Analytical microchips and analytical systems

Abstract

To mix a liquid sample and a medicine using a microchip and increase efficiency of work to analyze.SOLUTION: There is provided, a microchip for analysis to analyze a liquid sample. The microchip comprises: a mount part to which a sample tube to accommodate a liquid sample is mounted; an inflow part that permits the liquid sample to flow in from the sample tube mounted to the mount part; a first flow path which is connected to the inflow part on the upstream side and is connected to an inlet for guiding the liquid sample accommodated in the sample tube on the downstream side; a mixing part that is provided between the inflow part of the first flow path and the inlet, and that mixes the liquid sample guided to the first flow path with a medicine; a second flow path for analyzing the liquid sample flowing in from the mixing part, and which is connected to the mixing part; a waste liquid part that is connected to a downstream side of the second flow path, and that stores the liquid sample flowing in from the mixing part via the second flow path; and an on / off valve that opens the first flow path when the liquid sample flows in from the inflow part to the mixing part through the first flow path, and closes the first flow path when the liquid sample flows in from the mixing part to the second flow path.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a microchip and an analysis system for analyzing liquid samples. [Background technology]

[0002] Microchips formed by engraving grooves for the desired flow paths into a substrate and bonding a cover plate are used to analyze liquid samples such as blood. Specifically, it is known that a minute amount of liquid sample is introduced into a flow path within the microchip, where it reacts with an antibody or the like in a reaction field provided midway through the flow path, and the reactivity, properties, or components of the liquid sample are analyzed (e.g., Patent Document 1). To fabricate such a microchip, a known method involves bonding a substrate, on the surface of which grooves that will become the flow paths, to a film or substrate using an adhesive. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2009 / 069656 Summary of the Invention [Problem to be solved by the invention]

[0004] However, in conventional analytical techniques, the procedure for introducing a liquid sample to be analyzed into a microchip is complicated, placing a burden on the operator. The present invention has been made in consideration of these circumstances, and its purpose is to improve the efficiency of the work of mixing a liquid sample and a drug using a microchip and analyzing it. [Means for solving the problem]

[0005] In order to achieve the above object, one embodiment of the present invention employs the following configuration: That is, an analytical microchip for analyzing a liquid sample according to one embodiment includes an inflow section for allowing the liquid sample to flow in from a sample tube attached to an attachment section, a first flow path connected to the inflow section on the upstream side and connected to an inlet for introducing the liquid sample contained in the sample tube on the downstream side, a mixing section provided between the inflow section and the inlet of the first flow path and for mixing a drug with the liquid sample introduced into the first flow path, a second flow path connected to the mixing section and for analyzing the liquid sample introduced from the mixing section, a waste section connected downstream of the second flow path and for accumulating the liquid sample introduced from the mixing section via the second flow path, and an on-off valve that opens the first flow path when the liquid sample flows from the inflow section into the mixing section through the first flow path and closes the first flow path when the liquid sample flows from the mixing section into the second flow path.

[0006] Here, the inlet section may have an opening through which an insertion tube provided at the tip of the sample tube can be inserted. The on-off valve may be provided between the inlet section and the mixing section of the first flow path and between the intake port and the mixing section. The first flow path may also have a supply port through which oil is supplied, and the liquid sample contained in the mixing section is forced by the oil supplied from the supply port and flows out to the second flow path. The waste liquid section may also have an openable / closable vent for discharging air from inside the waste liquid section, and the vent may be closed when the liquid sample flows from the inlet section to the mixing section through the first flow path, and opened when the liquid sample contained in the mixing section flows into the second flow path. The mixing section may also have a stirrer for mixing a drug with the liquid sample. At least a portion of the inner surface of the flow path through which the liquid sample flows, including the inlet section and the mixing section, may be hydrophilized.

[0007] Another aspect of the present invention is a microchip for analysis, and a suction device connected to an inlet of the microchip for analysis, which draws a liquid sample contained in a sample tube from an inlet portion to a mixing portion through a first flow path. and a driver for closing and opening the vent of the waste liquid section.

[0008] The analytical system may include a control unit that controls an on-off valve of the analytical microchip to open the first flow path when the liquid sample flows from the inlet to the mixing unit through the first flow path, and to close the first flow path when the liquid sample flows from the mixing unit to the second flow path. The control unit may control the driver to close the vent port when the liquid sample flows from the inlet to the mixing unit through the first flow path, and to open the vent port when the liquid sample contained in the mixing unit flows into the second flow path. The analytical system may also include a supplier connected to a supply port of the analytical microchip and having a pressure sensor that detects the pressure in the second flow path of the liquid sample flowing out from the mixing unit. [Effects of the Invention]

[0009] According to the present invention, the work of mixing a liquid sample and a drug using a microchip and analyzing the mixture can be made more efficient. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a diagram showing an example of the configuration of a microchip according to an embodiment. FIG. [Figure 2] FIG. 10 is a diagram illustrating a flow path and an on-off valve that connect the holder and the mixing section. [Figure 3] FIG. 10 is a diagram illustrating a flow path and an on-off valve connecting an air suction port and a mixing section. [Figure 4] FIG. 10 is a diagram illustrating the introduction of a liquid sample contained in a sample tube into a mixing section. [Figure 5] FIG. 2 is a diagram illustrating a flow path connected to a mixing section and a measurement flow path. [Figure 6] FIG. 10 is a diagram illustrating the flow of a liquid sample contained in a mixing section into a waste section. [Figure 7] 10A and 10B are diagrams illustrating the introduction of a liquid sample into a mixing section and its flow into a measurement channel. [Figure 8] 10A and 10B are diagrams illustrating the opening and closing of an on-off valve. [Figure 9] 10A and 10B are diagrams illustrating opening and closing of a through hole. [Figure 10]FIG. 1 is a diagram illustrating an example of a configuration of an analysis system to be controlled according to an embodiment. [Figure 11] 10 is a flowchart illustrating an example of a processing flow of the analysis system according to the embodiment. [Figure 12] FIG. 4 is a diagram illustrating the shape of a mixing section. DETAILED DESCRIPTION OF THE INVENTION

[0011] A microchip for analyzing a liquid sample according to one embodiment will be described below with reference to the drawings. The configuration of the following embodiment is an example, and the present microchip is not limited to the configuration of the embodiment. Furthermore, unless otherwise specified, the dimensions, materials, shapes, relative positions, etc. of the components disclosed in this embodiment are not intended to limit the technical scope of the invention to only those.

[0012] [Embodiment 1] FIG. 1 is a diagram showing an example of the configuration of a microchip 1 according to this embodiment. FIG. 1 illustrates a perspective view of the overall configuration of the microchip 1. The microchip 1 according to this embodiment is configured by sandwiching a substrate 10, in which a flow path for the inflow and outflow of a liquid to be analyzed or the like is formed, between film materials adhered to the upper and lower surfaces. The size of the substrate 10 constituting the microchip 1 is, for example, 100 mm (X direction) × 100 mm (Y direction) × 5 mm (Z direction).

[0013] Liquids flowing in and out of the microchip 1 include liquid samples, reactants to react with the liquid samples, cleaning solutions, etc. The liquid samples are not particularly limited as long as they can be passed through the microchip 1, and examples include liquid samples obtained from living organisms such as blood and urine, or diluted solutions thereof, extracts from living organisms such as plants and animals, naturally occurring water such as rivers, oceans, and rainfall, cleaning solutions, waste liquids, etc. The components in the sample are also not particularly limited, and examples include proteins, nucleic acids, low-molecular-weight compounds, sugars, etc.

[0014] As shown in FIG. 1 , the microchip 1 includes a substrate 10, a holder 11, an air suction port 60, and an oil supply port 70. The holder 11 is a structure for mounting and holding a sample tube 50 or the like containing a liquid sample or the like on the substrate 10. In this embodiment, the holder 11 corresponds to an example of a "mounting portion." The air suction port 60 is a structure for introducing a liquid sample or the like contained in a sample tube 50 or the like mounted on the holder 11 into a flow path provided in the substrate 10. In this embodiment, the air suction port 60 corresponds to an example of an "intake port." The oil supply port 70 is a structure for supplying oil or the like to allow the liquid sample or the like introduced into the flow path of the substrate 10 to flow into a measurement flow path 23 for analyzing the sample. In this embodiment, the oil supply port 70 corresponds to an example of a "supply port." An aspirator such as a microsyringe or a suction pump is connected to the air suction port 60, and a supplier such as a microsyringe or a liquid feed pump for supplying mineral oil or the like is connected to the oil supply port 70. 1 illustrates an example in which the holder 11, air suction port 60, and oil supply port 70 are provided on the same surface of the substrate 10, but if the surface on which the holder 11 is provided is referred to as the front surface, the air suction port 60 and oil supply port 70 may be provided on the back surface opposite the front surface. In the following description, the surface of the substrate 10 on which the holder 11 is provided is referred to as the front surface.

[0015] The substrate 10 is provided with a first flow path consisting of flow paths (21a, 21b, 21c, and 21d), a flow path 22, a mixing section 14, a measurement flow path 23 for analyzing a liquid sample, and a waste liquid section 15. In this embodiment, the measurement flow path 23 corresponds to an example of a "second flow path." An on-off valve 12 is provided between flow paths 21a and 21b constituting the first flow path, and an on-off valve 13 is provided between flow paths 21c and 21d. The on-off valve 12 is connected to the downstream side of flow path 21a and the upstream side of flow path 21b, and opens and closes the flow path between flow paths 21a and 21b. The downstream side of flow path 21b is connected to the mixing section 14. Similarly, the on-off valve 13 is connected to the downstream side of flow path 21c and the upstream side of flow path 21d, and opens and closes the flow path between flow paths 21c and 21d. The on-off valves 12 and 13 are, for example, two-way valves. There are no limitations on the structure and operation of the on-off valves 12 and 13. The on-off valves 12 and 13 may be formed, for example, from an elastic material and opened and closed by a drive body controlled by an actuator or air cylinder that can be pressed up and down from the upper surface of the substrate 10. The actuator may be operated by piezoelectric, electrostatic, electromagnetic, or other mechanisms. For example, the on-off valves 12 and 13 may be opened and closed by the opening and closing operation of a piezoelectric element. The upstream side of the flow path 21c is connected to the mixing section 14, and the downstream side of the flow path 21d is connected to the air suction port 60.

[0016] Flow path 22 is connected to oil supply port 70 on the upstream side and to mixing section 14 on the downstream side. Mineral oil or the like supplied via oil supply port 70 is guided to mixing section 14 through flow path 22. Mixing section 14 is connected to the upstream side of measurement flow path 23. Measurement flow path 23 is connected to waste liquid section 15 on the downstream side. Waste liquid section 15 is provided with through holes 15a and 15b that penetrate from the interior of waste liquid section 15 to the surface of substrate 10.

[0017] At least a portion of the inner surface of mixing section 14 may be hydrophilized. This can prevent air bubbles from remaining in mixing section 14 when the liquid sample is drawn through the inner surface. There are no particular limitations on the portion of the inner surface of mixing section 14 that is hydrophilized, but it is preferable that the ceiling and side walls of mixing section 14 be hydrophilized. Examples of hydrophilization treatment include hydrophilizing agent treatment, corona treatment, plasma treatment, and excimer treatment. Hydrophilizing agent treatment is preferred because the hydrophilizing effect does not weaken over time after treatment.

[0018] Furthermore, by designing the mixing section 14 in a shape that allows air bubbles to escape easily, it is possible to prevent air bubbles from remaining. Figure 12 is a diagram illustrating the shape of the mixing section 14. Figures 12(a) and (b) show an example of a mixing section 14 formed in a cylindrical shape, (c) and (d) show an example of a mixing section 14 formed in an eccentric shape, and (e) and (f) show an example of a mixing section 14 formed in an upper rounded shape. 12(b) shows a cross-sectional view from the CC# direction in FIG. 12(a), FIG. 12(d) shows a cross-sectional view from the CC# direction in FIG. 12(c), and FIG. 12(f) shows a cross-sectional view from the CC# direction in FIG. 12(e). In this embodiment, the cylindrical mixing section 14 shown in FIGS. 12(a) and 12(b) is described as a basic type. However, as shown in FIGS. 12(c) to 12(f), it may also be formed in an eccentric or upper-curved shape. In an eccentric type in which the space within the mixing section 14 gradually narrows toward the flow channel 21c, or in an upper-curved type in which the upper part of the mixing section 14 is curved to form a dome-like shape, an air flow can be formed along the curved wall surface of the mixing section 14 when the liquid sample is introduced. This air flow formed within the mixing section 14 is expected to promote the removal of air bubbles remaining within the mixing section 14.

[0019] Mineral oil or the like supplied via oil supply port 70 is introduced into mixer 14 through flow path 22. In mixer 14, the liquid sample introduced via flow paths (21a, 21b) is mixed with a reagent or the like for analyzing the properties of the liquid sample. Such a reagent is, for example, pre-applied to a film material or the like that sandwiches mixer 14. Mixer 14 may be provided with a stirrer for stirring the liquid sample and the reagent or the like. The operation of the stirrer is controlled, for example, by a stirring mechanism that utilizes magnetic force.

[0020] In the mixing unit 14, mineral oil or the like supplied through the oil supply port 70 is layered on, for example, the liquid sample mixed with the reagent. The liquid sample is pressed into the measurement flow path 23 by, for example, the pressure of the layered mineral oil or the like.

[0021] A reaction substrate or the like that reacts with the liquid sample is applied to the measurement flow path 23. The liquid sample pressed from the mixer 14 flows into the downstream waste liquid section 15 while reacting with the reaction substrate or the like applied to the measurement flow path 23. In the waste liquid section 15, the liquid sample after the reaction is accumulated.

[0022] The channels, measurement channel 23, mixing section 14, waste liquid section 15, and through-holes formed in substrate 10 of microchip 1 can be formed using a blade or laser light, but can also be formed by injection molding when substrate 10 is made of plastic. Use of injection molding is expected to stabilize the quality of microchip 1 and improve production efficiency.

[0023] The components and properties of the liquid sample are analyzed and evaluated, for example, by measuring the inflow pressure of the liquid sample being forced to flow from the mixer 14 into the measurement flow path 23. A pressure sensor for detecting such inflow pressure is provided, for example, in a supplier that supplies mineral oil or the like via the oil supply port 70. A user of the microchip 1 for analyzing liquid samples can analyze the components and evaluate the properties of the liquid sample to be analyzed by measuring the progression of increasing and decreasing changes in the pressure detected via the pressure sensor.

[0024] 2 is a diagram illustrating the flow paths 21a, 21b and the on-off valve 12 that connect the holder 11 and the mixing section 14. FIG. 2 illustrates a cross-sectional view seen from the direction indicated by AA# in FIG. 1. As shown in FIG. 2, an opening 10a is formed in the holder 11, and an insertion tube 11a through which the sample tube 50 is inserted is provided with its tip facing upward. In this embodiment, In this case, the insertion tube 11a and the opening 10a correspond to an example of an "inflow section." A flow path 21a constituting the first flow path is connected to the opening 10a on the upstream side, and is connected to the input end of an on-off valve 12 enclosed by a dashed-dotted line frame on the downstream side. The flow path 21a is formed, for example, as a groove having a concave cross-sectional shape on the back surface side of the substrate 10. Note that the cross-sectional shape of the flow path 21a is not limited to a concave shape, and may be, for example, a U-shape or a V-shape.

[0025] At least a part of the inner surface of the flow path (first flow path, on-off valve 12, etc.) including the insertion tube 11a and through which the liquid sample flows from the insertion tube to the mixing section 14 may be hydrophilized, thereby preventing air bubbles from remaining in the mixing section 14 when the liquid sample is introduced. The portion of the inner surface of the flow path leading to the mixing section 14, including the pipe 11a, that is to be hydrophilized is not particularly limited, but it is preferable that the ceiling and sidewall portions of the flow path be hydrophilized. Examples of hydrophilization treatments include hydrophilizing agent treatment, corona treatment, plasma treatment, and excimer treatment, and hydrophilizing agent treatment is preferable because the hydrophilizing effect does not weaken over time after treatment.

[0026] Similarly, flow path 21b connected to the output end of on-off valve 12 on the upstream side is formed, for example, as a groove having a predetermined cross-sectional shape on the back surface side of substrate 10. Flow path 21b extends along the back surface side and is connected to mixing section 14 enclosed by a dashed-dotted line frame. Note that mixing section 14 formed in substrate 10 may be of any size as long as it is large enough to accommodate a desired amount of liquid sample (for example, 400 to 500 μL), and may be formed, for example, in a cylindrical or prismatic shape.

[0027] FIG. 3 is a diagram illustrating flow paths 21c, 21d, and on-off valve 13 that connect air suction port 60 and mixer 14. FIG. 3 also illustrates a cross-sectional view seen from the direction indicated by AA# in FIG. 1. As shown in FIG. 3, flow path 21c, which constitutes the first flow path, is connected on the upstream side to mixer 14, which is enclosed by a dashed-dotted line frame, and is connected on the downstream side to the input end of on-off valve 13, which is enclosed by a dashed-dotted line frame. Similarly, flow path 21d, which is connected on the upstream side to the output end of on-off valve 13, is connected on the downstream side to air suction port 60. The cross-sectional shapes of flow paths 21c and 21d are similar to those of flow path 21a, etc.

[0028] The upstream side of flow path 21c is formed as a groove with a predetermined cross-sectional shape on the front side of substrate 10, and is connected to mixing section 14. Flow path 21c formed on the front side of substrate 10 runs vertically through the substrate from the front side to the back side, and is connected to downstream flow path 21c formed as a groove with a predetermined cross-sectional shape on the back side of substrate 10. By forming the upstream side of flow path 21c connected to mixing section 14 on the front side, air can be preferentially removed when introducing the liquid sample into mixing section 14. Flow path 21d, which is connected to the output end of on-off valve 13 on the upstream side, is formed as a groove with a predetermined cross-sectional shape on the back side of substrate 10, and is connected to air suction port 60 provided on the front side of substrate 10.

[0029] FIG. 4 is a diagram illustrating the introduction of the liquid sample Z1 contained in the sample tube 50 to the mixing section 14. As shown in FIG. 4, the insertion tube 11a of the sample tube 50 containing the liquid sample Z1 is inserted into the opening 10a provided in the holder 11. Here, it is assumed that an aspirator such as a suction pump or a microsyringe is connected to the air suction port 60 on the downstream side of the first flow path (downstream side of the flow path 21d). Also, the on-off valves 12 and 13 provided in the first flow path are each controlled to an open state, and the through holes 15a and 15b provided in the waste liquid section 15 are each controlled to a closed state. It shall be.

[0030] 4, the flow path leading to the mixing section 14, which is composed of the flow path 21a, the on-off valve 12, and the flow path 21b, is put into a negative pressure state by suction from an aspirator connected to the air suction port 60, and the liquid sample Z1 contained in the sample tube 50 is drawn into the flow path 21a through the opening 10a. Then, the liquid sample Z1 drawn into the flow path 21a is drawn into the mixing section 14 through the open on-off valve 12 and the flow path 21b.

[0031] By suction by the aspirator, air is sucked from flow path 21b formed on the back side toward flow path 21c formed on the front side in the space in which the liquid sample is accommodated in mixing section 14. Then, in mixing section 14, which has been put into a negative pressure state by the suction of air by the aspirator, liquid sample Z1 is drawn into the space in the mixing section through flow path 21b formed on the back side of substrate 10 and accumulates from the lower side (back side) toward the upper side (front side). Note that suction by the aspirator is stopped when a desired amount of liquid sample Z1 is accommodated in the space in mixing section 14.

[0032] Next, the flow path 22, the mixing section 14, the measurement flow path 23, and the waste liquid section 15 will be described. FIG. 5 is a diagram illustrating the flow path 22 and the measurement flow path 23 connected to the mixing section 14. FIG. 5 illustrates a cross-sectional view taken from the direction indicated by BB# in FIG. 1. As shown in FIG. 5, the flow path 22 is formed, for example, as a groove having a predetermined cross-sectional shape on the back surface of the substrate 10, and is connected at its upstream side to an oil supply port 70 provided on the surface. The downstream side of the flow path 22 runs vertically through the substrate 10 from the back surface to the front surface, and is connected to the front surface of the mixing section 14. The measurement flow path 23 is connected at its upstream side to the back surface of the mixing section 14, and is formed at the back surface of the substrate 10 as a groove having a predetermined cross-sectional shape.

[0033] 5, a supplier such as a microsyringe or a liquid pump that supplies mineral oil Z2 is connected to oil supply port 70. As shown in FIG. 5, mineral oil Z2 supplied through oil supply port 70 flows through flow path 22 from the upper side (front side) of mixing section 14, which is enclosed by a dashed-dotted line frame, into the space containing the liquid sample. For example, if a liquid sample has already accumulated in the space containing the liquid sample in mixing section 14, mineral oil Z2 flowing through flow path 22 will be layered on top of the liquid sample. Therefore, the liquid sample accumulated in mixing section 14 is pressed downward (back side) by the pressure from the layered mineral oil Z2 and flows out into measurement flow path 23 connected to the back side of the mixing section.

[0034] FIG. 6 is a diagram illustrating the flow of the liquid sample Z1 contained in the mixing section 14 into the waste liquid section 15. FIG. 6 also illustrates a cross-sectional view taken from the direction indicated by BB# in FIG. 1. As shown in FIG. 6, the measurement flow path 23 is formed as a groove having a predetermined cross-sectional shape on the back surface of the substrate 10, and its upstream side is connected to the lower side (back surface) of the mixing section 14. The downstream side of the measurement flow path 23 is connected to the waste liquid section 15 from the lower side (back surface) of the substrate 10. The waste liquid section 15 formed in the substrate 10 may be large enough to accommodate the liquid sample Z1 accumulated in the mixing section 14. The waste liquid section 15 is provided with closable through-holes 15a and 15b that serve as air vents and penetrate from the space formed on the back surface of the substrate 10 to the front surface. In this embodiment, the through-holes 15a and 15b correspond to an example of an "air vent." The method of closing the through-holes 15a and 15b, i.e., the structure and operation for opening and closing, are not limited. The through-holes 15a and 15b may be opened and closed by, for example, an actuator or air cylinder that can press an elastic material vertically from the top surface of the substrate 10. The actuator may be piezoelectric, electrostatic, or electromagnetic. For example, the through-holes 15a and 15b may be opened and closed by a valve that can be opened and closed by a piezoelectric element or other device. Alternatively, a flexible film or other material may be fixed to cover the through-holes 15a and 15b. When the waste liquid section 15 is placed under negative pressure due to suction from the air suction port 60, the film or other material adheres to the through-holes 15a and 15b, maintaining the negative pressure. On the other hand, when mineral oil or other material is supplied from the oil supply port 70 and the waste liquid section 15 is placed under positive pressure, a portion of the film or other material flips over, allowing the air in the waste liquid section 15 to escape.

[0035] The liquid sample Z1 contained in the mixing section 14 is pressed and discharged into the measurement flow path 23, which is connected on the upstream side to the rear surface of the mixing section, by the pressure of mineral oil or the like supplied via the oil supply port 70. The liquid sample Z1 discharged from the mixing section 14 to the measurement flow path 23 is accumulated in the waste liquid section 15 on the downstream side while reacting with, for example, a reaction substrate or the like applied to the measurement flow path 23.

[0036] When analyzing the components and properties of a liquid sample, the through-holes 15a and 15b provided in the waste liquid section 15 are opened, so that air on the path through which the liquid sample Z1 flows, which is pressed by mineral oil or the like, can be discharged through the through-holes. Therefore, the post-reaction liquid sample Z3 that has flowed into the measurement flow path 23 from the mixing section 14 can be guided into the space of the waste liquid section 15. do.

[0037] 7 is a diagram illustrating the introduction of liquid sample Z1 into the mixing section 14 and its flow into the measurement flow path 23. As explained with reference to FIG. 4, when liquid sample Z1 is introduced into the mixing section 14 from the sample tube 50 attached to the holder 11, the on-off valves 12 and 13 formed in the first flow path are each opened to create a negative pressure inside the first flow path. The inside of the first flow path is controlled to a negative pressure state by suction from an aspirator such as a suction pump or a microsyringe connected to the air suction port 60.

[0038] However, waste liquid section 15, which is connected to mixing section 14 through measurement flow path 23, has through-holes 15a and 15b that penetrate from the space within the waste liquid section to the surface side. When through-holes 15a and 15b are open, air flows into mixing section 14 from the outside through the through-holes and measurement flow path 23. In microchip 1 of this embodiment, as described below, when liquid sample Z1 is introduced from sample tube 50 to mixing section 14, through-holes 15a and 15b are controlled to a closed state. This makes it possible to prevent unwanted air from mixing into liquid sample Z1 introduced to mixing section 14.

[0039] Similarly, as described with reference to FIGS. 5 and 6 , through-holes 15a and 15b extending from the interior of waste liquid section 15 to the surface are controlled to an open state to allow liquid sample Z1 to flow from mixing section 14 to measurement flow path 23 and waste liquid section 15. However, if on-off valve 12 connected to mixing section 14 via flow path 21b and on-off valve 13 connected via flow path 21c are open, liquid sample Z1 pressed from mixing section 14 will flow back into the first flow path. In the microchip 1 of this embodiment, as described below, when liquid sample Z1 is pressed from mixing section 14 into measurement flow path 23, on-off valves 12 and 13 formed in the first flow path are controlled to a closed state. This prevents unwanted backflow into the first flow path when liquid sample Z1 is pressed from mixing section 14 into measurement flow path 23. A user who measures the increasing and decreasing changes in pressure detected via a pressure sensor will not experience unnecessary measurement errors caused by backflow.

[0040] FIG. 8 is a diagram illustrating the opening and closing of the on-off valves 12 and 13. FIG. 8 illustrates a cross-sectional view taken from the direction indicated by AA# in FIG. 1. As shown in FIG. 8, the on-off valves 12 and 13 have a diaphragm valve structure in which the diaphragms are elastic bodies 12b and 13b made of a silicone resin such as polydimethylsiloxane (PDMS) resin. However, the valve structure shown in FIG. 8 is only one example of the structure of the on-off valves 12 and 13, and an appropriate structure can be adopted depending on the properties of the liquid sample to be analyzed, the measurement method, and the like. The following explanation will be given using the on-off valve 12 as an example. For the on-off valve 13, the corresponding flow paths and structures can be interpreted as appropriate.

[0041] The structure of the on-off valve 12 includes a guide 12a formed by carving from the front surface to the back surface of the substrate 10. A diaphragm made of an elastic body 12b is attached along the guide 12a, and the outer edge of the elastic body 12b is supported by the surface carved into the substrate 10. Furthermore, in the on-off valve 12, a convex structure 12c that protrudes toward the front surface of the substrate 10 is provided in an internal flow path that connects the flow path 21a and flow path 21b connected to the on-off valve. The liquid sample Z1 flowing through the internal flow path of the on-off valve 12 flows from the upstream flow path 21a to the downstream flow path 21b via the convex structure.

[0042] Elastic body 12b, which is placed along guide 12a, is pressed from the upper side (front side) to the lower side (rear side) via a driving body such as an actuator, so that the lower side of the elastic body is adhered to convex structure 12c provided in the internal flow path of on-off valve 12. This blocks the space between the upstream side (flow path 21a side) and the downstream side (flow path 21b side) of the internal flow path, and the state of on-off valve 12 is controlled to a closed state. Furthermore, by releasing the pressure on elastic body 12b, the state of on-off valve 12 is controlled to an open state.

[0043] 9A and 9B are diagrams illustrating the opening and closing of through-holes 15a and 15b. Fig. 9A is a perspective view of through-holes 15a and 15b in waste liquid section 15, Fig. 9B is a cross-sectional view of waste liquid section 15 in an open state, and Fig. 9C is a cross-sectional view of waste liquid section 15 in a closed state. As shown in Figs. 9A to 9C, through-holes 15a and 15b are formed so as to penetrate from the space of waste liquid section 15 formed on the back side of substrate 10 of microchip 1 to the front side.

[0044] As shown in FIG. 9(c), an elastic body 15c made of a silicone resin such as PDMS is pressed against the opening surfaces of through-holes 15a and 15b opening in the surface of substrate 10 via a driving body such as an actuator, thereby closing the through-holes. The close contact of elastic body 15c with the opening surfaces suppresses the inflow and outflow of air through through-holes 15a and 15b, controlling the openings of the through-holes to a closed state. Furthermore, as shown in FIG. 9(b), the pressure on elastic body 15c by the driving body is released, and elastic body 15c, which is adhered to the opening surfaces of through-holes 15a and 15b, is separated from the opening surfaces, controlling the through-holes to an open state. In microchip 1, the inflow and outflow of air through through-holes 15a and 15b can be controlled.

[0045] (Analysis System) FIG. 10 is a diagram showing an example of the configuration of an analysis system 100 according to this embodiment. The analysis system 100 according to this embodiment includes a control unit 80, which controls the opening and closing of the on-off valves 12 and 13 formed in the microchip 1 and the opening and closing of the through-holes 15a and 15b via the control unit. In this embodiment, the control unit 80 corresponds to an example of a "controller." The control unit 80 of the analysis system 100 also controls the suction and stopping of the aspirator connected to the air suction port 60, and the oil supply and stopping of the supplier connected to the oil supply port 70. The control unit 80 then measures the sensor detection value detected via a pressure sensor provided in the supplier.

[0046] As shown in FIG. 10 , the analysis system 100 includes an actuator 16a for driving an elastic body 12b attached to a guide 12a of an on-off valve 12 formed on the microchip 1. Similarly, the analysis system 100 includes an actuator 16b for driving an elastic body 13b attached to a guide 13a of an on-off valve 13. The analysis system 100 also includes an actuator 16c for driving an elastic body 15c attached to each opening surface of through-holes 15a and 15b formed in the waste liquid section 15. The analysis system 100 also includes an aspirator 61, such as a suction pump, connected to an air suction port 60, and a supplier 71, such as a liquid pump, connected to an oil supply port 70. The supplier 71 is provided with a pressure sensor 72. The pressure sensor 71 is pressed by, for example, mineral oil or the like supplied from the supplier 71 to detect the pressure in the measurement flow channel of the liquid sample Z1 flowing from the mixer 14 to the measurement flow channel 23.

[0047] The control unit 80 includes, for example, a processor such as a CPU (Central Processing Unit), The control unit 80 is a microcomputer unit equipped with memories such as RAM (Random Access Memory), ROM (Read Only Memory), and flash memory, as well as a communication interface with external devices. The memory stores, for example, an operating system (OS), various programs, various tables, etc. The control unit 80 also has input / output terminals such as digital I / O and analog I / O.

[0048] Control lines for controlling the actuators 16a, 16b, and 16c are connected to the input / output terminals of the control unit 80, and control signals (CNT_16a to CNT_16c) for driving the actuators are output via the input / output terminals. Similarly, control lines for controlling the aspirator 61 and the supplier 71 are connected to the input / output terminals, and Control signals (CNT_61, CNT_71) are output via the input / output terminals to control the suction / stop of the aspirator 61 and the supply / stop of the supply device 71. Note that a signal line is connected to the input / output terminals of the control unit 80 to input the sensor detection value detected by the pressure sensor 72.

[0049] Each of the above control signals is, for example, a binary status signal representing an active status or an inactive status. For example, when the control signal CNT_16a is in the active status, the actuator 16a of the on-off valve 12 presses the elastic body 12b, controlling the on-off valve 12 to an open state. When the control signal CNT_61 is in the inactive status, the actuator 16a of the on-off valve 12 releases the pressure on the elastic body 12b, controlling the on-off valve 12 to an open state. The actuator 16b of the on-off valve 13 and the actuator 16c of the through-holes 15a and 15b are also controlled by a similar logical status. Furthermore, the aspirator 61 performs suction when the control signal CNT_61 is in the active status and stops suction when the control signal CNT_61 is in the inactive status. Similarly, the supplier 71 delivers a liquid such as mineral oil when the control signal CNT_71 is in the active status and stops delivering the liquid when the control signal CNT_71 is in the inactive status. Hereinafter, the active status will also be referred to as the “ON state” and the inactive status as the “OFF state.”

[0050] The above-described form of status control using control signals is an example, and is set appropriately according to the control form of each actuator, aspirator 61, and supplier 71. It is sufficient to be able to control at least the opening and closing of on-off valves 12 and 13, the opening and closing of through-holes 15a and 15b, the suction and stopping of aspirator 61, and the oil supply and stopping of supplier 71.

[0051] (Processing flow) 11 is a flowchart showing an example of the processing flow of the analysis system 100 according to this embodiment. The processing of FIG. 11 is executed after the sample tube 50 containing the liquid sample Z1 is attached to the holder 11 of the microchip 1. The processing of FIG. 11 is also provided by the control unit 80.

[0052] In FIG. 11, after the start of the process, the on-off valves 12 and 13 connected to the first flow path are opened (step S1), and the process proceeds to step S2. The control unit 80 outputs control signals (CNT_16a and CNT_16b) in the OFF state to the actuators 16a and 16b. The on-off valves 12 and 13 release the pressure on the elastic bodies 12b and 13b, connecting the upstream and downstream sides of the internal flow paths. In step S2, the openings of the through-holes 15a and 15b provided in the waste liquid section 15 are blocked, and the process proceeds to step S3. The control unit 80 outputs a control signal (CNT_16c) in the ON state to the actuator 16c. The openings of the through-holes 15a and 15b formed on the surface side of the substrate 10 are blocked by the elastic body 15c pressed by the driving of the actuator 16c.

[0053] In step S3, when suction by aspirator 61 connected to air suction port 60 begins, the process proceeds to step S4. Control unit 80 outputs a control signal (CNT_61) in the ON state to aspirator 61. When aspirator 61 begins suction, the inside of the first flow path becomes negative pressure, and the liquid sample in sample tube 50 attached to holder 11 is received into mixer 14 through flow paths 21a and 21b that constitute the first flow path.

[0054] In step S4, it is determined whether a predetermined amount of liquid sample Z1 is contained in the mixing section 14. The capacity of the mixing section 14 formed in the substrate 10 is known. Therefore, it is sufficient to previously associate the driving conditions of the aspirator 61, such as the suction time and suction pressure, with the inflow amount of liquid sample Z1 that flows into the mixing section 14 through the flow paths 21a and 21b that constitute the first flow path. In step S4, if it is determined that a predetermined amount of liquid sample Z1 is contained in the mixing section 14, If so (step S4, "Yes"), the process proceeds to step S5, otherwise (step S4, "Yes"), the process returns to step S4. In step S5, when an OFF control signal (CNT_61) is output to the aspirator 61 and the suction operation is stopped, the process proceeds to step S6. Note that the suction operation may be stopped and step S6 may be started simultaneously.

[0055] In step S6, the on-off valves 12 and 13 connected to the first flow path are closed, and the process proceeds to step S7. The control unit 80 outputs control signals (CNT_16a and CNT_16b) in the ON state to the actuators 16a and 16b. In the on-off valves 12 and 13, the elastic bodies 12b and 13b are pressed, and the elastic bodies 12b and 13b are adhered to the convex structures 12c and 13c provided in the respective internal flow paths. This blocks the communication between the upstream and downstream sides of the internal flow paths, and the on-off valves 12 and 13 are closed. In step S7, the openings of the through-holes 15a and 15b provided in the waste liquid section 15 are opened, and the process proceeds to step S8. The control unit 80 outputs a control signal (CNT_16c) in the OFF state to the actuator 16c. The pressure on the elastic body 15c in the through-holes 15a and 15b is released by the driving of the actuator 16c.

[0056] In step S8, when the supply device 71 connected to the oil supply port 70 starts to supply mineral oil or the like, the process proceeds to step S9. The control unit 80 outputs an ON control signal (CNT_71) to the supply device 71. When the supply device 71 starts to supply liquid, the liquid sample Z1 contained in the mixing section 14 is pressed into the measurement flow path 23 by the pressure of the supplied mineral oil or the like and flows out. The liquid sample Z1 flowed out from the mixing section 14 to the measurement flow path 23 is accumulated in the waste liquid section 15 downstream while reacting with, for example, a reaction substrate or the like applied to the measurement flow path 23.

[0057] In step S9, when a sensor detection value detected by the pressure sensor 72 provided in the supplier 71 is acquired, the process proceeds to S10. The control unit 80 acquires the sensor detection value, for example, at a fixed sampling period. Then, the control unit 80 associates the acquired sensor detection value with sampling time information and stores them in a predetermined area of ​​the memory.

[0058] In step S10, it is determined whether or not the measurement of the components and properties of the liquid sample based on the detection value of the pressure sensor 72 has been completed. If it is determined in step S10 that the measurement has been completed (step S10, "Yes"), the process proceeds to step S11; if not (step S10, "NO"), the process returns to step S10. In step S11, the supply of mineral oil or the like from the supply device 71 is stopped. The control unit 80 outputs a control signal (CNT_71) in the OFF state to the supply device 71. After the processing of step S11, this routine is temporarily terminated.

[0059] As described above, the microchip 1 according to this embodiment can form a first flow path in the substrate 10, through which the liquid sample Z1 flows from the sample tube 50 attached to the holder 11 through the opening 10a. The first flow path is composed of flow paths (21a, 21b, 21c, 21d), and an air suction port 60 for introducing the liquid sample Z1 contained in the sample tube 50 can be connected downstream of the first flow path. Furthermore, the microchip 1 can form a mixing section 14 between the flow paths 21b and 21c of the first flow path for mixing a drug with the liquid sample Z1 introduced into the first flow path. The mixing section 14 can be formed so as to be connected upstream to the measurement flow path 23 for analyzing the liquid sample Z1. A waste liquid section 15 for accumulating the liquid sample can be formed downstream of the measurement flow path 23. The microchip 1 according to this embodiment can be provided with on-off valves 12 and 13 that open the first flow path when the liquid sample Z1 flows into the mixing section 14 through the first flow path, and close the first flow path when the liquid sample flows from the mixing section 14 into the measurement flow path 23. This makes it possible to prevent unnecessary backflow into the first flow path when the liquid sample Z1 is pressed from the mixing section 14 into the measurement flow path 23. In this case, unnecessary measurement errors caused by backflow to the first flow path side are not caused.

[0060] Furthermore, the microchip 1 according to this embodiment can form an opening 10a in the substrate 10, into which an insertion tube 11a provided at the tip of the sample tube 50 is inserted. This simplifies the preparatory steps for analyzing the liquid sample Z1, such as removing the cap of the sample tube 50 and dispensing the liquid sample Z1 into a reservoir tank using a micropipette, and prevents the liquid sample Z1 contained in the sample tube 50 from spilling.

[0061] Furthermore, the microchip 1 according to this embodiment can be connected to an oil supply port 70 for allowing mineral oil or the like to flow upstream of the mixing section 14. The liquid sample Z1 in the mixing section 14, which is pressed by the inflow of mineral oil or the like, can be caused to flow out into the measurement flow path 23.

[0062] Furthermore, the microchip 1 according to this embodiment can be formed with through-holes 15a and 15b that penetrate from the inside of the waste liquid section 15 to the surface side of the substrate 10. When the liquid sample Z1 in the mixing section 14 is pressed into the measurement flow path 23, air in the flow path from the mixing section 14 to the waste liquid section 15 can be discharged to the outside through the through-holes 15a and 15b. This can prevent unnecessary air from mixing into the liquid sample Z1 that flows from the mixing section 14 into the measurement flow path 23. [Explanation of symbols]

[0063] 1·· Microchip, 10·· Base material, 10a·· Opening, 11·· Holder, 11a·· Insertion tube, 12, 13·· Opening / closing valve, 12a, 13a·· Guide, 12b, 13b·· Elastic body, 12c, 13c·· Convex structure, 14·· Mixing section, 15·· Waste liquid section, 15a, 15b·· Through hole, 15c·· Elastic body, 16a, 16b, 16c·· Actuator, 21a ,21b,21c,21d··Flow path (first flow path), 22··Flow path, 23··Measurement flow path (second flow path), 50··Sample tube, 60··Air suction port, 61··Aspirator, 70··Oil supply port, 71··Supplier, 72··Pressure sensor, 80··Control unit, 100··Analysis system, Z1··Liquid sample, Z2··Mineral oil, Z3··Liquid sample after reaction

Claims

1. An analytical microchip for analyzing a liquid sample, a mounting portion for mounting a sample tube containing the liquid sample; an inlet portion through which the liquid sample flows from a sample tube attached to the attachment portion; a first flow path connected to the inlet portion on the upstream side and connected to an intake port for drawing in the liquid sample contained in the sample tube on the downstream side; a mixing section provided between the inlet and the inlet of the first flow path, for mixing a drug with the liquid sample introduced into the first flow path; a second flow path connected to the mixing section for analyzing the liquid sample flowing in from the mixing section; a waste liquid section connected to the downstream side of the second flow path and configured to accumulate the liquid sample flowing from the mixing section via the second flow path; an on-off valve that opens the first flow path when the liquid sample flows from the inflow section to the mixing section through the first flow path, and closes the first flow path when the liquid sample flows from the mixing section to the second flow path; An analytical microchip comprising:

2. 2. The analytical microchip according to claim 1, wherein the inlet portion has an opening formed therein into which an insertion tube provided at the tip of the sample tube is inserted.

3. The analytical microchip according to claim 1 , wherein the on-off valves are provided in the first flow path between the inlet and the mixing part and between the intake and the mixing part.

4. It has a supply port through which oil is supplied, 3. The analytical microchip according to claim 1, wherein the liquid sample contained in the mixing section is pressed by the oil supplied from the supply port and flows out into the second flow path.

5. the waste liquid section has an openable / closable vent for discharging air from inside the waste liquid section, 4. The analytical microchip according to claim 1, wherein the vent hole is closed when a liquid sample flows from the inflow portion to the mixing portion through the first flow path, and the vent hole is opened when a liquid sample contained in the mixing portion flows into the second flow path.

6. The analytical microchip according to claim 1 , wherein the mixing section has a stirrer for mixing a drug into the liquid sample.

7. 7. The analytical microchip according to claim 1, wherein at least a part of the inner surface of the flow channel into which the liquid sample flows, including the inflow section to the mixing section, is subjected to a hydrophilic treatment.

8. The analytical microchip according to any one of claims 1 to 7; an aspirator connected to an inlet of the analytical microchip, which draws the liquid sample contained in a sample tube from an inlet portion through a first flow path to a mixing portion; a driver for closing and opening the vent of the waste liquid section; An analysis system comprising:

9. 9. The analytical microchip according to claim 8, further comprising a control unit that controls an on-off valve that opens the first flow path when the liquid sample flows from the inflow portion to the mixing portion through the first flow path, and closes the first flow path when the liquid sample flows from the mixing portion to the second flow path. Analysis system.

10. The analysis system of claim 9, wherein the control unit controls the driver to close the vent when a liquid sample flows from the inlet portion to the mixing portion through the first flow path, and to open the vent when a liquid sample contained in the mixing portion flows into the second flow path.

11. 11. The analytical system according to claim 8, further comprising a supply unit having a pressure sensor connected to a supply port of the analytical microchip and detecting a pressure in a second flow path of the liquid sample flowing out of the mixing section.

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