JP6272023B2 - Microfluidic chip device - Google Patents

Description

  The present invention relates to a microfluidic chip device for performing cell culture, reagent screening, chemical analysis, etc. by flowing a culture solution, various reagents, etc. through a microfluidic channel of a microfluidic chip, and in particular, a channel configuration adapted to user needs The present invention relates to a microfluidic chip device that can quickly manufacture a chip device having a function at a low cost.

  2. Description of the Related Art Conventionally, for example, a microfluidic chip device having a microfluidic chip provided with a microfluidic channel in order to evaluate the function and response of a cell has been known. A microfluidic chip device has been proposed in which a culture solution is allowed to flow through a flow path to a culture part, and a reagent is allowed to flow to the culture part to perform cell culture or to evaluate the reagent.

JP 2013-106595 A

  However, this conventional microfluidic chip device fixes a microchip on a base via a fixture, attaches microdevices such as pumps and valves on the base, and supplies a large number of liquids on the base. A microfluidic channel is formed in the microchip so that the target cell culture is performed, and the microfluidic channel, the medium supply channel, the reagent supply channel, etc. are liquidated. It is manufactured by connecting to the supply port.

  In addition, this type of microfluidic chip device is usually designed and manufactured by cell researchers, chemical analysis researchers, etc. according to each researcher's own research method. The manufacturer manufactures a microfluidic chip device having a path form and function.

  In addition, since the microfluidic chip is manufactured by using a synthetic resin such as PDMS, PMMA, silicone resin, and the like, and provided with a microfluidic flow path, the manufacturer of the microfluidic chip device is in accordance with the user's request. It is necessary to design a microfluidic chip dedicated to the user and mold it with synthetic resin. For this reason, the production of the microfluidic chip device has a problem that a very large amount of time and man-hours and a large amount of cost are required.

  The present invention solves the above-mentioned problems, and by using a combination of various microchip modules manufactured in advance, a microfluidic chip device customized for various users can be manufactured inexpensively and rapidly. An object of the present invention is to provide a microfluidic chip device that can be used.

In order to achieve the above object, the microfluidic chip device of the present invention comprises:
A sheet-like microfluidic chip soft microfluidic channel is formed in a part of the microfluidic flow path, the valve portion for opening and closing the microfluidic flow path, a pump unit for feeding a liquid, or a liquid A microfluidic chip device in which at least one portion of a chamber portion to be stored is disposed, and a liquid is allowed to flow through the microfluidic channel,
The microfluidic chip pump module provided with the branch flow path module which is provided the microfluidic flow path that branches, the valve module provided the microfluidic channel and the valve section, the microfluidic channel and pump unit When, or a chamber module provided the microfluidic channel and the chamber part, at least two modules chosen from, dividedly formed by modularized into certain shape,
The branch flow path module, the valve module, the pump module, at least two modules of the chamber modules are joined, and in a state in which the microfluidic channel of the respective modules are connected to each other by a connector, all The module is housed in a holder having a plate-like main body and a cover plate covering the plate-like main body .

  According to the microfluidic chip device of the present invention, a branch channel module provided with a branching microfluidic channel, a valve module provided with a microfluidic channel and a tube valve unit, a microfluidic channel and a tube pump unit were provided. A chamber module provided with a pump module, a microfluidic channel, and a chamber part is manufactured in advance, and according to the user's request, a necessary module is selected from those modules, and these modules are combined to provide a user Therefore, a microfluidic chip device meeting the needs can be manufactured at low cost and quickly.

  Here, at least two of the branch flow path module, the valve module, the pump module, and the chamber module stored in the holder may be formed of a triangular sheet having a substantially triangular plane. preferable. Moreover, it is preferable that each port of the microfluidic channel in the module is configured to open at the center position of the side portion of the triangular sheet.

  According to this, the triangular sheet-like modules are in contact with each other, and the modules are arranged in combination. Therefore, the four triangular sheet-like modules are combined to form a micro fluid channel having a flow-type microfluidic channel. The fluid chip can be easily manufactured in a substantially triangular shape and in a small shape. Further, if the six modules are combined in an annular shape, a circulating microfluidic chip that circulates liquid by providing an annular microfluidic channel can be easily manufactured.

  Further, the microfluidic channel in the branch channel module is formed by branching into three channels, and each of the three channels opens at a central position of each side of the triangular sheet. preferable.

  Here, the holder is molded from a hard synthetic resin, the branch flow channel module, the valve module, the pump module, and the chamber module are molded from a soft transparent synthetic resin, and the microfluidic flow channel in each module is soft. It is preferable to form in a tube shape.

  The pump module is formed as a tube pump that rotates by pressing the rotating part of the pump driving unit against the tube in the module, and the valve module has the head part of the valve driving part as the tube pump part in the module. It is preferably formed as a valve that is pressed and driven.

  According to this, since the liquid contact part of the microfluidic chip device is only the microfluidic flow path of the microfluidic chip, when performing cell culture or chemical analysis, the microfluidic excluding the holder, the pump driving part, and the valve driving part The chip can be easily exchanged, washed, or used as a disposable, and contamination and bacterial contamination can be prevented.

  Moreover, it is preferable here that the said chamber module forms an opening part in the corresponding location of a holder so that a chamber part may be exposed. According to this, when the microfluidic chip device is used for cell culture, for example, the chamber portion of the chamber module can be used as a culture space, and the cell culture state can be easily observed with a microscope or the like.

  The holder has a sheet-like recess for a module formed on a plate-like main body formed in a plate-like shape, and a fastening means such as a fastening screw in a state where the plate-like main body is covered with a cover plate. Thus, the cover plate can be fastened and fixed. According to this, the holder can be easily disassembled, and the microfluidic chip accommodated therein can be easily replaced, washed, or disposable.

  Also, here, the microfluidic chip device is composed of a branch channel module, two pump modules, and a chamber module, and the branch channel module is positioned at the center, and the sides around the branch channel module Two pump modules and the chamber module are disposed in contact with each other, and can be formed in a substantially triangular shape as a whole.

  The microfluidic chip device includes the two-port two-way valve type valve module, the three-port two-way valve type valve module, the pump module, and the chamber module. It can comprise so that a side part may contact | connect.

  The microfluidic chip device includes the two-port two-way valve type valve module, the three-port two-way valve type two valve modules, the branch channel module, the two pump modules, and the chamber. A multi-channel module, the chamber module, the three-port two-way valve type valve module, the two-port two-way valve type valve module, the three-port two-way valve type valve module, and the pump The module can be configured to be arranged in a substantially hexagonal annular shape in contact with the side portion and another pump module is arranged in contact with the outer side portion of the branch channel module.

  According to the microfluidic chip device of the present invention, a microfluidic chip device customized for various users can be manufactured inexpensively and rapidly by combining various microchip modules manufactured in advance.

It is a plane lineblock diagram of the microfluidic chip device of a 1st embodiment of the present invention. It is a front view of the microfluidic chip device. It is a bottom view of the microfluidic chip device. It is IV-IV sectional drawing of FIG. It is a top view of each module. It is a top view of each module. It is a top view which shows the usage condition of the microfluidic chip device of 1st Embodiment. It is a schematic code diagram which shows the function of the microfluidic chip device. It is a top view which shows the modification of the microfluidic chip device of 1st Embodiment. It is a schematic code diagram which shows the function of the microfluidic chip device. It is a plane block diagram of the microfluidic chip device of a 2nd embodiment. It is a front view of the microfluidic chip device. It is a bottom view of the microfluidic chip device. It is XIV-XIV sectional drawing of FIG. It is a top view which shows the usage condition of the microfluidic chip device of 2nd Embodiment. It is a schematic code diagram which shows another aspect of the microfluidic chip device. It is a perspective view of the microfluidic chip device. It is the perspective view seen from the slanting lower side of the microfluidic chip device.

  Hereinafter, an embodiment of the present invention will be described with reference to the drawings. 1 to 8 show the microfluidic chip device according to the first embodiment, and this microfluidic chip device shows an example of a microfluidic chip device intended for cell culture.

  As shown in FIGS. 1 to 4, the microfluidic chip device stores the sheet-like microfluidic chip 1 in a sheet-like space formed in the plate-like holder 9, and the lower side of the holder 9. In addition, two pump driving units 18 are attached. As will be described later, the microfluidic chip 1 is configured by combining four substantially triangular chip modules each having a triangular sheet as a main body.

  The holder 9 includes a plate-like main body 9a and a cover body 9b covering the plate-like main body 9a. A sheet-like space for storing the microfluidic chip 1 is formed on the upper surface of the plate-like main body 9a so as to cover it. The cover body 9b is attached to. The cover body 9b is fastened and fixed on the plate-like main body 9a by fastening means such as a fastening screw 9d. Legs 9c are attached to the lower four places of the plate-like main body 9a, and the housed microfluidic chip 1 can be held in a horizontal state as shown in FIG. The plate-like main body 9a and the cover body 9b are formed of a hard transparent synthetic resin so that the liquid flowing in the microfluidic channel 10 of the microfluidic chip 1 inside can be observed.

  Moreover, the plate-like main body 9a and the cover body 9b of the holder 9 corresponding to the culture chamber 7a provided in the chamber module 7 described later are provided with openings, and the exposed culture chamber 7a can be easily observed with a microscope or the like. It can be done. Further, as shown in FIGS. 2 and 3, an attachment portion for attaching the pump drive portion 18 is provided at the lower portion of the plate-like main body 9 a together with the opening portion for the pump. The pump drive unit 18 presses the outer peripheral surface of the pump rotor against the tube pump unit 5a of the pump module 5 of the microfluidic chip 1, and drives the so-called peristaltic pump (tube pump) to drive the pump rotor and feed the liquid. It is.

  The pump drive unit 18 has a structure in which a cylindrical pump rotor is rotationally driven by a stepping motor, an air motor, or the like, and rotates while pressing the side surface of the roller provided on the pump rotor against the inner peripheral surface of the tube pump unit 5a. , Send liquid.

  As shown in FIGS. 1, 3, and 4, the microfluidic chip 1 accommodated in the holder 9 includes a branch channel module 2 provided with a branching microfluidic channel 10, a microfluidic channel 5b, and a tube pump unit. The pump module 5 provided with 5a and the chamber module 7 provided with the microfluidic channel 7b and the chamber part (culture chamber 7a) are combined in a substantially triangular shape and configured. Each module is formed from a soft transparent synthetic resin such as PDMS or silicone resin with a sheet-like triangular sheet as a main body, and a microfluidic channel, a tube valve portion, a tube pump portion, a chamber, and the like are formed therein.

  A microfluidic chip 1 shown in FIGS. 1, 3, and 4 is composed of a branch channel module 2, two pump modules 5, and a chamber module 7. The branch channel module 2 is located in the center, and the branch channel module The two pump modules 5 and the chamber module 7 are disposed in contact with the sides around 2 and formed in a substantially triangular shape as a whole.

  The branch channel module 2 is configured such that a port is opened at the center of its three sides and the three ports are connected by a substantially Y-shaped microfluidic channel 10. As shown in FIGS. 3 and 5, the pump module 5 is configured by opening a port of the microfluidic channel 5b at the center of the two sides of the main body and providing a tube pump unit 5a at a substantially central part of the microfluidic channel 5b. Is done. As described above, the pump rotor of the pump drive unit 18 attached to the lower part of the holder 9 is pressed against the tube pump unit 5a. The chamber module 7 is formed with a culture chamber (chamber) 7a substantially at the center of the main body, micro fluid channels 7b are extended on both sides of the culture chamber 7a, and the end portions of the micro fluid channels 7b are connected to the main body of the main body. It is opened at the port at the center of the two sides.

  As shown in FIGS. 1, 3, and 4, the microfluidic channels 5b, 7b, and 10 of each module open to ports provided in the center of the sides of the substantially triangular triangular sheet. A connector 12 made of stainless steel pipe is connected, and the connector 12 connects the microfluidic channels 5b, 7b, and 10 of the modules arranged adjacent to each other. As shown in FIG. 1, the connector 12 is also connected to an external connection port of each module, and a tube to the culture solution supply unit 13, reagent supply unit 14, or waste solution storage unit 15 connects these connectors 12. To the external connection port.

  When manufacturing a microfluidic chip device having the above-described configuration, various modules are designed and manufactured in the form of a substantially triangular shape as described above, and these modules are selected and combined according to the user's request. The fluid chip device can be easily and quickly manufactured.

  5 and 6 show examples of various modules manufactured in advance. Basically, each module is formed to have a substantially triangular sheet-like main body having the same shape, and inside the substantially triangular main body. In addition, a branch channel, a tube valve portion, a tube pump portion, a culture chamber (chamber) and the like are formed.

  The valve module 3 shown in FIG. 5 is provided with a tube valve portion 3a substantially at the center, extending a microfluidic channel 3b on both sides of the tube valve unit 3a, and providing end portions of the microfluidic channel 3b on two sides. It is configured to open with only 2 ports. The tube valve portion 3a of the valve module 3 has a structure in which the plunger tip (pressing portion) of the valve driving portion 17 attached to the lower portion of the holder 9 is pressed to open and close the valve by crushing the tube valve portion 3a. . In the case of an electromagnetic valve, a solenoid plunger of a solenoid valve is used as the valve drive unit 17, but a pneumatic air plunger can also be used. Further, the valve module 3 can be used as a simple flow path module having two ports when the valve driving unit 17 is not provided.

  The branch channel module 2 shown in FIG. 5 is a module that can also be used as the valve module 4. The branch channel module 2 is configured by providing three microfluidic channels 10 (4b) intersecting in a substantially T shape at the center, and the three microfluidic channels 10 (4b) are substantially triangular. Open in 3 ports provided on each side of the shaped sheet-like body. When the branch channel module 2 is used as the valve module 4, the middle portion of one microfluidic channel 4b branched at the center becomes the tube valve portion 4a, and the plunger tip ( The pressing part) is pressed to open and close the flow path. In the valve module 4, one microfluidic channel 4 b among the three branched channels is opened and closed by the operation of the valve driving unit 17.

  In the pump module 5 shown in FIG. 5, as described above, the two ports of the microfluidic channel 5b open at the center of the two sides of the substantially triangular sheet-like main body, and at the substantially central part of the microfluidic channel 5b. A tube pump unit 5a is provided. A pump rotor of a pump drive unit 18 attached to the lower part of the holder 9 is pressed against the tube pump unit 5a to feed the liquid in the microfluidic channel 5b.

  As described above, the chamber module 7 shown in FIG. 6 has a culture chamber (chamber) 7a formed substantially at the center of a substantially triangular body, and microfluidic channels 7b are extended on both sides of the culture chamber 7a. In this structure, the end of the microfluidic channel 7b is opened by a port provided at the center of the two sides of the main body. Further, the chamber module 8 of FIG. 6 has a culture chamber (chamber) 8a formed substantially at the center of a substantially triangular main body, and three microfluidic channels 8b are extended from the culture chamber 8a so that the microfluidic flow In this structure, the end of the path 8b is opened to a port provided at the center of the three sides of the main body.

  As modules other than those shown in FIGS. 5 and 6, the culture solution supply unit, the reagent supply unit, or the waste solution storage unit, which are externally attached in this embodiment, can be configured as a chip module.

  The microfluidic chip 1 shown in FIGS. 1 to 4 selectively uses a branch channel module 2, two pump modules 5, and chamber modules 7 and 8, which are arranged in a substantially triangular shape and combined. Each port opened in the center of each side is connected by a connector 12 to form a pressurized flow path for cell culture.

  That is, the microfluidic chip 1 shown in FIGS. 1 to 4 has a branch channel module 2 arranged upside down at the center, and one pump module 5 is arranged on the branch channel module 2. The other pump module 5 is arranged on the right side of the module 2 and the chamber module 7 is arranged on the left side of the branch channel module 2, and one side portion of each adjacent module is arranged in contact with each other. Since the port is located at the center of the unit, the microfluidic flow paths of the modules are connected to each other via the connector 12 at each port.

  That is, as shown in FIG. 4, the microfluidic channel 5 b that opens to the port on the lower side of one pump module 5 is connected to the microfluidic channel 10 and connector 12 that open to the upper port of the branch channel module 2. Connected through. The microfluidic channel 5 b that opens to the port on the left side of the other pump module 5 is connected to the microfluidic channel 10 that opens to the port on the right side of the branch channel module 2 via the connector 12. Further, the microfluidic channel 7 b that opens to the port on the right side of the chamber module 7 is connected to the microfluidic channel 10 that opens to the port on the left side of the branch channel module 2 via the connector 12.

  As shown in FIG. 1, the microfluidic channel 5 b that opens to the port on the left side of one pump module 5 is connected to an external culture solution supply unit 13 via a connector 12 by a tube or the like. The microfluidic flow path 5 b that opens to the port on the lower side of the other pump module 5 is connected to an external reagent supply unit 14 via a connector 12 by a tube or the like. In addition, the microfluidic flow path 7 b that opens to the port on the left side of the chamber module 7 is connected to an external waste liquid storage unit 15 via a connector 12 by a tube or the like.

  In this way, each module is formed in a substantially triangular shape with a triangular sheet as a main body, and therefore, as shown in FIGS. The held microfluidic chip 1 can be formed in a compact manner. In particular, a microfluidic chip having a circulating microfluidic channel can be configured compactly and easily by arranging the modules in an annular arrangement, as in the microfluidic chip 31 of FIGS. Can do.

  The microfluidic chip 1 is configured as a pressurized microfluidic chip. When the pump driving unit 18 is attached to the two pump modules 5 to drive liquid feeding, as shown in FIGS. 1 and 7, the culture is performed. The pressurization type is that the culture medium is sucked and pressurized from the liquid supply section 13 and fed to the culture chamber 7a, and further, the reagent is sucked and pressurized from the reagent supply section 14 and fed to the culture chamber 7a. However, as shown in FIGS. 9 and 10, it can be configured as a suction type microfluidic chip 21.

  In this case, as shown in FIG. 9 and FIG. 10, the microfluidic chip 21 has the valve module 3 of the two-way valve arranged upside down at the left end and the valve module 4 of the three-way valve on the right side. Are arranged in contact with each other, the pump module 5 is arranged on the right side thereof with the side part in contact and inverted upside down, and the chamber module 7 is arranged on the right side with the side part in contact with each other. Are arranged in a row. The three-port two-way valve of the valve module 4 is a valve that opens and closes one flow path, but it can also be a normal three-way valve that switches between two ports, and is a concept that includes it.

  Since the sides of each module are arranged in contact with each other, the ports of the modules (openings of the microfluidic channel) located at the center of each side abut at the same position, and each microfluidic flow of each module The ports of the paths 3b, 4b, 5b, and 7b are connected to each other by the connector 12. Then, the port of the microfluidic channel 3b that opens to the left end of the microfluidic chip 21 shown in FIG. 9 is connected to the culture solution supply unit 13 via a tube and opens to the lower end of the microfluidic chip 21. The port of the fluid flow path 4b is connected to the reagent supply unit 14 via a tube. In addition, the microfluidic chip 21 is connected to a port of the microfluidic flow path 7b opened at the right end portion of the microfluidic chip 21 via the connector 12 to the external waste liquid storage unit 15 with a tube or the like.

  When cell culture is performed using the microfluidic chip 21, the culture solution and the reagent are sucked and fed by the operation of the pump module 5. In the microfluidic chip 21, first, the tube valve portion 3 a of the valve module 3 is opened, the tube pump portion 5 a of the pump module 5 is operated to suck the culture solution, and the solution is fed into the culture chamber 7 a of the chamber module 7. . Next, the tube valve part 4a of the valve module 4 is opened, the tube valve part 3a of the valve module 3 is closed, the tube pump part 5a of the pump module 5 is operated, the reagent is sucked, and the culture chamber 7a of the chamber module 7 is filled. Deliver reagent. In this manner, by using the microfluidic chip 21 shown in FIGS. 9 and 10, a suction type microfluidic chip device can be configured.

  As described above, in the microfluidic chip device of the present invention, a plurality of modules having various functions in various forms are manufactured in advance, and a necessary module is selected from those modules according to the user's request. By combining them, it is possible to easily manufacture a microfluidic chip device that meets the needs of the user, and thus the device can be manufactured inexpensively and quickly.

  Next, the usage mode of the microfluidic chip device using the microfluidic chip 1 shown in FIGS. This microfluidic chip device is used for cell culture. In this case, as shown in FIG. 1, the culture solution is put in the culture solution supply unit 13, and the reagent such as a growth factor is put in the reagent supply unit 14. Thereafter, the cells are put into the culture chamber 7a. Collagen and fibrinogen are coated on the inner surface of the culture chamber 7a of the chamber module 7 in order to seed the cells, so that the cells can easily adhere in the culture chamber 7a.

  In this state, first, the culture medium pump drive unit 18 is driven, the tube pump unit 5a of the pump module 5 is operated, the culture solution is sucked from the supply unit 13, and the culture module 7a of the chamber module 7 Inject and inject. Next, the reagent pump drive unit 18 is driven, the tube pump unit 5a of the pump module 5 is operated, the reagent is sucked from the supply unit 14, and is fed into the culture chamber 7a of the chamber module 7 for injection. To do.

  In order to prevent unnecessary bubbles from entering the culture chamber 7a, it is effective to fill the culture chamber 7a with the culture solution before feeding the culture solution containing cells to the culture chamber 7a. .

  In such a state, the time required for cell culture is passed and the cells are cultured. Then, the culture solution in the culture chamber 7 a is drained through the microfluidic channel 7 b on the discharge side of the chamber module 7. The supply and disposal of the culture solution is repeated periodically until the cell culture is completed.

  As described above, the microfluidic chip 1 including all the liquid contact parts is formed in a sheet shape separately from the valve driving part 17 and the pump driving part 18, and can be easily taken out by removing the cover body 9 b of the holder 9. Therefore, the wetted part can be easily sterilized or washed, and can also be used as a disposable instrument. Thereby, contamination of a culture solution and mixing of bacteria can be prevented.

  11 to 18 show the microfluidic chip device of the second embodiment. In the following description of the microfluidic chip device according to the second embodiment, the same reference numerals as those in the above description are given to the same components as those in the first embodiment, and the detailed description thereof is omitted.

  In this microfluidic chip device, as shown in FIG. 11, the modules are combined so that the microfluidic channel of the microfluidic chip 31 is a circulating channel, and the culture solution and the reagent are circulated in the circulating channel. Configured.

  17 and 18, the microfluidic chip device accommodates a sheet-like microfluidic chip 31 in a sheet-like space formed in a plate-like holder 19, and 3 A single valve drive unit 17 and two pump drive units 18 are attached. Similarly to the above, the microfluidic chip 31 is configured by combining seven substantially triangular chip modules each having a triangular sheet as a main body.

  The holder 19 includes a plate-shaped main body 19a and a cover body 19b covering the plate-shaped main body 19a. A sheet-like space for accommodating the microfluidic chip 31 is formed on the upper surface of the plate-shaped main body 19a so as to cover it. The cover body 19b is attached to. The cover body 19b is fastened and fixed on the plate-like main body 19a by fastening means such as a fastening screw 9d. Leg portions 19c are attached to the lower four places of the plate-shaped main body 19a, and the microfluidic chip 31 accommodated therein can be held in a horizontal state.

  The plate-like main body 19a and the cover body 19b are formed of a hard transparent synthetic resin so that the liquid flowing in the microfluidic channel of the microfluidic chip 31 inside can be observed. Further, the plate-like main body 19a and the cover body 19b of the holder 19 corresponding to the culture chamber 7a of the chamber module 7 are provided with openings so that the exposed culture chamber 7a can be easily observed with a microscope or the like. .

  As shown in FIGS. 11, 13, 14, and 15, the microfluidic chip 31 accommodated in the holder 19 includes the branch channel module 2 provided with the branching microfluidic channel 10, the microfluidic channel 5b, and the tube. Two pump modules 5 provided with a pump unit 5a, a chamber module 7 provided with a microfluidic channel 7b and a culture chamber 7a, and a valve module 3 provided with a two-way microfluidic channel 3b and a tube valve unit 3a And two valve modules 4 provided with a three-direction microfluidic flow path 4b and a tube valve portion 4a that are branched in a T-shape are combined in a substantially hexagonal (abnormal hexagonal) ring shape. .

  As shown in FIG. 15, the microfluidic chip 31 includes six modules having a substantially triangular sheet-like main body arranged in a ring shape in a hexagonal shape, and one unit outside the branch channel module 2. The pump module 5 is arranged and added. The microfluidic chip 31 is arranged in contact with the sides of adjacent modules, so that the ports of the microfluidic channels 3b, 4b, 5b, 7b, and 10 that open to the center of each side are at the same position. By arranging them and connecting them with each other through the connector 12, a circulation channel using microfluidic channels can be formed compactly.

  As shown in FIG. 15, the microfluidic chip 31 is arranged on the right side of the branch channel module 2 with one pump module 5 turned upside down, and the other pump module 5 on the left side of the branch channel module 2. The chamber module 7 is arranged upside down below the branch channel module 2.

  Further, one valve module 4 having a microfluidic channel 4b and a tube valve portion 4a branched in three directions is arranged on the left side of the chamber module 7, and the valve module 3 of the two-way valve is moved up and down on the left side of the valve module 4. Further, the other valve module 4 having the microfluidic flow path 4b and the tube valve portion 4a branched in three directions on the valve module 3 is arranged. Since 1 to 3 sides of each adjacent module are arranged in contact with each other and the port is located at the center of each side, the microfluidic channel of each module must be accurately connected through the connector 12 at each port. Can do.

  As shown in FIG. 15, in this microfluidic chip 31, the port of the microfluidic channel 10 that opens to the left side of the branch channel module 2 is connected to the right side of one pump module 5 adjacent to the left side. Is connected to the port of the microfluidic channel 5b of the part via the connector 12. Further, the port of the microfluidic channel 5b that opens to the left side of the pump module 5 is connected to the port of the microfluidic channel 4b that opens to the right side of the valve module 4 adjacent to the left side of the connector 12. Connected through.

  Furthermore, the port of the microfluidic channel 4b that opens to the lower side of the valve module 4 is connected to the port of the microfluidic channel 3b that opens to the upper side of the valve module 3 adjacent thereto via the connector 12, and the valve The port of the microfluidic channel 3b that opens to the right side of the module 3 is connected to the port of the microfluidic channel 4b that opens to the left side of the other valve module 4 adjacent thereto. Furthermore, the port of the microfluidic channel 4b that opens to the right side of the valve module 4 is connected to the port of the microfluidic channel 7b that opens to the left side of the chamber module 7 adjacent to the right side via the connector 12. Connected.

  As shown in FIG. 15, the port of the microfluidic channel 5 b that opens to the right side of one pump module 5 is connected to an external reagent supply unit 14 via a connector 12 by a tube or the like. The port of the microfluidic channel 4b that opens to the left side of the other valve module 4 is connected to an external culture solution supply unit 13 via a connector 12 by a tube or the like. In addition, the port of the microfluidic channel 4b that opens to the lower side of the valve module 4 located on the lower side is connected to an external waste liquid storage unit 15 via a connector 12 by a tube or the like.

  Thus, since each module is formed in a substantially triangular shape with a triangular sheet as a main body, it can be easily combined into a substantially hexagonal shape as a whole, as shown in FIGS. The microfluidic chip 31 provided with the fluid flow path can be formed in a compact manner.

  When the pump module 5 connected to the reagent supply unit 14 does not have a closing function at the time of stop, the valve module 4 is connected to the flow path of the pump module 5 as shown in FIG. Is preferably performed.

  Next, a usage mode of the microfluidic chip device used for cell culture using the microfluidic chip 31 having the above configuration will be described. As shown in FIG. 11, the culture solution is put in the culture solution supply unit 13, and the reagent such as a growth factor is put in the reagent supply unit 14. Thereafter, the cells are put into the culture chamber 7a. The inner surface of the culture chamber 7a of the chamber module 7 is coated with collagen or fibrinogen in order to seed cells.

  When cell culture is performed, first, the valve drive unit 17 of the valve module 4 is operated, the tube valve unit 4a is opened, the pump drive unit 18 of the pump module 5 for culture solution is driven, and the tube pump of the pump module 5 is driven. The unit 5 a is operated to suck the culture solution from the supply unit 13, and feed and inject the solution into the culture chamber 7 a of the chamber module 7. Next, the pump drive unit 18 of the pump module 5 for reagent is driven, the tube pump unit 5a of the pump module 5 is operated, the reagent is sucked from the supply unit 14, and the reagent is sucked into the culture chamber 7a of the chamber module 7 Pump and inject.

  Then, in this state, the pump driving units 18 of the two pump modules 5 are driven to operate the tube pump units 5a of the two pump modules 5, and the microfluidic flow formed in the microfluidic chip 31 is operated. In the circulation path composed of the paths 3b, 4b, 5b, 7b, and 10 and the culture chamber 7a, the culture solution and the reagent are circulated for a necessary time to culture the cells. Then, after the cell culture is completed, the valve drive unit 17 of the valve module 4 is operated to open the tube valve unit 4a, and the culture fluid in the culture chamber 7a is used as the microfluidic flow path 7b on the discharge side of the chamber module 7. To the waste fluid container 15 through the microfluidic flow path 4b of the valve module 4.

  As described above, in the microfluidic chip device including the microfluidic chip 31, a circulation channel is formed, and cell culture can be performed by circulating the culture solution and the reagent for a desired time. Further, the microfluidic chip 31 including all the liquid contact parts is formed in a sheet shape separately from the valve driving part 17 and the pump driving part 18, and can be easily taken out by removing the cover body 19 b of the holder 19. Therefore, the wetted part can be easily sterilized or washed, and can also be used as a disposable instrument, thereby preventing contamination of the culture medium and contamination of bacteria.

  In the above embodiment, an example in which the microfluidic chip device of the present invention is used for cell culture has been described. However, it can also be used for various chemical synthesis and chemical analysis. In the above, the microfluidic channels of each module are connected by a stainless steel pipe connector, but a synthetic resin or the like can be used as the material of the connector.

DESCRIPTION OF SYMBOLS 1 Microfluidic chip 2 Branch channel module 3 Valve module 3a Tube valve part 3b Microfluidic channel 4 Valve module 4a Tube valve part 4b Microfluidic channel 5 Pump module 5a Tube pump part 5b Microfluidic channel 7 Chamber module 7a Culture Chamber 7b Microfluidic channel 8 Chamber module 8a Culture chamber 8b Microfluidic channel 9 Holder 9a Plate body 9b Cover body 9c Leg 10 Microfluidic channel 12 Connector 13 Supply unit 14 Supply unit 15 Waste liquid storage unit 17 Valve drive unit 18 pump drive unit 19 holder 19a plate-like body 19b cover body 19c leg 21 microfluidic chip 31 microfluidic chip

Claims (12)

A sheet-like microfluidic chip soft microfluidic channel is formed in a part of the microfluidic flow path, the valve portion for opening and closing the microfluidic flow path, a pump unit for feeding a liquid, or a liquid A microfluidic chip device in which at least one portion of a chamber portion to be stored is disposed, and a liquid is allowed to flow through the microfluidic channel,
The microfluidic chip pump module provided with the branch flow path module which is provided the microfluidic flow path that branches, the valve module provided the microfluidic channel and the valve section, the microfluidic channel and pump unit When, or a chamber module provided the microfluidic channel and the chamber part, at least two modules chosen from, dividedly formed by modularized into certain shape,
The branch flow path module, the valve module, the pump module, at least two modules of the chamber modules are joined, and in a state in which the microfluidic channel of the respective modules are connected to each other by a connector, all The microfluidic chip device is housed in a holder having a plate-like main body and a cover plate covering the plate-like main body .
At least two of the branch channel module, the valve module, the pump module, and the chamber module housed in the holder are formed from a triangular sheet having a substantially triangular plane. The microfluidic chip device according to claim 1.   3. The microfluidic chip device according to claim 2, wherein an end of the microfluidic channel in the module opens at a center position of a side of the triangular sheet.   The holder is molded from a hard synthetic resin, the branch channel module, the valve module, the pump module, and the chamber module are molded from a soft transparent synthetic resin, and the microfluidic channel in each module is soft 2. The microfluidic chip device according to claim 1, wherein the microfluidic chip device is formed in a tube shape.   The microfluidic channel in the branch channel module is formed by branching into three channels, and the ports of the three channels open to the center positions of the respective sides of the triangular sheet. The microfluidic chip device according to claim 2, wherein   2. The microfluidic chip device according to claim 1, wherein the pump module is formed as a tube pump that is driven to rotate by pressing a rotating part of a pump driving unit against a tube in the module.   2. The microfluidic chip device according to claim 1, wherein the valve module is formed as a valve that is driven by pressing a head portion of a valve driving unit against a tube in the module. As the chamber portion of the chamber module is exposed, the microfluidic chip device according to claim 4, wherein the opening is formed in the corresponding portion of the holder.
The holder, on the plate-like body formed in a plate shape, a sheet-like recess for the module is formed while covering the upper plate-like body in said cover plate, the cover plate by means tightening microfluidic chip device is fastened claim 1, wherein Rukoto.
  The microfluidic chip device is composed of the branch channel module, the two pump modules, and the chamber module, and the branch channel module is positioned at the center, and on the side portion around the branch channel module. 2. The microfluidic chip device according to claim 1, wherein the two pump modules and the chamber module are arranged in contact with each other and formed in a substantially triangular shape as a whole.   The microfluidic chip device is composed of the two-port two-way valve type valve module, the three-port two-way valve type valve module, the pump module, and the chamber module. The microfluidic chip device according to claim 1, wherein the microfluidic chip device is disposed in contact with each other.   The microfluidic chip device includes the two-port two-way valve type valve module, the three-port two-way valve type two valve modules, the branch channel module, the two pump modules, and the chamber module. The branch channel module, the chamber module, the three-port two-way valve type valve module, the two-port two-way valve type valve module, the three-port two-way valve type valve module, and the pump module 2. A microfluidic chip device according to claim 1, wherein said pump module is arranged in contact with an outer side portion of said branch channel module in a substantially hexagonal annular shape. .

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