JP2010044006A - Microdispenser - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compact microdispenser that can efficiently and accurately measure a minute amount of a sample inside a chip and transport it to a target chip. <P>SOLUTION: The microdispenser includes: a micro dispensing chip having a sample introduction tube for introducing a fluid sample, a sample dispensing tube for dispensing the sample, and a sampling and leading-out tube for introducing a predetermined amount of a sample through the sample introduction tube according to a reduced pressure and selectively leading out the introduced sample to any one of a plurality of sample dispensing tubes according to an applied pressure; a micro multi-directional switching valve chip having a selective release tube driven in a latching manner so as to selectively open one of the sample dispensing tubes to the atmosphere; and a pressure-switching micro-pump chip having a pump selecting tube driven in a latching manner so as to alternately connect the opening ends of a suction port and an exhaust port of a micro-pump with the sampling and leading-out tube. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a micro-dispensing device capable of dividing a micro-scale fluid into multi-branches and multi-scales (nL to μL).

  Micro Total Analysis System (hereinafter referred to as “μ-TAS”) developed rapidly mainly in Europe and the United States, and in the 1990s, DNA chips, protein chips, microchip electrophoresis, etc. were developed and marketed for custom-made medicine. There are great expectations. However, at present, only the micro flow path is used for the reaction field / analysis field, and the entire apparatus has become large as a whole. Even if a chip is used for analysis, there are many cases where complicated steps are required for sample injection or the like. These problems are one of the causes that μ-TAS is not widely used. For this reason, there is a great need for a small device for handling microfluids for the development of analytical devices for personal use, hospitals, corporate laboratories and the like.

  Naturally, many research and development examples of micropumps and microvalves alone have been reported so far. However, many of these reports are seed-oriented and few are developed in needs-oriented. For this reason, it is not suitable for the use which cuts out the microscale fluid sample into a fixed quantity, and injects it in a chip. On the other hand, commercially available microinjectors that can be injected in the order of submicroliters (μL) are known. However, the microinjector has a problem of dead volume at the time of introduction of the flow path in addition to the problem that the whole apparatus becomes large. Therefore, there is a great need for microfluidic control devices that can be measured and transported within the chip.

As a research report for introducing a sample in a chip, there is a method using a cross-shaped microchannel. However, in the case of this means, there is a problem that reproducibility is low due to the influence of flow velocity distribution and residual pressure. There are also problems such as the presence of a sample that is wasted for each dispensing and the sequential control of a plurality of actuators in parallel. As such a prior art, there exist a thing like patent document 1 and patent document 2. FIG.
JP-A-11-271273 International Publication Number WO2005 / 033713

  Accordingly, an object of the present invention is to provide a small micro-dispensing device that can accurately measure and dispense a small amount of sample in a chip without waste.

  As means for solving the above problems, the following inventions are provided.

  The first aspect of the present invention is a micro-dispensing device comprising a micro multi-branch switching valve chip, a micro-dispensing chip, and a pressurizing / depressurizing switching micro-pump chip. Connected to a sample introduction tube having an introduction port and a check valve, a sample dispensing tube composed of a plurality of tubes for dispensing a sample, a sample introduction tube, a sample dispensing tube, and a pressure-reducing / switching micropump Then, a predetermined amount of sample is introduced from the sample introduction tube according to the reduced pressure from the pressure-increasing / decreasing switching micro pump chip, and a predetermined amount of sample introduced according to the pressurization from the increasing / decreasing switching micro-pump chip is sampled. A sampling outlet tube for selectively extruding to any one of the plurality of pipes of the injection tube; A micropump for switching pressure-increasing pressure, having a selective open pipe that is latch-driven to selectively connect with one of the plurality of pipes and opens the inside of the sample dispensing pipe through the connected pipe to the atmosphere. The chip has a suction port with a check valve and a discharge port with a check valve, is driven by an external power source and repeats suction and discharge, an opening end of the suction port, and an opening of the discharge port A micro-dispensing device is provided having a pump selection tube that is latch-driven to alternately connect an end with the sampling outlet tube.

  The second invention is based on the first invention, and further includes a sampling detection sensor for detecting that a sample has been introduced into a predetermined position of the sampling lead-out tube, and according to detection of sample introduction by the sampling detection sensor. A micro-dispensing device having a first pump selection pipe drive unit that latch-drives the pump selection pipe of the pressure-intensification switching micro pump chip is provided.

  The third invention is based on the first invention or the second invention, and further includes a dispensing detection sensor for detecting that a sample has been dispensed at a predetermined position of the sample dispensing tube, and a dispensing detection sensor. Provided is a micro-dispensing device having a second pump selection pipe driving section that latch-drives the pump selection pipe of a pressure-intensification switching micro pump chip in response to detection of sample dispensing.

  The fourth invention is based on any one of the first invention to the third invention, and the micro multi-branch switching valve chip, the pressurization / depressurization switching micro pump chip and the micro dispensing chip of the micro dispensing device can be separated and assembled. The used micro-dispensing tip is replaced with a new micro-dispensing tip, and the micro multi-branch switching valve tip and the pressurizing / depressurizing switching micro-pump tip can be used repeatedly. To do.

  With the micro-dispensing device of the present invention, it is possible to accurately measure and dispense in a micro order without waste using only a small amount of sample.

  Further, since this device is a small device, it is excellent in portability, enables real-time analysis even on site, and is expected to dramatically expand the application range of μ-TAS.

  Furthermore, it is expected to be applied to a wide range of applications such as portable health care devices such as blood tests and portable environmental analysis devices.

Hereinafter, the best mode for carrying out the present invention will be described in detail with reference to the drawings. In addition, this invention is not limited to these embodiment at all, and can be implemented with various aspects in the range which does not deviate from the summary.
<Overview>

  A schematic diagram of the micro-dispensing device of the present embodiment is shown in FIG. As shown in the figure, the micro-dispensing device of this embodiment includes a “micro-dispensing chip” (0110), a “micro multi-branch switching valve chip” (0120), and a “pressure-intensification switching micro-pump chip” (0130). ), And these chips can be easily separated and assembled.

  The outline of the flow of processing is as follows.

  First, the micropump (0132) is pumped in a state where the pump selection pipe (0131) of the pressure-intensification switching micropump chip (0130) is connected to the suction port (0133) of the micropump (0132). The pumping operation in such a state is an operation for depressurizing the inside of the micro-dispensing tip (0110) connected to the pressurizing / depressurizing switching micro pump tip (0130).

  Then, a fluid sample is introduced into the sample introduction tube (0112) from the introduction port (0111) of the micro-dispensing tip (0110). When the pumping of the micro pump (0132) is continued thereafter, the fluid sample introduced into the sample introduction pipe (0112) moves into the sampling outlet pipe (0113) connected to the sample introduction pipe (0112). .

  Then, when the sampling detection sensor (0141) detects that the fluid sample has passed a predetermined position in the sampling outlet pipe (0113), the pump of the pressure increasing / decreasing pressure switching micro pump chip (0130) is triggered by the detection. The selection tube (0131) is latch-driven so as to be connected to the discharge port (0134) of the micropump (0132). By the switching, the pumping operation of the micro pump (0132) is switched to an operation of pressurizing the inside of the micro dispensing tip (0110).

  When the pumping of the micro pump (0132) is continued thereafter, only the fluid sample located in the sampling outlet pipe (0113) is pushed out in the direction of the sample dispensing pipe (0114). At this time, a plurality of divided pipes of the sample dispensing pipe (0114) are opened to the atmosphere by the micro multi-branch switching valve chip (0120), and the other pipes are closed. It has become. Therefore, the fluid sample pushed in the direction of the sample dispensing pipe (0114) selectively moves into the pipe (0114A) that is open to the atmosphere.

  Thereafter, when a dispensing detection sensor or the like (not shown) detects that the fluid sample has been dispensed at a predetermined position of the sample dispensing tube (0114), it is used as a trigger for the pressure-intensification switching micro pump chip (0130). The pump selection pipe (0131) is latch-driven so as to be connected to the suction port (0133) of the micropump (0132). By this switching, the pumping operation of the micropump (0132) is switched to an operation of depressurizing the inside of the microdispensing tip (0110).

  If the pumping operation is continued thereafter, the above process is repeated.

Since the micro-dispensing device of the present embodiment having the functions as described above can be reduced in size, it is excellent in portability and can perform on-site real-time analysis. For reference, an image using the micro-dispensing device of the present embodiment is shown in FIG. The micro-dispensing device of the present embodiment can be downsized to the extent shown in the drawing, and thus is very convenient. In addition, FIG. 17 is a utilization image to the last, and the implementation example of the micro dispensing apparatus of the present embodiment is not limited to the shape of the micro dispensing apparatus in the drawing.
<Functional configuration>

  As shown in FIG. 1, the micro-dispensing device of this embodiment includes a “micro-dispensing tip” (0110), a “micro multi-branch switching valve tip” (0120), and a “pressure-intensification switching micro-pump tip” (0130). ).

Hereinafter, each functional configuration will be described in detail. In the following, the “micro pipetting tip”, “micro multi-branch switching valve chip”, “pressure-intensifying switching micro pump chip”, “tubes of those components”, “ The shape, length, thickness and the like of the “housing” are merely examples, and are not limited to those shown in the drawings unless otherwise specified.
<< Micro dispensing tip (0110) >>

As shown in FIG. 2, the “micro dispensing tip” includes a “sample introduction tube” (0212), a “sample dispensing tube” (0214), a “sampling derivation tube” (0213), and the like.
<<< Sample introduction tube (0212) >>>

  The “sample introduction pipe” (0212) is configured to include an introduction port (0211) for introducing a fluid sample and a check valve (0215).

  The configuration of the inlet (0211) (open end diameter, material, etc.) is not particularly limited, and can be arbitrarily designed using conventional techniques according to the type and characteristics of the fluid sample to be introduced. .

  The check valve (0215) is not particularly limited in configuration. For example, it is formed of a silicon rubber alone, and has a hat-hat shape as shown in FIG. 3, and has one slit (0301) that divides into two. It may be. Such a check valve can be manufactured using molding.

  4A and 4B show the operation of the check valve in FIG. 4A and 4B are cross-sectional views showing a state where the check valve (0402) is embedded in the pipe (0401). FIG. 4A shows a state in which the fluid is moving from the bottom to the top in the pipe (0401). FIG. 4B shows the inside of the pipe (0401). FIG. 3 shows a state in which the fluid is moving from top to bottom in the figure. In FIG. 4A, the fluid that has moved from the bottom to the top in the figure applies a force in the direction to open the slit of the check valve (0402). On the other hand, in FIG. 4B, the fluid that has moved from the top to the bottom in the drawing applies a force in the direction of closing the slit of the check valve (0402). As a result, the hat-hat-shaped check valve (0402) operates as shown in FIGS. 4A and 4B to allow the fluid to pass only in one direction.

  Here, for reference, the opening pressure of a hat-hat-shaped check valve having a size as shown in FIG. 3 (height: about 1 mm to 1.5 mm) is about 3.0 ± 0.4 kPa on average. . The pressure resistance is about 300 kPa. These values are almost the same due to the difference in check valve height, and there is almost no performance variation.

As shown in FIG. 2, the check valve (0215) provided in the sample introduction pipe (0212) is only in the direction from the introduction port (0211) to the sampling outlet pipe (0213) (indicated by an arrow in the figure). Attached to allow fluid to pass through.
<<< Sample dispensing tube (0214) >>>

  The “sample dispensing tube” (0214) is composed of a plurality of divided tubes for dispensing a sample (the number of divided tubes is an arbitrary design matter). The sample dispensing tube (0214) is connected to the sampling derivation tube (0213) as shown in FIG.

Here, the plurality of open ends of the plurality of sample dispensing tubes (0214) are all closed when the sampling outlet tube (0213) is depressurized by the pressure-increasing / decreasing pressure micropump chip, and sampling is derived. When the pipe (0213) is pressurized by the pressurization / depressurization switching micro pump chip, only the open end of one pipe is open to the atmosphere. The above configuration can be realized by a “micro multi-branch switching valve chip” described below. Details will be described below.
<<< Sampling tube (0213) >>>

  The “sampling lead-out pipe” (0213) is connected to the sample introduction pipe (0212), the sample dispensing pipe (0214), and the pressure-intensification switching micro pump chip. Then, a predetermined amount of sample is introduced from the sample introduction pipe (0212) in accordance with the depressurization from the pressure increasing / decreasing switching micro pump chip, and the sample is introduced according to the pressurization from the increasing / decreasing pressure switching micro pump chip. Is selectively pushed out to any one of the plurality of tubes of the sample dispensing tube (0214).

  Here, in FIG. 5A, when the sampling outlet tube (0513) is depressurized by the pressurization switching micropump chip (hereinafter referred to as “depressurized state”), The flow is indicated by arrows.

  In the reduced pressure state, as described above, the open ends of all the tubes of the sample dispensing tube (0514) are closed. Therefore, in the tube of the micro-dispensing tip, the atmosphere is sucked only from the inlet (0511) of the sample introduction tube (0512) that is open to the atmosphere, and a flow as indicated by the arrows in the figure is generated. That is, when a fluid sample is sucked from the inlet (0511) in a reduced pressure state, the sample moves in a flow as indicated by arrows in the figure. In the figure, the dotted arrow next to the check valve indicates the passing direction allowed by the check valve (the same applies to other drawings).

  Further, in FIG. 5B, when the sampling outlet pipe (0513) is pressurized by the pressurization / depressurization switching micropump chip (hereinafter referred to as “pressurized state”), the microdispensing chip is discharged into the pipe. The flow is shown by arrows.

  In the pressurized state, as described above, among the plurality of tubes of the sample dispensing tube (0514), only the open end (0514A) of one tube is open to the atmosphere, and the open ends of the other tubes are closed. It has become. In the pressurized state, the inlet (0511) of the sample introduction pipe (0512) is closed by the action of the check valve (0515). Therefore, in the tube of the micro-dispensing chip, the air in the tube is exhausted only from the open end (0514A) of one tube of the sample dispensing tube (0514) that is open to the atmosphere, and a flow as shown by the arrow in the figure is generated. . That is, in the pressurized state, the fluid sample existing in the sampling outlet pipe (0513) moves in a flow as indicated by an arrow.

  Here, as a means for the sampling lead-out pipe (0513) to introduce only a “predetermined amount” of sample from the sample introduction pipe (0512), for example, “sampling detection sensor” (0541) and “first pump selection pipe” It can be realized by a functional configuration of a “driving unit” (not shown). Details will be described below.

  The switching between the pressurized state and the reduced pressure state in the sampling outlet pipe (0513) is realized by a functional configuration of a “pressurizing / depressurizing switching micropump chip” (not shown) connected to the sampling outlet pipe (0513). can do. Details will be described below.

  << Micro multi-branch switching valve chip (0120) >>

  The micro multi-branch switching valve chip (see FIG. 1: 0120) is configured to have a selective open tube (0125). The selective open tube (0125) is latch-driven so as to be selectively connected to one of the plurality of tubes of the sample dispensing tube (0114) (0114A), and the sample distribution tube is connected via the connected tubes. The inside of the pipe (0114A) is open to the atmosphere.

  FIG. 6 shows a conceptual diagram of a micro multi-branch switching valve chip. As shown in the figure, the micro multi-branch switching valve chip is provided with one exhaust port (0622) at the approximate center of the octagonal portion of the housing (0621). The connection port (0623) connected with the some pipe | tube of a sample dispensing pipe | tube is provided on the top (the number of some connection ports is arbitrary design matters). A rotor (0624) is incorporated in the housing (0621), and the exhaust port (0622) and one connection port (0623) are selectively connected in the rotor (0624). An "open tube" (0625) is provided. A solenoid (0626) for rotating the rotor (0624) is provided in the housing (0621). FIG. 6 is a conceptual diagram simply showing the rotor (0624) and the like so that it can be easily grasped.

  Next, FIGS. 7A and 7B are conceptual diagrams for explaining the rotational drive of the rotor (0624 in FIG. 6). The figure is a transparent diagram in which only a part of the micro multi-branch switching valve chip is extracted for easy understanding. FIG. 8 shows a cross-sectional view of the micro multi-branch switching valve chip of FIGS. 7 (A) and 7 (B).

  As shown in FIGS. 7A and 7B, the micro multi-branch switching valve chip has one exhaust port (0722) in the approximate center of the housing (0721) and a plurality of connection ports (0723) on the circumference thereof. Is provided. The rotor (0724) incorporated in the housing (0721) is provided with a “selective open pipe” (0725) for selectively connecting the exhaust port (0722) and one connection port (0723). It has been. That is, when the rotor (0724) is rotated by aligning the centers of the rotor (0724) and the housing (0721), the selective open pipe (0725) is rotationally driven and connected to the exhaust port (0722) (0723). ) Will be switched.

  Here, the rotation of the rotor (0724) can be realized by pushing the solenoid. In such a case, it is desirable to provide the rotor (0724) with a gear (0727) so as to effectively receive the pushing force of the solenoid push rod (0726). Further, the rotation angle of the rotor (0724) by one stroke of the push rod (0726) of the solenoid is made constant, and after one stroke, one end of the selective release pipe (0725) is connected to one connection port (0723). It is desirable to use a gear corresponding to the connection port so that it can be connected.

  When configured in this manner, as shown in FIG. 7A, when the push rod (0726) of the solenoid pushes one tooth of the gear (0727) and the rotor (0724) rotates by a predetermined angle, FIG. ), The tooth next to the tooth pushed in the gear (0727) pushes the push rod (0726) upward in the figure, and the push rod (0726) is disengaged from the gear (0727). . With this configuration, even if the pushing amount by the solenoid is not controlled, the rotation angle of the rotor (0724) by one stroke of the solenoid push rod (0726) is always constant, and the solenoid push rod (0726) is rotated once. After this stroke, one end of the selective open tube (0725) is positioned to be connectable with one of the connection ports (0723).

  A positioning mechanism is provided that corrects the position of one end of the selective release pipe (0725) after one stroke of the solenoid push rod (0726) to an accurate position that can be connected to one connection port (0723). It may be. As such a positioning mechanism, for example, as shown in FIGS. 7 and 8, a rotor (0724, 0824) is provided with a storage chamber for storing steel balls (0728, 0828). Then, silicon rubber springs (0729, 0829) are arranged in the storage chamber so that the steel balls (0728, 0828) are always pushed outward from the center of the rotor (0724, 0824). , 0828). Further, grooves (072A, 082A) into which the steel balls (0728, 0828) are fitted are provided in the housing (0721, 0821) at predetermined intervals. The groove (072A, 082A) comes to a position where one end of the selective release pipe (0725, 0825) is just connected to one of the connection ports (0723, 0823) when the steel ball (0728, 0828) is fitted. It is provided as follows. Further, the shape of the groove (072A, 082A) makes it possible to correct the position appropriately even when the rotor (0724, 0824) rotates slightly or not enough. It has become.

  Here, as shown in FIG. 8, silicon rubber (082B) is embedded as a sealing material in the exhaust port (0822) and the connection port (0823) of the housing (0821), and a pressure spring is provided above the rotor (0824). (082C) is provided and the rotor (0824) is pushed into the housing (0821) (from the top to the bottom in the figure), so that the exhaust port (0822), the connection port (0823), and the rotor (0824) are provided. You may make it improve adhesiveness with a selective open pipe (0825). Thereby, a liquid leak can be prevented effectively. Further, the other connection port (0823) that is not connected to the exhaust port (0822) is completely closed when the rotor (0824) is pushed in.

  In FIG. 8, the steel ball (082D) disposed between the housing (0821) and the rotor (0824) has a function of aligning the center positions of the housing (0821) and the rotor (0824).

  << Relationship between micro dispensing tip (0110) and micro multi-branch switching valve tip (0120) >>

  Each of the plurality of tubes of the sample dispensing tube (0214) of the micro dispensing tip (see FIG. 2) has a plurality of connection ports (which are provided in the housing (0621) of the micro multi-branch switching valve chip (see FIG. 6)). 0623). And the exhaust port (0622) provided in the housing (0621) of the micro multi-branch switching valve chip (see FIG. 6) is open to the atmosphere.

  With this configuration, the micro multi-branch switching valve chip (see FIG. 6) is connected to the connection port (0623) connected to the exhaust port (0622) via the selective open pipe (0625) provided in the rotor (0624). One of the sample dispensing tubes (FIG. 2: 0214) is open to the atmosphere. In this case, as a matter of course, the other connecting port (0623) is not connected to the exhaust port (0622), so that the open end of the pipe connected to the connecting port (0623) is closed.

  In addition, instead of connecting a plurality of sample dispensing tubes (FIG. 2: 0214) to all the connection ports (0623) of the micro multi-branch switching valve chip (see FIG. 6), every other sample dispensing tube is connected. You may comprise so that the several pipe | tube (FIG. 2: 0214) may be connected. A conceptual diagram of this configuration is shown in FIG.

  In such a case, when the selective open pipe (1525) is latch-driven by a predetermined angle by the rotational drive of the rotor of the micro multi-branch switching valve chip, the selective open pipe (1525) is “one of the sample pipes of the micro pipette tip. The configuration is such that “connect to one tube” → “not connect to any” → “connect to one tube” → “not connect to any”.

In other words, the sample dispensing tube of the micro-dispensing tip is “all tubes open end closed” → “one tube open to the atmosphere” → “all tubes open end closed” → “one tube open” “Only open to the atmosphere” is repeated.
<< Pressurization switching micro pump chip (0130) >>

As shown in FIG. 1, the pressurization / depressurization switching micro pump chip (0130) is configured to have a micro pump (0132) and a pump selection pipe (0131).
<<< Micro pump >>>

  As shown in the conceptual diagram of FIG. 9, the “micropump” includes a suction port (0933) having a check valve (0935) and a discharge port (0934) having a check valve (0935). It is driven by a power source (not shown) and configured to repeat suction and discharge.

  Here, the configuration of the check valve (0935) is not particularly limited. For example, a hat-hat-shaped check valve as shown in FIG. 3 may be used.

  Moreover, although it does not restrict | limit especially as an external power source, For example, you may comprise with a drive unit as shown in FIG. The drive unit of FIG. 16 is configured such that when the user rotates the wheel with a finger or the like, the force is transmitted from “worm” → “worm wheel” → “cam” and the “piston rod” moves up and down. Yes. Then, the vertical movement of the piston rod causes the membrane (0936 in FIG. 9) made of rubber or the like to move up and down, and the micropump repeats suction and discharge.

  The “pump selection pipe” (0931) is latch-driven so that the opening end of the suction port (0933) and the opening end of the discharge port (0934) of the micro pump are alternately connected to the connection port (0938). It is configured as follows. Here, the connection port (0938) is connected to the sampling outlet tube of the micro-dispensing tip. That is, the pump selection pipe (0931) is latch-driven so as to connect the opening end of the suction port (0933) of the micro pump and the opening end of the discharge port (0934) alternately with the sampling outlet pipe of the micro dispensing tip. Is equivalent to

  The configuration is based on the configuration of the “micro multi-branch switching valve chip” (see FIG. 6) described above. The number of connection ports (0623) provided in the housing (0621) (arbitrary design matters) The configuration of the “pipe (0625) for connecting the connection port (0623) and the exhaust port (0622)” provided in the above can be realized by appropriately modifying.

  Specifically, as shown in FIGS. 9 and 10, the rotor is provided with ten connecting ports (0937 and 1037) arranged concentrically. The connection ports (0937, 1037) are selectively connected to the suction port (0933) or the discharge port (0934) of the micropump. Of the 10 connecting ports (0937, 1037), 5 connecting ports (0937, 1037) are connected to the center of the rotor by 5 pump selection pipes (0931, 1031). (0938, 1038). The remaining five connection ports (0937) are opened to the atmosphere by a pipe (1039) provided so as to penetrate the rotor.

  As shown in FIG. 10, the ten connecting ports (1037) are alternately connected to the connecting port (0938) and opened to the atmosphere. As a result, as shown in FIG. 9, the suction port (0933) and the discharge port (0934) of the micro pump are connected to two adjacent connection ports (0937) in the 10 connection ports (0937). In this case, one of the suction port (0933) and the discharge port (0934) of the micro pump is always opened to the atmosphere, and one of them is connected to the connection port (0938) provided in the center of the rotor. .

For reference, an example of realization of a pressurization / reduction switching micropump chip is shown in FIG. Note that the principle of latch driving of the pressure increase / decrease switching micropump chip is the same as that of the micro multi-branch switching valve chip, and a detailed description thereof will be omitted here.
<< Relationship between Micro Dispensing Tip (0110) and Pressurized / Depressurized Switching Micro Pump Tip (0130) >>

  As shown in FIG. 1, the connection port (0138) provided at the center of the rotor of the pressurization / decompression micropump chip (0130) is connected to the sampling outlet pipe (0113) of the micro-dispensing chip (0110).

  Therefore, when the pumping is performed in a state where the suction port (0133) of the micro pump (0132) is connected to the connection port (0138) at the center of the rotor, the inside of the tube of the micro dispensing tip (0110) is in a reduced pressure state.

  On the other hand, when the pumping is performed in a state where the discharge port (0134) of the micropump (0132) is connected to the connection port (0138) at the center of the rotor, the inside of the microdispensing tip (0110) is pressurized.

That is, by rotating the rotor of the pressurization switching micropump chip (0130) and switching the micropump ports (suction port, discharge port) connected to the sampling outlet tube (0113) of the micro-dispensing chip (0110), The pressurization state / depressurization state in the tube of the micro-dispensing tip (0110) can be switched.
<< Sampling detection sensor and first pump selection pipe drive >>

  As shown in FIG. 1, the “sampling detection sensor” (0141) is installed at a predetermined position of the sampling outlet tube (0113) of the micro-dispensing tip (0110), and the sample is placed at a predetermined position of the sampling outlet tube (0113). It is configured to detect that it has been installed.

  The phrase “installed at a predetermined position of the sampling outlet tube (0113) of the micro dispensing tip (0110)” means that the sampling detection sensor (0141) is configured as a part of the micro dispensing tip (0110). It is not a thing. That is, the sampling detection sensor (0141) and the micro-dispensing chip (0110) are different components, and are configured to be separately separated and assembled.

  Here, the sampling detection sensor (0141) is not particularly limited as a means for detecting the introduction of fluid, but in the case of the present embodiment, it is necessary to detect a very small amount of fluid with high sensitivity. Therefore, for example, the following means using LEDs and photodiodes may be used.

  Specifically, the light emitted from the LED is detected by a photodiode, but detection is performed by using a change in the refractive index of the tube surface when a fluid is present in the tube.

  FIG. 12 shows a microfluidic detection experiment chip. This is manufactured using PDMS, which is easy to manufacture, and consists of an upper device in which an optical fiber is embedded at an angle of 45 degrees with respect to a channel having a side of 300 μm, and a lower device in which a photodiode is embedded. The two are used in a superimposed manner.

  Next, the detection experiment results are shown in FIG. When no fluid is present in the flow path, the photodiode cannot detect light because the optical fiber is installed at a position where the photodiode is not irradiated with light, and the output waveform indicates 5 V (FIG. 13 ( A)). On the other hand, when a fluid is present in the flow path, the refractive index of the flow path surface changes, the light is refracted and detected by the photodiode, and the output waveform shows 0 V (FIG. 13B). .

  From the experimental results, it can be seen that a trace amount of fluid can be detected with high sensitivity by using the means.

  The “first pump selection pipe drive unit” (see FIG. 1: not shown) is configured to select the pump selection pipe of the pressure-intensification switching micro pump chip (0130) in response to detection of sample introduction by the sampling detection sensor (0141). (0131) is latch-driven.

  That is, when the sampling detection sensor (0141) detects the introduction of the sample, the first pump selection pipe driving unit triggers the pump selection pipe (0131) of the pressure increase / decrease switching micro pump chip (0130) at a predetermined angle. Latch drive. Specifically, when a sample introduction detection signal is received from the sampling detection sensor, the solenoid may be controlled by using the signal as a trigger, and the solenoid push rod may be driven for one stroke.

  The sampling drive pipe (0113) of the micro dispensing tip (0110) is connected to the discharge port (0134) of the micro pump of the pressurization / reduction switching micro pump tip (0130) by the latch driving. As a result, when the pumping of the micropump is continued, the inside of the micro dispensing tip (0110) is switched from the reduced pressure state to the pressurized state. By the switching, the movement of the sample from the sample introduction tube (0112) to the sampling outlet tube (0113) in the micro dispensing tip (0110) is stopped.

  With the functional configuration of the “sampling detection sensor” and the “first pump selection pipe drive unit” as described above, it is possible to realize introduction of a sample of “predetermined amount” into the sampling lead-out pipe (0113).

  The “predetermined amount” sample introduced into the sampling lead-out tube (0113) as described above is sampled when the inside of the micro-dispensing tip (0110) is pressurized by pumping of the micropump thereafter. It will be pushed out toward the dispensing pipe (0114).

  FIG. 14 is a conceptual diagram showing the flow of the processing. As shown in FIG. 14 (A), when the inside of the micro-dispensing tip is in a reduced pressure state, the fluid sample moves from the sample introduction tube to the sampling outlet tube, and as shown in FIG. 14 (B), When the sensor senses that the fluid sample that has moved into the sampling outlet pipe has moved to a predetermined position, the sampling outlet pipe of the micro-dispensing chip is triggered by the sensor. It becomes connected with the discharge port. As a result, when the pumping of the micropump is continued, the inside of the pipe of the microdispensing tip is switched from the reduced pressure state to the pressurized state.

  Thereafter, when the inside of the tube of the micro-dispensing tip is in a pressurized state, as shown in FIG. 14C, a predetermined amount of fluid sample that was present in the sampling outlet tube when the pressure was changed from the reduced pressure state to the pressurized state. Will be pushed out towards the sample dispensing tube.

  Here, the selective open pipe (0125) of the micro multi-branch switching valve chip (0120) may be latch-driven in response to the detection of sample introduction by the sampling detection sensor (0141).

  Specifically, the sample dispensing tube (0114) is driven by latch driving of the selective open tube (0125), so that “the open ends of all the tubes are closed” → “only one tube is open to the atmosphere” → “all the tubes The open end is closed ”→“ only one tube is opened to the atmosphere ”(see FIG. 15). Then, in response to detection of sample introduction by the sampling detection sensor (0141), the selective open pipe (0125) is latch-driven, and the sample dispensing pipe (0114) is changed from “the open ends of all the pipes are closed” to “ Switch to “open one tube to the atmosphere”.

By such switching operation and switching operation according to the detection of the dispensing detection sensor described below, when the inside of the tube of the micro-dispensing tip (0110) is in a reduced pressure state, “open all tubes” of the sample dispensing tube. When the end is in the “closed state” and the inside of the tube of the micro-dispensing tip (0110) is in a pressurized state, the sample dispensing tube (0114) can be configured to be “open to the atmosphere”.
<< Dispensing detection sensor and second pump selection pipe drive section >>

  The “dispensing detection sensor” (not shown) is configured to detect that a sample has been dispensed at a predetermined position of the sample dispensing tube (0114) of the micro dispensing tip (0110). The specific configuration is the same as that of the “sampling detection sensor”, and only the arrangement position is different. The position to be arranged is an arbitrary design matter, and may be, for example, near the approximate center of each of the plurality of tubes of the sample dispensing tube (0114).

  A “second pump selection pipe drive unit” (not shown) latches the pump selection pipe (0131) of the pressure-intensification switching micro pump chip (0130) in response to detection of sample dispensing by the dispensing detection sensor. It is configured to drive.

  That is, when the dispensing detection sensor detects the dispensing of the sample, the second pump selection pipe drive unit triggers the pump selection pipe (0131) of the pressure-intensification switching micro pump chip (0130) by a predetermined angle. Latch drive. Specifically, when a sample dispensing detection signal is received from the dispensing detection sensor, the solenoid may be controlled by using the signal as a trigger, and the solenoid push rod may be driven for one stroke.

  The sampling drive pipe (0113) of the micro dispensing tip (0110) is connected to the suction port (0133) of the micro pump of the pressurization / depressurization switching micro pump tip (0130) by the latch driving. As a result, when the pumping of the micropump is continued, the inside of the micro dispensing tip (0110) is switched from the pressurized state to the reduced pressure state. By this switching, sample introduction from the sample introduction tube (0112) to the sampling outlet tube (0113) is started again in the micro-dispensing tip (0110).

  Here, the selective open pipe (0125) of the micro multi-branch switching valve chip (0120) may be latch-driven in response to detection of sample dispensing by the dispensing detection sensor.

  Specifically, the sample dispensing tube (0114) is driven by latch driving of the selective open tube (0125), so that “the open ends of all the tubes are closed” → “only one tube is open to the atmosphere” → “all the tubes The open end is closed ”→“ only one tube is opened to the atmosphere ”(see FIG. 15). Then, the selective open pipe (0125) is latch-driven in response to the detection of sample introduction by the dispensing detection sensor, and “only one pipe is opened to the atmosphere” of the sample dispensing pipe (0114), Switch so that the open ends of all tubes are in the closed state.

  By such switching operation and switching operation according to the detection of the sampling detection sensor, when the inside of the micro dispensing tip (0110) is in a pressurized state, “only one tube is opened to the atmosphere” of the sample dispensing tube. When the inside of the tube of the micro-dispensing tip (0110) is in a pressurized state, the sample dispensing tube (0114) can be configured such that “the open ends of all the tubes are closed”. .

  Note that the micro multi-branch switching valve chip, the pressurization / depressurization switching micro pump chip, and the micro dispensing chip of the micro dispensing device of the present embodiment may be configured to be separable and assembled. Further, when the sampling detection sensor and the dispensing detection sensor are included in the constituent elements, these may be configured to be separable / assembleable.

  By configuring in this way, after use, only the used micro-dispensing chip into which the fluid sample has been introduced is replaced with a new one, a micro multi-branch switching valve chip, a pressure increasing / decreasing pressure switching micro pump chip, a sampling detection sensor The dispensing detection sensor can be used repeatedly.

Here, the “micro dispensing tip”, “micro multi-branch switching valve chip”, and “pressurization / depressurization switching micro pump chip” constituting the micro dispensing apparatus of the present embodiment are based on the conventional micro stereolithography method and the like. Can be produced using.
<Process flow>

  Hereinafter, the detailed processing flow of the micro-dispensing chip of this embodiment will be described with reference to FIG.

  First, the open ends of all of the sample dispensing tubes (0114) of the micro dispensing tip (0110) are closed, and the sampling outlet tube (0113) of the micro dispensing tip (0110) is added. The micro pump (0132) is pumped in a state connected to the micro pump suction port (0133) of the reduced pressure switching micro pump chip (0130).

  Then, the inside of the tube of the micro dispensing tip (0110) is in a reduced pressure state, and the fluid sample is sucked from the introduction port (0111) of the sample introduction tube (0112). When the pumping of the micro pump (0132) is continued thereafter, the fluid sample in the sample introduction pipe (0112) is guided into the sampling outlet pipe (0113).

  Then, when the sampling detection sensor (0141) detects that the fluid sample has passed through a predetermined position in the sampling lead-out pipe (0113), it is used as a trigger to selectively open the micro multi-branch switching valve chip (0120). (0125) and the pump selection pipe of the pressure-intensification switching micro pump chip (0130) is latch-driven by a predetermined angle. By the latch driving, the sample dispensing tube (0114) of the micro dispensing tip (0110) is in a state where only one tube is opened to the atmosphere. In addition, the sampling lead-out tube (0113) of the micro-dispensing tip (0110) is connected to the discharge port (0134) of the micropump of the pressurization / reduction switching micropump tip (0130).

  When the pumping of the micropump (0132) is continued in the above state, the inside of the pipe of the microdispensing tip (0110) is in a pressurized state, and a predetermined amount of sample introduced into the sampling outlet pipe (0113) The tube (0114) moves into the tube that is open to the atmosphere. Then, when a dispensing detection sensor (not shown) detects that the fluid sample has passed through a predetermined position in the sample dispensing tube (0114), the micro multi-branch switching valve chip (0120) is triggered by the detection. The selective open pipe (0125) and the pump selection pipe of the pressure-intensification switching micro pump chip (0130) are latch-driven by a predetermined angle. By the latch driving, the sample dispensing tubes (0114) of the micro dispensing tips (0110) are in a state where the open ends of all the tubes are closed. In addition, the sampling lead-out tube (0113) of the micro-dispensing tip (0110) is connected to the suction port (0134) of the micropump of the pressurization / reduction switching micropump tip (0130).

  After that, when the pumping of the micro pump (0132) is continued, the same processing as described above is repeated, and a predetermined amount of sample is injected into a different pipe of the sample dispensing pipe (0114).

  In FIG. 1, there is a “portion bifurcated and provided with two check valves” (0116) in the sampling outlet tube (0113) of the micro-dispensing tip (0110). In order to prevent the sampling lead pipe (0113) connected to the pressure-intensification switching micro pump chip (0130) from becoming long (the volume of the pipe becomes large) and the dispensing accuracy according to the above-described principle from decreasing, Thus, the distance between the tubes is short and separated.

Therefore, when the distance of the connecting portion between the sampling outlet tube (0113) and the pressurization / reduction pressure switching micro pump chip (0130) is sufficiently short, the bifurcated portion (0116) is not necessary, and only one You may comprise only this pipe | tube.
<Effect>

  The micro-dispensing device of this embodiment makes it possible to accurately measure without waste using only a small amount of sample and transport the sample to the target chip.

  Further, since this device is a small device, it is excellent in portability, enables real-time analysis even on site, and is expected to dramatically expand the application range of μ-TAS.

  Furthermore, it is expected to be applied to a wide range of applications such as portable health care devices such as blood tests and portable environmental analysis devices.

Overall conceptual diagram of the micro-dispensing device of the present invention Conceptual diagram of the micro dispensing tip of the present invention Conceptual diagram of hat-shaped check valve Conceptual diagram explaining the operation of a hat-hat check valve Conceptual diagram explaining the micro-dispensing tip in a reduced pressure state Conceptual diagram explaining the micro-dispensing tip in the pressurized state Conceptual diagram of micro multi-branch switching valve chip Conceptual diagram of a part of a micro multi-branch switching valve chip Partial cross-sectional conceptual diagram of micro multi-branch switching valve chip Conceptual diagram of pressure-induction switching micro pump chip Conceptual diagram of rotor of pressure-induction switching micropump chip The figure which shows an example of a pressurization switching micropump chip Microfluidic detection experiment chip Results of detection experiments using microfluidic detection chips Conceptual diagram for explaining how a predetermined amount of sample is weighed Conceptual diagram explaining the connection between the micro multi-branch switching valve chip and the sample pipe The figure which shows an example of a micro pump drive unit Application image of the micro-dispensing device of the present invention

Explanation of symbols

0110 Micro dispensing tip 0111 Inlet port 0112 Sample introducing tube 0113 Sampling outlet tube 0114 Sample dispensing tube 0115 Check valve 0120 Micro multi-branch switching valve chip 0125 Select open tube 0130 Pressure-depressurization switching micro pump chip 0131 Pump selection tube 0132 Micro pump 0133 Suction port 0134 Discharge port 0138 Connection port

Claims (4)

A micro-dispensing device comprising a micro multi-branch switching valve chip, a micro-dispensing chip, and a pressurizing / depressurizing switching micro-pump chip,
Micro dispensing tips are
A sample introduction pipe provided with an inlet and a check valve for introducing a fluid sample;
A sample dispensing tube comprising a plurality of tubes for dispensing the sample;
Connected to the sample introduction tube, sample dispensing tube, and pressure-increasing / decreasing pressure switching micropump, and according to the pressure from the pressure-increasing / decreasing pressure switching micropump chip, a predetermined amount of sample is introduced from the sample introduction tube, A sampling derivation tube for selectively extruding a predetermined amount of sample introduced in response to the pressurization of the sample into one of the plurality of tubes of the sample dispensing tube;
Have
Micro multi-branch switching valve chip
A selective open pipe that is latch-driven to selectively connect with one of the plurality of pipes of the sample pipe, and opens the inside of the pipe of the sample pipe through the connected pipe.
Pressurized pressure switching micro pump chip
A micropump having a suction port with a check valve and a discharge port with a check valve, driven by an external power source and repeating suction and discharge;
A pump selection pipe that is latch-driven to alternately connect the open end of the suction port and the open end of the discharge port with the sampling outlet tube;
A micro-dispensing device. A sampling detection sensor for detecting that a sample has been introduced into a predetermined position of the sampling outlet tube;
A first pump selection pipe drive unit that latch-drives the pump selection pipe of the pressure increase / decrease switching micropump chip in response to detection of sample introduction by the sampling detection sensor;
The microdispensing device according to claim 1, further comprising: A dispensing detection sensor for detecting that a sample has been dispensed at a predetermined position of the sample dispensing tube;
A second pump selection pipe drive unit that latch-drives the pump selection pipe of the pressure-intensification switching micropump chip in response to detection of sample dispensing by the dispensing detection sensor;
The microdispensing device according to claim 1 or 2, further comprising: The micro multi-branch switching valve chip, the pressure increase / decrease switching micro pump chip and the micro dispensing chip of the micro dispensing device are configured to be separable and assembled.
The used micro-dispensing tip is replaced with a new micro-dispensing tip, and the micro multi-branch switching valve tip and the pressurizing / depressurizing switching micro-pump tip are configured to be reusable. The micro-dispensing device described.