JP2006272230A - Integrated micro fluid device and method for correcting deviation of flow rate in the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To restrain a deviation of the volume flow velocity, which is caused by the individual variation of each of a plurality of micro fluid devices connected to one another in parallel, of a fluid flowing in each of them when they are operated while distributing/supplying the fluid to them from a fluid driving mechanism such as one pump and a pressurized storage tank. <P>SOLUTION: This integrated micro fluid device is characterized in that a flow passage inlet of each of the plurality of micro fluid devices each having an individual variation in pressure loss is connected to one fluid driving mechanism by a branched connection pipeline. A correction pipeline is arranged in a portion of the branched connection pipeline from a branched part thereof to the flow passage inlet and/or at a flow passage outlet of each of them. The correction pipeline is prepared so that the value obtained by dividing the standard deviation of the sum of pressure losses of the correction pipeline and the micro fluid device connected thereto by the mean of the sum of the pressure losses is made smaller than the value obtained by dividing the standard deviation of the pressure loss of the connected micro fluid device by the mean of the pressure losses and made equal to or smaller than 5%. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an integrated microfluidic device in which a plurality of microfluidic devices having individual differences in pressure loss are connected in parallel, and the integrated microfluidic device in which a deviation in flow rate due to the individual differences in pressure loss is reduced Further, the present invention relates to a flow rate deviation reduction method caused by individual differences in the pressure loss.

  A microfluidic device is also called a microchannel, a microchannel chip, a chemical IC (IC), a microreactor, a microanalysis chip, a microtas (μ-TAS), and the like. This device is used for reaction, processing, analysis, detection, etc., such as chemical, biochemical, and electrochemical. For example, chemical or biochemical synthesis or degradation reaction devices; membrane filtration, dialysis, deaeration, inhalation, extraction, dispersion, mixing, oil / water separation and other chemical engineering processing devices; DNA analysis, protein analysis, sugar chain analysis , Electrophoresis, liquid chromatography, gas analysis, water analysis, and other analytical devices; and micro nozzles for producing microarrays such as DNA chips and microparticles.

  In microfluidic devices, especially in the fields of chemistry, biochemical reactions, and chemical engineering processing, it is possible to speed up processing, reduce by-products, speed up conditions, etc., and determine optimum operating conditions. And by operating the same number of microfluidic devices in parallel for the required production volume (pile-up production system), production can be performed without consideration of scale-up, from the end of basic research to the operation of the production plant. It is said that the time and cost can be greatly reduced, and it is expected as a chemical reaction apparatus and chemical engineering processing apparatus in the future. Also, in the field of (bio) chemical analysis, it is said that a large number of parallel operations can be easily performed in analysis and preprocessing, and the efficiency of analysis can be improved and the cost can be reduced.

  As what connected such a microfluidic device in parallel, the microreactor system which connected the microreactor in parallel is disclosed, for example (refer patent document 1). This is to suppress inconvenience such as a decrease in reaction yield in a microreactor system in which these are connected in parallel by suppressing pressure fluctuations of individual microreactors. However, it is actually difficult to suppress the pressure fluctuation of each microreactor because it is necessary to produce a fine structure with high precision, and the pressure loss of each microreactor due to manufacturing errors and changes over time. There was a tendency for individual differences to occur.

  This situation is the same for microfluidic devices other than microreactors. When a fluid is supplied from one pump or pressurized reservoir to microfluidic devices installed in parallel, the pressure loss of each microfluidic device is reduced. Due to individual differences, there is a difference in the volume flow rate (volume flow rate per unit time) of the fluid flowing through each microfluidic device, which causes deviation (variation) in product characteristics and analysis results.

JP 2004-16904 A

  The problem to be solved by the present invention is to connect a plurality of microfluidic devices in parallel and distribute and supply a fluid from a fluid drive mechanism such as a single pump or a pressurized reservoir. By improving the deviation of the flow rate of the fluid flowing through each microfluidic device due to individual differences, it is to improve the uniformity of the characteristics and analysis results of the products manufactured by the fluidic device systems connected in parallel.

  In order to suppress deviations in the flow rate of fluid flowing through a plurality of microfluidic devices connected in parallel and having individual differences in pressure loss, the present inventors have used microdrives from fluid drive mechanisms such as pumps and pressurized reservoirs. It is only necessary to reduce the deviation of the total pressure loss between the pipe and the flow path until the fluid flows out through the flow path of the fluid device, and the pressure loss of the pipe can be adjusted by adjusting the length of the pipe. Since it can be adjusted accurately and simply, it has been found that the problem can be solved by adjusting the pressure loss of the pipe so that the sum of the pressure losses of both is constant, and the present invention has been achieved.

  That is, according to the present invention, each flow path inlet of a plurality of microfluidic devices having individual differences in pressure loss from the flow path inlet to the flow path outlet is connected to one fluid drive mechanism via a branched connection pipe. (1) correction pipes are provided as portions from the branching portion of the connection pipe to the flow path inlet, and / or corrections are made at the flow path outlet of the device, respectively. And (2) the value obtained by dividing the standard deviation of the sum of the pressure losses of the correction pipe and the microfluidic device connected thereto by the average of the sum of the pressure losses is the pressure of the microfluidic device. Each of the correction pipes is prepared such that the standard deviation of the loss is smaller than a value obtained by dividing the standard deviation of the pressure loss and is 5% or less. Providing b fluidic device.

  In addition, the present invention provides a single fluid drive mechanism to each flow channel inlet with a plurality of microfluidic devices having individual differences in pressure loss from the flow channel inlet to the flow channel outlet through a branched connection pipe. A method for correcting a flow rate deviation flowing in each microfluidic device of the connected integrated microfluidic device, wherein (1) a correction pipe is provided as a part from the branch portion of the connection pipe to the flow path inlet, And / or providing correction pipes at the outlets of the flow paths of the devices, respectively, and (2) the correction pipes having a standard deviation of the sum of pressure losses of the correction pipes and the microfluidic devices connected thereto. And adjusting the correction piping so that the standard deviation of the pressure loss of the microfluidic device is smaller than the value obtained by dividing the pressure loss by an average and not more than 5%. Providing flow rate difference correction method according to symptoms.

  The present invention relates to the construction of an integrated microfluidic device in which a plurality of microfluidic devices having individual differences in pressure loss are connected in parallel and a fluid is distributed and supplied from a single fluid drive mechanism. The deviation of the flow rate caused by the individual difference between the two can be corrected to improve the uniformity of the characteristics and analysis results of the product manufactured by the integrated microfluidic device.

[Microfluidic device]
A capillary channel provided in a microfluidic device (hereinafter sometimes simply referred to as “device”) is a flow having a function as a field for reaction and detection in addition to a channel for simple fluid transfer. Including roads. The size and shape of the flow path are arbitrary, and can be set to a suitable size and shape according to the purpose of use. For example, the cross-sectional shape can be a circle, a semicircle, a rectangle, a trapezoid, a slit, or the like. Although the cross-sectional area of a flow path is arbitrary, 1-100000 micrometers ² are preferable and 100-10000 micrometers ² are more preferable. In this range, the pressure loss (hereinafter referred to as “(in the flow path) fluid at a constant volume flow rate) when the fluid is flowed through the flow path of the microfluidic device at a constant volume flow velocity (volume flow rate per unit time). The “pressure loss in the case of flowing the flow” is simply referred to as “pressure loss (of the flow path)”, which is a value at which the effect of the present invention is easily exhibited.

  The pressure loss of the microfluidic device is arbitrary, but the pressure loss under the usage conditions of the microfluidic device is preferably 100 Pa to 1 MPa, and more preferably 1 to 300 kPa. When a microfluidic device having a pressure loss in this range is used, the present invention can be easily implemented, and the effects of the present invention are sufficiently exhibited. The pressure loss refers to the pressure loss of the flow path from the flow path inlet to the flow path outlet of the microfluidic device. The pressure loss value is an average value of a plurality of microfluidic devices connected in parallel.

  An integrated microfluidic device of the present invention (hereinafter sometimes simply referred to as “integrated device”) is configured by connecting the microfluidic devices in parallel. The degree of individual difference in the pressure loss of the devices constituting the integrated device, that is, the deviation (variation) is not particularly limited, but the effect of the present invention is exhibited as the deviation is larger. For example, the pressure loss deviation of the microfluidic device is a value obtained by dividing the standard deviation by the average (hereinafter referred to as a coefficient of variation. That is, the coefficient of variation = 100 × standard deviation / average, (%)] is 3% or more. The upper limit of the coefficient of variation need not be limited, and the effect of the present invention can be exhibited no matter how large, but is preferably 100% or less, and preferably 30% or less. Within this range, the deviation of the pressure loss can be improved to a practical level without excessively increasing the length of the correction pipe, which will be described later, and without increasing the pressure loss of the correction pipe so much. When the pressure loss of the microfluidic device is as low as 0.1 to 1 kPa, for example, even if the coefficient of variation in the pressure loss of the device is as large as 1000%, it is sufficient without any inconvenience. It can be improved.

  In this sense, the microfluidic device constituting the integrated device of the present invention is provided with a flow path having fillers and holding materials such as beads and fibers inside, and a structure such as a porous layer, irregularities, and pillars on the inner surface. Compared to a simple capillary channel, a structure having a structure other than a simple channel, such as a filtration membrane, a nozzle, a check valve, a pressure valve, an on-off valve, a channel switching valve, etc. Therefore, the deviation of the pressure loss tends to be large, which is preferable because the effects of the present invention are easily exhibited.

  Note that if there is a deviation in pressure loss among a plurality of microfluidic devices, a deviation occurs in the volume flow rate when a fluid is flowed at a pressure common to these devices. Since the volume flow rate and the pressure loss are in an inversely proportional relationship, the standard deviation of the volume flow rate is proportional to the standard deviation of the reciprocal of the pressure loss, and the variation coefficient of the volume flow rate coincides with the variation coefficient of the reciprocal of the pressure loss.

  The number of microfluidic devices connected in parallel in the present invention is arbitrary as long as it is 2 or more, preferably 2 to 100,000, more preferably 10 to 100,000, and most preferably 10 to 10,000. When the number connected in parallel is in the above range, the pressure loss of each microfluidic device can be measured relatively easily.

[Fluid drive mechanism]
The plurality of microfluidic devices described above are connected to a fluid drive mechanism for flowing fluid. The fluid driving mechanism is arbitrary, and examples thereof include a pump, a pressurized storage tank, a decompression storage tank, and an ultrasonic drive unit. The type of the pump is arbitrary, and examples thereof include a pump whose discharge amount is dependent on discharge pressure, such as a syringe pump, a plunger pump, and an electroosmotic pump. Examples of the pressurized storage tank include a pressurized storage tank pressurized with a gas and a liquid storage tank in which a liquid is allowed to flow due to a difference in height of the liquid. In the case where the fluid drive mechanism is driven by suction, the same pump, reduced pressure storage tank, and liquid storage tank reduced in pressure due to the height difference of the liquid can be used.

[Connection piping]
In the present invention, the plurality of microfluidic devices are connected from one fluid drive mechanism by connection piping branched according to the number of the plurality of microfluidic devices. The connection pipes may be branched and connected directly from the fluid drive mechanism by the number of microfluidic devices, or after branching from the fluid drive mechanism through one common pipe part, each individual pipe part is micro-connected. It may be connected to a fluid device, or may be branched after passing through a plurality of common piping parts from the fluid driving mechanism, and each individual piping part may be connected to the microfluidic device, or a plurality of stages in a dendritic shape. Each branch may be connected to the microfluidic device by repeating this branching. Here, the individual piping portion refers to a piping portion from the branching portion to the microfluidic device in the piping connected between the fluid drive mechanism and the microfluidic device, and a part of the piping continuous with the common piping portion or the branching portion. It may be a separate pipe connected to the branching portion. The individual pipe portion can be a correction pipe as will be described later.

[Outlet piping]
An outlet side pipe may be connected to the outlet of the flow path of each microfluidic device for the purpose of collecting the discharged fluid. The outlet side pipe, when the inlet side pipe is a correction pipe, is a pipe for collecting fluid discharged from the flow path outlet of the microfluidic device, a pipe for supplying to other devices, etc. Any pipe may be used. Further, as will be described later, the outlet side pipe may be a correction pipe.

[Correction piping]
In the present invention, at least one of the individual pipe portion of the connection pipe and the outlet side pipe is a correction pipe. When one of the individual piping part of the connection pipe and the outlet side pipe is used as a correction pipe, which one of the correction pipes is used may be different for each microfluidic device connected in parallel. It is preferable that they are unified. By unifying, the pressure difference applied to each microfluidic device is reduced, and it becomes easy to reduce the pressure loss deviation of the correction pipe.

  When the individual pipe portion of the connection pipe is a correction pipe (this is the first aspect), the presence / absence of the outlet side pipe and the pressure loss characteristics are arbitrary.

  When the outlet side pipe is a correction pipe (this is the second mode), the pressure loss of the connection pipe is arbitrary.

  Both the connection pipe and the outlet side pipe may be correction pipes. That is, the first aspect and the second aspect may be used in combination. In this case, the length of the correction pipe and the pressure loss are the sum of the individual pipe portion of the connection pipe and the correction pipe on the outlet side. This embodiment is preferable when the pressure loss of the microfluidic device is large or when the deviation of the pressure loss of the microfluidic device is large.

  In the present invention, the value obtained by dividing the standard deviation of the sum of the pressure losses of the correction pipe and the microfluidic device connected thereto by the average of the sum of the pressure losses (that is, the coefficient of variation) is the integrated type. It is smaller than the variation coefficient of pressure loss of the microfluidic device constituting the microfluidic device, and the variation coefficient is 5% or less, preferably 3% or less, more preferably 2% or less, and most preferably 1% or less. Further, each of the correction pipes is adjusted.

[First aspect]
In the first aspect of the present invention, the individual piping portion of the connecting piping from the branch portion of the connecting piping to the flow channel inlet of each microfluidic device is used as the correction piping. Each correction pipe determines the pressure loss so that the sum of the pressure loss of the correction pipe and the pressure loss of the device connected thereto is constant. The method for determining the pressure loss of the correction piping as described above is arbitrary.For example, (1) a fluid is flowed to each microfluidic device at a constant volume flow rate, the pressure loss of each microfluidic device is measured, and accordingly (2) Measure the total pressure loss in the same way as in (1) above, with the fixed pressure loss correction pipe connected to each microfluidic device. Then, adjust the length by cutting the correction piping so that the total pressure loss becomes a constant value. (3) In (1) above, let the fluid flow with a constant pressure difference instead of a constant volume flow rate. A method of measuring the volume flow rate and correcting it by converting it to pressure loss. (4) In the above (2), instead of a constant volume flow rate, a fluid is flowed with a constant pressure difference so that each volume flow rate becomes constant. Adjust the length of the correction pipe to correct it. It can be.

  In addition, the method of determining the pressure loss of the correction pipe is also arbitrary, (1) a method of measuring the pressure loss per fixed length of the pipe, calculating the length corresponding to the pressure loss to be corrected, and preparing ( 2) A method of obtaining a correction pipe having a target pressure loss can be exemplified by measuring the pressure loss.

  The pressure loss of the correction piping having the minimum pressure loss (ie, the minimum correction amount of pressure loss) is arbitrary, but is preferably not more than 10 times the pressure loss of the microfluidic device to which it is connected, more preferably 3 No more than twice, most preferably no more than 1 time. The pressure loss of other correction piping is determined according to the pressure loss deviation of the microfluidic device. By making this range, when correcting the pressure loss with the length of the correction pipe, even if the coefficient of variation of the pressure loss of the pipe used as the correction pipe is large, the error as the standard deviation of the pressure loss is reduced. High-precision correction can be easily performed. Furthermore, it is not necessary to increase the pressure resistance of the correction pipe and the pressure resistance of the connection portion between the connection pipe and the fluid drive mechanism, and a low discharge pressure can be used as the fluid drive mechanism. The lower limit of the pressure loss of the correction pipe may be zero for the correction pipe connected to the device exhibiting the highest pressure loss among the microfluidic devices constituting the integrated device of the present invention. The lower limit of the pressure loss of the correction piping connected to the microfluidic device exhibiting the lowest pressure loss among the devices constituting the integrated device is the maximum pressure loss and the lowest pressure in the device constituting the integrated device. The difference in loss.

  By the way, in this 1st aspect, the pressure loss of the common piping part of the said connection piping is arbitrary when this common piping part is one, and those pressure losses are the same when there are two or more. If present, the value can be arbitrarily obtained. However, the pressure loss is preferably sufficiently smaller than the pressure loss of the individual piping part that is the correction piping, for example, preferably 10% or less, more preferably 5% or less, and most preferably 2% or less. The lower limit is preferably as close to zero as possible. By setting it as this range, the influence by the error of the position which connects correction | amendment piping to a common piping part becomes small, and the fluctuation improvement effect of this invention is fully exhibited.

  The pressure loss of the correction pipe can be adjusted by selecting the inner diameter (or cross-sectional area) and the length. In the present invention, the inner diameter of the correction pipe is preferably in the range of 10 to 200 μm, more preferably 20 to 100 μm. The inner diameter of the correction pipe can be selected according to the volume flow rate of the fluid flowing through the microfluidic device used and the pressure loss of the microfluidic device. The smaller the volume flow rate when using the microfluidic device, It is preferable to use a smaller diameter as the pressure loss is higher. Of course, the inner diameter does not need to be constant, and may change, for example, from the middle. The cross-sectional shape of the flow path of the connecting pipe is preferably a circle, but if it is other than a circle, it has a cross-sectional area corresponding to the inner diameter.

  The length of the correction pipe is arbitrary, and if the pressure loss is adjusted as described above, a suitable value can be obtained depending on the size of the integrated microfluidic device and the number of parallel connections. For example, the length of the shortest correction pipe is determined according to the pressure loss deviation of the microfluidic device. Moreover, it is also preferable to set it as 0.01 m or more, and cutting and connection of piping become easy. Furthermore, it is also preferable to set it as 0.5 m or more, and correction | amendment piping can combine the function of connection piping or outlet side piping. The upper limit of the length of the shortest correction pipe is preferably 5 m or less, and more preferably 3 m or less. By making it below this range, it can correct | amend compactly. The inner diameter can be selected so that the length falls within a preferred range.

  In the present invention, the coefficient of variation in pressure loss of a certain length of the pipe used as the correction pipe is arbitrary, but is smaller than the coefficient of variation in pressure loss of the microfluidic device, for example, preferably Is preferably less than 1 time, more preferably less than 1/2, and most preferably less than 1/4. As a result, the pressure loss can be estimated with sufficient accuracy from the length of the correction pipe, so the correction pipe can be formed by simply cutting to the calculated length without measuring the pressure loss. It becomes extremely easy. In addition, the coefficient of variation of commercially available industrial products of pipes that can be used as correction pipes is usually less than 2%.

  Moreover, although the material of correction | amendment piping is arbitrary, what has high hardness is preferable when raising the dimensional accuracy of correction | amendment piping. In particular, when the sum of the pressure loss of the correction pipe and the microfluidic device is large, for example, 100 kPa or more, it is preferable to reduce the fluctuation of the inner diameter of the correction pipe during operation. The material of the correction pipe has, for example, a Young's modulus of preferably 1 MPa or more, more preferably 2 MPa or more, and most preferably 3 MPa or more. The upper limit of the Young's modulus is preferably higher if the piping is not fragile, and it is not particularly necessary to provide an upper limit, but it is preferably 500 MPa, more preferably 200 MPa or less from the viewpoint of ease of production. The correction pipe may be a metal, glass, crystal such as quartz, an organic polymer, or the like, but the organic polymer is preferable because it has both flexibility and high breaking strength. Of course, these composites may also be used.

  Organic polymers include thermosetting resins such as polyimide, (aromatic) polyamide, polytetrafluoroethylene, polyethylene, polypropylene, polysulfone, polyetheretherketone, polyphenylene sulfide, polyvinyl chloride, polyvinylidene chloride, polyfluoride. Thermoplastic resins such as vinylidene fluoride and PFA (copolymer of tetrafluoroethylene and alkoxyfluoroethylene) are preferably used. Of course, the organic polymer may be a copolymer or a blend.

  In this first aspect, when an outlet side pipe is connected to the channel outlet side of the microfluidic device, the pressure loss of the outlet side pipe is arbitrary, but the standard deviation of the pressure loss of the outlet side pipe is The standard deviation of the total pressure loss of the correction pipe and the microfluidic device is preferably smaller than the standard deviation. When the standard deviation of the pressure loss is small, the effect of the present invention is not impaired even if the pressure loss of the piping used is large.

  Further, the pressure loss of the outlet side pipe is preferably less than the sum of the pressure loss of the correction pipe and the device, more preferably less than 50%, and most preferably less than 20% of the sum. By reducing the pressure loss, the standard deviation of the pressure loss becomes smaller than the above sum even when a pipe having a large variation coefficient of the pressure loss is used, and the effect of the present invention is not impaired.

  Alternatively, in the present invention, it is also preferable that the sum of the pressure loss of the outlet side pipe and the pressure loss of the microfluidic device is regarded as the pressure loss of the microfluidic device, and the deviation of the pressure loss is corrected by the correction pipe. This method is preferable when the deviation of the pressure loss of the outlet side pipe is not so large as to be negligible compared to the deviation of the pressure loss of the microfluidic device, and the deviation of the pressure loss of the outlet side pipe can be corrected at the same time. .

  In this first aspect, even if the pressure loss of the correction piping is large, the pressure applied to the microfluidic device does not increase. Therefore, it is necessary to increase the pressure resistance of the microfluidic device itself and the pressure resistance of the connecting portion between the correction piping and the device. There is no.

[Second embodiment]
In the second aspect of the present invention, the outlet side pipe connected to the flow path outlet of each microfluidic device is a correction pipe. The processing of the other end of the correction pipe is arbitrary. For example, each of the correction pipes may be open to the atmosphere, or may be merged at once or stepwise, just opposite to the connection pipe. However, in the case of merging, the outlet side piping from the channel outlet of each microfluidic device to the merging portion is used as the correction piping. In this case, the pressure loss of the outlet side pipe to the junction and the coefficient of variation thereof are the same as those of the individual pipe of the connection pipe in the first aspect, and the pressure loss of the common pipe after the junction is The same as the common pipe portion of the connection pipe in the first aspect.

  The magnitude of the pressure loss, the coefficient of variation of the pressure loss, the length of the pipe, the cross-sectional area of the pipe, the material, etc. in this embodiment are the same as those of the correction pipe in the first embodiment.

  In this embodiment, the pressure loss of the connecting pipe connecting the fluid drive device and the microfluidic device and the coefficient of variation thereof are arbitrary, but are the same as the outlet side pipe in the first embodiment.

  In the present invention, the sum of the pressure loss of the connecting pipe connecting the fluid drive device and the microfluidic device and the pressure loss of the microfluidic device is regarded as the pressure loss of the microfluidic device, and the deviation of the pressure loss is corrected. It is also preferable to correct by. This method is preferable when the deviation of the pressure loss of the connecting pipe is so large that it cannot be ignored as compared with the deviation of the pressure loss of the microfluidic device, and the deviation of the pressure loss of the connecting pipe can be corrected at the same time.

  In the second aspect, since it is not necessary to combine the outlet side pipes into one, connection and correction of the pipes are easy.

EXAMPLES Hereinafter, although this invention is demonstrated in more detail using an Example, this invention is not limited to the range of a following example. In this example, “part” means “part by mass”, and “%” means “% by mass”.

[Preparation of UV-curable composition (X1)]
As a polymerizable compound, 50 parts of dicyclopentanyl diacrylate “DCA-200” (manufactured by Dainippon Ink Chemical Co., Ltd.) and a trifunctional urethane acrylate oligomer “Unidic V-4263” having an average molecular weight of about 2000 (Dainippon Ink Chemical Co., Ltd.) 50 parts by Kogyo Co., Ltd., 5 parts 1-hydroxycyclohexyl phenyl ketone “Irgacure 184” by Ciba Geigy as photopolymerization initiator, and 2,4-diphenyl-4-methyl- by Kanto Chemical Co., Ltd. as a polymerization retarder An ultraviolet curable composition (X1) was prepared by uniformly mixing 0.1 part of 1-pentene.

[Preparation of UV-curable composition (X2)]
An ultraviolet curable composition (X2) was prepared in the same manner as the ultraviolet curable composition (X1) except that 2,4-diphenyl-4-methyl-1-pentene was not added.

[Preparation of film-forming solution (Y1)]
As a polymerizable compound, 40 parts of “DCA-200”, 50 parts of “Unidic V-4263”, 10 parts of glycidyl methacrylate (manufactured by Wako Pure Chemical Industries, Ltd.), methyl decanoate (Wako Pure) 240 parts of Yakuhin Kogyo Co., Ltd. and 5 parts of “Irgacure 184” as an ultraviolet polymerization initiator were uniformly mixed to prepare a film-forming solution (Y1).

[UV irradiation]
Using a light source unit for multi-light 251W series exposure apparatus manufactured by USHIO INC. Using a 250 W high-pressure mercury lamp as a light source, UV light with an ultraviolet intensity at 365 nm of 50 mW / cm 2 was irradiated in the atmosphere at room temperature unless otherwise specified. .

[Reference example]
In this reference example, the pressure loss and coefficient of variation of the microfluidic device used in the examples were measured.

[Production of microfluidic devices]
A composition (X2) is applied on a substrate 1 made of an acrylic plate having a thickness of 1 mm by a spin coater, and the coating film is irradiated with ultraviolet rays for 2 seconds so that the polymerizable functional group still remains. A first resin layer 2 in which the composition (X2) was semi-cured was formed.

  On top of that, a film-forming solution (Y1) is applied with a spin coater, and the coating film is irradiated with ultraviolet rays for 60 seconds, so that the polymerizable compound in the film-forming solution (Y1) is polymerized and simultaneously with the poor solvent. Separated to form a porous body. Thereafter, the poor solvent in the pores of the porous body was washed away with ethanol and dried at room temperature to form the porous layer 3 fixed on the first resin layer 2.

  When the composition (X1) is applied onto the porous layer 3 with a spin coater, a part of the composition (X1) fills the pores of the porous layer 3, and further on the porous layer 3. An uncured coating was formed. Next, the portion other than the portion to be the flow path 5 is irradiated for 40 seconds through a photomask to form the second dendritic layer 4 in which the composition (X1) is semi-cured to such an extent that the polymerizable functional group still remains. Then, the uncured composition (X1) in the non-irradiated portion is washed and removed with a 50% aqueous ethanol solution to form a groove to be the flow path 5 of the second resin layer 4, and the bottom surface of the groove is porous again. The quality layer 3 was exposed. And the part other than this groove | channel of the porous layer 3 hardened | cured in the state with which the composition (X1) was filled with the pore, and was made nonporous.

A biaxially stretched polypropylene sheet (OPP sheet) (manufactured by Nimura Chemical Co., Ltd.) having a thickness of 60 μm was used as a temporary support (not shown), and the composition (X2) was coated thereon with a spin coater, and an ultraviolet lamp Is irradiated with ultraviolet rays for 2 seconds to be semi-cured to form a third resin layer 6, which is laminated on the second resin layer 4 of the previously produced laminated member and fixed by irradiation with ultraviolet rays for 120 seconds. Then, the temporary support (not shown) was peeled off.
As described above, a microfluidic device precursor having a capillary flow path 5 having a zigzag shape in plan view and having a rectangular cross section and a porous layer formed on the bottom surface was obtained.

  From the substrate 1 side of the microfluidic device precursor to the second resin layer 4, holes at diameters of 0.3 mm are drilled at both ends of the flow path 5 to form an inlet 7 and an outlet 8, A microfluidic device was obtained.

[Dimension measurement of microfluidic device]
After measuring the pressure loss of the following microfluidic device and the pressure loss of the integrated microfluidic device, 10 pieces are randomly taken out from the microfluidic device, cut, and caliper, optical microscope, and scanning electron The dimensions of each part of the device were measured using a microscope. As a result, the outer dimensions of the microfluidic device are 75 × 50 × 1.19 mm, the average thickness of the substrate 1 is 1.00 mm, the average thickness of the first resin layer 2 is 31 μm, and the average thickness of the porous layer is The average thickness of the second resin layer 4 excluding the portion impregnated in the porous layer 3 is 8 μm, the average thickness of the third resin layer 6 is 98 μm, the average width of the flow path 5 is 106 μm, and the flow path 6 The average length of was 50 cm.

[Measurement of pressure loss of microfluidic devices]
The pressure loss and the coefficient of variation of the 10 microfluidic devices produced by the above process were measured.

  A microsyringe pump (not shown) with a pressure gauge (not shown) that can measure the discharge pressure is hydrophilized at the end by plasma treatment. The outer diameter is 1.6 mm, the inner diameter is 500 μm, and the length is 1.0 m ± 0. A 5 mm Teflon (registered trademark) tube (not shown) (APCHURCH SCIENTIHIC) was connected, and the other end of the Teflon (registered trademark) tube (not shown) was perforated as shown in FIG. Each inflow port 7 of the microfluidic device 10 is bonded to a 7 × 7 × 3 mm acrylic resin connecting member 9 with a silicone adhesive and clamped (not shown) via a silicone packing 18 having a thickness of 1 mm. Connected to.

A 0.1% sodium dodecylbenzenesulfonate aqueous solution is fed from the microsyringe pump at a volume flow rate of 3.0 mm ³ / min, and the discharge pressure of the microsyringe pump (not shown) (that is, the pressure of the piping and the microfluidic device) Loss). The results are shown in Table 1. Since the variation coefficient of pressure loss is 9.4%, when these microfluidic devices are connected in parallel and the aqueous solution is flowed under the same pressure applied to all the microfluidic devices, each microfluidic device The coefficient of variation of the volumetric flow rate of the aqueous solution flowing through is calculated to be 9.8%.

  Note that the pressure loss when the connection member 9 was measured without being connected to the microfluidic device 10, that is, the pressure loss of the Teflon (registered trademark) tube was a small value of less than 0.1 kPa. It can be seen that the pressure loss shown is that of a microfluidic device.

[Example 1]
In this example, an example of the first aspect of the present invention is shown.
[Production of pipes for correction piping]
A tube made of polyetheretherketone (PEEK) (APCHURCH SCIENTIHIC) having an outer diameter of 1.6 mm and an inner diameter of 50 μm is cut into a length of 1000 mm, and the ends are hydrophilized by plasma treatment, and the micro syringe pump (not shown) ) And the pressure loss of the PEEK tube was measured in the same manner as the pressure loss measurement of the microfluidic device, and was found to be 335.0 kPa. That is, it can be seen that this tube has a pressure loss of 0.335 kPa per mm at the above flow rate. The PEEK tube having a length of 1 m measured above was connected to a microfluidic device No. 1 correction pipe (correction pipe No. 1), the microfluidic device No. 1 and correction piping No. 1 No. 1 is calculated as 372.9 kPa. 2-No. For each of the 10 microfluidic devices, the length was calculated so that the total pressure loss was 372.9 kPa, the PEEK tube was cut, the ends were hydrophilized by plasma treatment, and the corrected piping No. 2-No. 10 was produced. Table 2 shows the length of each correction pipe.

[Fabrication of integrated microfluidic devices]
Connected to the gear pump 12 attached with a pressure gauge (not shown) capable of measuring the discharge pressure, as a common pipe part 13 of the connecting pipe, is a brass pipe having an inner diameter of 5 mm and a length of 10 cm, which is closed at one end, As the individual piping part 14 of the connecting piping, the correction piping No. 1-No. 10 connected.

  A connecting member 9 was bonded to the other end of each correction pipe, and connected to the inlet 7 of each microfluidic device 10 by a clamp (not shown) through a silicone packing 18 having a thickness of 1 mm.

  In addition, a Teflon (registered trademark) tube having an outer diameter of 1.6 mm, an inner diameter of 500 μm, and a length of 1.0 m ± 0.5 mm, which has been hydrophilized by plasma treatment, is connected to the outlet 8 of each microfluidic device. 9, a packing 18 and a clamp (not shown) were connected to form an outlet side pipe 15, and the other end of the Teflon (registered trademark) tube was inserted into the test tube 16. One drop of liquid paraffin for preventing evaporation was injected into each test tube 16, and the mass of each test tube 16 was weighed in this state.

  The microfluidic devices 10 were placed horizontally on a table, and the heights of the ends of the outlet side pipes 15 inserted into the test tubes 16 were all the same. The suction port of the pump 12 was connected to the liquid storage layer 11 with a Teflon (registered trademark) tube 17 having an inner diameter of 5 mm.

[Measurement of volumetric flow velocity of integrated microfluidic devices]
Using a 0.1% sodium dodecylbenzenesulfonate aqueous solution as a test solution, the pump 12 was operated in advance, and the aqueous solution was put into all the connection pipes 13 and 14, the flow paths of the microfluidic device 10, and the outlet side pipe 15. After filling, the end of the connection pipe 14 was inserted into the test tube 16 as described above, and the pump 12 was fed at a volume flow rate of 300 mm ³ / min. As a result, the discharge pressure of the pump 12 (pipe and microfluidic device The total pressure loss) was 373 kPa.

  After pumping from the pump 12 for 1 hour, the pump 12 was stopped, the amount of the aqueous solution accumulated in each test tube 16 was weighed, and the value of the volume flow rate flowing through each microfluidic device was obtained. The results are shown in Table 2. From this, the coefficient of variation of the volume flow rate was calculated to be 0.18%, indicating a significant improvement effect.

  Thereafter, the outlet side piping 15 was removed from each microfluidic device, and the pump was driven at the same volume flow rate, but there was no change in the pump discharge pressure. From this, it can be seen that the pressure loss of the outlet side pipe 15 is negligibly small as compared with the microfluidic device, and the outlet side pipe 15 does not affect the measurement of the volume flow velocity.

[Example 2]
In this embodiment, an example of the second aspect of the present invention will be shown.
In the integrated microfluidic device manufactured in Example 1, as an individual pipe 14 connected to the inlet 7, a Teflon (inner diameter 500 μm, length 1000 ± 0.5 mm) whose end is hydrophilized by plasma treatment (registered) Trademark) tube, and the outlet piping 15 is the correction piping No. 1-No. 10 was used. Otherwise, the same measurement as in Example 1 was performed. As a result, the coefficient of variation in volume flow rate was 0.17%, which was almost the same as in Example 1.

  That is, even when the correction pipe is connected to the downstream side of the microfluidic device, the effect of improving the deviation of the volume flow velocity is obtained, similar to the doting connected to the upstream side.

[Example 3]
As shown in Table 3, the correction piping No. 1-No. Instead of the correction pipe No. 10, the length of the correction pipe (No. 11) having the smallest correction amount is set to 100 mm. 11-No. 20 and a Teflon (registered trademark) tube with an outer diameter of 1.6 mm, an inner diameter of 500 μm, and a length of 500 ± 0.5 mm connected to the downstream end of each correction pipe by plasma treatment Then, the same test as in Example 2 was performed except that the total of the correction pipe and the Teflon (registered trademark) tube was set as the outlet side pipe 15. The obtained volume flow rate values are shown in Table 3. The coefficient of variation of the volume flow rate was 0.24%, and a remarkable improvement effect was recognized.

It is a perspective exploded view of the microfluidic device produced in an example. It is a sketch of the integrated type microfluidic device produced in the Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Base material 2 1st resin layer 3 Porous layer 4 2nd resin layer 5 Flow path 6 3rd resin layer 7 Inlet 8 Outlet 9 Connection member 10 Microfluidic device 11 Storage tank 12 Pump (gear pump)
13 Common Piping Port for Connection Piping 14 Individual Piping Port for Connection Piping 15 Outlet Side Piping 16 Test Tube 17 Pump Suction Side Piping 18 Packing

Claims (9)

An integrated microfluidic device in which each channel inlet of a plurality of microfluidic devices having individual differences in pressure loss from the channel inlet to the channel outlet is connected to one fluid drive mechanism via a branched connection pipe A device,
(1) Correction pipes are provided as portions from the branch portion of the connection pipe to the flow path inlet, and / or correction pipes are provided at the flow path outlet of the microfluidic device,
as well as,
(2) The value obtained by dividing the standard deviation of the sum of the pressure losses of the correction pipe and the microfluidic device connected thereto by the average of the sum of the pressure losses is the standard deviation of the pressure loss of the microfluidic device. Each of the correction pipes is prepared to be smaller than the value divided by the average pressure loss and not more than 5%,
An integrated microfluidic device. An integrated microfluidic device in which each channel inlet of a plurality of microfluidic devices having individual differences in pressure loss from the channel inlet to the channel outlet is connected to one fluid drive mechanism via a branched connection pipe A device,
(1) Correction pipes are provided as portions from the branch portion of the connection pipe to the flow path inlet, and pipes other than the correction pipe are provided at the flow path outlet of the microfluidic device,
Alternatively, the connection pipe is connected to each flow path inlet of the microfluidic device, and a correction pipe is provided at each flow path outlet of the microfluidic device, and (2) the correction pipe and connected thereto. A value obtained by dividing the standard deviation of the sum of the pressure loss between the microfluidic device and the piping part other than the correction pipe connected to the microfluidic device by the average of the sum of the pressure loss is the microfluidic device, The correction is made so that the standard deviation of the sum of the pressure losses with the pipes other than the correction pipe connected to the microfluidic device is smaller than the value obtained by dividing the average of the sum of the pressure losses by 5% or less. That each pipe is prepared,
An integrated microfluidic device. The integrated microfluidic device according to claim 1, wherein the correction pipe is corrected by adjusting a length of the correction pipe. The integrated microfluidic device according to claim 1, wherein the number of connected microfluidic devices is in the range of 2 to 100,000. The integrated microfluidic device according to claim 1, wherein an inner diameter of the correction pipe is in a range of 10 to 200 μm. Integrated microfluidic device according to claim 1, the flow path cross-sectional area of the microfluidic device is in the range of 1~100000μm ^2. An integrated micro that is connected to each channel inlet with a plurality of microfluidic devices that have individual differences in pressure loss from the channel inlet to the channel outlet from one fluid drive mechanism via a branched connection pipe A method of correcting a flow rate deviation flowing in each microfluidic device of a fluidic device, comprising:
(1) Providing a correction pipe as a portion from the branch portion of the connection pipe to the flow path inlet, and / or providing a correction pipe at a flow path outlet of the device, and (2) the correction pipe. The standard deviation of the sum of the pressure loss of the correction pipe and the microfluidic device connected thereto is a value obtained by dividing the standard deviation of the pressure loss of the correction pipe and the microfluidic device by the average of the pressure loss. Adjusting the correction piping to be small and less than 5%,
A flow deviation correction method characterized by the above. An integrated micro that is connected to each channel inlet with a plurality of microfluidic devices that have individual differences in pressure loss from the channel inlet to the channel outlet from one fluid drive mechanism via a branched connection pipe A method of correcting a flow rate deviation flowing in each microfluidic device of a fluidic device, comprising:
(1) Providing a correction pipe as a part from the branch portion of the connection pipe to the flow path inlet, and providing an arbitrary pipe at the flow path outlet of the microfluidic device,
Alternatively, the connection pipe is connected to each flow path inlet of the microfluidic device, and a correction pipe is provided at each flow path outlet of the microfluidic device,
(2) The standard deviation of the sum of the pressure loss between the correction pipe, the microfluidic device connected to the correction pipe, and the pipe portion other than the correction pipe connected to the microfluidic device is calculated by the correction pipe and the microfluidic The standard deviation of the sum of the pressure loss between the device and the pipe portion other than the correction pipe connected to the microfluidic device is smaller than the value obtained by dividing the average of the sum of the pressure loss by 5% or less. Adjusting the correction piping to
A flow deviation correction method characterized by the above. The flow rate deviation correction method according to claim 6, wherein the correction pipe is prepared by adjusting the length of the correction pipe.

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