation column with a simple configuration.

[0078] (Item 5) The microfluidic device described in Item 1 may further include a column mounting mechanism, wherein the connection portion is a columnar shape extending in one direction, the separation column has a port connectable to the connection portion and a protrusion protruding outward around the port, and the column mounting mechanism may include: a storage member having an insertion hole into which the protrusion of the separation column can be inserted and having a storage space capable of accommodating the protrusion; and a pressing portion fixed to the connection portion within the storage space and configured to be able to press the protrusion against the storage member so that the storage member and the protrusion engage with each other.

[0079] According to the microfluidic device described in paragraph 5, it is possible to connect the main body to the separation column without using components such as ferrules and nuts. Furthermore, since there is no need to tighten nuts when connecting to the separation column, there is no need to use tools. Therefore, it is possible to connect the main body to the separation column more easily.

[0080] (Item 6) In the microfluidic device described in any one of Items 1 to 5, the plurality of members may be plate-shaped.

[0081] According to the microfluidic device described in item 6, it is possible to realize a thin device.

[0082] (Item 7) In the microfluidic device described in any one of Items 1 to 6, the switching member may be switchable between a state in which the sample holding section and the introduction channel are connected, and a state in which the sample holding section and the introduction channel are not connected.

[0083] In the microfluidic device described in item 7, the connection state between the sample holder and the introduction channel can be easily switched.

[0084] (Item 8) In another aspect of the liquid chromatograph, the plurality of flow paths further include a first port connected to a pump that delivers a mobile phase and a second port connected to a sample filling section that fills with a sample, and the switching member is switchable between a first state that connects the second port and the sample holding section and a second state that connects the first port, the sample holding section and the introduction flow path, the liquid chromatograph comprising: the microfluidic device described in any one of items 1 to 6; the pump; the sample filling section; the separation column; and a detection section that detects components that have passed through the separation column.

[0085] According to the liquid chromatograph described in paragraph 8, when the switching member is in the first state, the sample aspirated by the sample filling unit is introduced into the sample loop from the second port. This allows the sample to be retained in the sample loop. When the switching member is in the second state, the mobile phase delivered by the pump is introduced into the sample loop from the first port. This allows the sample retained in the sample loop to be introduced into the separation column together with the mobile phase. In this way, the mobile phase does not pass through unnecessary flow paths such as piping before being introduced into the separation column, thereby suppressing diffusion of the sample in the mobile phase.

[0086] (Item 9) A connection device according to another aspect is a connection device that connects the microfluidic device according to claim 1 or 2, the separation column, and a detector, and includes: a first fixing member that can fix the microfluidic device and can connect the connection portion of the microfluidic device to the inlet port of the separation column; a second fixing member that can fix the detector and can connect the inlet port of the detector and the outlet port of the separation column; a guide rail configured to allow at least one of the first fixing member and the second fixing member to be moved relative to the other; and a clamp mechanism that can shorten the distance between the first fixing member and the second fixing member arranged on the guide rail.

[0087] According to the connection device described in paragraph 9, the separation column is positioned between the first and second fixing members while maintaining a distance between them. In this case, the microfluidic device, the separation column, and the detector can be connected while the separation column is clamped between the first and second fixing members by the clamping mechanism. Therefore, the microfluidic device, the separation column, and the detector can be connected with a simpler configuration.

[0088] (Item 10) A microfluidic device according to another aspect comprises: a main body having a plurality of flow paths; and a switching member slidably connected to the main body and capable of selectively switching and connecting the plurality of flow paths of the main body by sliding relative to the main body; wherein the main body comprises a first plate-like member and a second plate-like member; and the plurality of flow paths include a sample holding flow path formed in the first plate-like member for holding a sample, and a column flow path formed in the second plate-like member for separating the sample into components.

[0089] According to the microfluidic device described in paragraph 10, since the flow channels and column flow channels are formed in multiple plate-like members (chips), the flow channels to the sample separation member are shorter than when the flow channels are formed using piping or the like. This allows the internal volume of the flow channel through which the mobile phase flows to be reduced, thereby suppressing sample diffusion within the mobile phase. Furthermore, the multiple plate-like members are composed of a first plate-like member having a sample-holding flow channel and a second plate-like member having a column flow channel. In this case, when changing the volume of the sample-holding flow channel, only the first plate-like member including the sample-holding flow channel can be replaced, and when the column flow channel does not meet the analytical requirements, only the second plate-like member including the column flow channel can be replaced. As a result, when changing the configuration of the microfluidic device to suit analytical conditions, only a portion of the configuration needs to be replaced, thereby improving sample analysis accuracy and convenience.

[0090] (Item 11) In the microfluidic device described in Item 10, the main body further includes a third plate-like member, and the third plate-like member includes a connection portion connectable to a detection portion that detects components that have passed through the column flow path, and the multiple flow paths include a first port connected to a pump that delivers a mobile phase, a second port connected to a sample filling portion that fills with a sample, and a discharge port formed in the connection portion that discharges the components that have passed through the column flow path to the detection portion, and the switching member may be switchable between a first state in which the second port and the sample holding flow path are connected, and a second state in which the first port, the sample holding flow path, the column flow path, and the discharge port are connected.

[0091] According to the microfluidic device described in paragraph 11, when the switching member is in the first state, the sample aspirated by the sample aspirator is guided from the second port to the sample holding channel. This causes the sample to be held in the sample holding channel. When the switching member is in the second state, the mobile phase delivered by the pump is guided from the first port to the sample holding channel. This causes the sample held in the sample holding channel to be guided to the column channel together with the mobile phase. The sample guided to the column channel is separated into individual substances and then guided to the discharge port. In this way, the mobile phase does not pass through unnecessary channels such as piping before being guided to the column channel, thereby suppressing diffusion of the sample in the mobile phase.

[0092] (Item 12) A liquid chromatograph according to another aspect includes the microfluidic device according to item 11, the pump, the sample filling section, and the detection section.

[0093] According to the liquid chromatograph described in item 12, it is possible to suppress the diffusion of the sample in the mobile phase.

Claims

1. A microfluidic device comprising a main body portion composed of one or more members, the main body portion including a connection portion connectable to a separation column, and a plurality of flow paths, the plurality of flow paths including a sample holder portion for holding a sample, and an introduction flow path capable of introducing the sample into the separation column which separates the sample, and further comprising a switching member slidably connected to the main body portion and capable of switching the connections of the plurality of flow paths to selectively connect them by sliding relative to the main body portion.

2. The microfluidic device according to claim 1, further comprising: a sleeve having a cylindrical outer surface, the connecting portion being shaped like a rectangular pillar extending in one direction, the sleeve being capable of passing through the connecting portion and having an inner circumferential surface engageable with the connecting portion; a nut having a first through-hole being capable of passing through the sleeve and a first thread groove being capable of threading into a main thread groove formed in an inlet port of the separation column; and a ferrule having a second through-hole being capable of passing through the sleeve and capable of sealing a flow path within the separation column.

3. The microfluidic device according to claim 1, wherein the connecting portion has a cylindrical shape extending in one direction, and further comprises: a nut having a first through-hole that can pass through the connecting portion and a first screw groove that can be threaded into a main screw groove formed in an inlet port of the separation column; and a ferrule having a second through-hole that can pass through the connecting portion and that can seal a flow path within the separation column.

4. The microfluidic device according to claim 1, further comprising a nut having a first screw groove that can be threaded onto a main screw groove formed in an inlet port of the separation column, wherein the connecting portion includes a first cylindrical member extending in one direction, and a second cylindrical member that extends further in the one direction from the first cylindrical member, has a larger diameter than the first cylindrical member, and has a sealing surface that intersects with the one direction, and wherein the nut is formed with a first through-hole that can pass through the first cylindrical member, and a slot that extends in the one direction and allows the first cylindrical member to be attached to the first through-hole.

5. A microfluidic device according to claim 1, further comprising a column mounting mechanism, wherein the connection portion is in the shape of a pillar extending in one direction, and the separation column has a port connectable to the connection portion and a protrusion protruding outward around the port, and the column mounting mechanism comprises: a storage member having an insertion hole into which the protrusion of the separation column can be inserted and having a storage space capable of accommodating the protrusion; and a pressing portion fixed to the connection portion within the storage space and configured to be able to press the protrusion against the storage member so that the storage member and the protrusion engage.

6. The microfluidic device according to any one of claims 1 to 5, wherein the plurality of members are plate-shaped.

7. A microfluidic device according to any one of claims 1 to 5, wherein the switching member is switchable between a state in which the sample holder and the introduction flow path are connected, and a state in which the sample holder and the introduction flow path are not connected.

8. A microfluidic device according to any one of claims 1 to 5, wherein the plurality of flow paths further include a first port connected to a pump that delivers a mobile phase and a second port connected to a sample filling section that fills with a sample, and the switching member is switchable between a first state in which the second port and the sample holding section are connected, and a second state in which the first port, the sample holding section, and the introduction flow path are connected; the microfluidic device comprising: the pump; the sample filling section; the separation column; and a detection section that detects components that have passed through the separation column.

9. A connection device for connecting the microfluidic device of claim 1, the separation column, and a detector, comprising: a first fixing member capable of fixing the microfluidic device and capable of connecting the connection portion of the microfluidic device to the inlet port of the separation column; a second fixing member capable of fixing the detector and capable of connecting the inlet port of the detector and the outlet port of the separation column; a guide rail configured to allow at least one of the first fixing member and the second fixing member to move relatively to the other; and a clamp mechanism capable of shortening the distance between the first fixing member and the second fixing member arranged on the guide rail.

10. A microfluidic device comprising: a main body having a plurality of flow paths; and a switching member slidably connected to the main body and capable of switching and selectively connecting the plurality of flow paths in the main body by sliding relative to the main body, wherein the main body includes a first plate-like member and a second plate-like member, and the plurality of flow paths include a sample holding flow path formed in the first plate-like member for holding a sample, and a column flow path formed in the second plate-like member for separating the sample into components.

11. A microfluidic device as described in claim 10, wherein the main body further includes a third plate-like member, the third plate-like member including a connection portion connectable to a detection portion that detects components that have passed through the column flow path, the plurality of flow paths including: a first port connected to a pump that delivers a mobile phase; a second port connected to a sample filling portion that fills with a sample; and a discharge port formed in the connection portion that discharges components that have passed through the column flow path to the detection portion, and the switching member is switchable between a first state in which the second port and the sample holding flow path are connected, and a second state in which the first port, the sample holding flow path, the column flow path, and the discharge port are connected.

12. A liquid chromatograph comprising: the microfluidic device according to claim 11; the pump; the sample loading section; and the detection section.

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