JP2006153494A - Fluid conveyance method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fluid conveyance method capable of mixing two kinds of solutions at a desired ratio, and conveying a fixed quantity of the mixed solution to an analysis part or the like. <P>SOLUTION: This liquid conveyance method has a process for preparing a fluid conveyance device having a passage A, at least two passages B whose each one end is connected to the passage A, and a passage C, and equipped with each valve in the middle of each passage of the passages B and the passage C; a process of introducing the first fluid into the passage A, the passages B and the passage C; a process of introducing at least either fluid of the second fluid and the third fluid from one end of the passages B to the direction of the other end connected to the passage A, and filling a section in the passage A specified by a crossing part between the passages B and the passage A and a crossing part between the passage C and the passage A with the second fluid and the third fluid; and a process of conveying the second fluid and the third fluid, with which the section in the passage A specified by the two crossing parts to one end of the passage A. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a fluid conveyance method using a fluid conveyance device having a valve for controlling the flow of fluid. In particular, the present invention relates to a fluid conveyance method using a valve for controlling the flow of fluid in a miniaturized analysis system (μ-TAS: Micro Total Analysis System) that performs chemical analysis or chemical synthesis on a chip.

  In recent years, with the development of three-dimensional microfabrication technology, attention has been focused on a system that integrates minute flow channels, fluid elements such as pumps and valves, and sensors on a substrate such as glass or silicon, and performs chemical analysis on the substrate. ing. These systems are called miniaturized analysis systems, μ-TAS (Micro Total Analysis System) or Lab on a Chip. By reducing the size of the chemical analysis system, it is possible to reduce the ineffective volume and greatly reduce the amount of the sample. In addition, the analysis time can be shortened and the power consumption of the entire system can be reduced. Furthermore, the low price of the system can be expected by downsizing. Since μ-TAS can reduce the size and cost of the system and significantly reduce the analysis time, it can be applied in the medical field such as home medical care and bedside monitor, and in the bio field such as DNA analysis and proteome analysis. Expected.

  Up to now, when two kinds of solutions are mixed and analyzed in μTAS, for example, a Y-shaped channel pattern as shown in FIG. 6 has been used. The solution A is introduced into the channel 601 and the solution B is introduced into the channel 602. The introduced solution A and solution B are merged by the merge unit 603 and mixed in the channel 604. The mixed solution of the solution A and the solution B can be analyzed by the analysis means 605 installed in the downstream portion of the flow path 604. A DNA analysis kit to which this is applied is disclosed in Patent Document 1.

In μTAS, the operation of taking a certain amount of liquid sample from the flow path and transporting it to the next step is very useful. For example, Patent Document 2 discloses an injector that injects a fixed amount of a liquid sample into a column portion (analysis portion) of HPLC (High Performance Liquid Chromatography). FIG. 7 shows a method of injecting a certain amount of liquid sample into the HPLC column 703 using the sampling valve 701. In FIG. 7, the liquid sample is indicated by a thick line, and the buffer solution is indicated by a thin line. First, the sampling valve is arranged as shown in FIG. The liquid sample fills the sample loop flow path 704 and the buffer fills the analysis flow path 705. Next, as shown in FIG. 7B, the sampling valve 701 is rotated, and the liquid sample 706 in the sampling valve 701 is inserted into the analysis flow path 705. Next, as shown in FIG. 7C, by driving the pressure generation source 702, the liquid sample 706 in the sampling valve is cut out and transported to the HPLC column 703.
JP 2000-287682 A U.S. Pat. No. 6,290,909 B1

  In the prior art shown in FIG. 6, it is necessary to fill all the micro flow paths between the joining part and the detection part of the two flow paths with two types of solutions. In this case, a large amount of sample may be wasted when a plurality of analyzes are performed by changing the type of solution, mixing ratio, liquid feeding conditions, and the like.

  In the prior art shown in FIG. 7, when analyzing a sample in which two types of solutions are mixed, it is necessary to mix the two liquids outside the system and then introduce them into the system and inject a certain amount of sample. is there. When a plurality of analyzes are performed by changing the type of solution and the mixing ratio, it is necessary to prepare a sample outside the system for each combination and mixing ratio. For example, when the analysis is performed with a combination of dozens or more of samples and further changing the mixing ratio, this work is very laborious. In addition, it is necessary to prepare much more samples for each combination and mixing ratio than the amount necessary for analysis (the amount to be injected into the analysis unit), which may waste samples.

  The present invention provides a fluid conveying method capable of mixing two kinds of solutions in a system at a desired ratio and conveying a certain amount of the mixed solution to an analysis unit or the like.

A fluid conveyance method provided by the present invention is a fluid using a fluid conveyance device including a flow path for flowing a fluid and a valve located in the middle of the flow path for controlling the flow of the fluid. A transport method,
Fluid flow having a flow path A and at least two flow paths B and C each having one end connected to the flow path A, and having the valve in the middle of each of the flow paths B and C The process of preparing the device,
Introducing a first fluid into the channel A, the channel B and the channel C;
At least one of the second fluid and the third fluid is introduced from one end of the channel B to the other end connected to the channel A, and only the one fluid is introduced from one end of the channel B. In this case, the other fluid is introduced from another channel D having one end connected to channel A separately from channel B and channel C, and the intersection of channel B and channel A Filling the section of the flow path A defined by the intersection of C and the flow path A with the second fluid and the third fluid;
And transferring the first and second fluids in the flow path A to one end of the flow path A, the second and third fluids filling the section of the flow path A defined by the two intersections,
It is characterized by having.

  The valve operates according to a pressure difference generated between an upstream side and a downstream side of the valve when a fluid flows through the flow path provided with the valve, and the pressure difference is a predetermined value. 2. The fluid conveyance method according to claim 1, wherein when the pressure difference is less than the value, the valve allows the fluid to pass therethrough, and when the pressure difference is equal to or greater than a predetermined value, the fluid flow is interrupted.

  The valve used in the present invention allows a fluid to flow in a predetermined direction, passes the fluid when it flows in a direction opposite to the predetermined direction, and passes the fluid when the pressure difference is less than the predetermined value. When the pressure difference is greater than or equal to a predetermined value, it can be cut off.

  In the present invention, after the second and third fluids are introduced into the flow path C, the second and third fluids that satisfy the section of the flow path A defined by the two intersections are connected to one end of the flow path A. It includes carrying out the step of transporting.

  In the present invention, both the second and third fluids introduced from the flow path B to the flow path A are connected to the end portion of the flow path B opposite to the end portion connected to the flow path A. What is introduced into channel B via another channel is also included.

Furthermore, the present invention provides a fluid conveyance comprising at least four channels of a first channel, a second channel, a third channel, and a fourth channel to which one end of these three channels is connected. A fluid conveyance method using an apparatus,
(A) A step of introducing a first fluid from one end of the fourth flow path and filling the first to fourth flow paths with the first fluid (b) The first to third flow paths From one end opposite to the one end connected to the fourth channel of any one of the channels,
Introducing a second fluid,
Among the first to third channels, from one end opposite to the one end connected to the fourth channel of the channel other than the channel into which the second fluid is introduced,
Introducing a second fluid,
Of the sections of the fourth flow path,
From the first intersection where the flow path introducing the second fluid, the flow path introducing the third fluid, and the fourth flow path intersect,
A section from the first to third channels to the second intersection where the second channel and the fourth channel intersect with another channel and the fourth channel,
Filling with both the second fluid and the third fluid (c) introducing the first fluid from one end of the fourth flow path;
A fluid conveying method including a step of conveying the second liquid and the third liquid that are in a section from the first intersecting portion to the second intersecting portion to the other end of the fourth flow path. Include.

Furthermore, the present invention provides a fourth channel and a fifth channel,
A fluid conveyance method using a fluid conveyance device comprising at least three channels of a sixth channel to which one ends of these two channels are connected,
(D) introducing a fourth fluid from one end of the sixth channel and filling the fourth to sixth channels with the fourth fluid (e) the fourth and fifth channels The fifth fluid and the sixth fluid are simultaneously introduced from one end opposite to the one connected to the sixth flow channel of any one of the flow channels,
Of the sections of the sixth flow path,
From the third intersection where the fifth fluid and the sixth fluid flow channel and the sixth flow channel intersect,
A section from the fourth and fifth flow paths to a fourth intersection where the sixth flow path intersects with a flow path different from the flow path into which the fifth fluid and the sixth fluid are introduced. The
Filling with the fifth fluid and the sixth fluid (f) introducing the first fluid from one end of the sixth flow path;
Including a fluid conveyance method including a step of conveying the fifth fluid and the sixth fluid in the section from the third intersection to the fourth intersection to the other end of the sixth flow path. To do.

  The present invention has an effect that a mixed fluid can be transported with a small sample amount and a desired mixing ratio, mixing time, and liquid feeding conditions as compared with the conventional technique. Further, the present invention has an effect that two kinds of fluids can be mixed in a desired ratio inside the system, and a certain amount of the mixed fluid can be conveyed.

  Next, preferred embodiments of the present invention will be described in detail with reference to the drawings. In the following description, a method of mixing two kinds of liquids in a flow channel at a desired mixing ratio and conveying a certain amount of the mixed solution to the analysis unit will be described, but the application of the present invention is limited to the analysis system only. Is not to be done. The present invention can be used for any application in which two kinds of fluids are mixed and transported in a flow path at a desired mixing ratio.

  The fluid in the present invention refers to a liquid or a gas. In the following description, liquid will be described as an example of the fluid, but the same applies even if the fluid is gas.

(Configuration of fluid transfer device)
FIG. 1 is a conceptual diagram for explaining a configuration of a fluid conveyance device that can be applied when performing a fluid conveyance method of the present invention.

  1 includes a first flow path 101, a second flow path 102, a third flow path 103, a fourth flow path 104, a first valve 105, a second valve 106, and a third flow path. The valve 107, the first intersecting portion 108, the second intersecting portion 109, the liquid feeding means 110, and the analyzing portion 111. Here, the first channel 101 is the channel C defined in the claims, the second channel 102 is the channel D, the third channel 103 is the channel B, and the fourth channel. 104 respectively correspond to the flow paths A.

  Moreover, each component mentioned above is arrange | positioned like FIG. The fourth flow path 104 connects the liquid feeding means 110 and the analysis unit 111. The first channel 101 and the fourth channel 104 intersect at the first intersection 108. The second channel 102, the third channel 103, and the fourth channel 104 intersect at the second intersection 109. The first valve 105, the second valve 106, and the third valve 107 are arranged in the middle of the first flow path 101, the second flow path 102, and the third flow path 103, respectively.

  When a fluid flows from the first to the third valve, a pressure difference is generated before and after each valve according to the flow rate flowing through each valve. The first valve, the second valve, and the third valve are respectively related to the first flow path, the second flow path, and the flow in the direction flowing from the third flow path to the fourth flow path. Regardless of the pressure difference and flow rate generated before and after the valve by the flow, it has a structure that allows it to always pass. On the other hand, regarding the flow in the direction flowing out from the fourth flow path to the first flow path, the second flow path, and the third flow path, the flow rate or the pressure difference generated before and after the valve has a certain threshold value. In the above case, it has a characteristic of blocking and allowing it to pass if it is less than a certain threshold value. An example of a detailed configuration of the valve unit for providing the above-described characteristics will be described later.

  In order to facilitate the opening and closing operation of the valve and to convey a certain amount of fluid with high accuracy, it is preferable that the threshold values of the first to third valves are the same.

  The transfer device applied to the present invention uses a passive valve that opens and closes due to a pressure difference generated by the flow of fluid. Therefore, an actuator and a power source for driving the valve are unnecessary, and the device can be easily downsized. Further, since the valve is driven according to the flow, there is no need to control the valve driving timing by monitoring the flow rate with a flow meter or the like.

  Further, since the valve is opened and closed by the flow itself, the liquid feeding means is not particularly limited. Whether it is a pressure flow or an electroosmotic flow, the valve can be closed by setting the flow rate or the pressure difference generated before and after the valve to a threshold value or more. Examples of the liquid feeding means include commercially available liquid chromatography pumps, syringe pumps, and electroosmotic pumps. When driving the pump, it may be driven in a mode for controlling the pressure or in a mode for controlling the flow rate. Further, a pipette or the like may be used as the liquid feeding means. Further, the fluid may be driven by heating the fluid with a heater provided in the flow path.

  It is preferable that the channel resistances of the liquid feeding means 110 and the analysis unit 111 are very high compared to other parts. Thereby, in the step (a) -2, which will be described later, the sample can be introduced only into the portion of the fourth channel 104 that is fractionated by the first intersecting portion 108 and the second intersecting portion 109. Thus, the mixed solution can be transported to the analysis unit 111 with high accuracy. When the flow path resistance of the liquid feeding unit 110 or the analysis unit 111 is low, a portion between the second intersection and the analysis unit 111 or between the first intersection and the liquid feeding unit 110 in the fourth channel. The channel resistance may be increased by narrowing the channel width of this part. Further, for example, a material having a high flow path resistance such as a porous material is used as a part of the fourth flow path between the second crossing part and the analysis part 111 or between the first crossing part and the liquid feeding means 110. It may be inserted into the part.

  The analysis unit includes, for example, a separation unit such as an HPLC column and a detection unit of a spectrophotometer.

  In addition, although the flow path etc. which comprise the fluid conveying apparatus applicable to this invention can set the width | variety and depth of a flow path suitably, these general values can be selected from the range of 1 micrometer-5000 micrometers. .

(Fluid mixing and transport method)
The fluid conveyance method of the present invention is a fluid conveyance method using a fluid conveyance device including a flow path for flowing a fluid and a valve located in the middle of the flow path for controlling the flow of the fluid. There,
Fluid flow having a flow path A and at least two flow paths B and C each having one end connected to the flow path A, and having the valve in the middle of each of the flow paths B and C The process of preparing the device,
Introducing a first fluid into the channel A, the channel B and the channel C;
At least one of the second fluid and the third fluid is introduced from one end of the channel B to the other end connected to the channel A, and only the one fluid is introduced from one end of the channel B. In this case, the other fluid is introduced from another channel D having one end connected to channel A separately from channel B and channel C, and the intersection of channel B and channel A Filling the section of the flow path A defined by the intersection of C and the flow path A with the second fluid and the third fluid;
And transferring the first and second fluids in the flow path A to one end of the flow path A, the second and third fluids filling the section of the flow path A defined by the two intersections,
It is characterized by having.

  Here, using FIG. 1 and FIG. 2, the channel A (fourth channel 104), the channel B (third channel 103), the channel C (first channel 101), the channel An example of a fluid conveyance method using D (second flow path 102) will be described, but the present invention is not limited to the following description.

(A) Conveying the mixed solution Here, the description will be made focusing on the flow rate threshold value of the valve, but focusing on the differential pressure generated before and after the valve due to the flow, the liquid feeding conditions (flow rate, generated pressure, etc.) of each step are set. Even if it is determined, the same conveyance is possible.

(A) -1
In this step, the first to fourth flow paths, the first and second intersections, the first to third valves, and the analysis unit 111 are filled with the first liquid 112.

  First, using the liquid feeding means 110, the first liquid is fed so that the flow rate in each valve is equal to or less than the threshold flow rate of each valve. Thereby, the first to fourth flow paths are filled with the first liquid.

  At this time, the flow path resistance of the analysis unit 111 is large compared to the first to third flow channel sides, and the entire analysis unit may not be filled with the first liquid. In such a case, following the process described above, the liquid is fed using the liquid feeding means 110 so that the flow rate of the first to third valves is larger than the threshold flow rate of each valve. Thereby, each valve | bulb will be in a closed state and an analysis part will be filled with the 1st liquid. After the entire analysis unit is filled with the first liquid, the liquid feeding is stopped. By stopping the liquid feeding, the first to third valves are returned to the open state. If the valve does not return to the open state even after the liquid supply is stopped, the valve may be returned to the open state by, for example, releasing the pressure of the liquid supply means.

  When this step is completed, the first to fourth flow paths, the first and second intersections, the first to third valves, and the analysis unit are filled with the first liquid 112. The first to third valves are in an open state (FIG. 2 (a)).

(A) -2
Next, the second liquid 113 is introduced from the second channel 102 and the third liquid 114 is introduced from the third channel 103. As shown in FIG. 2B, the second liquid 113 and the third liquid 114 merge at the second intersection 109, and pass through the fourth flow path 104 toward the first intersection 108. After flowing and flowing into the first flow path 101 at the first intersection 108, it is discharged outside the apparatus. At this time, as described above, since the liquid feeding means 110 and the analysis unit 111 have a very high flow path resistance, the second liquid 113 and the third liquid 114 are not supplied to the liquid feeding means and the analysis part side. Does not flow.

  At this time, the liquid feeding conditions are set so that the flow rate flowing through the first valve 105 is less than the threshold flow rate of the first valve. As a result, the first valve 105 is opened. Moreover, since the direction of the flow which flows into the 2nd valve | bulb 106 and the 3rd valve | bulb 107 is a direction which always passes a flow, the 2nd valve | bulb 106 and the 3rd valve | bulb 107 will be in an open state.

(A) -3
Next, using the liquid feeding means 110, the first liquid is fed so that the flow rate in each valve is equal to or higher than the threshold flow rate of each valve. As a result, the first to third valves are immediately closed, and the second liquid 113 and the third liquid 114 in the portion divided into the first intersection 108 and the second intersection 109 are separated. As shown in FIG. 2C, the coexistence region 115 is cut out while being sandwiched between the first liquids 112 and conveyed to the analysis unit 111. The second liquid 113 and the third liquid 114 in the coexistence region 115 are mixed before reaching the analysis unit 111.

  In the present invention, the section of the channel A defined by the intersection of the channel B and the channel A and the intersection of the channel C and the channel A is defined by the second fluid and the third fluid. The second and third fluids that fill the section of the flow path A defined by the two intersections by moving the first fluid in the flow path A and the filling process are transferred to one end of the flow path A. It has the process to do. The section of the channel A defined by the two intersections defined in the present invention is the intersection of the channel B (third channel 103 in the example) and the channel A (fourth channel 104 in the example). And a section defined by the intersection of the channel C (the first channel 101 in the example) and the channel A (the fourth channel 104 in the example). Here, the intersection and the section defined by the intersection are not strictly defined by the position where each channel is provided, but the type of fluid flowing through the channel, the flow rate, the amount of fluid flowing, and the channel Fluctuates somewhat depending on the cross-sectional area. Therefore, the section defined by the intersection can also be regarded as a section defined by the boundary between the first fluid and the coexistence region 115 of the second and third fluids.

  In the fluid conveyance method of the present invention, the liquids of various combinations are mixed by repeating the above steps (a) -2 to (a) -3 by changing the types of the second liquid and the third liquid. It is possible to send the solution to the analysis unit.

  Further, by changing the ratio of introduction of the second liquid and the third liquid in the (a) -2 step, the mixing ratio of the mixed solution conveyed to the analysis unit 111 in the (a) -3 step can be changed. Is possible.

  In particular, when the Reynolds number is small, the flow is laminar. In this case, in the step (a) -2, the second liquid itself and the third liquid itself are not mixed to form an interface. The component of the second liquid and the component of the third liquid are interdiffused through the interface. The interface position is determined by the ratio of the viscosity of both liquids and the ratio of the amount introduced.

  In the step (a) -3, the volume of the coexistence region 115 of the second liquid and the third liquid conveyed to the analysis unit 111 is the second intersection 108 and the first intersection in the fourth channel. It is equal to the volume of the portion fractionated into the portion 109. Thereby, it is possible to convey a fixed amount of the mixed solution to the analysis unit 111 each time.

  In the step (a) -3, the driving condition of the liquid feeding means 110 is the driving condition in which the first to third valves are closed, that is, the driving in which the flow rate in each valve is equal to or higher than the threshold flow rate of each valve. If it is conditions, there will be no restriction | limiting in particular.

  In the case of a flow with a low Reynolds number, the mixing and reaction of the components of the second liquid and the third liquid in the coexistence region 115 are performed by mutual diffusion in the transport process to the analysis unit 111 in the above step (a) -3. proceed. In order to perform analysis in a state where mixing and reaction are completely completed, mixing and reaction must be completed when the coexistence region 115 reaches the analysis unit 111. For this purpose, the flow path length from the second intersection 109 to the analyzer 111 may be sufficiently long. Further, the first liquid may be fed at a sufficiently low flow rate within the range of the liquid feeding conditions in which the first to third valves are closed.

  Further, the second liquid and the third liquid at the time when the coexistence region 115 reaches the analysis unit 111 by changing the flow rate within the range of the liquid feeding condition in which the first to third valves are closed. It is possible to change the reaction time or mixing time of the liquid. Thereby, it is also possible to analyze the mixing process and reaction process of both liquids.

  Moreover, when analyzing a mixed solution using the fluid conveyance method of this invention, it is not necessary to fill all the flow paths from the junction part of two liquids to an analysis part with a mixed solution. Therefore, when the analysis is performed many times by changing the mixing ratio and the type of the solution to be mixed, the amount of the sample can be saved.

  In the step (a) -2, the same liquid can be used as the second liquid and the third liquid. Thereby, the fluid conveyance apparatus of this invention can be used as a fluid conveyance apparatus which cuts out a fixed amount sample and conveys it to the analysis part 111. FIG.

(Other channel configurations)
As another embodiment, the flow path and valve configuration shown in FIG. 8 can be used. FIG. 8 shows a first channel 101 (channel C), a third channel 103 (channel B), a fourth channel 104 (channel A), and a third channel 103 (channel). B) shows a configuration using another flow path constituted by 801 and 802 connected to B).

  In this case, the second liquid is introduced from the flow path 801 and the third liquid is introduced from the flow path 802 in the step corresponding to (a) -2. The second liquid and the third liquid merge at the intersection 802, and flow through the flow path 103 and the valve 107 in the order of the intersection 109, the intersection 108, the flow path 101, and the valve 105. Other than that, it is possible to cut out the second fluid and the third fluid of the portion divided by the intersection 108 and the intersection 109 and transport them to the analysis unit 111 in the same manner as described above. It is. The configuration described in FIG. 8 has an advantage that the number of valves to be installed is small.

  As yet another embodiment, a flow path and a valve can be configured as shown in FIG. FIG. 9 shows the first channel 101 (channel C), the second channel (channel D), the third channel 103 (channel B), and the fourth channel 104 (channel A). And the structure using the flow path 901 is shown.

  In this case, in the step corresponding to (a) -2 above, when the second liquid is introduced from the flow path 102 and the third liquid is introduced from the flow path 103, both liquids merge at the intersection 109, and The four flow paths 104 flow toward the intersection 108, and at the intersection 108, the flow is divided into the flow paths 101 and 901. The separated liquid is discharged to the outside through the flow path 101 and the flow path 901. Other than that, it is possible to cut out the second fluid and the third fluid of the portion divided by the intersection 108 and the intersection 109 and transport them to the analysis unit 111 in the same manner as described above. It is. In the configuration shown in FIG. 9, when the portion where the second liquid and the third liquid are mixed by mutual diffusion flows out into only the flow channel 101 or the flow channel 901, there is one type in the other flow channel. Only the liquid. Thereby, there exists an advantage that collection | recovery and reuse of a liquid become easy.

  9 is used, in the step corresponding to (a) -2 above, for example, the second liquid is caused to flow from the flow path 101 to the flow path 901 through the intersection 108, and the third liquid. May flow from the flow path 102 to the flow path 104 via the intersection 109. Thereby, in the process corresponding to the above (a) -3, the second liquid in the intersecting portion 108 and the third liquid in the intersecting portion 109 are in contact with each other because the first fluid is in between. It is conveyed to the analysis unit without any problems. In this case, for example, by using a standard sample as the second liquid and also using a sample to be analyzed as the third liquid, there is an advantage that the standard sample and the analysis sample can be analyzed almost simultaneously under the same conditions.

(Explanation of valve)
In the fluid conveyance device applicable to the present invention, as described above, a valve that cuts off the flow when the flow rate exceeds a specific value can be used. The valve has a characteristic that a flow in a specific direction is always allowed to pass regardless of a pressure difference and a flow rate generated before and after the valve due to the flow. FIG. 3 is a schematic view showing an example of such a valve structure. FIG. 3 is merely an example, and the valve may be a valve having a characteristic of blocking the flow when the flow rate of the flow or the pressure difference generated by the flow exceeds a specific value.

  3A is a top view of the valve 300, and FIG. 3B is a cross-sectional view. The flow path in the valve is divided into an area having a thin flow path 303 and an area having thick flow paths 304 and 305. The shielding part is in the shape of a flat plate shown in 301, and the flat plate 301 elastically supported by the spring 302 is installed between the flow paths 304 and 305 so as to be perpendicular to the flow path and at a certain distance from the entrance of the flow path 303. Has been. The diameter of the flat plate 301 is larger than the diameter of the flow path 303. When the flat plate 301 is displaced toward the flow path 303 and reaches the boundary between the flow path 303 and the flow path 305, the fluid flow can be blocked. .

  FIG. 4A shows a path when liquid flows through the valve from the flow path 304 to the flow path 303. In such a flow, while the liquid flows through the flow path 305, a pressure drop corresponding to the flow rate occurs. As a result, a pressure difference is generated between the flow path 304 side and the flow path 305 side on the surface of the flat plate 301. This pressure difference becomes a driving force, and the flat plate 301 is displaced toward the entrance of the flow path 303.

  FIG. 4B shows a case where the flow rate of the liquid from the channel 304 to the channel 305 is lower than the threshold value. The flat plate 301 is displaced by the pressure difference between the flow channel 304 side and the flow channel 305 side, but does not reach the entrance of the flow channel 303 by the restoring force due to the elasticity of the spring 302 that holds the flat plate 301. Therefore, the fluid flows from the flow path 304 to 303 as shown in FIG. When the conveyance of the liquid is stopped, the flat plate 301 returns to the original position by the restoring force of the spring 302.

  On the other hand, FIG. 4C shows a case where the flow rate of the liquid from the flow path 304 to the flow path 303 is equal to or greater than the threshold value. The flat plate 301 is displaced due to a pressure difference between the flow path 304 side and the flow path 305 side, and eventually closes the entrance of the flow path 303. As a result, the fluid flow is blocked by the flat plate 301 as shown in FIG. The flat plate 301 continues to be held in a state where the inlet of the channel 303 is sealed by the pressure of the liquid. When the pressure applied from the flow path 304 side is removed, the flat plate 301 is separated from the entrance of the flow path 303 by the restoring force of the spring 302, and returns to the original position when the liquid transport stops.

  In addition, it is apparent from the structure that this valve always allows the flow from the flow path 303 to the flow path 304 to pass. For this reason, this valve has the same function as the check valve only when the flow rate from the flow path 304 to the flow path 303 is operated at a threshold value or more.

  The threshold flow rate (or threshold pressure difference) of the valve is determined by the spring constant of the spring 302, the distance between the flat plate 301 and the flow path 303, the diameter of the flat plate 301, the diameter of the flow path 303, and the viscosity of the fluid flowing through the valve. This inner spring constant is determined by the length, thickness, number, and material of the spring 302. By optimizing these, a valve having a desired threshold characteristic can be designed. Further, since the flat plate 301 is held by the fluid pressure when the valve is closed, a high sealing effect can be expected and the strength is high.

  Further, when the transport of the liquid is stopped, the flat plate 301 returns to the original position by the restoring force of the spring. Thus, sticking, which is likely to be a problem with the conventional microvalve, that is, the problem that the plate does not return to its original state due to surface tension is unlikely to occur.

  When Sticking is not a problem, the spring constant is weakened so that the flat plate 301 is maintained in the closed state without returning to the original position due to the surface tension even after the liquid is stopped. It is also possible to do. In such a case, it is possible to return the flat plate 301 to the original position by applying pressure from the flow path 303 side. The above can also be realized by shortening the distance between the flat plate 301 and the flow path 303 and reducing the restoring force of the spring in the closed state.

  The material of the spring 302 and the flat plate 301 is preferably, for example, silicon that is resistant to the solution to be analyzed and has some resistance to elastic deformation. It is also possible to use a resin such as silicone. If necessary, the surface may be coated. The other substrates forming the flow path are not particularly limited as long as they are materials resistant to the solution to be analyzed. For example, glass, silicon, silicone resin, etc. are mentioned. In addition, when an electroosmotic flow is used for transporting a liquid, a material that generates the electroosmotic flow can be selected.

  Further, by forming the shielding portion in a flat plate shape and forming a gap between the opposing substrate, a pressure drop occurs when a fluid flows between the gaps, and a pressure difference is generated above and below the shielding portion. Due to this pressure difference, the shielding part moves toward the substrate. Further, the shape of the shielding part is not particularly limited as long as it is a shape capable of shielding the facing opening. A circular shape is particularly preferable from the viewpoint of flow symmetry. In particular, it is preferable to arrange a circular flat plate having the same center as that of the flow path with respect to the flow path having a circular cross section. Thereby, the fluid flow and pressure distribution in the flow path 305 are symmetric with respect to the central axis, and the displacement of the shielding portion can be stabilized.

  The valve shown in FIG. 3 has a configuration in which a flat plate 301 is supported by a spring 302. In the case of such a form, it is also possible to displace the position of the flat plate 301 by deforming only the spring portion without substantially deforming the flat plate. In this case, since the displacement of the flat plate 301 is stabilized, a stable threshold pressure can be obtained. When only the spring 302 is deformed, the spring constant is designed to be small. By making the spring 302 thin and long, the spring constant of each spring becomes small. The spring constant of the entire valve may be reduced by reducing the number of springs. Alternatively, the flat plate 301 may be designed to have a shape that is difficult to deform by increasing the thickness of the flat plate 301.

  Further, by appropriately designing the shapes of the flat plate 301 and the spring 302, both the flat plate and the spring can be deformed. In this case, the spring 302 is designed to have a large spring constant. Or you may make it easy to deform | transform by making a flat plate thin. When both the flat plate and the spring are deformed, the central portion of the flat plate 301 is deformed into a concave shape, and the flow path 303 can be blocked along the outer edge portion. Thereby, improvement in sealing performance can be expected.

  The cross-sectional shape of the spring 302 is not particularly limited. The cross section shown in FIG. 3 may be a rectangular plate shape, a curved shape, or a meandering shape. The thickness of the spring portion may be different from that of the flat plate portion.

  For example, when a circular flat plate having the same center as the flow path is supported in a flow path having a circular cross section, the support position by the spring 302 is preferably a symmetric position with respect to the central axis. Thereby, the pressure distribution in the flow path 305 is symmetric with respect to the central axis, and the displacement of the flat plate is also symmetric. As a result, stable threshold characteristics can be obtained. Also, the sealing performance in the closed state is improved.

  When a flat plate is supported by a plurality of springs, it is preferable in terms of stability of displacement of the flat plate that the flat plates are supported by a plurality of springs having the same spring constant. Further, in this section, the mode in which the shielding portion on the flat plate is elastically supported by the plate spring has been described as an example, but the embodiment of the present invention is not limited to this. For example, like a cantilever beam or a double-supported beam, one end or both ends of the shielding portion may be fixed and elastically supported.

  Hereinafter, the present invention will be described in more detail with reference to examples. Note that the dimensions, shape, material, and manufacturing process conditions in the examples are merely examples, and can be arbitrarily changed as design matters as long as they satisfy the requirements of the present invention.

  In the present embodiment, an example of a liquid transport apparatus applicable to the present invention, in which two kinds of liquids are mixed and a certain amount of mixed solution is cut out and transported, is shown.

  FIG. 5 shows a specific example of the liquid transport apparatus described with reference to FIG. As shown in FIG. 5B, the liquid transport device includes a flow path substrate 501 and a valve substrate 502. FIG. 5A is a plan view of the flow path substrate 501 on which the flow path pattern shown in FIG. 1 is formed, and corresponds to a cross-sectional view taken along line AA ′ in FIGS. 5B and 5C. To do. 5B is a cross-sectional view between BB ′ and B ″ -B ″ ′ in FIG. 5A, and FIG. 5C is between CC ′ in FIG. 5A. A cross-sectional view is shown. In FIG. 5, for the sake of explanation, the thickness of each flow path is emphasized.

  On the flow path substrate 501, a first flow path 503, a second flow path 504, a third flow path 505, and a fourth flow path 506 are formed. Each flow path intersects at a first intersection 507 and a second intersection 508.

  A first valve 509, a second valve 510, and a third valve 511 are formed on the valve substrate 502. Further, through holes 512 to 516 are formed. The through hole 515 is connected to an HPLC pump (not shown) as a liquid feeding means via a tube (not shown). The through hole 516 is connected to an HPLC column (not shown) as an analysis unit via a tube (not shown).

  The example of the dimension of each part is as follows. The channel substrate 501 is made of Pyrex (registered trademark) glass and has a thickness of 500 μm. The main material of the valve substrate 502 is silicon, and its thickness is 700 μm. The width of the flow path formed on the flow path substrate is 100 μm and the depth is 50 μm. The through hole formed in the valve substrate has a diameter of 100 μm. The diameter of the area formed by the thick flow paths in each valve is 300 μm. The flat plate 301 forming each valve has a diameter of 200 μm and a thickness of 5 μm, and the spring 302 has a length of 50 μm, a thickness of 5 μm, and a width of 10 μm. The length of the flow path 305, that is, the distance between the flat plate 301 and the flow path 303 without displacement is 5 μm.

  The threshold flow rate of each valve when water is allowed to flow at room temperature is approximately 60 μl / min.

  The flow path substrate is produced by photolithography and etching with an HF (hydrofluoric acid) solution. The valve substrate is manufactured by processing an SOI (Silicon on Insulator) substrate and a silicon substrate using a micromachining technique and bonding them by a thermal fusion method. The fluid conveyance device shown in FIG. 5 is obtained by bonding the flow path substrate and the valve substrate manufactured as described above by using an anodic bonding method.

  Next, an example in which two types of solutions are mixed and analyzed in the apparatus by HPLC (high performance liquid chromatography) using the apparatus of Example 1 will be described.

  As a mobile phase solution that is the first liquid, a solution (hereinafter referred to as solution A) in which a phosphate buffer and methanol are mixed at 75:25 is prepared. In addition, benzoic acid, salicylic acid, and phenol were dissolved in 100 mM phosphate buffer (pH = 7.0; KH2PO4-Na2HPO4) as the second liquid and third liquid, which are sample solutions to be analyzed. Prepare different types of aqueous solutions (solution B, solution C, and solution D, respectively). Further, as the separation unit, a reverse phase chromatography column using an ODS (octadecylated silica) column is used, and each separated component is detected by an ultraviolet light absorption detector.

  First, analysis is performed using the solution B as the second liquid and the solution C as the third liquid. The procedure is shown below.

  First, the first to fourth flow paths, the first and second intersecting portions, the first to third valves, and the analysis portion are filled with the solution A. That is, the solution A is fed from the through hole 515 at a flow rate of 50 μl / min using an HPLC pump (not shown). Under this liquid feeding condition, since the flow rate in the valves 509 to 511 is less than the threshold flow rate of each valve, each valve remains open. After feeding for a certain time, the flow paths 503 to 506, the valves 509 to 511, and the through holes 512 to 516 are filled with the solution A. After a certain period of time, the solution A is fed from the through hole 515 at a flow rate of 500 μl / min. As a result, the flow rate in the valves 509 to 511 is equal to or higher than the threshold flow rate of each valve, each valve is closed, and the HPLC column (not shown) connected to the through hole 516 is also filled with the solution A. Next, the liquid feeding is stopped, and the valves 509 to 511 are returned to the open state again by releasing the pressure in the fourth flow path using the purge valve of the HPLC pump. In this state, the first to fourth flow paths, the first and second intersecting portions, the first to third valves, and the analysis portion are filled with the solution A, and the first to third valves are opened. It is in a state.

  Next, a syringe pump (not shown) is connected to the through hole 513 and the through hole 514 via a tube (not shown). Using the syringe pump, the solution B is sent from the through hole 513 and the solution C is sent from the through hole 514 at a flow rate of 25 μl / min. Under this liquid feeding condition, since the flow rate flowing through the first valve 509 is less than the threshold flow rate, the first valve 509 remains open. Since the flow flowing through the second valve 510 and the third valve 511 can always pass, the second valve 510 and the third valve 511 remain open. As shown in FIG. 2B, the solution B and the solution C merge at the second intersecting portion 508 (109), and the second intersecting portion and the first intersection in the fourth channel 506 (104). It flows through the portion fractionated by the intersecting portion, flows into the first flow path 503 (101) at the second intersecting portion, and is discharged out of the apparatus through the through hole 512.

  Next, the solution A is fed from the through hole 515 at a flow rate of 500 μl / min using an HPLC pump (not shown). The flow rate in the valves 509 to 511 is equal to or higher than the threshold flow rate of each valve, and each valve is immediately closed. As shown in FIG.2 (c), it was in the part fractionated by the 2nd crossing part 508 (109) and the 1st crossing part 507 (108) among the 4th flow paths 506 (104). Solution B and solution C are cut out and conveyed to an HPLC column (not shown) while mixing by mutual diffusion.

  Next, each component separated by the HPLC column is detected by an ultraviolet light absorption detector. The wavelength of the ultraviolet light is 280 nm. As a result, two distinct output signal peaks based on the difference in elution time between benzoic acid and salicylic acid can be obtained.

  Similarly, the solution B is used as the second liquid, and the solution D is used as the third liquid, and the two solutions are mixed, transported, separated, and detected. As a result, two distinct output signal peaks based on the difference in elution time between benzoic acid and phenol can be obtained.

  Similarly, the solution C is used as the second liquid, and the solution D is used as the third liquid, and the two solutions are mixed, transported, separated, and detected. As a result, two distinct output signal peaks based on the difference in elution time between salicylic acid and phenol can be obtained.

  Next, an example will be described in which the two types of solutions are mixed in the apparatus at different mixing ratios and analyzed by HPLC (high performance liquid chromatography) using the apparatus of Example 1.

  As a mobile phase solution that is the first liquid, a solution (solution A) in which a phosphate buffer and methanol are mixed at 75:25 is prepared. As a second liquid, an aqueous solution (solution B) in which benzoic acid is dissolved in a 100 mM phosphate buffer (pH = 7.0; KH2PO4-Na2HPO4) is prepared. As a third liquid, an aqueous solution (solution C) in which salicylic acid is dissolved in a 100 mM phosphate buffer (pH = 7.0; KH2PO4-Na2HPO4) is prepared. Further, as the separation unit, a reverse phase chromatography column using an ODS (octadecylated silica) column is used, and each separated component is detected by an ultraviolet light absorption detector.

  First, as in Example 2, the first to fourth flow paths, the first and second intersecting portions, the first to third valves, and the analysis portion are filled with the solution A.

  Next, in the same procedure as in Example 2, the solution B is fed from the through hole 513 at a flow rate of 10 μl / min, and the solution C is fed from the through hole 514 at a flow rate of 40 μl / min. Under this liquid feeding condition, since the flow rate flowing through the first valve 509 is less than the threshold flow rate, the first valve 509 remains open. Since the flow that flows through the second valve 510 and the third valve 511 is always in a passable direction, the second valve and the third valve remain open. As shown in FIG. 2B, the solution B and the solution C merge at the second intersection 508 (109), and the second intersection 508 (109) of the fourth channel 506 (104). ) And the first intersection 507 (108), flows into the first flow path 503 (101) at the first intersection, and is discharged out of the apparatus through the through hole 512.

  Next, the solution A is fed from the through hole 515 at a flow rate of 500 μl / min using an HPLC pump (not shown). The flow rate in the valves 509 to 511 is equal to or higher than the threshold flow rate of each valve, and each valve is immediately closed. As shown in FIG.2 (c), it was in the part fractionated by the 2nd crossing part 508 (109) and the 1st crossing part 507 (108) among the 4th flow paths 506 (104). Solution B and solution C are cut out and conveyed to an HPLC column (not shown) while mixing by mutual diffusion.

  Next, each component separated by the HPLC column is detected by an ultraviolet light absorption detector. The wavelength of the ultraviolet light is 280 nm. As a result, two distinct output signal peaks based on the difference in elution time between benzoic acid and salicylic acid can be obtained.

  In this state, the valves 509 to 511 are returned to the open state again by releasing the pressure in the fourth flow path using the purge valve of the HPLC pump. Next, the solution B is fed from the through hole 513 at a flow rate of 20 μl / min, and the solution C is fed from the through hole 514 at a flow rate of 30 μl / min, and the solution B and the solution B are mixed, conveyed, separated, and detected.

  Hereinafter, the peak intensity based on the ratio of the introduction amount of the solution B and the solution C is changed by changing the introduction amount of the solution B and the solution B and performing mixing, transporting, separation, and detection by the same procedure. You can see the changes.

It is a conceptual diagram which shows one Embodiment of the fluid conveying apparatus applicable to this invention. It is a conceptual diagram which shows one Embodiment of the fluid conveyance method of this invention. It is a conceptual diagram which shows one Embodiment of the valve | bulb driven by the fluid flowing. It is a conceptual diagram which shows the process which a valve drives with the pressure difference which arises when a fluid flows. It is a conceptual diagram which shows the Example of the liquid conveying apparatus applicable to this invention. It is a conceptual diagram which shows the conventional liquid conveying method. It is a conceptual diagram which shows the conventional liquid conveying method. It is a conceptual diagram which shows one Embodiment of the fluid conveying apparatus applicable to this invention. It is a conceptual diagram which shows one Embodiment of the fluid conveying apparatus applicable to this invention.

Explanation of symbols

101 First channel (channel C)
102 Second channel (channel D)
103 3rd flow path (flow path B)
104 Fourth channel (channel A)
105 1st valve 106 2nd valve 107 3rd valve 108 1st crossing part 109 2nd crossing part 110 Liquid feeding means 111 Analysis part 112 1st liquid 113 2nd liquid 114 3rd liquid 115 Region of coexistence of second liquid and third liquid 300 Valve 301 Flat plate 302 Spring 303, 304, 305 Channel 501 Channel substrate 502 Valve substrate 503 First channel 504 Second channel 505 Third channel 506 Fourth flow path 507 First intersecting portion 508 Second intersecting portion 509 First valve 510 Second valve 511 Third valve 512, 513, 514, 515, 516 Through hole 601, 602, 604 Flow Path 603 Junction section 605 Analytical means 701 Sampling valve 702 Pressure source 703 HPLC column 704 Sample loop flow path 05 analytical channel 706 liquid samples 801, 802, passage 803 intersecting portion 901 flow passage 902 valve

Claims (5)

A fluid transport method using a fluid transport device comprising a flow path for flowing a fluid and a valve for controlling the flow of the fluid located in the middle of the flow path,
Fluid flow having a flow path A and at least two flow paths B and C each having one end connected to the flow path A, and having the valve in the middle of each of the flow paths B and C The process of preparing the device,
Introducing a first fluid into the channel A, the channel B and the channel C;
At least one of the second fluid and the third fluid is introduced from one end of the channel B to the other end connected to the channel A, and only the one fluid is introduced from one end of the channel B. In this case, the other fluid is introduced from another channel D having one end connected to channel A separately from channel B and channel C, and the intersection of channel B and channel A Filling the section of the flow path A defined by the intersection of C and the flow path A with the second fluid and the third fluid;
And transferring the first and second fluids in the flow path A to one end of the flow path A, the second and third fluids filling the section of the flow path A defined by the two intersections,
A liquid conveying method characterized by comprising:   The valve operates according to a pressure difference generated between an upstream side and a downstream side of the valve when a fluid flows through the flow path provided with the valve, and the pressure difference is a predetermined value. 2. The fluid conveyance method according to claim 1, wherein when the pressure difference is less than the value, the valve allows the fluid to pass therethrough, and when the pressure difference is equal to or greater than a predetermined value, the fluid flow is interrupted.   When the fluid flows in a predetermined direction, the valve passes the fluid. When the fluid flows in a direction opposite to the predetermined direction, the valve passes the fluid when the pressure difference is less than the predetermined value. 3. The fluid conveying method according to claim 2, wherein when the value is equal to or greater than a predetermined value, the fluid is blocked.   After introducing the second and third fluids into the channel C, the step of conveying the second and third fluids filling the section of the channel A defined by the two intersections to one end of the channel A The fluid conveying method according to claim 1, wherein: Both the second and third fluids introduced from the flow path B to the flow path A pass through another flow path connected to the end of the flow path B opposite to the end connected to the flow path A. The fluid conveyance method according to claim 1, wherein the fluid conveyance method is introduced into the flow path B.

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