Microfluidic system

Abstract

A microfluidic system (100) includes a chip holding section (10) that holds a microchip having a plurality of liquid storage sections, a chip cover, a sealing member, a dispensing probe (30), a suction mechanism (40), a first storage section (51) that stores a first cleaning solution, a second storage section (52) that stores a second cleaning solution, a pump (70), a path switching section (60) configured to be able to be at least either of a first state in which an upstream side of the pump (70) communicates with the first storage section (51) and a second state in which a downstream side of the pump (70) communicates with the first storage section (51), and a control section that controls operations of the path switching section (60) and the pump (70) to thereby inject the second cleaning solution from the dispensing probe (30) to the liquid storage section after suctioning the first cleaning solution in the second state and injecting the first cleaning solution from the dispensing probe (30) to the liquid storage section in the first state.

Description

TECHNICAL FIELD

[0001] The present application relates to a microfluidic system. BACKGROUND

[0002] A microfluidic system is developed in which a sample is filled in a fine flow path formed in a microchip and electrophoresis or the like is performed to analyze the sample. In this microfluidic system, in order to repeatedly use the microchip, the flow path and the reservoir after analysis are cleaned.

[0003] In a case where a component from the sample or a fluorescent dye is adsorbed in the flow path, sometimes the peak shape of the analysis result is changed, or the time delay of the electrophoresis is delayed, or the separation ability in the flow path is reduced, or the baseline is raised.

[0004] In a case where the microchip is cleaned using only a cleaning solution of a water system, if a component from the sample or a fluorescent dye is adsorbed in the flow path with a strong adsorption force, the cleaning can be insufficient. Therefore, as described in Japanese Patent No. 5640557 (Patent Document 1), sometimes a cleaning solution containing an organic solvent such as alcohol is used.

[0005] Prior art documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent No. 5640557 SUMMARY

[0008] Problem to be solved by the invention

[0009] The cleaning solution containing an organic solvent such as alcohol as described in Patent Document 1 has a low surface tension. Therefore, in a case where a cleaning solution of an amount close to the reservoir capacity is injected into the flow path, the cleaning solution spreads on the surface of the microchip, and a problem that the cleaning is difficult to be automatically performed mechanically can occur.

[0010] If a worker injects a predetermined amount of a cleaning solution into the microchip by a manual operation, the microchip can be reliably cleaned, but such an operation is complicated.

[0011] In order to avoid such a complication, it is also possible to operate as follows, that is, to reduce the amount of liquid injected into the microchip and to fill a cleaning solution of an organic solvent system into the flow path by a capillary phenomenon, and then to flow a cleaning solution of a water system in the flow path. However, in such a case, the amount of the cleaning solution of the organic solvent system is small, and the cleaning effect is also limited, and it cannot be said that the cleaning is sufficient.

[0012] The present application has been made in view of the above-described problems, and an object of the present application is to provide a microfluidic system capable of efficiently cleaning a microchip.

[0013] Solution to solve the problem

[0014] The microfluidic system of the present application includes a chip holding portion that holds a microchip having at least one flow path including a separation flow path for separating a sample inside, and having a plurality of liquid storage portions that open at each end of the flow path; a chip cover that is disposed opposite the microchip held by the chip holding portion, and has a plurality of probe insertion portions provided at positions corresponding to each of the plurality of liquid storage portions; a plurality of sealing members that seal between the plurality of probe insertion portions and the plurality of liquid storage portions in a manner that the plurality of probe insertion portions and the plurality of liquid storage portions can communicate; a dispensing probe disposed so as to be able to discharge liquid to any one of the plurality of liquid storage portions; a suction mechanism including a plurality of suction nozzles disposed so as to be able to suction liquid from each of the plurality of liquid storage portions; a first storage portion that stores a first cleaning liquid for cleaning the flow path; a second storage portion that stores a second cleaning liquid for cleaning the flow path; a pump disposed so as to be able to repeatedly perform suction of liquid and discharge of liquid; a path switching portion configured to be able to switch between a path for suctioning the first cleaning liquid from the first storage portion and a path for suctioning the second cleaning liquid from the second storage portion; and a control portion that controls at least the operation of the path switching portion and the pump.

[0015] Effects of the invention

[0016] According to the present application, a microfluidic system capable of efficiently cleaning a microchip can be provided. BRIEF DESCRIPTION OF DRAWINGS

[0017] Fig. 1 is a schematic view of the microfluidic system of Embodiment 1.

[0018] Fig. 2 is a block diagram showing the structure of the microfluidic system of Embodiment 1.

[0019] Fig. 3 is a plan view of a microchip for the microfluidic system of Embodiment 1.

[0020] Fig. 4 is a view showing a flow path formed in the microchip shown in Fig. 3

[0021] Fig. 5 is a cross-sectional view of the microchip shown in Fig. 3

[0022] Fig. 6 is a cross-sectional view showing a state in which the chip holding portion of the microfluidic system of Embodiment 1 holds the microchip on which the chip cover is mounted.

[0023] ​​Fig. 7 is a view showing a process of sucking the first cleaning solution from the first storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 1.

[0024] Fig. 8 is a view showing a process of injecting the first cleaning solution into the liquid storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 1.

[0025] Fig. 9 is a view showing a process of sucking the first cleaning solution from the microchip at the time of cleaning the microchip in the microfluidic system of Embodiment 1 and a process of cleaning the dispensing probe.

[0026] Fig. 10 is a view showing a process of sucking the second cleaning solution from the second storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 1 and a process of injecting the second cleaning solution into the liquid storage section.

[0027] Fig. 11 is a view showing a process of sucking the second cleaning solution from the microchip at the time of cleaning the microchip in the microfluidic system of Embodiment 1 and a process of cleaning the dispensing probe.

[0028] Fig. 12 is a view showing a schematic configuration of the microfluidic system of Embodiment 2 and is a view showing a process of sucking the first cleaning solution from the first storage section at the time of cleaning the microchip.

[0029] Fig. 13 is a view showing a process of injecting the first cleaning solution into the liquid storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 2.

[0030] Fig. 14 is a view showing a process of sucking the second cleaning solution from the second storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 2.

[0031] Fig. 15 is a view showing a process of injecting the second cleaning solution into the liquid storage section at the time of cleaning the microchip in the microfluidic system of Embodiment 2. DETAILED DESCRIPTION

[0032] Embodiments of the present application will be described below in detail with reference to the accompanying drawings. In the embodiments shown below, the same or common parts are denoted by the same reference numerals in the drawings, and the description thereof will not be repeated.

[0033] Further, in the following embodiments, in the case where a number, an amount, and the like are mentioned, the range of the present application is not necessarily limited to the number, the amount, and the like, except for the case where it is particularly described. In addition, in the following embodiments, each of the constituent elements is not necessarily essential to the present application, except for the case where it is particularly described. In addition, in the case where a plurality of embodiments exist in the following, it is initially intended that the characteristic portions of each of the embodiments can be appropriately combined, except for the case where it is particularly described.

[0034] (Embodiment 1)

[0035] Fig. 1 is a schematic view of a microfluidic system of Embodiment 1. Fig. 2 is a block diagram showing the structure of the microfluidic system of Embodiment 1. Refer to Fig. 1 and Fig. 2 The microfluidic system 100 of Embodiment 1 is described.

[0036] As shown in Fig. 1 , the microfluidic system 100 of Embodiment 1 includes a chip holding portion 10, a dispensing probe 30, a suction mechanism 40, a first storage portion 51, a second storage portion 52, a path switching portion 60, a pump 70, a first path 81, a second path 82, a third path 83, a fourth path 84, and a cleaning portion 90.

[0037] The chip holding portion 10 holds a microchip 200 described later. The microchip 200 can supply a liquid via a plurality of probe insertion portions 250 described later.

[0038] The dispensing probe 30 is provided so as to be able to inject a liquid to any one of the plurality of probe insertion portions 250. The dispensing probe 30 is provided so as to be able to move. The dispensing probe 30 is moved by a probe moving mechanism not shown. The dispensing probe 30 has a tapered portion 30a which becomes thin as it goes toward a tip end.

[0039] The suction mechanism 40 is provided so as to be able to suck a liquid from each of the plurality of probe insertion portions 250. The suction mechanism 40 includes a plurality of suction nozzles 41, 42, 43, 44, a nozzle holding portion 45, a valve switching portion 46, and a suction pump 47.

[0040] The plurality of suction nozzles 41, 42, 43, 44 are nozzles for sucking a liquid from each of the plurality of probe insertion portions 250. The plurality of suction nozzles 41, 42, 43, 44 are held by the nozzle holding portion 45.

[0041] The nozzle holding section 45 is arranged so as to be movable in the up-and-down direction and the horizontal direction. The nozzle holding section 45 is moved by a nozzle moving mechanism. The plurality of suction nozzles 41, 42, 43, 44 are inserted into the plurality of probe insertion sections 250 by moving the nozzle holding section 45.

[0042] The plurality of suction nozzles 41, 42, 43, 44 are connected to a suction pump 47 via a valve switching section 46. The valve switching section 46 has a plurality of valves 461, 462, 463, 464 and is capable of switching the opening and closing of the plurality of valves 461, 462, 463, 464. The liquid is suctioned from the desired suction nozzle by switching the opening and closing of the plurality of valves 461, 462, 463, 464. The suction pump 47 generates a negative pressure for suctioning the liquid and transports the suctioned liquid to a waste liquid tank 94.

[0043] The first storage section 51 stores a first cleaning liquid for cleaning the flow path (introduction flow path 221, separation flow path 222) possessed by the microchip 200 (refer to FIG. 2). Fig. 4 As the first cleaning liquid, a water-based cleaning liquid such as pure water can be used.

[0044] The second storage section 52 stores a second cleaning liquid for cleaning the flow path (introduction flow path 221, separation flow path 222) possessed by the microchip 200. As the second cleaning liquid, for example, an organic solvent-based cleaning liquid can be used. As the organic solvent, for example, alcohol and / or acetonitrile can be listed. As the alcohol, in particular, methanol, ethanol, isopropanol, or the like is used. Furthermore, the second cleaning liquid is not limited to the organic solvent-based cleaning liquid and can be a water-based cleaning liquid.

[0045] The second storage section 52 is provided integrally with a well plate 53 capable of storing a plurality of samples, for example. The second storage section 52 can be provided independently of the well plate 53.

[0046] The path switching section 60 is configured so as to be capable of switching the path of suctioning the first cleaning liquid from the first storage section 51 and the path of suctioning the second cleaning liquid from the second storage section 52.

[0047] The path switching section 60 has a first port 61, a second port 62, a third port 63, a fourth port 64, a start filling port 66, a movable path 67, and a movable path 68.

[0048] The first port 61, the second port 62, the third port 63, the fourth port 64, and the start filling port 66 are arranged in a circumferential direction. The movable path 67 and the movable path 68 are arranged so as to be capable of connecting the ports adjacent to each other.

[0049] The first port 61 is connected to the dispensing probe 30 via a first channel 81. The second port 62 is connected to the downstream side of the pump 70 (more specifically, downstream side of the storage chamber 71 described later) in the discharge direction of the pump 70 through a second channel 82.

[0050] The third port 63 is connected to the upstream side of the pump 70 (more specifically, the upstream side of the storage chamber 71) in the discharge direction via the third path 83. The fourth port 64 is connected to the first reservoir 51 via the fourth path 84. The priming port 66 is connected to the priming device 54 via the path 87. The priming device 54 is used to fill the path with liquid.

[0051] The movable paths 67 and 68 are configured to be rotatable in the same direction. By moving the movable paths 67 and 68 , at least one pair of mutually adjacent ports among the first port 61 , the second port 62 , the third port 63 , the fourth port 64 , and the priming port 66 is connected.

[0052] The pump 70 is provided so as to be able to repeatedly suck in and discharge the liquid. The pump 70 is, for example, a metering pump and is able to suck in a predetermined amount of liquid. The pump 70 has a storage chamber 71 that can store the liquid therein.

[0053] The cleaning portion 90 is a port for cleaning the dispensing probe 30. The cleaning portion 90 includes two cleaning tanks 91 and 92.

[0054] One of the two cleaning tanks, cleaning tank 91, is configured to store a first cleaning liquid. By immersing the tip of the dispensing probe in the first cleaning liquid stored in cleaning tank 91, the outer periphery of the tip of the dispensing probe 30 can be cleaned. Furthermore, by draining the first cleaning liquid from the dispensing probe 30 toward cleaning tank 91, the inner periphery of the dispensing probe 30 can also be cleaned.

[0055] The other of the two cleaning tanks, cleaning tank 92, is configured to store a second cleaning liquid. By immersing the tip of the dispensing probe in the second cleaning liquid stored in cleaning tank 92, the outer periphery of the tip of the dispensing probe 30 can be cleaned. Furthermore, by discharging the second cleaning liquid within the dispensing probe 30 into cleaning tank 92, the inner periphery of the dispensing probe 30 can also be cleaned.

[0056] like Fig. 2 As shown, the microfluidic system 100 further includes a control unit 95 , a detection unit 96 , and a voltage application unit 97 . The control unit 95 controls the operations of the dispensing probe 30 , the suction mechanism 40 , the path switching unit 60 , the pump 70 , the detection unit 96 , and the voltage application unit 97 .

[0057] The control section 95 controls the movement of the dispensing probe 30 by controlling the operation of the probe movement mechanism described above. The control section 95 controls the movement of the plurality of suction nozzles 41, 42, 43, 44 by controlling the operation of the nozzle movement mechanism described above. In addition, the control section 95 controls the suction operation of the plurality of suction nozzles 41, 42, 43, 44 by controlling the operation of the valve switching section 46 and the suction pump 47 of the suction mechanism 40.

[0058] The control section 95 controls the suction operation or the discharge operation of the dispensing probe 30 by controlling the operation of the path switching section 60 and the pump 70.

[0059] The control section 95 controls the operation of the voltage application section 97. The voltage application section 97 applies a voltage to both end portions of the introduction flow path 221 (refer to Fig. 4 ) and the separation flow path 222 (refer to Fig. 4 ) provided in the microchip 200, respectively. In the case where a plurality of microchips 200 are held, the voltage application section 97 applies a voltage to both end portions of the introduction flow path 221 and the separation flow path 222 of each of the microchips 200, respectively. Thereby, it is possible to cause electrophoresis of the sample in the separation flow path 222.

[0060] The control section 95 controls the operation of the detection section 96. The detection section 96 performs, for example, fluorescence detection of the sample component separated in the separation flow path 222. The detection section 96 has, for example, an irradiation section and a light receiving section. The irradiation section irradiates an excitation light to a part of the separation flow path. The light receiving section receives fluorescence generated by the sample component moving in the separation flow path 222 being excited by the excitation light.

[0061] Fig. 3 is a plan view of a microchip of the microfluidic system according to Embodiment 1. Fig. 4 is a view showing a flow path formed in the microchip shown in Fig. 3 . The flow path is formed in the microchip 200. Fig. 5 is a cross-sectional view of the microchip shown in Fig. 3 . The flow path is formed in the microchip 200. Fig. 3 to Fig. 5 The structure of the microchip 200 will be described with reference to

[0062] As shown in Fig. 3 to Fig. 5 , the microchip 200 has at least one flow path including a separation flow path 222 for separating a sample inside, and has a plurality of reservoirs 211, 212, 213, 214 which are opened at each end portion of the at least one flow path.

[0063] Specifically, the microchip 200 includes a first substrate 210 and a second substrate 220. The first substrate 210 is provided on the second substrate 220. The first substrate 210 and the second substrate 220 are configured to be able to transmit light therethrough. The first substrate 210 and the second substrate 220 are formed of, for example, a glass substrate. Further, the first substrate 210 and the second substrate 220 can be formed of a transparent resin substrate.

[0064] An introduction flow path 221 and a separation flow path 222 are provided on one main surface of the second substrate 220 in a manner of intersecting each other. The introduction flow path 221 and the separation flow path 222 are groove portions formed on the surface. The introduction flow path 221 is a flow path for introducing a sample. The separation flow path 222 is a flow path for electrophoresis of the introduced sample.

[0065] On the first substrate 210, a plurality of liquid reservoirs 211, 212, 213, 214 are provided at positions corresponding to both end portions of the introduction flow path 221 and both end portions of the separation flow path 222. The plurality of liquid reservoirs 211, 212, 213, 214 are configured by a plurality of through-holes that penetrate the first substrate 210.

[0066] The plurality of liquid reservoirs 211, 212, 213, 214 each form a port for applying a voltage. An electrode pattern (not shown) is formed from an inner wall surface of each of the plurality of liquid reservoirs 211, 212, 213, 214 to a surface of the first substrate 210. Each of the electrode patterns is electrically connected to the voltage application portion 97.

[0067] Fig. 6 is a cross-sectional view showing a state in which the chip holding portion of the microfluidic system of Embodiment 1 holds the microchip on which the chip cover is mounted.

[0068] As shown in Fig. 6 , the microfluidic system 100 further includes a chip cover 230 and a plurality of sealing members 240.

[0069] The chip cover 230 is disposed opposite to the microchip 200 held by the chip holding portion 10. The chip cover 230 includes a plurality of probe insertion portions 250 provided at positions corresponding to the plurality of liquid reservoirs 211, 212, 213, 214.

[0070] The plurality of probe insertion portions 250 are configured by a plurality of through-holes 232 formed in the chip cover 230 at positions corresponding to the plurality of liquid reservoirs 211, 212, 213, 214 and a plurality of cylindrical members 251 respectively inserted into the plurality of through-holes 232.

[0071] The plurality of cylindrical members 251 are inserted into the through-holes 232 in a manner of protruding from a main surface 230a of the chip cover 230 opposite to the microchip 200 toward the microchip 200 side.

[0072] The cylindrical member 251 inserted into the plurality of liquid reservoirs 211 , 212 , and 213 is formed of a cylindrical member having a substantially uniform inner diameter.

[0073] The cylindrical member 251 inserted into the through hole 232 provided at a position corresponding to the liquid reservoir 214 has a tapered portion 251 a whose inner diameter decreases toward the microchip 200 side.

[0074] When injecting liquid into the liquid reservoir 214 , the tapered portion 30 a of the dispensing probe 30 is pressed against the tapered portion 251 a , thereby maintaining the probe insertion portion 250 and the dispensing probe 30 at a position corresponding to the liquid reservoir 214 in a liquid-tight manner.

[0075] The plurality of sealing members 240 seals between the plurality of probe insertion sections 250 and the plurality of liquid reservoirs 211, 212, 213, 214 so that the plurality of probe insertion sections 250 can communicate with the plurality of liquid reservoirs 211, 212, 213, 214. The plurality of sealing members 240 are provided between the microchip 200 and the cylindrical member 251.

[0076] The plurality of sealing members 240 have an annular shape and are formed of an elastic member.

[0077] In the microfluidic system 100, the microchip 200 is repeatedly used while held in the chip holder 10. After sample analysis, residual separation polymer and sample remain in the introduction channel 221, separation channel 222, and the multiple liquid reservoirs 211, 212, 213, and 214. Therefore, to ensure repeated use of the microchip 200, the microchip 200 is cleaned after analysis and after the residual separation polymer and sample are aspirated using the aspiration mechanism 40.

[0078] Fig. 7 to Fig. 11 1 is a diagram showing each step of cleaning a microchip in the microfluidic system of the first embodiment. Fig. 7 to Fig. 11 , the operation of the microfluidic system 100 when cleaning the microchip 200 will be described.

[0079] Fig. 7 This is a diagram showing a process of aspirating the first cleaning liquid from the first reservoir when cleaning the microchip in the microfluidic system of the first embodiment.

[0080] like Fig. 7 As shown, in the process of sucking the first cleaning liquid from the first storage section 51, first, the control section 95 controls the operation of the path switching section 60, thereby setting the second state in which the third port 63 and the fourth port 64 are connected and the upstream side of the pump 70 is connected to the first storage section 51.

[0081] Specifically, the movable path 68 is used to connect the third port 63 and the fourth port 64, and the upstream side of the pump 70 is connected to the first storage section 51 via the third path 83, the movable path 68, and the fourth path 84.

[0082] Next, the control section 95 controls the operation of the pump 70 to cause the first cleaning solution to be sucked from the first storage section 51 by the pump 70 in the above-mentioned second state. At this time, a predetermined amount of the first cleaning solution is sucked into the storage chamber 71.

[0083] Fig. 8 is a view showing a process of injecting the first cleaning solution into the liquid storage section when cleaning the microchip in the microfluidic system of Embodiment 1.

[0084] Next, as shown in Fig. 8 , in the process of injecting the first cleaning solution into the liquid storage section, as shown in Fig. 8 , the control section 95 controls the operation of the path switching section 60 and the pump 70 to switch from the above-mentioned second state to a first state in which the first port 61 and the second port 62 are connected and the downstream side of the pump 70 is in communication with the dispensing probe 30, thereby injecting the first cleaning solution from the dispensing probe 30 into the liquid storage section 214 that becomes a pressurizing port.

[0085] Specifically, the control section 95 moves the movable path 67 and the movable path 68, releases the second state in which the third port 63 and the fourth port 64 are connected by the movable path 68, and sets the first state in which the first port 61 and the second port 62 are connected by the movable path 67.

[0086] By connecting the first port 61 and the second port 62, the downstream side of the pump 70 can be brought into communication with the dispensing probe 30, thereby discharging the first cleaning solution from the dispensing probe 30.

[0087] Next, the control section 95 moves the dispensing probe 30 into the probe insertion section 250 provided at a position corresponding to the liquid storage section 214. Then, the control section 95 brings the outer peripheral surface of the tip end of the dispensing probe 30 into close contact with the tapered section 251a that constitutes a part of the probe insertion section 250. Thus, the dispensing probe 30 and the probe insertion section 250 are maintained liquid-tight, and leakage of the liquid injected from the dispensing probe 30 into the liquid storage section 214 to the outside of the liquid storage section can be suppressed.

[0088] Further, the movement of the dispensing probe 30 can be performed after the switch from the second state to the first state, or can be performed before the switch.

[0089] Next, the control section 95 controls the operation of the pump 70 to discharge the first cleaning solution from the dispensing probe 30. Specifically, the pump 70 is caused to generate a positive pressure and discharge the first cleaning solution from the dispensing probe 30.

[0090] At this time, the first cleaning solution is injected in an amount exceeding the capacity of each of the plurality of liquid storage portions 211, 212, 213, 214. Thereby, the first cleaning solution is delivered to the plurality of liquid storage portions 211, 212, 213 via the separation flow path 222 and the introduction flow path 221 and fills the plurality of liquid storage portions 211, 212, 213, 214.

[0091] Fig. 9 is a view showing a process of sucking the first cleaning solution from the microchip and a process of cleaning the dispensing probe in the microfluidic system of Embodiment 1.

[0092] Next, as shown in Fig. 9 , in the process of sucking the first cleaning solution from the microchip, the control section 95 controls the suction mechanism 40, whereby the first cleaning solution is sucked from the plurality of liquid storage portions 211, 212, 213, 214 by the plurality of suction nozzles 41, 42, 43, 44.

[0093] Specifically, the plurality of suction nozzles 41, 42, 43, 44 are inserted into the plurality of liquid storage portions 211, 212, 213, 214 and the suction pump 47 is driven. At this time, the valve switching section 46 can also appropriately switch the opening and closing of the plurality of valves 461, 462, 463, 464.

[0094] In addition, cleaning of the dispensing probe 30 is also performed. Specifically, in the process of cleaning the dispensing probe, the control section 95 inserts the dispensing probe 30 into the cleaning tank 91 of the cleaning section 90 described above and discharges the first cleaning solution from the dispensing probe 30. Thereby, the inside of the dispensing probe 30 is cleaned. In addition, by immersing the tip side of the dispensing probe 30 in the first cleaning solution stored in the cleaning tank 91, the outer peripheral portion of the tip side of the dispensing probe 30 is cleaned. The remaining first cleaning solution is recovered by the waste tank 94.

[0095] The cleaning of the dispensing probe 30 in the cleaning tank 91 can be performed during the suction operation of the first cleaning solution described above, or can be performed before and after the suction operation of the first cleaning solution described above.

[0096] Fig. 10 is a view showing a process of sucking the second cleaning solution from the second storage portion and a process of injecting the second cleaning solution into the liquid storage portion in the microfluidic system of Embodiment 1.

[0097] Next, as shown in Fig. 10 , in the process of sucking the second cleaning solution from the second storage portion and the process of injecting the second cleaning solution into the liquid storage portion, the control section 95 controls the operation of the path switching section 60 and the pump 70, whereby the second cleaning solution is sucked from the second storage portion 52 by the pump 70 and the second cleaning solution is injected into the liquid storage portion 214.

[0098] Specifically, the control section 95 inserts the dispensing probe 30 into the second storage section 52 and drives the pump 70 to draw the second cleaning solution from the second storage section 52 into the dispensing probe 30. Next, the control section 95 moves the dispensing probe 30 into the probe insertion section 250 provided at a position corresponding to the reservoir section 214. Then, the control section 95 brings the outer peripheral surface of the tip end of the dispensing probe 30 into close contact with the tapered section 251a constituting a part of the probe insertion section 250.

[0099] Next, the control section 95 controls the operation of the pump 70 to discharge the second cleaning solution from the dispensing probe 30. Specifically, the control section 95 causes the pump 70 to generate positive pressure and discharge the second cleaning solution from the dispensing probe 30. Thus, the second cleaning solution is injected into the reservoir section 214, and the second cleaning solution also fills the plurality of reservoir sections 211, 212, 213 via the separation flow path 222 and the introduction flow path 221. The microchip 200 is left for a predetermined time in the state in which the second cleaning solution is filled therein. The predetermined time is, for example, about 1 to 3 minutes. Further, in the case where cleaning is repeated a plurality of times, the last cleaning can be left for about 60 minutes, for example. In this way, by filling the second cleaning solution in advance in the plurality of reservoir sections 211, 212, 213, 214 and in the introduction flow path 221 and the separation flow path 222 for a predetermined time, it is possible to effectively remove components adsorbed to the surfaces of the flow paths and the reservoir sections.

[0100] Fig. 11 is a view showing a procedure of drawing the second cleaning solution from the microchip and a procedure of cleaning the dispensing probe in the microfluidic system of Embodiment 1.

[0101] Next, as shown in Fig. 11 , in the procedure of drawing the second cleaning solution from the microchip, the control section 95 controls the suction mechanism 40 to draw the second cleaning solution from the plurality of reservoir sections 211, 212, 213, 214 using the plurality of suction nozzles 41, 42, 43, 44.

[0102] Further, the control section 95 controls the operation of the path switching section 60 to maintain the above-described first state during the period from the procedure shown in Fig. 8 to the procedure shown in Fig. 11 .

[0103] In addition, cleaning of the dispensing probe 30 is also performed. Specifically, in the procedure of cleaning the dispensing probe, the control section 95 inserts the dispensing probe 30 into the cleaning tank 92 of the cleaning section 90 and discharges the second cleaning solution from the dispensing probe 30. Thus, the inside of the dispensing probe 30 is cleaned. In addition, by immersing the tip end side of the dispensing probe 30 in the second cleaning solution stored in the cleaning tank 92, the outer peripheral portion of the tip end side of the dispensing probe 30 is cleaned. The remaining second cleaning solution is recovered by the waste tank 94.

[0104] Further, the cleaning of the dispensing probe 30 in the cleaning tank 92 can be performed in the above-described suction operation of the second cleaning liquid, or can be performed before and after the above-described suction operation of the second cleaning liquid.

[0105] By performing the above-described procedure once or a plurality of times, the microchip 200 can be cleaned.

[0106] As described above, in the microfluidic system 100 of Embodiment 1, the cleaning liquid can be injected into the flow path via the probe insertion portion and the liquid storage portion while maintaining the liquid-tight state between the probe insertion portion and the liquid storage portion by the elastic member. Therefore, compared with the case where a small amount of cleaning liquid is injected into the liquid storage portion by the capillary phenomenon, the amount of cleaning liquid used in the cleaning can be increased. In addition, even if the amount of cleaning liquid is increased, since the liquid-tight state is maintained between the probe insertion portion and the liquid storage portion by the elastic member, the cleaning liquid can be prevented from leaking out to the surface of the microchip.

[0107] Further, in the microfluidic system 100 of Embodiment 1, the path switching portion 60 is configured to be capable of switching between a first state in which the first port 61 and the second port 62 are connected and the downstream side of the pump 70 communicates with the dispensing probe 30, and a second state in which the third port 63 and the fourth port 64 are connected and the upstream side of the pump 70 communicates with the first liquid storage portion 51. Also, the control portion 95 controls the operation of the path switching portion 60 and the pump, so that in cleaning at least one flow path, after the first cleaning liquid is sucked into the first liquid storage portion 51 by the pump 70 in the second state, the first cleaning liquid is injected from the dispensing probe into the liquid storage portion 214 by switching to the first state. In addition, the control portion 95 controls the operation of the path switching portion 60 and the pump 70, so that after the first cleaning liquid is injected, the second cleaning liquid is sucked from the second liquid storage portion 52 and injected from the dispensing probe 30 into the liquid storage portion 214.

[0108] As described above, the injection of the first cleaning liquid into the liquid storage portion and the injection of the second cleaning liquid into the liquid storage portion can be automatically switched by controlling the operation of the path switching portion 60 and the pump 70. Thus, the continuous operation can be performed fully automatically.

[0109] As described above, the leakage of the cleaning liquid to the surface of the microchip can be prevented, the amount of cleaning liquid can be increased, the injection of the first cleaning liquid and the injection of the second cleaning liquid can be automatically switched, so that the microchip can be efficiently cleaned.

[0110] (Embodiment 2)

[0111] Fig. 12 is a schematic view showing the microfluidic system of Embodiment 2. Referring to Fig. 12 The microfluidic system 100A of Embodiment 2 will be described.

[0112] As Fig. 12As shown, the path switching section 60 of the microfluidic system 100A of Embodiment 2 further includes a 5th port 65 connected to the 2nd reservoir 52 via a 5th path 85, and the switching method of the path mainly realized by the path switching section 60 is different from that of the microfluidic system 100 of Embodiment 1. The other structures are substantially the same.

[0113] The path switching section 60 has a 1st port 61, a 2nd port 62, a 3rd port 63, a 4th port 64, a 5th port 65, priming ports 661, 662, a movable path 67, a movable path 68, and a movable path 69.

[0114] The 2nd port 62, the 3rd port 63, the 4th port 64, the 5th port 65, and the priming ports 661, 662 are arranged in a circumferential direction in a manner of surrounding the 1st port 61.

[0115] The 1st port 61 is connected to the dispensing probe 30 via a 1st path 81. The 2nd port 62 is connected to a downstream side of the pump 70 (more specifically, a downstream side of a reservoir chamber 71 described later) via a 2nd path 82.

[0116] The 3rd port 63 is connected to an upstream side of the pump 70 (more specifically, an upstream side of the reservoir chamber 71) via a 3rd path 83. The 4th port 64 is connected to the 1st reservoir 51 via a 4th path 84. The 5th port 65 is connected to the 2nd reservoir 52 via a 5th path 85.

[0117] The priming port 661 is connected to the priming device 54 via a path 87. The priming port 662 is connected to the priming device 55 via a path 88. The priming devices 54, 55 are used to fill a liquid in the path.

[0118] The movable paths 67, 68, and 69 are provided to be movable. By moving the movable paths 67 and 68, at least one group of ports adjacent to each other among the 2nd port 62, the 3rd port 63, the 4th port 64, the 5th port 65, and the priming ports 661, 662 are connected.

[0119] The movable path 69 is provided to be able to select a state of being connected to any one of the 2nd port 62, the 3rd port 63, the 4th port 64, the 5th port 65, and the priming ports 661, 662 and a state of not being connected to any one of these ports.

[0120] In the path switching section 60, at least any one of a 1st state, a 2nd state, and a 3rd state is obtained by moving the movable paths 67, 68, and 69.

[0121] The first state is a state in which the first port 61 and the second port 62 are connected and the downstream side of the pump 70 communicates with the dispensing probe 30. The second state is a state in which the third port 63 and the fourth port 64 are connected and the upstream side of the pump 70 communicates with the first reservoir 51. The third state is a state in which the third port 63 and the fifth port 65 are connected and the upstream side of the pump 70 communicates with the second reservoir 52.

[0122] Also in Embodiment 2, the microchip 200 is repeatedly used in a state of being held in the chip holding section 10. After performing analysis of a sample, a separation polymer and a sample can remain in the introduction flow path 221 and the separation flow path 222, the plurality of reservoirs 211, 212, 213, 214. Therefore, in order to repeatedly use the microchip 200, after performing analysis and after sucking the remaining separation polymer and sample by the suction mechanism 40, the microchip 200 is cleaned.

[0123] Reference Signs List Fig. 12 to Fig. 15 The operation of the microfluidic system 100A when cleaning the microchip 200 will be described.

[0124] Fig. 12 is a view showing a process of sucking the first cleaning solution from the first reservoir when cleaning the microchip.

[0125] As shown in Fig. 12 In the process of sucking the first cleaning solution from the first reservoir 51, first, the control section 95 controls the operation of the path switching section 60, thereby setting the second state in which the third port 63 and the fourth port 64 are connected and the upstream side of the pump 70 communicates with the first reservoir 51.

[0126] Specifically, the third port 63 and the fourth port 64 are connected by the movable path 68, and the upstream side of the pump 70 and the first reservoir 51 are connected via the third path 83, the movable path 68, and the fourth path 84.

[0127] Next, the control section 95 controls the operation of the pump 70, and in the above-described second state, the first cleaning solution is sucked into the first reservoir 51 by the pump 70. At this time, a predetermined amount of the first cleaning solution is sucked into the reservoir chamber 71.

[0128] Further, the movable path 67 connects the fifth port 65 and the start filling port 662, and becomes a state in which the second cleaning solution is filled in the fifth path 85.

[0129] Fig. 13 is a view showing a process of injecting the first cleaning solution into the reservoir when cleaning the microchip in the microfluidic system of Embodiment 2.

[0130] As shown in Fig. 13As shown, in the step of injecting the first cleaning liquid into the liquid reservoir, the operations of the path switching unit 60 and the pump 70 are controlled to be in the first state, and the first cleaning liquid is injected from the dispensing probe 30 into the liquid reservoir 214 .

[0131] Specifically, the control unit 95 controls the operation of the path switching unit 60 to connect the first port 61 and the second port 62 via the movable path 69. The control unit 95 then moves the dispensing probe 30 into the probe insertion unit 250, which is located at a position corresponding to the liquid reservoir 214. The control unit 95 then controls the operation of the pump 70 to inject the first cleaning liquid into the liquid reservoir 214 via the probe insertion unit 250.

[0132] As a result, the first cleaning liquid is injected into the liquid reservoir 214 , and the first cleaning liquid is also filled into the plurality of liquid reservoirs 211 , 212 , and 213 via the separation channel 222 and the introduction channel 221 .

[0133] Next, similarly to Embodiment 1, in the step of aspirating the first cleaning liquid from the microchip, the control unit 95 controls the aspiration mechanism 40 to aspirate the first cleaning liquid from the plurality of liquid reservoirs 211, 212, 213, and 214 using the plurality of aspiration nozzles 41, 42, 43, and 44. Also, similarly to Embodiment 1, in the step of cleaning the dispensing probe, the first cleaning liquid is used in the cleaning tank 91 to clean the dispensing probe 30.

[0134] Fig. 14 This is a diagram showing a process of aspirating the second cleaning liquid from the second reservoir when cleaning a microchip in the microfluidic system of the second embodiment.

[0135] like Fig. 14 As shown, during the process of sucking the second cleaning liquid from the second reservoir 52 , the control unit 95 controls the operation of the path switching unit 60 and the pump 70 to switch to the third state, so that the second cleaning liquid is sucked from the second reservoir 52 by the pump 70 .

[0136] Specifically, the control unit 95 moves the movable path 69 to disconnect the first port 61 from the second port 62 and moves the movable path 67 to connect the third port 63 to the fifth port 65. At this time, the control unit 95 moves the movable path 68 to connect the fourth port 64 to the priming port 661.

[0137] In this state, the pump 70 is driven, and a predetermined amount of the second cleaning liquid is sucked into the pump 70 via the fifth path 85 , the movable path 67 , and the third path 83 .

[0138] Fig. 15 This is a diagram showing a step of injecting a second cleaning liquid into a liquid reservoir when cleaning a microchip in the microfluidic system of the second embodiment.

[0139] like Fig. 15As shown, in the process of injecting the second cleaning solution into the reservoir, the operation of the path switching section 60 and the pump 70 is controlled so as to be set to the above-mentioned first state, and the second cleaning solution is injected from the dispensing probe 30 into the reservoir 214.

[0140] Specifically, the control section 95 controls the operation of the path switching section 60 so as to connect the first port 61 and the second port 62 with the movable path 69. Next, the control section 95 moves the dispensing probe 30 into the probe insertion section 250 provided at a position corresponding to the reservoir 214. Then, the control section 95 controls the operation of the pump 70 so as to inject the second cleaning solution into the reservoir 214 via the probe insertion section 250.

[0141] Thus, the second cleaning solution is injected into the reservoir 214, and the second cleaning solution is also filled into the plurality of reservoirs 211, 212, 213 via the separation flow path 222 and the introduction flow path 221.

[0142] Next, as in Embodiment 1, in the process of aspirating the second cleaning solution from the microchip, the control section 95 controls the aspiration mechanism 40 so as to aspirate the second cleaning solution from the plurality of reservoirs 211, 212, 213, 214 with the plurality of aspiration nozzles 41, 42, 43, 44. Also, as in Embodiment 1, in the process of cleaning the dispensing probe, the dispensing probe 30 is cleaned with the second cleaning solution in the cleaning tank 92.

[0143] Also in the case of being configured as above, the microfluidic system 100A of Embodiment 2 can obtain substantially the same effects as Embodiment 1. Also, the first storage section 51 and the second storage section 52 are connected to the path switching section 60, and the operation of aspirating and injecting the first cleaning solution from the first storage section 51 and the operation of aspirating and injecting the second cleaning solution from the second storage section 52 are switched with the movement of the movable path, and thus continuous operation can be performed automatically.

[0144] [Notes]

[0145] As above, the present embodiment includes the following.

[0146] [Structure 1]

[0147] A microfluidic system, wherein the microfluidic system has:

[0148] a chip holding section that holds a microchip having at least one flow path including a separation flow path for separating a sample inside, and having a plurality of reservoirs that open at each end of the at least one flow path;

[0149] a chip cover that is disposed opposite the microchip held by the chip holding section, and includes a plurality of cylindrical sections provided at positions corresponding to each of the plurality of reservoirs.

[0150] a chip cover disposed opposite the microchip held by the chip holding portion, and provided with a plurality of probe insertion portions at positions corresponding to the respective liquid storage portions of the plurality of liquid storage portions;

[0151] a plurality of sealing members that seal between the plurality of probe insertion portions and the plurality of liquid storage portions in a manner that the plurality of probe insertion portions and the plurality of liquid storage portions are communicable;

[0152] a dispensing probe disposed so as to be able to discharge liquid to any one of the plurality of liquid storage portions;

[0153] a suction mechanism including a plurality of suction nozzles disposed so as to be able to suction liquid from the respective liquid storage portions of the plurality of liquid storage portions;

[0154] a first storage portion that stores a first cleaning liquid for cleaning the at least one flow path;

[0155] a second storage portion that stores a second cleaning liquid for cleaning the at least one flow path;

[0156] a pump disposed so as to be able to repeatedly perform suction of liquid and discharge of liquid;

[0157] a path switching portion configured to be able to switch between a path through which the first cleaning liquid can be discharged from the dispensing probe and a path through which the second cleaning liquid can be discharged; and

[0158] a control portion that controls at least an operation of the path switching portion and the pump.

[0159] [Structure 2]

[0160] The microfluidic system according to Structure 1, wherein

[0161] the path switching portion includes: a first port connected to the dispensing probe via a first path; a second port connected to a downstream side of the pump in a discharge direction of the pump when discharging liquid from the pump via a second path; a third port connected to an upstream side of the pump in the discharge direction of the pump via a third path; and a fourth port connected to the first storage portion via a fourth path,

[0162] the path switching portion is configured to be able to be set to at least either of a first state in which the first port and the second port are connected and the downstream side of the pump is communicable with the dispensing probe, and a second state in which the third port and the fourth port are connected and the upstream side of the pump is communicable with the first storage portion,

[0163] The control section controls the operation of the path switching section and the pump, thereby, when the flow path is cleaned, after the first cleaning liquid is sucked from the first storage section by the pump in the second state, the first state is set, and the first cleaning liquid is discharged from the dispensing probe to any one of the plurality of liquid storage sections,

[0164] The control section controls the operation of the path switching section and the pump, thereby, after the first cleaning liquid is discharged, the second cleaning liquid is sucked from the second storage section, and the second cleaning liquid is discharged from the dispensing probe to any one of the plurality of liquid storage sections.

[0165] [Structure 3]

[0166] The microfluidic system according to Structure 2, wherein

[0167] The path switching section further includes a fifth port connected to the second storage section,

[0168] The path switching section is configured to be able to be set to at least any one of the first state, the second state, and a third state in which the third port and the fifth port are connected and the upstream side of the pump communicates with the second storage section,

[0169] The control section controls the operation of the path switching section and the pump, thereby, after the second cleaning liquid is sucked from the second storage section by the pump in the third state, the first state is set, and the second cleaning liquid is discharged from the dispensing probe to any one of the plurality of liquid storage sections.

[0170] [Structure 4]

[0171] The microfluidic system according to any one of Structures 1 to 3, wherein

[0172] The control section controls the suction mechanism, thereby, after the first cleaning liquid in an amount exceeding the capacity of the plurality of liquid storage sections is injected into any one of the plurality of probe insertion sections and left for a predetermined time, the first cleaning liquid is sucked from the plurality of liquid storage sections by the plurality of suction nozzles.

[0173] [Structure 5]

[0174] The microfluidic system according to any one of Structures 1 to 4, wherein

[0175] The dispensing probe has a tapered portion that becomes thinner as it goes toward the tip end,

[0176] When the first cleaning liquid is injected into any one of the plurality of liquid storage sections, the liquid tightness between any one of the plurality of probe insertion sections and the dispensing probe is maintained by pressing the tapered portion against the inner wall of any one of the plurality of probe insertion sections.

[0177] [Structure 6]

[0178] The microfluidic system according to any one of Structures 1 to 5, wherein

[0179] The microfluidic system further comprises a cleaning section for cleaning the dispensing probe,

[0180] The cleaning section comprises two cleaning tanks,

[0181] One of the two cleaning tanks is configured to store the first cleaning solution,

[0182] The dispensing probe is cleaned by immersing the tip side of the dispensing probe in the first cleaning solution stored in the one cleaning tank.

[0183] The embodiments of the present application described above are exemplary and not limiting. The scope of the application is indicated by the claims, encompassing all equivalents of the subject matter recited therein, and all modifications made within the scope of the claims and their equivalents.

[0184] Explanation of reference numerals

[0185] 10, chip holding section; 30, probe; 30a, tapered portion; 40, suction mechanism; 41, 42, 43, 44, suction nozzle; 45, nozzle holding section; 46, valve switching section; 47, suction pump; 51, first storage section; 52, second storage section; 53, orifice plate; 54, 55, priming device; 60, path switching section; 61, first port; 62, second port; 63, third port; 64, fourth port; 65, fifth port; 66, priming port; 67, 68, 69, movable path; 70, pump; 71, storage chamber; 81, first path; 82, second path; 83, third path; 84, fourth path; 85, fifth path; 87, 88, path; 90, cleaning section; 91, 92, cleaning tank; 94, waste tank; 95, control section; 96, detection section; 97, voltage application section; 100, 100A, microfluidic system; 200, microchip; 210, first substrate; 211, 212, 213, 214, liquid storage section; 220, second substrate; 221, introduction flow path; 222, separation flow path; 230, chip cover; 230a, main surface; 232, through-hole; 240, sealing member; 250, probe insertion section; 251, cylindrical member; 251a, tapered portion; 461, 462, 463, 464, valve; 661, 662, priming port.

Claims

1. A microfluidic system, wherein: The microfluidic system has: a chip holding portion that holds a microchip having at least one flow channel including a separation flow channel for separating a sample therein, and a plurality of liquid reservoirs open at respective ends of the at least one flow channel; a chip cover arranged to face the microchip held by the chip holding portion and having a plurality of probe insertion portions provided at positions corresponding to the respective liquid reservoirs; a plurality of sealing members for sealing between the plurality of probe insertion portions and the plurality of liquid reservoirs so that the plurality of probe insertion portions and the plurality of liquid reservoirs can communicate with each other; a dispensing probe configured to be able to inject liquid into any one of the plurality of liquid reservoirs; a suction mechanism comprising a plurality of suction nozzles configured to be able to suck liquid from each of the plurality of liquid reservoirs; a first storage portion storing a first cleaning liquid for cleaning the at least one flow path; a second storage portion storing a second cleaning liquid for cleaning the at least one flow path; a pump configured to repeatedly suck in and discharge liquid; a path switching portion configured to switch between a path for sucking the first cleaning liquid from the first storage portion and a path for sucking the second cleaning liquid from the second storage portion; as well as a control unit that controls at least the operation of the path switching unit and the pump, The path switching portion includes: a first port connected to the dispensing probe via a first path; a second port connected to the downstream side of the pump in the discharge direction when the pump discharges liquid via a second path; a third port connected to the upstream side of the pump in the discharge direction via a third path; and a fourth port connected to the first storage portion via a fourth path. The path switching portion is configured to be capable of being set to at least either a first state in which the first port and the second port are connected and the downstream side of the pump communicates with the dispensing probe, or a second state in which the third port and the fourth port are connected and the upstream side of the pump communicates with the first reservoir. The control unit controls the operation of the path switching unit and the pump so that, when cleaning the at least one flow path, after the first cleaning liquid is sucked from the first reservoir by the pump in the second state, the first state is set to the first state, and the first cleaning liquid is injected from the dispensing probe into any one of the plurality of liquid reservoirs. The control unit controls the operation of the path switching unit and the pump so that after the first cleaning liquid is injected, the second cleaning liquid is sucked from the second reservoir and the second cleaning liquid is injected from the dispensing probe into any one of the plurality of liquid reservoirs. The first cleaning liquid is an aqueous cleaning liquid. The second cleaning liquid is an organic solvent-based cleaning liquid, When the second cleaning liquid is sucked from the second reservoir, the dispensing probe is inserted into the second reservoir and the pump is driven to suck the second cleaning liquid from the second reservoir into the dispensing probe.

2. The microfluidic system according to claim 1, wherein The control unit controls the suction mechanism so that after the first cleaning liquid in an amount exceeding the capacity of the liquid reservoirs is injected into any one of the probe insertion portions and left for a predetermined time, the first cleaning liquid is sucked from the liquid reservoirs using the suction nozzles.

3. The microfluidic system according to claim 1, wherein The dispensing probe has a tapered portion that becomes thinner toward the tip. When the first cleaning liquid is injected into any of the liquid reservoirs, the tapered portion is pressed against the inner wall of any of the probe insertion portions, thereby maintaining liquid-tightness between any of the probe insertion portions and the dispensing probe.

4. The microfluidic system according to claim 1, wherein The microfluidic system further comprises a cleaning unit for cleaning the dispensing probe. The cleaning section includes two cleaning tanks. One of the two cleaning tanks is configured to store the first cleaning liquid. The outer peripheral portion of the distal end side of the dispensing probe is cleaned by immersing the dispensing probe in the first cleaning liquid stored in the one cleaning tank.

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