FLUIDIC DEVICE AND SYSTEM

A fluidic device that can feed a fluid along a flow path without causing a leakage of gas is provided. The fluidic device includes: a first substrate and a second substrate which are bonded to each other at a bonding surface and at least one of which includes a flow path that is open on the bonding surface; and three or more valve portions that are disposed at a position facing the flow path and that are configured to adjust a flow of a fluid in the flow path by deformation. The first substrate includes a through-hole penetrating the first substrate at positions facing the valve portions. The valve portions are disposed on the same circumference centered on an axis extending in a normal direction of the bonding surface.

TECHNICAL FIELD

The present invention relates to a fluidic device and a system.

BACKGROUND

Recently, development of micro-total analysis systems (μ-TASs) for the purpose of increasing speed, efficiency, and the degree of integration of tests in the field of in-vitro diagnosis or microminiaturization of test equipment has attracted attention, and active study thereof has progressed around the world.

A μ-TAS is better than test equipment in the related art because a μ-TAS can measure and analyze a small amount of a sample, can be carried, can be used and discarded at a low cost, and the like.

μ-TASs have attracted attention as systems with high usefulness when a reagent of a high price is used or when small amounts and large numbers of samples are tested.

A device including a flow path and a pump disposed in the flow path has been reported as an element of a μ-TAS (Non-Patent Document 1). In such a device, a plurality of solutions are mixed in the flow path by injecting the plurality of solutions into the flow path and activating the pump.

RELATED ART DOCUMENT

SUMMARY OF INVENTION

According to a first aspect of the invention, there is provided a fluidic device including: a first substrate and a second substrate which are bonded to each other at a bonding surface and at least one of which includes a flow path that opens on the bonding surface; and three or more valve portions that are disposed at a position facing the flow path and that are configured to adjust a flow of a fluid in the flow path by deformation, wherein the first substrate includes a through-hole penetrating the first substrate at positions facing the valve portions, and the valve portions are disposed on the same circumference centered on an axis extending in a normal direction of the bonding surface.

According to a second aspect of the invention, there is provided a system including: the fluidic device according to the first aspect of the present invention; and a drive device configured to press-drive the valve portions of the fluidic device, wherein the drive device includes: a movable member that is movable between a first position at which the valve portion is pressed to close the flow path with a tip of the movable member via the through-hole and a second position at which the movable member retreats in a direction of the axis from the first position to open the flow path when the fluidic device is set in the drive device; a rotation device that is rotatable around the axis; and a cam portion that is disposed on the same circumference in the rotation device as the valve portions of the fluidic device, supports a base end of the movable member, and is configured to move the movable member in the direction of the axis.

DESCRIPTION OF EMBODIMENTS

Hereinafter, a fluidic device and a system according to an embodiment of the invention will be described with reference toFIGS. 1 to 22.

In the drawings which are used in the following description, in order to facilitate understanding of features, feature parts may be enlarged for the purpose of convenience, and sizes, proportions, and the like of elements may not be the same as actual ones.

FIG. 1is a sectional view illustrating a principal part of a system SYS including a fluidic device100A according to an embodiment.FIG. 2is a plan view of the system SYS from the fluidic device100A side.

As illustrated inFIG. 1, the system SYS includes a fluidic device100A and a drive device DR. The fluidic device100A is set in the drive device DR for use. The fluidic device100A is disposed in the drive device DR, and is used in a state in which it is fixed or pressed. The drive device DR includes pressing pins (movable members) P1to P3that face valve portions which will be described later when the fluidic device100A is set therein.

The fluidic device100A according to this embodiment includes a device that detects a sample material which is a detection object included in a test sample by hybridization, an immune reaction and an enzyme reaction, or the like. The sample material is, for example, biomolecules or particles such as nucleic acid, DNA, RNA, peptides, proteins, and extracellular endoplasmic reticula

The fluidic device100A includes a first substrate6and a second substrate9. The first substrate6and the second substrate9are, for example, plate-shaped substrates and are formed of, for example, a resin material (a hard material such as polypropylene or polycarbonate). The first substrate6and the second substrate9may also be referred to as a first substrate and a second substrate. The fluidic device100A includes the first substrate and the second substrate which are bonded to each other at a bonding surface. For example, the first substrate6and the second substrate9are bonded to each other by welding techniques such as ultrasonic welding and laser welding. The first substrate6and the second substrate9include, for example, a plurality of (for example, two) positioning holes (not illustrated) that penetrate the substrates in a bonding direction and are used for positioning in an in-plane direction. The first substrate6and the second substrate9can be stacked (multilayered) in a state in which they are positioned in the in-plane direction by inserting shaft members into the positioning holes (not illustrated). At least one of the first substrate6and the second substrate9includes a groove that forms a flow path40when the two substrates are bonded to each other on the bonding surface. In this embodiment, the second substrate9includes the flow path40that opens on the bonding surface9awith the first substrate6. The flow path40is, for example, a groove with a width or a depth of about several μm to several hundreds of mm

In the following description, it is assumed that the first substrate6and the second substrate9are disposed along a horizontal plane and the first substrate6is disposed on the bottom side (on the drive device DR side) of the second substrate9. The first substrate6may be also referred to as an upper plate and the second substrate9may be referred to as a base plate. This is merely defining the horizontal direction and the vertical direction for the purpose of convenience of explanation, and does not define a direction at the time of use of the fluidic device100A and the system SYS according to this embodiment.

The fluidic device100A includes a pump P that is used to feed a solution in the flow path40. The pump P includes valve portions V11to V13that are disposed with intervals therebetween. In this embodiment, three valve portions V11to V13are provided. The pump P has to include at least three valve portions but may include, for example, three to twelve valve portions. The valve portions V11to V13are formed of a flexible member60. The flexible member60is an elastic member. The flexible member60is formed in a sheet shape with a size including three valve portions V11to V13, and is provided on a top surface6aof the first substrate6facing the flow path40. When the flexible member60is a single sheet common to the valve portions V11to V13, a fluidic device can be manufactured as a stacked structure in which a sheet is provided between the first substrate6and the second substrate9. Accordingly, there is consistency with a general process of manufacturing a fluidic device, in which plate-shaped or sheet-shaped substrates having a groove or a recess formed therein are stacked and bonded. The flexible member60may be provided separately for each of the valve portions V11to V13. That is, the valve portions V11to V13may independently include flexible members60. In all cases including the case in which the flexible member60is provided in a sheet shape and the case in which the flexible member60is provided separately for each of the valve portions V11to V13, it is preferable that the flexible member be a molded product which has been integrally molded with the first substrate6. By integrally molding the flexible member60with the first substrate6, it is possible to enhance manufacturing efficiency. The diameter of each of the valve portions V11to V13ranges from about several μm to several hundreds of mm. It is preferable that the diameter be 1.2 times to three times the width of the flow path40. For example, when the width of the flow path is 1.5 mm, it is preferable that each valve used herein have a diameter equal to or greater than 2 mm.

In the first substrate6, exposing portions51to53are formed at positions facing the valve portions V11to V13. The exposing portions51to53are formed as through-holes penetrating the first substrate6in a vertical direction (a thickness direction of the first substrate6). That is, the valve portions V11to V13are formed of parts of the flexible member60which is exposed to the outside (the bottom side) by the exposing portions51to53.

For example, a material that is deformed by pressure such as an elastic member can be used as a material of the flexible member60, and examples thereof include a thermoplastic elastomer such as a polyolefin-based elastomer, a styrene-based elastomer, and a polyester-based elastomer.

As illustrated inFIG. 2, the valve portions V11to V13are disposed at intervals on the same circumference centered on an axis C extending in a normal direction of the bonding surface9a. For example, the valve portions V11to V13are disposed at intervals of 75° centered on the axis C. A part of the flow path40is formed in a <- shaped (V-shaped) path in a plan view connecting the valve portion V11and the valve portion V12and connecting the valve portion V12and the valve portion V13. It is preferable that the distance between the valves be two times to five times the diameter of each valve.

An angle between a straight line connecting the valve portion V11and the valve portion V12which are adjacent to each other in a circumferential direction and a straight line connecting the valve portion V12and the valve portion V13which are adjacent to each other in the circumferential direction is 105° when the valve portions V11to V13are disposed at intervals of 75°.

The drive device DR includes the pressing pins P1to P3, a rotational drive source61, a rotation device62, and holding plates63and64. The pressing pins P1to P3have the same configuration and thus only the pressing pin P1will be described below. The pressing pin P1includes a pressing portion71, a flange portion72, and a sliding portion73which are sequentially arranged from the tip side. The pressing portion71has a cylindrical shape extending in the direction of the axis C and a tip thereof is formed in a semispherical shape. The diameter of the pressing portion71is less than the diameter of the exposing portions51to53.

The flange portion72is formed in a disc shape with a diameter greater than the diameter of the pressing portion71. The sliding portion73is formed in a cylindrical shape extending in the direction of the axis C downward from the flange portion72. The lower end of the sliding portion73is formed in a semispherical shape. The diameter of the sliding portion73is less than the diameter of the pressing portion71. The lower end of the sliding portion73is supported from below by a cam portion65which is formed in the rotation device62as will be described later.

The holding plates63and64are positioned with respect to each other and are integrally bonded in the vertical direction. The holding plate63is set to be in contact with the bottom surface6bof the first substrate6when the valve portions V11to V13of the fluidic device100A are driven. The holding plate63includes holding holes71aand cavity portions72aat positions facing the valve portions V11to V13when the first substrate6has been set. The holding holes71apenetrate the holding plate63in the direction of the axis C. The holding holes71ahold the pressing portions71of the pressing pins P1to P3to be movable in the direction of the axis C. The cavity portions72aare recesses with a bottom72bextending the direction of the axis C and open on the bottom surface63aof the holding plate63. The diameter of each cavity portion72ais greater than the diameter of the corresponding flange portion72.

The holding plate64includes holding holes73awhich are formed coaxially with the holding holes71aand the cavity portions72a. The holding holes73apenetrate the holding plate64in the direction of the axis C. The holding holes73ahold the sliding portions73of the pressing pins P1to P3to be movable in the direction of the axis C.

The length of the pressing pins P1to P3is a length with which the tips of the pressing portions71can press the valve portions V11to V13from below via the exposing portions51to53to come into contact with the bottom surface of the flow path40and to block the flow path40when the lower ends of the sliding portions73are located at a first position at which the lower ends are supported by peak portions65aof the cam portion65, similarly to the pressing pin P1illustrated inFIG. 1. The length of the pressing pins P1to P3is a length with which the tips of the pressing portions71are inserted into the exposing portions51to53to open the flow path40in a state in which the tips do not press the valve portions V11to V13when the lower ends of the sliding portions73are located at a second position at which the lower ends are supported by valley portions65bof the cam portion65, similarly to the pressing pins P2and P3illustrated inFIG. 1.

The thickness and the position in the direction of the axis C of the flange portions72are set to a thickness and a position with which the flange portions72do not come into contact with the bottom surfaces72bof the cavity portions72awhen the pressing pins P1to P3are located at the first position and do not come into contact with the holding plate64when the pressing pins P1to P3are located at the second position.

In each cavity portion72a, a compression spring74of which the top in the length direction is in contact with the bottom surface72band the bottom is in contact with the top surface of the corresponding flange portion72is provided as a biasing member in a compressed state. The compression springs74of which the top is in contact with the bottom surface72bapply a downward force to the pressing pins P1to P3located at the first position and the second position by normally pressing the flange portions72downward.

FIG. 3is a diagram schematically illustrating a configuration of the rotational drive source61and the rotation device62. The rotation device62is formed in a disc shape. The rotation device62rotates around the axis C with rotational driving of the rotational drive source61such as a motor. The cam portion65is provided to protrude on the top surface of the rotation device62. The cam portion65protrudes in a ring shape around the axis C. The cam portion65is disposed on the same circumference as the valve portions V11to V13and supports the sliding portions73of the pressing pins P1to P3from below. Since the pressing pins P1to P3are normally pressed downward by the compression springs74, the sliding portions73of the pressing pins P1to P3slide over the top surface of the cam portion65when the rotation device62rotates around the axis C.

The cam portion65includes the peak portions65athat support the pressing pins P1to P3at the first position and the valley portions65athat are formed lower than the peak portions65aand supports the pressing pins P1to P3at the second position. The peak portions65aand the valley portions65bare alternately disposed at intervals of 90°.

FIG. 4is a diagram illustrating development of the cam portion65around the axis C. InFIG. 4, for example, an end in the circumferential direction of the peak portion65ais set as a reference.

As illustrated inFIG. 4, in the cam portion65, the peak portions65aare disposed in a range of 0° to 90° and a range of 180° to 270°, and the valley portions65bare disposed in a range which is greater than 90° and less than 180° and a range which is greater than 270° and less than 360°.

In the cam portion65according to this embodiment, the peak portions65aand the valley portions65bare disposed at two positions to perform a solution feed cycle in which a solution is fed in the flow path40two times as will be described later while the rotation device62rotates one turn. In order to enable the solution feed cycle to be performed two times while the rotation device62rotates one turn, it is preferable that the valve portions V11to V13be disposed in an angle range equal to or less than 180°, and it is more preferable that the total range in which the valve portions V11to V13are disposed at intervals of 75° be equal to or less than 150°.

The valley portions65binclude inclined portions which are provided between areas located at the lowermost position (an area in which the pressing pins P1to P3are located at the second position) and the peak portions65a. When the sliding portions73slide over the inclined portions, the position at which the pressing pins P1to P3are supported can be smoothly changed between the peak portions65aand the valley portions65b. When the sliding portions73are supported by the inclined portions, the pressing portions71of the pressing pins P1to P3move downward and thus the valve portions V11to V13are elastically deformed to partially release blocking of the flow path40. In the following description, it is assumed that the case in which the sliding portions73are supported by the inclined portions is an open state in which at least a part of the flow path40is open.

The operation of the pump P in the system SYS having the aforementioned configuration will be described below with reference toFIGS. 5 to 14.

In this embodiment, an example in which a solution is fed in the flow path40by switching the open/closed states of the valve portions V11to V13to six phases will be described with reference toFIGS. 5 to 11.

FIG. 5is a timing chart illustrating the relationship between the cam position at which the pressing pins P1to P3are supported by the cam portion65illustrated inFIG. 4when a solution is fed in a six-phase type pumping cycle and the open/closed state of the flow path40for each of the valve portions V11to V13.FIGS. 6 to 11are diagrams illustrating the open/closed states of the valve portions V11to V13and a flow of a solution in the flow path40. InFIGS. 6 to 11, the first substrate6and the pressing pins P1to P3are not illustrated.

Angles described below are angles with respect to the reference in the cam portion65illustrated inFIG. 5unless otherwise mentioned. InFIGS. 6 to 11, a flow direction of a solution in the flow path40will be described with the valve portion V11side as a left side and with the valve portion V13side as a right side.

FIG. 6is a sectional view in a first phase of the solution feed cycle.

The first phase is performed in a range of 30° to 60°. In the first phase, the valve portion V11blocks the flow path40and the valve portions V12and V13open the flow path40. Accordingly, the solution in the flow path40is divided by the valve portion V11.

FIG. 7is a sectional view in a second phase of the solution feed cycle.

The second phase is performed in a range of 60° to 90°. In the second phase, the valve portion V12blocks the flow path40with respect to the first phase. Since the valve portion V11still blocks the flow path40, the solution on the right side of the valve portion V11is fed rightward as indicated by an arrow when the valve portion V12blocks the flow path40.

FIG. 8is a sectional view in a third phase of the solution feed cycle.

The third phase is performed in a range of 90° to 120°. In the third phase, the valve portion V11opens the flow path40with respect to the second phase. Since the valve portion V12still blocks the flow path40, the solution on the left side of the valve portion V11moves rightward to the valve portion V12as indicated by an arrow to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V11when the valve portion V11opens the flow path40.

FIG. 9is a sectional view in a fourth phase of the solution feed cycle.

The fourth phase is performed in a range of 120° to 150°. In the fourth phase, the valve portion V13blocks the flow path40with respect to the third phase. Since the valve portion V12still blocks the flow path40, the solution on the right side of the valve portion V12is fed rightward as indicated by an arrow when the valve portion V13blocks the flow path40.

FIG. 10is a sectional view in a fifth phase of the solution feed cycle.

The fifth phase is performed in a range of 180° to 210°. In the fifth phase, the valve portion V12opens the flow path40with respect to the fourth phase. Since the valve portion V13still blocks the flow path40, the solution on the left side of the valve portion V12moves rightward to the valve portion V13as indicated by an arrow to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V12when the valve portion V12opens the flow path40.

FIG. 11is a sectional view in a sixth phase of the solution feed cycle.

The sixth phase is performed in a range of 240° to 270°. In the sixth phase, the valve portion V11blocks the flow path40with respect to the fifth phase. Accordingly, the solution of the flow path40on the left side of the valve portion V13is partitioned by the valve portion V11. Since the valve portion V13still blocks the flow path40, the solution in the flow path40moves leftward as indicated by an arrow when the valve portion V11blocks the flow path40.

Thereafter, by returning the solution feed cycle to the first phase and causing the valve portion V13to open the flow path40, the solution on the right side of the valve portion V13moves leftward to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V13.

Thereafter, by repeating the first to sixth phases, the solution in the flow path40can be fed rightward (from the valve portion V11side to the valve portion V13side).

In this embodiment, an example in which a solution is fed in the flow path40by switching the open/closed states of the valve portions V11to V13to three phases will be described with reference toFIG. 12.

FIG. 12is a timing chart illustrating the relationship between the cam position at which the pressing pins P1to P3are supported by the cam portion65when a solution is fed in a three-phase type pumping cycle and the open/closed state of the flow path40for each of the valve portions V11to V13.

In the case of the three-phase type pumping cycle, in the cam portion65, the peak portions65aare disposed in a range of 0° to 120° and the range of 180° to 300°, and the valley portions65bare disposed in a range which is greater than 120° and less than 180° and a range which is greater than 300° and less than 360°.

A first phase is performed in a range of 0° to 60°. In the first phase, similarly to the sixth phase of the six-phase type pumping cycle (seeFIG. 11), the valve portions V11and V13block the flow path40and the valve portion V12opens the flow path40. Accordingly, the solution in the flow path40is divided by the valve portions V11and V13.

A second phase is performed in a range of 60° to 120°. In the second phase, similarly to the second phase of the six-phase type pumping cycle (seeFIG. 7), the valve portion V12blocks the flow path40and the valve portion V13opens the flow path40with respect to the first phase. Since the valve portion V11still blocks the flow path40, the solution on the right side of the valve portion V11is fed rightward as indicated by an arrow when the valve portion V12blocks the flow path40.

A third phase is performed in a range of 120° to 180°. In the third phase, similarly to the fourth phase of the six-phase type pumping cycle (seeFIG. 9), the valve portion V11opens the flow path40and the valve portion V13blocks the flow path40with respect to the second phase. Since the valve portion V11opens the flow path40, the solution in the flow path40on the left side of the valve portion V11moves rightward to the valve portion V12to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V11. Since the valve portion V12still blocks the flow path40, the solution on the right side of the valve portion V12is fed rightward as indicated by an arrow when the valve portion V13blocks the flow path40.

Thereafter, the solution feed cycle returns to the first phase, the valve portion V12opens the flow path40, and the valve portion V11blocks the flow path40with respect to the third phase. Accordingly, the solution in the flow path40is partitioned by the valve portions V11and V13. When the valve portion V11blocks the flow path40, some of the solution in the flow path40moves leftward as indicated by an arrow and some of the solution moves rightward to the valve portion V13to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V12.

Thereafter, by repeating the first to third phases, the solution in the flow path40can be fed rightward (from the valve portion V11side to the valve portion V13side).

In this embodiment, an example in which a solution is fed in the flow path40by switching the open/closed states of the valve portions V11to V13to four phases will be described with reference toFIG. 13.

FIG. 13is a timing chart illustrating the relationship between the cam position at which the pressing pins P1to P3are supported by the cam portion65when a solution is fed in a four-phase type pumping cycle and the open/closed state of the flow path40for each of the valve portions V11to V13.

In case of the four-phase type pumping cycle, in the cam portion65, similarly to the six-phase type pumping cycle illustrated inFIG. 4, the peak portions65aare disposed in a range of 0° to 90° and a range of 180° to 270°, and the valley portions65bare disposed in a range which is greater than 90° and less than 180° and the range which is greater than 270° and less than 360°.

A first phase is performed in a range of 0° to 45°. In the first phase, similarly to the first phase of the six-phase type pumping cycle (seeFIG. 6), the valve portion V11blocks the flow path40and the valve portions V12and V13open the flow path40. Accordingly, the solution in the flow path40is divided by the valve portion V11.

A second phase is performed in a range of 45° to 90°. In the second phase, similarly to the second phase of the six-phase type pumping cycle (seeFIG. 7), the valve portion V12blocks the flow path40with respect to the first phase. Since the valve portion V11still blocks the flow path40, the solution on the right side of the valve portion V11is fed rightward as indicated by an arrow when the valve portion V12blocks the flow path40.

A third phase is performed in a range of 90° to 135°. In the third phase, similarly to the fourth phase of the six-phase type pumping cycle (seeFIG. 9), the valve portion V11opens the flow path40and the valve portion V13blocks the flow path40with respect to the second phase. Since the valve portion V11opens the flow path40, the solution in the flow path40on the left side of the valve portion V11moves rightward to the valve portion V12to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V11. Since the valve portion V12still blocks the flow path40, the solution on the right side of the valve portion V12is fed rightward as indicated by an arrow when the valve portion V13blocks the flow path40.

A fourth phase is performed in a range of 135° to 180°. In the fourth phase, similarly to the fifth phase of the six-phase type pumping cycle (seeFIG. 10), the valve portion V12opens the flow path40with respect to the third phase. Since the valve portion V13still blocks the flow path40, the solution on the left side of the valve portion V12moves rightward to the valve portion V13as indicated by an arrow to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V12when the valve portion V12opens the flow path40.

Thereafter, the solution feed cycle returns to the first phase, the valve portion V13opens the flow path40, and the valve portion V11blocks the flow path40with respect to the fourth phase. Accordingly, the solution in the flow path40is partitioned by the valve portion V11. When the valve portion V11blocks the flow path40, some of the solution in the flow path40moves leftward. When the valve portion V13opens the flow path40, the solution on the right side of the valve portion V13moves leftward to compensate for an increase in volume of the flow path40due to release of elastic deformation of the valve portion V13.

Thereafter, by repeating the first to fourth phases, the solution in the flow path40can be fed rightward (from the valve portion V11side to the valve portion V13side).

In this embodiment, an example in which a solution is fed in the flow path40by switching the open/closed states of the valve portions V11to V13to five phases will be described with reference toFIG. 14.

FIG. 14is a timing chart illustrating the relationship between the cam position at which the pressing pins P1to P3are supported by the cam portion65when a solution is fed in a five-phase type pumping cycle and the open/closed state of the flow path40for each of the valve portions V11to V13.

In case of the five-phase type pumping cycle, in the cam portion65, the peak portions65aare disposed in a range of 0° to 72° and the range of 180° to 252°, and the valley portions65bare disposed in a range which is greater than 72° and less than 180° and the range which is greater than 252° and less than 360°.

(First to Fourth Phases)

In the five-phase type pumping cycle, the first to fourth phases are different from those of the four-phase type pumping cycle in only the angle of the cam portion65at which the flow path40is opened and blocks, and are the same as those in a drive pattern of the valve portions V11to V13. That is, the first phase of the five-phase type pumping cycle is performed in a range of 0° to 36°, and the second phase is performed in a range of 36° to 72°. The third phase of the five-phase type pumping cycle is performed in a range of 72° to 108°, and the fourth phase is performed in a range of 108° to 144°.

The fifth phase is performed in a range of 144° to 180°. In the fifth phase, the valve portion V13opens the flow path40with respect to the fourth phase. Accordingly, all the valve portions V11to V13open the flow path40.

Thereafter, by repeating the first to fifth phases, the solution in the flow path40can be fed rightward (from the valve portion V11side to the valve portion V13side).

As described above, in the fluidic device100A and the system SYS according to this embodiment, since the valve portions V11to V13are disposed on the same circumference centered on the axis C and the flow path40is opened/blocked by synchronously driving the valve portions V11to V13via the cam portion65and the pressing pins P1to P3which rotate around the axis C by rotational driving of the rotational drive source61, it is possible to feed a solution in the flow path40without causing leakage of a fluid unlike a case in which the valve portions V11to V13are driven using a fluid such as air.

In the fluidic device100A and the system SYS according to this embodiment, since the rotational drive source61is electrically driven, it is not necessary to provide a gas compression device such as a gas cylinder or a compressor unlike a case in which the valve portions V11to V13are driven using a fluid and to extend versatility. When the rotational drive source is used, it is possible to easily change a feed speed of a solution by adjusting a rotation speed thereof to change drive periods of the valve portions V11to V13.

In the fluidic device100A and the system SYS according to this embodiment, by appropriately selecting a rotation device62including a cam portion65with a different disposing pattern of the peak portions65aand the valley portions65b, it is possible to arbitrarily select a drive pattern such as a six-phase type, a three-phase type, or a four-phase type as described above.

[Examples of Fluidic Device and System]

Examples of the fluidic device and the system will be described below with reference toFIGS. 15 to 21.

FIG. 15is a plan view schematically illustrating a fluidic device300.

As illustrated inFIG. 15, the fluidic device300includes a substrate209in which a flow path and valve portions V11to V13are formed. The fluidic device300includes a first circulating flow path210and a second circulating flow path220that are formed in the substrate209and that circulate a solution including a sample material. The first circulating flow path210and the second circulating flow path220include a shared flow path202which are shared thereby. The first circulating flow path210includes an unshared flow path211which is not shared by the second circulating flow path220, and the second circulating flow path220includes an unshared flow path221which is not shared by the first circulating flow path210.

The shared flow path202connects ends of the unshared flow path211of the first circulating flow path210. The shared flow path202connects ends of the unshared flow path221of the second circulating flow path220. The shared flow path202includes a pump P, a first capturing portion4, and an assisting material detecting portion5.

A discharge flow path227connected to a waste solution tank7is connected to the shared flow path202. A discharge flow path valve O3is provided in the discharge flow path227.

The pump P is constituted by the aforementioned three valve portions V11to

V13which are disposed in parallel in the flow path. The valve portions V11to V13are driven by the aforementioned drive device DR (only the cam portion65is illustrated inFIGS. 15 to 18). The valve portions V11to V13are disposed on the same circumference as that of the cam portion65. The pump P can control a solution feed direction of a solution in the circulating flow paths by controlling opening/blocking of the three valve portions V11to V13. The number of valve portions V11to V13may be four or more. The first capturing portion4captures and collects a sample material in the solution circulating in the first circulating flow path210. The configuration of the first capturing portion4includes, for example, a magnetic force source such as a magnet (not illustrated). The magnetic force source is disposed in the vicinity of the shared flow path202from below.

The assisting material detecting portion5is provided to detect a marker material for assisting with detection of a sample material (a detection assisting material) by binding the marker material to the sample material. When an enzyme is used as the marker material, deterioration of the enzyme may occur with the elapse of a storage time and there is concern about a decrease in detection efficiency in a detection portion3including a magnetic sensor provided in the second circulating flow path220. The assisting material detecting portion5detects the marker material and measures the degree of deterioration of the enzyme.

(First circulating flow path) The first circulating flow path210includes a plurality of valves V1, V2, W1, and W2in the unshared flow path211. Out of these valves, the valves V1, V2, and W2serve as quantification valves. The valves W1and W2serve as unshared flow path end valves. That is, the valve W2serves as a quantification valve and also serves as an unshared flow path end valve.

The quantification valves V1, V2, and W2are disposed such that sections of the first circulating flow path210which are partitioned by the quantification valves have a predetermined volume. The quantification valves V1and V2partition the first circulating flow path210into a first quantification section A1, a second quantification section A2, and a third quantification section A3.

The first quantification section A1includes the shared flow path202.

Introduction flow paths212and213are connected to the unshared flow path211of the first quantification section A1. An introduction flow path214and a discharge flow path217are connected to the second quantification section A2. An introduction flow path215, a discharge flow path218, and an air flow path216are connected to the third quantification section A3.

The introduction flow paths212,213,214, and215are provided to introduce different solutions into the first circulating flow path210. Introduction flow path valves Il,12,13, and14that open and block the corresponding introduction flow paths are provided in the introduction flow paths212,213,214, and215. Solution-introduction inlets212a,213a,214a, and215athat open on the surface of the substrate209are provided at ends of the introduction flow paths212,213,214, and215.

The air flow path216is provided to discharge or introduce air from or into the first circulating flow path210. An air flow path valve G1that opens and blocks the flow path is provided in the air flow path216.

An air-introduction inlet216athat opens on the surface of the substrate209is provided at an end of the air flow path216.

The discharge flow paths217and218are provided to discharge a solution from the first circulating flow path210. Discharge flow path valves O1and O2that open and block the corresponding discharge flow paths are provided in the discharge flow paths217and218. The discharge flow paths217and218are connected to a waste solution tank7. An outlet7athat is connected to an external suction pump (not illustrated) and opens on the surface of the substrate for the purpose of negative-pressure suction is provided in the waste solution tank7. In the fluidic device300according to this embodiment, the waste solution tank7is disposed an area inside the first circulating flow path210. Accordingly, it is possible to achieve a decrease in size of the fluidic device300.

A meandering portion219is provided in the unshared flow path211of the first quantification section A1. The meandering portion219is a part of the unshared flow path211of the first quantification section A1and is a part that is formed to meander to the right and left sides. The meandering portion219increases the volume of the unshared flow path211of the first quantification section A1.

The second circulating flow path220includes valves W3and W4serving as unshared flow path end valves and a second capturing portion4A in the unshared flow path221. The second capturing portion4A captures and collects a sample material in a solution flowing in the unshared flow path221. The second capturing portion4A may be configured to capture carrier particles bound to a sample material. Since the second capturing portion4A captures the sample material or carrier particles bound to the sample material, the sample material can be collected from the solution flowing in the unshared flow path221. Since the fluidic device300includes the second capturing portion4A, it is possible to effectively realize condensation, cleaning, and feed of the sample material.

The carrier particles are magnetic beads or magnetic particles. Other examples of the second capturing portion4A include a column including a filler that can be bound to the carrier particles and an electrode that can attract the carrier particles. When the sample material is hexane, the second capturing portion4A may be an hexane array to which hexane hybridizing with the hexane is fixed.

The carrier particles are, for example, particles which can react with a sample material which serves as a detection object. Examples of the reaction of the carrier particles with the sample material include binding between the carrier particles and the sample material, adsorption between the carrier particles and the sample material, modification of the carrier particles due to the sample material, and chemical change of the carrier particles due to the sample material. Examples of the carrier particles include magnetic beads, magnetic particles, gold nanoparticles, agarose beads, and plastic beads.

Carrier particles having a material, which can be bound to or adsorbed on the sample material, on surfaces thereof may be used to bind the sample material to the carrier particles. For example, when carrier particles are bound to protein, an antibody on the surface of a carrier particle can be bound to protein using carrier particles having an antibody, which can be bound to protein, on the surface thereof. A material which can be bound to the sample material can be appropriately selected depending on the type of the sample material. Examples of a combination of a material which can be bound to or adsorbed onto a sample material/the sample material or a site included in the sample material include various receptor proteins/ligands thereof such as biotin-binding protein such as avidin and streptavidin/biotin, active ester group such as succinimidyl group/amino group, acetyl iodide group/amino group, maleimide group/thiol group (—SH), maltose-binding protein/maltose, G protein/guanine nucleotide, polyhistidine peptide/metal ion of nickel, cobalt, or the like, glutathione-S-transferase/glutathione, DNA-binding protein/DNA, antibody/antigen molecules (epitope), calmodulin/calmodulin-binding peptides, ATP-binding protein/ATP, and estradiol receptor protein/estradiol.

The sample material captured by the second capturing portion4A is detected by the detection portion3including a magnetic sensor. In an example in which a sample material is detected, the sample material may be bound to a detection assisting material that assists with detection of the sample material. When a marker material (a detection assisting material) is used, the sample material is bound to the detection assisting material by circulating the sample material along with the marker material in the second circulating flow path220and mixing them.

FIG. 16is a plan view of a magnetic sensor which is included in the detection portion3.

As illustrated inFIG. 16, the detection portion3includes a total of 80 magnetic sensors3aand3bwhich are arranged in a 8×10 lattice shape (matrix shape). The magnetic sensors3aand3bare alternately arranged in the longitudinal direction and the lateral direction. An antibody A such as a human tissue immunostaining antibody (anti-EGFR antibody) is fixed to each magnetic sensor3a. The magnetic sensors3bindicated by R are for reference and no antibody is fixed thereto. The magnetic sensors3aand3bare provided to face the unshared flow path221in the second capturing portion4A.

Examples of the marker material (the detection assisting material) include a fluorochrome, fluorescent beads, a fluorescent protein, quantum dots, gold nanoparticles, a biotin, an antibody, an antigen, an energy-absorbing material, a radioactive isotope, a chemiluminescent element, and an enzyme.

Examples of the enzyme include alkaline phosphatase, peroxidase, and β-galactosidase.

An introduction flow path222and a collecting flow path223are connected to the unshared flow path221of the second circulating flow path220. A solution reserving portion223aand a valve I10are provided in the collecting flow path223. The valve I10is located between the solution reserving portion223aand the second circulating flow path220. Introduction flow paths224and225and an air flow path226are connected to the solution reserving portion223a. Introduction flow path valves15,16, and17are provided in a path of the introduction flow paths222,224, and225, and introduction inlets222a,224a, and225aare provided at ends thereof. Similarly, an air flow path valve G2is provided in the path of the air flow path226, and an air-introduction inlet226ais provided at an end thereof.

A mixing method, a capturing method, and a detection method of a sample material using the fluidic device300according to this embodiment. In the detection method according to this embodiment, an antigen (a sample material or a biomolecule) which is a detection object included in a test sample is detected by an immune reaction and an enzyme reaction.

First, the valves V1, V2, and W2of the first circulating flow path210are closed, the valve W1is opened, and the unshared flow path end valves W3and W4of the second circulating flow path220are closed. Accordingly, the first circulating flow path210is partitioned into the first quantification section A1, the second quantification section A2, and the third quantification section A3.

Subsequently, as illustrated inFIG. 17, a sample solution (a first solution) L1including a sample material is introduced into the first quantification section A1from the introduction flow path213and is quantified (a sample solution introducing step). A second reagent solution L3including a marker material (a detection assisting material) is introduced into the second quantification section A2from the introduction flow path214(a second reagent solution introducing step). A first reagent solution (a second solution) L2including carrier particles is introduced into the third quantification section A3from the introduction flow path215and is quantified (a first reagent solution introducing step).

In this embodiment, the sample solution L1includes an antigen which is a detection object (a sample material). Examples of the sample solution include a body fluid such as blood, urine, saliva, blood plasma, or serum, a cellular extract, and a tissue-crushed solution.

In this embodiment, magnetic particles are used as the carrier particles included in the first reagent solution L2. An antibody A1(for example, biotin-binding protein such as streptavidin) which is singularly bound to an antigen (a sample material) which is the detection object is fixed to the surfaces of the magnetic particles.

In this embodiment, the second reagent solution L3contains an antibody A2which is singularly bound to the antigen which is the detection object. For example, biotin (a detection assisting material) is fixed to and marked on the antibody A2.

Subsequently, as illustrated inFIG. 18, the sample solution L1, the first reagent solution L2, and the second reagent solution L3are circulated and mixed in the first circulating flow path210to acquire a mixed solution L4by opening the valves V1, V2, and W2and driving the pump P of the shared flow path202(a first circulation step). By mixing the sample solution L1, the first reagent solution L2, and the second reagent solution L3, the antibody A2having biotin fixed thereto is bound to the antigen and the antibody A1fixed to the carrier particles is bound to the antigen via biotin. Accordingly, carrier-antigen-protein complexes are produced in the mixed solution L4.

In the first circulation step, an extra marker material which is not used to produce the carrier-antigen-protein complex is captured by the assisting material detecting portion5.

After binding between the sample material and the carrier particles has progressed sufficiently, a magnet for capturing magnetic particles in the first capturing portion4is brought close to the flow path in a state in which the mixed solution L4is circulated in the first circulating flow path210. Accordingly, the first capturing portion4captures the carrier-antigen-protein complex. The complex is captured on the inner wall surface of the first circulating flow path210in the first capturing portion4and is separated from a liquid component.

Subsequently, although a diagram illustrating the step is omitted, the air flow path valve G1and the discharge flow path valves O1, O2, and O3are opened in a state in which the carrier-antigen-protein complex is captured in the first capturing portion4, and negative-pressure suction from the outlet7aof the waste solution tank7is performed to discharge the liquid component (a mixed solution discharging step). Accordingly, the mixed solution is removed from the shared flow path202and the carrier-antigen-protein complex is separated from the mixed solution.

Subsequently, although a diagram illustrating the step is omitted, the air flow path valve G1and the discharge flow path valves O1, O2, and O3are blocked and a cleaning solution is introduced into the first circulating flow path210from the introduction flow path212. By driving the pump P of the shared flow path202, the cleaning solution is circulated in the first circulating flow path210and the carrier-antigen-protein complex is cleaned. After circulation of the cleaning solution for a predetermined time has been performed, the cleaning solution is discharged to the waste solution tank7.

The cycle of introduction, circulation, and discharge of the cleaning solution may be performed a plurality of times. By repeatedly performing introduction, circulation, and discharge of the cleaning solution, it is possible to enhance removal efficiency of unnecessary substance.

Subsequently, as illustrated inFIG. 19, the valves W1and W2of the first circulating flow path210are blocked, the unshared flow path end valves W3and W4of the second circulating flow path220are opened, a feed solution L5is introduced from the introduction flow path222to fill the second circulating flow path220with the feed solution L5. Subsequently, by releasing capturing of the carrier-antigen-protein complex in the first capturing portion4and driving the pump P, the carrier-antigen-protein complex is fed to the second circulating flow path220.

In the carrier-antigen-protein complex fed to the second circulating flow path220, the antigen is bound to the antibody A fixed to the magnetic sensor3ain the detection portion3.

Subsequently, the valve W4is blocked, the air flow path valve G2of the air flow path226and the discharge flow path valve O3of the discharge flow path227are opened, and negative-pressure suction from the outlet7ais performed. Accordingly, the liquid component (waste solution) of the feed solution L5separated from the carrier-antigen-protein complex is discharged clockwise from the second circulating flow path.

Thereafter, by detecting signals acquired from a plurality of magnetic sensors3a, it is possible to measure an amount of magnetic particles (that is, antigen) adsorbed on the antibody A fixed to the magnetic sensors3a.

In the aforementioned detection method, the sample solution L1including an antigen, the first reagent solution L2including carrier particles having the antibody A1fixed thereto, and the second reagent solution L3including an antibody A2are mixed to produce a carrier-antigen-protein complex and the carrier-antigen-protein complex is adsorbed on an antibody A fixed to the magnetic sensors3a, but the detection method is not limited to that order. For example, first, the sample solution L1including an antigen and the second reagent solution L3including an antibody A2are circulated and mixed in the circulating flow path220and an antigen having the antibody A2fixed thereto is bound to the antibody A (antigen-antibody mixture).

Then, after the circulating flow path220has been drained, the carrier particles may be adsorbed on the antigen by circulating the first reagent solution L2including the carrier particles having the antibody A1fixed thereto in the circulating flow path220and binding the antibody A1to the antibody A2fixed to the antigen bound to the antibody A in the magnetic sensors3a(an antigen-antibody reaction). When this order is employed, it is possible to measure an amount of magnetic particles (that is, antigen) adsorbed on the antibody A fixed to the magnetic sensors3aby detecting signals acquired from the plurality of magnetic sensors3a.

When the detection portion3includes, for example, a member transmitting light instead of the magnetic sensors and an imaging device is provided in an external device, the antigen adsorbed on the carrier particles and the antibody A are bound with an enzyme as the antibody A2, the unshared flow path end valves W3and W4of the second circulating flow path220are opened, a substrate solution L6is introduced from the introduction flow path224, and the second circulating flow path220is filled with the substrate solution L6(a substrate solution introducing step). For example, the substrate solution L6includes 3-(2′-spiroadamantane)-4-methoxy-4-(3″-phosphoryloxy) phenyl-1,2-dioxetane (AMPPD), 4-Aminophenyl Phosphate (pAPP), or 4-Nitrophenyl Phosphate (pNPP) which serves as a substrate when the enzyme is an alkaline phosphatase (enzyme). The substrate solution L6reacts with the enzyme of a carrier-antigen-enzyme complex in the second circulating flow path220. By circulating the substrate solution L6and the carrier-antigen-enzyme complex in the second circulating flow path220, the substrate solution L6can be made to react with the enzyme of the carrier-antigen-enzyme complex to generate a color with the second capturing portion4A. By imaging this color with an imaging device, it is possible to detect a reaction product.

[Verification of Detection Variation in Magnetic Sensors Depending on Drive Frequency of Pump P]

Verification of an influence which the drive frequency of the pump P gives to detection unevenness (variation) in the magnetic sensors will be described below.

This verification employed the sequences of adsorbing carrier particles on an antigen by circulating and mixing the sample solution L1including an antigen and the second reagent solution L3including an antibody A1marked with biotin in the circulating flow path220to bind the antigen having the antibody A1fixed thereto to the antibody A and circulating the first reagent solution L2including carrier particles having streptavidin fixed thereto in the circulating flow path220to bind streptavidin to biotin of the antibody A1fixed to the antigen bound to the antibody A in the magnetic sensors3a. The sequences were performed by assigning conditions 1 to 3 set in the specifications described in Table 1 to an L18orthogonal table, and a variation coefficient (C.V. (%)) was calculated by averaging ten high points of a signal intensity in a plurality of magnetic sensors3a. The drive frequency of the pump P in Table 1 represents the number of times the first to fifth phases are driven for one second.

In the conditions, an EGFR antigen with a concentration of 25 ng/ml was quantified by 10 μl and used as an antigen, an EGFR antigen was quantified by 57 μl and used as the antibody A2, and magnetic particles of ϕ30 nm having streptavidin fixed thereto were quantified by 67 μl and used as the antibody A1.

FIG. 20is a diagram illustrating the relationship between drive frequency of the pump P and signal intensity which is detected by a magnetic sensor in an antigen-antibody reaction. As illustrated inFIG. 20, it could be ascertained that the signal level of the magnetic sensor becomes higher as the drive frequency of the pump P becomes higher.

FIG. 21is a diagram illustrating the relationship between drive frequency of the pump P and inter-sensor unevenness (C.V. (%) value) in an antigen-antibody reaction. As illustrated inFIG. 21, it could be ascertained that the unevenness between the magnetic sensors becomes smaller as the drive frequency of the pump P becomes higher and the unevenness decreases to a half, for example, when the drive frequency of the pump P is 20 Hz in comparison with a case in which the drive frequency is 1 Hz.

While exemplary embodiments of the invention have been described above with reference to the accompanying drawings, the invention is not limited to the embodiments. All shapes, combinations, and the like of the constituent members described in the above embodiments are only examples and can be modified in various forms on the basis of a design request or the like without departing from the gist of the invention.

For example, the configuration in which three valve portions are provided has been described in the aforementioned embodiments, but a configuration in which four or more valve portions are provided may be employed. The configuration in which the cam portion65can perform the pumping cycle two times while the rotation device62rotates by one turn has been described in the aforementioned embodiments, but the invention is not limited thereto and a configuration in which the pumping cycle can be performed once or less while the rotation device62rotates by one turn or a configuration in which the pumping cycle can be performed three or more times may be employed.

The valve portions V11to V13have a circular shape in the aforementioned embodiments, but the valve portions may have a cylindrical shape. The shapes and sizes of the valve portions V11to V13may be the same or different between the valve portions V11to V13. For example, when three valve portions V11to V13are used, it is preferable that the valve portion (V12) located at the center be larger than the valve portions (V11and V13) located at both ends, in that more solution can be made to flow and solution feed efficiency is higher.

The exposing portions (through-holes)51to53are provided to correspond to the valve portions V11to V13in the aforementioned embodiments, but the invention is not limited thereto. For example, a configuration which one exposing portion (through-hole) with a size including the valve portions V11to V13is provided and the valve portions V11to V13are driven via the one through-hole may be employed. When this configuration is employed, it is possible to further relax position accuracy of the exposing portion (through-hole) and to further enhance manufacturing efficiency of the fluidic device in comparison with an exposing portion (through-hole) is provided for each of the valve portions V11to V13.

A configuration in which the flexible member60is formed in a sheet shape with a size including three valve portions V11to V13has been described in the aforementioned embodiments, but the invention is not limited thereto. For example, as illustrated inFIG. 22, the flexible member60is divided and independently provided for each of the three valve portions V11to V13may be employed.

A configuration in which the valve portions V11to V13are disposed at intervals of 75° has been described in the aforementioned embodiments, but the invention is not limited thereto and, for example, the valve portions may be disposed at intervals of 45° and the peak portions65aand the valley portions65bin the cam portion65may be disposed at intervals of 90°. When this configuration is employed, the angle between a straight line connecting the valve portion V11and the valve portion V12which are adjacent to each other in the circumferential direction and a straight line connecting the valve portion V12and the valve portion V13which are adjacent to each other in the circumferential direction is 135°. In this case, all the valve portions V11to V13can open the flow path40at the second position at which the lower ends of the sliding portions73of the pressing pins P1to P3are supported by the valley portion65bin the cam portion65. By setting a state in which all the valve portions V11to V13open the flow path40as an origin state, the pump P can be considered to be a part of the flow path40in the origin state, and control can be facilitated at the time of quantification or at the time of processing a waste solution.

DESCRIPTION OF THE REFERENCE SYMBOLS