JP4743487B2 - Apparatus and method for controlling fluid flow in a microchip - Google Patents

Description

  The present invention relates to a fluid flow control apparatus and method in a microchip for controlling a fluid flow state in a microchannel in the microchip.

  In recent years, analysis using a microchip, which is called μ-TAS (Micro Total Analysis Systems) or LOC (Lab-on-a-chip), has attracted attention. As shown in FIG. 8, the microchip is formed by forming minute grooves (channels) 802 on a base plate 801 made of glass or resin by using a fine processing technique, and attaching a cover plate 803 to the base plate 801. A flow path 804 is configured. In analysis using this type of microchip, it is expected to reduce the amount of reagents and wastes such as reagents and samples, increase the reaction speed, and increase the accuracy. For example, analysis of chain lengths of gene fragments such as DNA and RNA Applicable.

  By the way, when performing analysis using a microchip, controlling the flow state of the fluid in the microchannel 804 is one of the important issues.

  For example, an electromagnetic valve or the like is installed outside the microchip, and the valve is connected to the microchannel 804 in the microchip to control the fluid flow state in the microchannel 804. Yes.

  Further, in Patent Document 1 and the like, a motor is installed on a microchip, a hole is formed in the microchip, and a valve mechanism for inserting a valve body into the microchannel from the hole is configured. It is disclosed that the cross-sectional area is variable.

JP 2005-851 A

  However, when a valve is installed outside the microchip for the purpose of controlling the flow state of the fluid in the microchannel 804 other than the valve for introducing the sample into the microchip or discharging the waste liquid, The number of pipes for connecting the valves increases, which not only increases the overall size, but also hinders the miniaturization of samples and waste liquids, the speeding up of the reaction, and the increase in accuracy. In addition, a solid sample (for example, a biological sample such as microbeads or cells) may be circulated through the microchannel 804 together with the buffer solution. In this case, the solid sample is mixed inside the valve, and the durability of the valve Will be easily damaged.

  On the other hand, when the valve is provided on the microchip itself as disclosed in Patent Document 1 or the like, it is necessary to process the microchip itself, which increases the cost and is not suitable for mass production.

  The present invention has been made in view of the above points, and the minimum number of valves to be connected to the microchip and the need for processing into the microchip itself are eliminated, and the microchip has a simple configuration. It is an object of the present invention to be able to control the flow state of fluid in an inner microchannel.

The fluid flow control device in the microchip according to the present invention forms a micro flow path by bonding a cover plate to a base plate in which a micro groove is formed, and at least one of the base plate and the cover plate is made of an elastic material. A microfluidic fluid flow control apparatus comprising: a first flow path connecting a sample supply port and a sample outlet as the micro flow path; and a forward path and a return path connected to the first flow path. A second flow path that constitutes a reaction field is configured, and the forward path and the return path that extend to the reaction field in the second flow path, and the second path in the first flow path. A flow path portion located closer to the sample supply port than the forward path and the return path of the flow path, and the forward path of the second flow path and the forward path of the first flow path The flow path portion located on the sample outlet side of the path is aligned in parallel, pressing a part of the base plate or the cover plate made of the elastic member, and changing the cross-sectional area of the micro flow path, A pressing member that controls the flow state of the fluid in the microchannel includes a channel portion that includes the forward path and the return path, a channel portion that is positioned on the sample supply port side, and a flow that is positioned on the sample outlet side. A plurality of cams are rotated by a single driving source, and each pressing member is advanced and retracted at each timing by the rotation of each cam, and pressed against the base plate or cover plate made of the elastic member. It has a feature in that it is released or released.
The method for controlling fluid flow in a microchip according to the present invention includes a cover plate bonded to a base plate on which a minute groove is formed to form a minute flow path, and at least one of the base plate and the cover plate is made of an elastic material. A microfluidic fluid flow control method comprising: a first flow path connecting a sample supply port and a sample outlet as the micro flow path; and a forward path and a return path connected to the first flow path. A second flow path that constitutes a reaction field is configured, and the forward path and the return path that extend to the reaction field in the second flow path, and the second path in the first flow path. A flow path portion located closer to the sample supply port than the forward path and the return path of the flow path, and the forward path of the second flow path and the forward path of the first flow path The flow path portion located on the sample outlet side of the path is aligned in parallel, pressing a part of the base plate or the cover plate made of the elastic member, and changing the cross-sectional area of the micro flow path, A pressing member that controls the flow state of the fluid in the microchannel includes a channel portion that includes the forward path and the return path, a channel portion that is positioned on the sample supply port side, and a flow that is positioned on the sample outlet side. A plurality of cams are rotated by a single driving source, and each pressing member is advanced and retracted at each timing by the rotation of each cam, and pressed against the base plate or cover plate made of the elastic member. It has a feature in that it is released or released.

  According to the present invention, a part of the base plate or cover plate made of an elastic member is pressed by the pressing member, and the cross-sectional area of the microchannel is changed to control the fluid flow state in the microchannel. As a result, the number of valves connected to the microchip is the minimum required, and the processing of the microchip itself is not required, and the fluid flow state in the microchannel in the microchip is controlled with a simple configuration. can do.

Preferred embodiments of the present invention will be described below with reference to the accompanying drawings.
FIG. 1 best represents the features of the present invention and shows the relationship between the microchip 1 and the pins 2. As shown in FIG. 1A, the microchip 1 of the present embodiment is formed by forming minute grooves (channels) 4 in a base plate 3 made of an elastic material such as PDMS (polydimethylsiloxane) (depth is about 200 μm, A size of up to about 400 μm in width) is formed by adhering a cover plate 5 made of glass to the base plate 3 to form a micro flow path 6.

  Then, as shown in FIG. 1B, a part of the base plate 3 made of an elastic material, specifically, a portion on the microchannel 6 is pressed by the tip of the pin 2, and the portion is pressed on the microchannel 6 side. The fluid flow state in the microchannel 6 is controlled by changing the cross-sectional area of the microchannel 6 by elastic deformation. As is clear from this, the elastic material referred to in the present invention is such that when a part is pressed, the cross-sectional area of the microchannel can be changed by elastically deforming the portion to the microchannel side. It means a material having elasticity.

  Hereinafter, the fluid flow control device and method in the microchip of this embodiment will be described in detail. As shown in FIG. 2, ports 7, 8, 9, 10 penetrating the base plate 3 are formed at appropriate positions of the microchip 1. In the microchip 1, the micro flow path 6 that connects the ports 7 and 8 and forms the reaction field 6d at the intermediate position, and the micro flow path 6 is connected to the port 9 on the port 7 side from the reaction field 6d. A microchannel 11 and a microchannel 12 that connects the microchannel 6 to the port 10 on the port 8 side from the reaction field 6d are configured.

  In the example shown in FIG. 2, port 7 is a sample supply port, and port 8 is a sample outlet.

  Further, the port 9 is connected to the three-way valve 14 via the external pipe 13. The three-way valve 14 is arranged to connect the port 9, the buffer 15, and the three-way valve 19. The connection port 14 a is connected to the port 9, the connection port 14 b is connected to the buffer 15, and the connection port 14 c is connected to the three-way valve 19. Connecting.

  Further, the port 10 is connected to the three-way valve 17 via the external pipe 16. The three-way valve 17 is arranged to connect the port 10, the buffer 18, and the three-way valve 19. The connection port 17 a is connected to the port 10, the connection port 17 b is connected to the buffer 18, and the connection port 17 c is connected to the three-way valve 19. Connecting.

  The three-way valve 19 is arranged to connect the three-way valve 14, the three-way valve 17, and the syringe pump 20. The connection port 19 a is connected to the syringe pump 20, the connection port 19 b is connected to the three-way valve 17, and the connection port 19 c is connected. Connect to three-way valve 14.

  In the microchip 1 configured as described above, the flow channel portion (forward path and return path) 6a extending to the reaction field 6d in the micro flow channel 6 and the connection position between the micro flow channel 6 and the micro flow channel 11 (sample) The flow path portion 6b on the side of the port 7 which is the supply port and the flow path portion 6c on the downstream side (port 8 side which is the sample outlet) of the micro flow path 6 from the connection position with the micro flow path 12 are parallel. There is a place to line up. At that location, the flow state of the fluid in the flow path portion (forward path and return path) 6a, the flow state of the fluid in the flow path portion 6b, and the flow state of the fluid in the flow path portion 6c are respectively shown. The control is based on the principle described in 1.

  3 to 5 show configuration examples of the fluid flow control device in the microchip. As shown in FIGS. 3 to 5, the output shaft 101 a of the motor 101 attached to the casing 102 and the camshaft 103 rotatably supported by the casing 102 are coaxially connected via a coupling 104.

  Three cams 105a to 105c are connected to the camshaft 103 at a predetermined interval. As will be described in detail later, the shape of the cam 105a is designed to stop (closed) or allow (open) the fluid flow in the flow path portion (forward path and return path) 6a at a predetermined timing. ing. The shape of the cam 105b is designed to stop (closed state) or allow (open state) the fluid flow in the flow path portion 6b at a predetermined timing. The shape of the cam 105c is designed to stop (closed state) or allow (open state) the flow of fluid in the flow path portion 6c at a predetermined timing.

  A pair of upper and lower leaf springs 106u and 106l are arranged below the cams 105a to 105b as shown in FIG. One end of the pair of upper and lower leaf springs 106u and 106l is supported, and the other end thereof is located just below each of the cams 105a to 105c, and a spacer 107 is provided between the leaf springs 106u and 106l at that position. It has been.

  Further, three shafts 108 are accommodated in the casing 102. The upper ends of the shafts 108 are connected to the spacers 107 through the lower leaf springs 106l, and the pins 2a to 2c are connected to the lower ends. Each pin 2 a to 2 c can be advanced and retracted through a guide hole formed in the lower part of the casing 102.

  A pair of inclined surfaces is formed at the tip portions of the pins 2a to 2c, and the tip surfaces are elongated and rectangular. That is, the tip surface having a long and narrow rectangular shape is pressed against the base plate 3 of the microchip 1. In this case, the longitudinal direction of the tip surface having the rectangular shape coincides with the width direction of the flow path portions 6a to 6c. It is supposed to be. In this embodiment, the pin 2a for the flow path portion 6a controls the fluid flow in two micro flow paths (forward path and return path), so that the tip is processed wider than the pins 2b and 2c on both sides. Has been.

  In the present embodiment, the example in which the tip surfaces of the pins 2a to 2c are elongated rectangular has been described. For example, as shown in FIG. 1, the tip of the pin 2 is processed into a tapered shape, and the tip surface has a small diameter circle. You may make it become a shape.

  In the fluid flow control device in such a microchip, when the motor 101 is driven and the camshaft 103 is rotated, the cams 105 a to 105 c are rotated together with the camshaft 103. When the circular arc surface R (see FIG. 3B) of each of the cams 105a to 105c comes into contact with the upper leaf spring 106u as the cams 105a to 105c rotate, the leaf springs 106u and 106l are elastically deformed, and the shaft 108 Furthermore, the pins 2a to 2c move downward. As a result, the tips of the pins 2a to 2c press the base plate 3 of the microchip 1 and elastically deform the portions thereof, so that the cross-sectional areas of the flow path portions 6a to 6c become substantially zero, so The flow of fluid in the path portions 6a to 6c is stopped (closed state).

  When the cams 105a to 105c rotate and the surfaces other than the arcuate surface R of the cams 105a to 105c move away from the upper leaf spring 106u, the leaf springs 106u and 106l are elastically restored, and the shaft 108 and the pin 2a to 2c move upward. As a result, the tips of the pins 2a to 2c are separated from the base plate 3 of the microchip 1, and the portion thereof is elastically restored to return the cross-sectional area of the flow path portions 6a to 6c to the original cross-sectional area. The flow of fluid in the flow path portions 6a to 6c is allowed (open state).

  Next, control of the fluid flow state in the present embodiment will be described with reference to FIGS.

  First, the cams 105a to 105c are set to the origin positions shown in FIG. 3, and the flow path portions 6a to 6c are all opened (step S101).

  In this state, the buffer solution is introduced from the buffer 15 into the syringe pump 20 (step S102). That is, as shown in FIG. 7A, the connection port 14a is closed and the connection ports 14b and 14c are opened in the three-way valve 14, the connection ports 17a to 17c are all closed in the three-way valve 17, and the connection port is connected in the three-way valve 19. 19 b is closed and the connection ports 19 a and 19 c are opened, and suction is performed by the syringe pump 20. Thereby, the buffer solution can be introduced from the buffer 15 into the syringe pump 20 as indicated by an arrow in the figure. The buffer solution is used as a carrier liquid for preventing the sample from directly touching the syringe pump 20 or the like.

  Next, the cams 105a to 105c are set to the 60-degree rotation position shown in FIG. 4, and the flow path portion 6a is opened and the flow path portions 6b and 6c are closed (step S103).

  In this state, the buffer solution is filled into the microchip 1 (step S104). That is, as shown in FIG. 7B, the three-way valve 14 closes the connection port 14b and opens the connection ports 14a and 14c, and the three-way valve 17 closes the connection port 17c and opens the connection ports 17a and 17b. In the valve 19, the connection port 19b is closed and the connection ports 19a and 19c are opened, and the buffer liquid in the cylinder pump 20 is discharged. Thereby, as shown by the arrow in the figure, the buffer solution can be filled into the microchip 1.

  Next, although illustration is omitted, the cams 105a to 105c are set to a 120-degree rotation position, the flow path portions 6a and 6b are opened, and the flow path portion 6c is closed (step S105).

  In this state, a sample is sucked into the microchip 1 (step S106). That is, as shown in FIG. 7C, all the connection ports 14a to 14c are closed in the three-way valve 14, the connection port 17b is closed and the connection ports 17a and 17c are opened in the three-way valve 17, and the connection ports 17a and 17c are opened. 19 c is closed and the connection ports 19 a and 19 b are opened, and suction is performed by the syringe pump 20. Thereby, as shown by the arrow in the figure, the sample can be sucked into the microchip 1 from the port 7 which is the sample supply port.

  Next, although illustration is omitted, the cams 105a to 105c are set to the 180-degree rotation position, and the flow path portion 6a is opened (step S107). In this case, the flow path portions 6b and 6c may be open or closed.

  In this state, the reaction in the reaction field 6d is started (step S108). In this case, as shown in FIG. 7D, all the connection ports 14a to 14c are closed in the three-way valve 14, all the connection ports 17a to 17c are closed in the three-way valve 17, and all the connection ports 19a to 19c in the three-way valve 19. Keep closed.

  Next, after a predetermined time has passed and the reaction is completed (step S109), although not shown, the cams 105a to 105c are set to a 240-degree rotation position, the flow path portions 6a and 6c are opened, and the flow path portion 6b is closed (step S110).

  In this state, the sample after reaction is taken out from the microchip 1 (step S111). That is, as shown in FIG. 7E, the connection port 14 b is closed and the connection ports 14 a and 14 c are opened in the three-way valve 14, all the connection ports 17 a to 17 c are closed in the three-way valve 17, and the connection port is connected in the three-way valve 19. 19b is closed and the connection ports 19a and 19c are opened, and the syringe pump 20 discharges. Thereby, as shown by the arrow in the figure, the sample after reaction can be taken out from the inside of the microchip 1 through the port 8 which is the sample discharge port.

  As described above, the portions of the base plate 3 made of an elastic member on the micro flow path 6 are pressed by the pins 2a to 2c, and the cross-sectional areas of the flow path portions 6a to 6c are changed to thereby change the flow path portions 6a to 6c. The fluid flow state at 6c can be controlled. This minimizes the number of valves connected to the microchip and eliminates the need for processing the microchip itself, thereby controlling the fluid flow state in the microchannel in the microchip with a simple configuration. be able to.

  In the above embodiment, as a control of the fluid flow state in the microchannel 6, the function of the open / close valve that opens the microchannel 6 with the cross-sectional area of the microchannel 6 set to substantially zero or the fully open state is set. The example in which the flow path is provided has been explained, but the flow rate and the flow rate are adjusted by changing the degree of pressing of the pin 2 to change the cross-sectional area of the micro flow path 6 more finely than simply opening and closing. It is also possible to give the function of a valve to perform.

  As mentioned above, although this invention was demonstrated with embodiment, this invention is not limited only to embodiment, A change etc. are possible within the scope of the present invention. For example, the microchip 1 described in the above embodiment is merely an example, and as long as at least one of the base plate 3 and the cover plate 5 is made of an elastic material, how is the material, the arrangement of the microchannels, and the like? It doesn't matter if it's something. In this case, the base plate 3 is pressed in the above embodiment, but the cover plate 5 may be pressed if the cover plate 5 is made of an elastic material.

It is a figure which shows the relationship between a microchip and a pin. It is a top view which shows the microchip in this embodiment. It is a figure which shows the structural example of the fluid flow control apparatus in a microchip. It is a figure which shows the structural example of the fluid flow control apparatus in a microchip. It is a figure which shows the structural example of the fluid flow control apparatus in a microchip. It is a flowchart for demonstrating control of the flow state of the fluid in this embodiment. It is a figure for demonstrating one procedure of control of the flow state of the fluid in this embodiment. It is a figure for demonstrating one procedure of control of the flow state of the fluid in this embodiment. It is a figure for demonstrating one procedure of control of the flow state of the fluid in this embodiment. It is a figure for demonstrating one procedure of control of the flow state of the fluid in this embodiment. It is a figure for demonstrating one procedure of control of the flow state of the fluid in this embodiment. It is sectional drawing which shows the structure of a microchip.

Explanation of symbols

1 Microchip 2, 2a to c Pin 3 Base plate 4 Groove (channel)
5 Cover plate 6 Micro flow path 101 Motor 102 Casing 103 Camshaft 104 Coupling 105a-105c Cam 106u, 106l Leaf spring 107 Spacer 108 Shaft

Claims (3)

A fluid flow control device in a microchip, in which a cover plate is bonded to a base plate in which a minute groove is formed to form a minute flow path, and at least one of the base plate and the cover plate is made of an elastic material. ,
As the microchannel, at least a first channel that connects a sample supply port and a sample outlet, and a second channel that forms a reaction field by connecting an outward path and a return path to the first channel The forward supply and the return path extending to the reaction field in the second flow path, and the sample supply from the forward path and the return path of the second flow path in the first flow path. The flow path portion located on the mouth side and the flow path portion located on the sample outlet side of the second flow path of the first flow path from the first flow path are arranged in parallel. ,
A pressing member that presses a part of a base plate or a cover plate made of the elastic member and changes a cross-sectional area of the micro flow path to control a fluid flow state in the micro flow path includes the forward path and the return path Each of the flow path part, the flow path part located on the sample supply port side, and the flow path part located on the sample outlet side ,
A plurality of cams are rotated by a single driving source, and the respective pressing members are advanced and retracted at the respective timings by the rotation of the respective cams, so that the base plate or the cover plate made of the elastic member is pressed or released. A fluid flow control device in a microchip.   2. The fluid flow control device in a microchip according to claim 1, wherein the pressing member is a pin, and a base plate or a cover plate made of the elastic member is pressed by a tip of the pin. A fluid flow control method in a microchip in which a cover plate is bonded to a base plate in which a minute groove is formed to form a minute flow path, and at least one of the base plate and the cover plate is made of an elastic material. ,
As the microchannel, at least a first channel that connects a sample supply port and a sample outlet, and a second channel that forms a reaction field by connecting an outward path and a return path to the first channel The forward supply and the return path extending to the reaction field in the second flow path, and the sample supply from the forward path and the return path of the second flow path in the first flow path. The flow path portion located on the mouth side and the flow path portion located on the sample outlet side of the second flow path of the first flow path from the first flow path are arranged in parallel. ,
A pressing member that presses a part of a base plate or a cover plate made of the elastic member and changes a cross-sectional area of the micro flow path to control a fluid flow state in the micro flow path includes the forward path and the return path Each of the flow path part, the flow path part located on the sample supply port side, and the flow path part located on the sample outlet side ,
A plurality of cams are rotated by a single driving source, and the respective pressing members are advanced and retracted at the respective timings by the rotation of the respective cams, so that the base plate or the cover plate made of the elastic member is pressed or released. A fluid flow control method in a microchip characterized by

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