JP4683066B2 - Liquid mixing mechanism - Google Patents

Description

  The present invention relates to a liquid mixing mechanism, and more particularly to a liquid mixing mechanism that mixes a small amount of liquid.

  [mu] -TAS ([mu] -Total Analysis System) is much smaller in size than a flask or test tube that has been used conventionally. Therefore, attention has been paid as one of the features that the amount and cost of reagents and specimens to be used, and disposal can be suppressed, and that minute amounts can be synthesized and detected. μ-TAS can be applied to clinical analysis chips, environmental analysis chips, gene analysis chips (DNA chips), hygiene analysis chips, chemical / biochemical synthesis chips, and the like.

  For example, Japanese translations of PCT publication No. 2000-512541 discloses an extraction apparatus having a flow path of about 10 μm to about 100 μm.

  In addition, “LIQUID-SHEEET BREAKUP IN MICROMIXERS” is disclosed in “Current Status and Prospects of Microreactor Technology” (supervised by Kinki Chemical Society Robot Synthesis Research Group). In this system, a liquid and a gas are flowed in opposite directions on the same plane, merged, and taken out directly above.

  In the world of a micro flow channel whose channel is a micro scale, both the size and the flow velocity are small, and the Reynolds number is 200 or less. For example, when water is flowed at a flow rate of 2 mm / s through an average channel having a width of 200 μm used in the microchannel, the Reynolds number is 0.4. Therefore, the world of minute channels (for example, the channel width of water is about 500 μm or less) is not a turbulent flow control as in a conventional reactor, but a laminar flow control world.

  In the microscale space, the specific interface area is large, which is advantageous for diffusive mixing at the interface where the laminar flow contacts. The time required for mixing depends on the cross-sectional area of the interface between the two liquids and the thickness of the liquid layer.

According to the diffusion theory, the time (T) required for mixing is proportional to W ² / D, where W is the channel width and D is the diffusion coefficient. Therefore, the smaller the channel width, the more the mixing (diffusion). Time gets faster. The diffusion coefficient D is given by the following equation.
D = Kb × T / 6 × π × μ × r (1)
(However, T: liquid temperature, μ: viscosity, r: particle radius, Kb: Boltzmann constant)

  For example, the relationship between the channel width (channel width), the specific interface area (S / V), and the diffusion time (t) when using particles having a particle diameter of 10 nm (0.01 μm) is as shown in FIG. become. In addition, S is an interface area and V is a volume.

  In other words, in the microscale space, molecular transport, reaction, and separation can be performed quickly only by spontaneous behavior of molecules / particles without using mechanical stirring.

  Recently, research on the type of diffusion in the channel width direction has been announced, but it is relatively easy to create a channel width of up to about 200 μm, and even if a pump is combined, the increase in channel resistance is a problem. It is not a level to become. However, depending on the application, there is a problem that it takes too much time when mixing by spontaneous diffusion is performed with a channel width of 200 μm level.

  For example, a typical example is a case where a blood coagulation test is performed by diffusing plasma in a microchannel.

Plasma is a component excluding blood cells, all considered to be particles of 100 nm or less, and the viscosity is assumed to be an average of 2 cps. The reagent to be mixed is considered to be about 45 nm or less. The febrinogen involved in clotting in plasma is about 45 nm molecules, the diffusion coefficient is D = 5 × 10 ⁻⁸ cm ² / sec, and the diffusion time for moving 100 μm is calculated as 2000 seconds. For a 25 μm movement, the diffusion time is 125 seconds.

  However, in reality, many proteins and molecules are contained in plasma, interact with each other, and depending on the type of reagent (solvent, concentration) that is desired to be mixed with plasma, the concentration difference (molar fraction) that serves as a driving force for diffusion ), It is necessary to correct and calculate the mutual diffusion coefficient. Also, depending on the specimen, the viscosity may be high. For example, if the viscosity is 20 cps, the diffusion time will be 10 times as long as the above result.

  As a result of the coagulation test, it is necessary to measure the time until it is mixed with the reagent and solidified with a resolution of 0.1 second. However, if it takes 2000 seconds to mix as shown in the above calculation result, it will be 2000 seconds in the width direction. It is detected with a viscosity gradient of. From a detection standpoint, it is a challenge.

  In addition, the biggest problem is that in the case of an examination in which coagulation is completed in a short time, for example, within 10 seconds, coagulation occurs at the interface between the two liquids while diffusion hardly progresses in the minute flow path. It becomes a barrier and diffusion does not progress. In the case of a blood coagulation test that needs to be mixed instantaneously in this way, the test cannot be performed in a flow path having a width of 100 μm. In addition to blood coagulation, mixing in a very short time is generally required in many fields and has many uses.

  However, if the flow path width is made extremely small in order to increase the diffusion time efficiently, the flow resistance becomes extremely large and not only the liquid feeding control is possible, but also a very large pressure for the liquid feeding. Is required, and the liquid feeding mechanism becomes large, and the total micro system cannot be obtained. In addition, the extremely small flow path width means that the amount of fluid is extremely small, the detection limit is lowered, and a more sensitive detection mechanism is required, and the current detection method has limited applications.

  Therefore, the technical problem to be solved by the present invention is to provide a liquid mixing mechanism that can efficiently perform diffusion mixing in a minute region.

  In order to solve the above technical problems, the present invention provides a liquid mixing mechanism having the following configuration.

  The liquid mixing mechanism includes minute first and second flow paths that intersect or merge at an intersection or a merge section, and the first liquid flowing in the first flow path and the second flow path flowing in the second flow path. This is a type in which the two liquids intersect or merge at the intersection or junction. At least one of the first and second liquids is sent to the intersecting part or merging part while pulsating.

  In the above configuration, at least one of the pulsating first and second liquids is intermittently supplied to the intersection or the junction. Accordingly, the first liquid mass and the second liquid mass are alternately arranged at the intersection or the merge portion and the downstream side thereof, and the adjacent first liquid mass and the second liquid mass are arranged. Diffusive mixing can occur between the two.

  According to the above configuration, the distance between the adjacent first liquid mass and the second liquid mass in the direction perpendicular to the interface is reduced by appropriate pulsation, and the first and second liquids are made uniform in a short time. Can be mixed.

  Accordingly, diffusion mixing can be performed efficiently in a minute region.

  Preferably, the cross-sectional area in the direction perpendicular to the flow path of the intersecting portion or the merging portion is smaller than the cross-sectional area in the direction perpendicular to the flow path of the flow path before and after the intersection or the merge portion.

  According to the said structure, since the cross-sectional area of a cross | intersection part or a confluence | merging part is small, the distance of the interface orthogonal direction of the adjacent 1st and 2nd liquid lump can be made small, and mixing time can be shortened. By partially reducing only the cross-sectional area of the intersection or the merging portion, it is possible to minimize the increase in flow resistance due to the reduction in cross-section. Furthermore, by increasing the cross section in the flow path downstream of the intersecting portion or the merging portion, the liquid mass spreads in an umbrella shape, for example, the first and second liquid layers become thin, and the first and second liquids The distance in the direction perpendicular to the interface of the lump is reduced, and it is possible to mix in a shorter time.

  Preferably, at least one of the first and second liquids is not less than 1/5 times the volume of the intersection or merging portion at a time, and an amount that is sufficiently small with respect to the flow path width before and after that. It pulsates.

  In the above configuration, the flow rate per pulsation is on the same order as the volume of the intersection or the junction. According to the said structure, the 1st and 2nd lump of a liquid comparable as the volume of a crossing part or a junction part can be formed in a crossing part or a junction part, and it can mix efficiently.

  Preferably, the first and second liquids intersect or merge at approximately the opposite phase at the intersecting portion or the merging portion.

  According to the above configuration, the first liquid mass and the second liquid mass can be alternately formed in the intersecting portion or the merge portion, and the first and second liquids can be mixed efficiently.

  Preferably, one of the first and second liquids pulsates and the other is rectified, and is sent to the intersecting part or the joining part.

  According to the above configuration, only one of the first and second liquids needs to be pulsated, and timing adjustment with the other is not necessary, so that mixing can be performed with simple control.

  Preferably, the first and second flow paths merge after intersecting.

  In the above configuration, the first and second flow paths once intersect at the intersecting portion, the downstream side from the intersecting portion is separated, and merged again at the joining portion. The first and second liquids are mixed together between the intersecting portion and the merging portion of the first and second flow paths. The first and second liquids can be mixed more uniformly by joining these at the junction.

  Preferably, a micropump is provided on the upstream side of the intersecting portion or the merging portion of at least one of the first and second flow paths.

  According to the above configuration, the liquid can be fed while pulsating the liquid by the micropump. If a micropump is used, it is easy to simplify the overall configuration and reduce the size. For example, it is suitable when the liquid mixing mechanism is configured in a microchip.

  Preferably, a diaphragm is provided on the upstream side of the intersecting portion or the merging portion of at least one of the first and second flow paths.

  According to the said structure, a pulsation can be given to liquid feeding by driving a diaphragm in the state sent with the suitable means. Since the diaphragm only gives pulsation, the load capacity is small, the configuration is simple, and the size can be easily reduced. For example, it is suitable when the liquid mixing mechanism is configured in a microchip.

  According to the present invention, by appropriate pulsation, the distance in the direction perpendicular to the interface between the adjacent first liquid mass and the second liquid mass is reduced, and the first and second liquids are made uniform in a short time. Can be mixed.

  Hereinafter, the liquid mixing mechanism according to each embodiment of the present invention will be described with reference to FIGS.

  First, the liquid mixing mechanism 30 according to the first embodiment will be described with reference to FIGS.

  As shown in the configuration diagram of FIG. 2, the liquid mixing mechanism 30 generally includes the first and second flow paths 31 a and 31 b intersecting in an X shape at the intersecting portion 37, and a portion 36 on the downstream side thereof The merge part 38 merges in a Y shape, and the merge channel 31x is connected to the downstream side thereof.

  The first and second flow paths 31a and 31b are provided with liquid inlets 32a and 32b for introducing liquids such as specimens and reagents at their respective ends. Micro pumps 34a and 34b are provided between the liquid inlets 32a and 32b and the intersection 37, respectively. The width of the intersecting portion 37 and the merge portion 38 is smaller than the width of the flow paths 31a, 31b, and 31x before and after the cross section 37, and the cross section in the direction perpendicular to the flow path in the vicinity of the intersect portion 37 and the merge section 38 , 31b, 31x are narrower than the cross section in the direction perpendicular to the flow path.

As the micro pumps 34a and 34b, for example, as shown in the cross-sectional views of FIGS. 3 and 4, a diffuser type pump is used. In the micropumps 34a and 34b, PZT [Pb (Zr, Ti) O ₃ ] 35s, which is a ceramic piezoelectric material, is attached to a diaphragm 320 that faces the pump chamber 35b. When a drive voltage is applied by the drive unit 340, the PZT 35s is bent toward the pump chamber 35b, and the volume of the pump chamber 35b varies. At this time, the liquid is fed due to the difference in flow path impedance between the front and rear diffusers 35a and 35c.

  Even if the pressure change in the pump chamber 35b is abrupt or gentle, the downstream diffuser 35c has a relatively small change in flow path impedance because the liquid flows in a laminar flow state.

  In contrast, the upstream diffuser 35a has a relatively large change in flow path impedance. That is, when the pressure change in the pump chamber 35b is abrupt, the upstream diffuser 35a generates a turbulent flow, so that the flow path impedance is larger than that of the downstream diffuser 35c. On the other hand, when the pressure change in the pump chamber 35b is gradual, no turbulent flow occurs, so that the flow path impedance is smaller than that of the downstream diffuser 35c.

  For example, when a sawtooth drive voltage that repeats a sudden rise and a gradual fall is applied to the PZT 35s, the volume of the pump chamber 35b suddenly decreases due to a sudden change in voltage, as shown by an arrow 364 in FIG. In addition, the liquid is discharged from the diffuser 35c on the downstream side. Next, due to a gradual change in voltage, the volume of the pump chamber 35b slowly returns to its original state, and liquid is sucked into the pump chamber 35b from the diffuser 35a on the upstream side as indicated by an arrow 362 in FIG. At this time, the liquid is also sucked back into the pump chamber 35b from the downstream diffuser 35c. By repeating this, the liquid is sent forward as a whole.

  When mixing using the liquid mixing mechanism 30, the first and second liquids, for example, liquid specimens and reagents are supplied to the liquid inlets 32 a and 32 b, respectively, and the micropumps 34 a and 34 b are driven, whereby the first And the 2nd liquid is alternately sent toward the confluence | merging flow path 31x.

  For example, as shown in FIG. 5, the micropumps 34a and 34b (designated as “pump 1” and “pump 2”) are periodically driven in opposite phases, and the pulsation amplitude W is applied to the first and second liquids. Alternately. As a result, the first and second liquids flow into the intersecting portion 37 approximately alternately, and the first and second liquids are provided downstream of the intersecting portion 37 of the first and second flow paths 31a and 31b. In this state, the lump is alternately arranged in the flow direction. At this time, spontaneous diffusion occurs between the first and second liquid masses (liquid layers).

  The liquid on the downstream side 36 joins again at the junction 38. In the merging portion 38, the liquid mass on the first flow path 31a side and the liquid mass on the second flow path side 31b are alternately arranged, and spontaneous diffusion similarly occurs.

  When the liquid flowing through the merge portion 38 enters the merge channel 31x, the cross-sectional area of the merge channel 31x in the direction perpendicular to the flow path is larger than the cross-sectional area in the direction perpendicular to the flow path of the merge portion 38, so The lump spreads out in a generally umbrella shape, and the liquid layer becomes thinner.

  As described above, the liquid layers of the first and second liquids can be thinned, the moving distance of the particles can be shortened, and the first and second liquids can be uniformly mixed in an extremely short time.

  In the first embodiment, the micropumps 32a and 32b are necessary for the flow paths 31a and 31b, respectively, and it is necessary to drive them in consideration of the phase difference between the pulsations. According to the embodiment, mixing can be performed by a simpler method.

  Next, the liquid mixing mechanism 40 of the second embodiment will be described with reference to the configuration diagram of FIG.

  The liquid mixing mechanism 40 is generally configured in the same manner as in the first embodiment, and the first and second flow paths 41a and 41b intersect in an X shape at the intersecting portion 47, and the downstream portion 46 joins. In the part 48, it merges in Y shape and connects with the confluence | merging flow path 41x.

  On the other hand, unlike the first embodiment, the liquid introduction port 42 and the micropump 44 are provided only in the first flow path 41a, and the pulsation is given to the liquid supply of the first liquid supplied to the liquid introduction port 42. So that it can be fed.

  As shown by the arrow 49, the second liquid 41 can be injected into the second channel 41b at a constant flow rate. For example, an external pump or syringe (not shown) is connected to the second flow path 41b, or a deformable diaphragm is pressed by an appropriate means (for example, pushing by an external actuator or a shape memory pasted on the diaphragm). The liquid is fed at a constant flow rate by being deformed and pushed by a bimetallic deformation of a thin alloy plate.

  The mixing of the liquid is performed by intermittently interrupting the first liquid pulsating by the micropump 44 into the flow of the second liquid that flows constantly. That is, at the intersection 47, the first liquid mass and the second liquid mass are alternately arranged in the flow path traveling direction, and are mixed by spontaneous diffusion as in the first embodiment.

  Next, the liquid mixing mechanism 50 of the third embodiment will be described with reference to the block diagram of FIG.

  The liquid mixing mechanism 50 is generally configured similarly to the first embodiment. That is, the first and second flow paths 51a and 51b intersect in an X shape at the intersection 57, and the downstream side 56 joins in a Y shape at the merge section 58 and is connected to the merge flow path 51x. It is like that. Liquid inlets 52a and 52b are provided at the ends of the first and second flow paths 51a and 51b, respectively.

  On the other hand, unlike the first embodiment, as indicated by an arrow 59, the first and second liquids supplied to the liquid inlets 52a and 52b are fed by suction from the merging channel 51x side. It has become. For example, a syringe or pump (not shown) is connected to the merging channel 51x for suction. Suction may be performed using vacuum suction or capillary force.

  The first flow path 51a is provided with a diaphragm 54, which is vibrated by an appropriate means so as to give pulsation to liquid feeding. For example, the diaphragm 54 is deformed by attaching a piezoelectric element to the diaphragm, deformed by an electrostatic attraction force, or attached with an external vibration mechanism to give pulsation to liquid feeding. The diaphragm 54 does not need to give a propulsive force to the liquid, and only needs to cause pulsation. Therefore, the diaphragm 54 can have a simple shape and configuration as compared with the micropump.

  The diaphragm 54 may be provided in both the first and second flow paths 52a and 52b. In this case, it is necessary to control the timing of pulsation, but the mixing efficiency is considered to be improved.

  Further, instead of suction from the merging channel 51x side, the liquid may be pushed out from the liquid introduction ports 52a and 52b side.

  Next, the liquid mixing mechanism 60 of the fourth embodiment will be described with reference to the block diagram of FIG.

  The liquid mixing mechanism 60 has a configuration in which the intersecting portion 37 is eliminated from the first embodiment. That is, the first and second flow paths 61a and 61b provided with the liquid introduction ports 62a and 62b and the micropumps 64a and 64b are merged in a Y shape at the merge section 66 and connected to the merge flow path 61x. It is like that.

  When mixing using the liquid mixing mechanism 60, the first and second liquids supplied to the liquid introduction ports 62a and 62b are joined at the joining unit 66 by driving the micropumps 64a and 64b, as in the first embodiment. Let At this time, for example, the first liquid mass and the second liquid mass are alternately arranged in the flow path traveling direction so that the first and second liquids are supplied to the merging portion 66 in opposite phases. Bring to state and mix by spontaneous diffusion.

  The liquid mixing mechanism 60 cannot obtain the effect of remixing, but since the shape is simple, processing is easy and the problem that bubbles remain is unlikely to occur.

  In the second and third embodiments, the intersecting portions 47 and 57 can be eliminated, and only the merging portions 48 and 58 can be mixed.

  Next, a liquid mixing mechanism 70 of the fifth embodiment will be described with reference to the configuration diagram of FIG.

  The liquid mixing mechanism 70 is a combination of the fourth embodiment, and the first, second, and third flow paths 71a, 71b, 71c are sequentially joined. That is, the first and second flow paths 71a and 71b merge in a Y shape at the merge portion 76a and connect to the front merge flow path 71s. The pre-merging channel 71s joins the third channel 71c in a Y shape at the merging portion 76b and is connected to the merging channel 71x. Liquid inlets 72a, 72b, 73c and micropumps 74a, 74b, 74c are provided at the ends of the first, second and third flow paths 71a, 71b, 71c, respectively.

  Next, a liquid mixing mechanism 80 of the sixth embodiment will be described with reference to the configuration diagram of FIG.

  In the liquid mixing mechanism 80, the first, second, and third flow paths 81a, 81b, and 81c are merged at the merge section 86 at a time and connected to the merge flow path 81x. The first, second and third flow paths 81a, 81b and 81c are provided with liquid introduction ports 82a, 82b and 83c and micro pumps 84a, 84b and 84c, respectively.

  In the liquid mixing mechanism 80, the first, second, and third liquids supplied to the liquid inlets 82a, 82b, and 83c are gradually shifted in phase by driving the micropumps 84a, 84b, and 84c. By feeding to 86, the lumps of the first, second and third liquids can be arranged in the flow path traveling direction and mixed by spontaneous diffusion.

  In addition, when arrange | positioning a flow path planarly, if the number of flow paths increases, the confluence | merging part vicinity will become overcrowded. Therefore, by laminating a plurality of substrates each having a flow path and connecting the flow paths with through holes, it is possible to feed and mix more types of liquids in one place.

  Next, an example in which the liquid mixing mechanism is configured as a microchip will be described with reference to FIGS. 13 and 14.

  The microchip 20 shown in the perspective view of FIG. 13 can be tested by mixing and reacting blood components obtained by blood cell separation with reagents on the microchip 20.

  In the microchip 20, a transparent glass plate 20b is bonded to the upper and lower surfaces of the silicon substrate 20a on which the flow path 21 is formed. The microchip 20 can also be formed using a resin or the like.

  The micro flow channel 21 is formed so that the first flow channel 21a and the second flow channel 21b intersect with the third flow channel 21c after intersecting at the intersecting portion 21x. Although not shown, the channel width in the vicinity of the junction with the intersection 21x and the third channel 21c may be narrower than the width of the channels before and after the first embodiment. .

  In the second channel 21b, a filter receiving portion 23a is formed at an end portion, and a diaphragm 23b is formed at an intermediate position. In the first channel 21a and the second channel 21b, water repellent valves 24a and 24b each having a partially reduced channel cross section are formed in the vicinity of the intersection 21x. A liquid reservoir 23c is formed on the end side of the third flow path 21c.

  The upper glass plate 20b has a reagent introduction port 25a that communicates with the end of the first channel 21a, a blood receiver 25b that communicates with the filter receiver 23a, and a suction hole that communicates with the end of the third channel 21c. 25c, an air communication port 22a that communicates with the first channel 21a and the outside, and an air communication port 22b that communicates the second channel 21b and the outside.

  An appropriate reagent is introduced into the reagent introduction port 25a. The introduced reagent advances through the first flow path 21a by capillary action, and stops when the tip reaches the water repellent valve 24a.

  The blood receiver 25b is loaded with a filter for separating blood cells. When whole blood is dropped onto this filter, the blood component from which blood cells have been removed by the filter travels through the first flow path 21b by capillary action, fills the diaphragm 23b, and stops when the tip reaches the water repellent valve 24b.

  The reagent and blood components that are stopped by the water repellent valves 24a and 24b are sucked at an appropriate pressure from a suction hole 25c with a syringe (not shown) or the like with the air communication ports 22a and 22b closed. Guide to the channel 21c and mix. At this time, the diaphragm 23b is pushed in at an appropriate cycle to pulsate blood components.

  And the change of the liquid mixture in the 3rd flow path 21c is detected. For example, a light source (not shown) (for example, a light emitting diode) irradiates the third flow path 21c with light, and transmitted light transmitted through the third flow path 21c or scattered light from the third flow path 21c is not illustrated. Detection is performed with a photodetector (for example, a photodiode). Thereby, tests (APTT, PT, complex factor T, febrinogen, etc.) such as biochemical tests and blood coagulation tests can be performed.

  For example, the external dimensions of the microchip 20 are about 20 mm × 40 mm × 0.5 mm, the width of the flow path 21 is 200 μm, and the depth is about 100 μm. However, dimensions and shapes are not limited to this. The smaller the microchannel 21 is, the smaller the amount of sample and reagent to be used can be, and the cost can be reduced and the burden on the subject can be reduced.

  Next, the manufacturing process of the microchip 20 will be described with reference to FIG.

  As shown in FIG. 14A, a silicon substrate 400 is prepared. As the silicon substrate 400, for example, a silicon wafer having a thickness of 200 μm is used.

  Next, as shown in FIG. 14B, oxide films 410 and 412 are formed on the upper and lower surfaces of the silicon substrate 400. The oxide films 410 and 412 are formed by thermal oxidation, for example, so that each thickness becomes 1.0 μm.

  Next, as shown in FIG. 14C, a polysilicon film 420 is formed on the lower surface. The polysilicon film 420 is formed by epitaxial so as to have a thickness of 30 μm, for example.

  Next, a resist is applied to the upper surface, a predetermined mask pattern is exposed, developed, and the oxide film 410 is etched. Then, after removing the resist on the upper surface, the resist is applied again, and exposure, development, and etching are performed. As a result, as shown in FIG. 14D, a portion 416 from which the oxide film 410 has been completely removed and a portion 414 from which the oxide film 410 has been removed halfway in the thickness direction are formed. For resist application, for example, a resist such as OFPR800 is used and spin-coated by a spin coater, and the thickness of the resist film is set to 1 μm, for example. Exposure is performed by an aligner, and development is performed by a developer. For example, RIE is used for etching the oxide film. For stripping the resist, a stripping solution such as sulfuric acid / hydrogen peroxide is used.

  Next, after the silicon etching is partially performed on the upper surface, the oxide film 414 is completely removed by etching, and the silicon etching is performed again. As shown in FIG. 14E, a portion 404 penetrating the silicon substrate 400 is obtained. And a portion 402 removed halfway. For silicon etching, for example, ICP (High Frequency Inductively Coupled Plasma, Inductively Coupled Plasma) is used.

  Next, the oxide film 410 on the upper surface is completely removed using, for example, BHF. And as shown in FIG.14 (f), the glass plate 430 is affixed on the upper surface of the silicon substrate 400. FIG. For example, anodic bonding is performed at 900 V and 400 ° C.

  When a micropump is provided, PZT is bonded to the diaphragm portion of the pump chamber as shown in FIG.

  Next, simulation results of liquid mixing are shown in FIGS.

  FIG. 12 shows a simulation result when mixing is performed only at the junction. In the simulation model, the first flow path 100 and the second flow path 102 are merged in the flow paths 104 and 106 having a narrow merge portion, and then connected to the merge flow path 108. The narrow channel 106 has a width of 20 μm, and the merge channel 108 has a width of 200 μm. The second liquid is supplied to the second channel 102 at a constant pressure of 500 Pa. The first liquid 130 is pulsated in the first flow path 100 by turning it ON / OFF at 2000 Pa and 500 Hz. The merge channel 108 is prefilled with a buffer solution. FIGS. 12A to 12H show the flow state every 1 ms. Reference numeral 122 denotes a boundary between the buffer liquid and the second liquid. When the liquid enters the converging flow path 108 from the narrow flow path 106, the liquid spreads in an approximately umbrella shape, and the thin first liquid layers 132, 134, 136 and the second liquid layers 142, 144, 146 are in the flow path moving direction. It is formed alternately.

  FIG. 11 shows a simulation result when mixing is performed using the intersection and the junction. In the simulation model, the narrow channel 204 connected to the first channel 200 and the narrow channel 202 connected to the second channel (not shown) intersect at the intersection 206, and then the mouth It bends in the shape of a letter, merges at the merge section 208, and connects to a wide merge channel 210. The merge channel 210 is prefilled with a buffer solution. FIGS. 11A to 11D show a flow state every 5 ms. When the first and second liquids flow through the intersection 206 and the junction 208 and flow into the junction channel 210, the respective liquid layers are too thin and are already mixed.

  As described above, the liquid mixing mechanism can simultaneously mix at least two liquids. By mixing using pulsation, a number of very thin liquid diffusion layers are formed in the direction of flow of the flow path, so diffusion mixing is completed in an extremely short time. For example, the time for diffusively mixing relatively large febrinogen in the width direction of a 100 μm wide channel is calculated to be about 2000 seconds. This is calculated to be about 0.8 seconds for diffusing and mixing the thin layer (2 μm) in the flow path direction.

  Further, since diffusion in the flow path direction is used, it is not necessary to narrow the flow path width, and the burden of liquid feeding due to an increase in flow path resistance is reduced. That is, it is not necessary to increase the pressure generated by the pump or increase the configuration to withstand high pressure.

  In addition, the configuration of the liquid mixing mechanism is relatively simple, can be formed on a single substrate in a planar manner, and the number of components is small.

  Since the feed amount of each liquid is controlled by the drive waveform, the feed amount of each liquid can be arbitrarily changed, and the mixing ratio can also be arbitrarily set. Further, the mixing ratio can be arbitrarily changed depending on the time.

  The micropump may be driven by combining pulse groups. That is, as shown in FIG. 15A, the pump A is driven by alternately applying the pulse train Pa and the pump B is alternately supplied with the pulse train Pb. This drive pulse group is a set of voltage on / off, and the movement of the pump is controlled by its pulse shape, pulse voltage, and number of pulses. By performing such drive control, it is possible to increase the accuracy of liquid supply and to expand the degree of freedom.

  As shown in FIG. 15A, when the same shape, voltage, and number of pulse groups are given to the pump A and the pump B, the liquid supplied from each pump becomes 1: 1. The liquid mixing ratio can be arbitrarily controlled by changing the pulse shape or voltage or number, or some combination thereof.

  Further, as shown in FIG. 15B, by mixing the two liquids by pulsation and rectification, the pump A is pulsated by the pulse train Pa and the pump B is a rectification pump.

  Furthermore, a solution having a concentration gradient, a pH gradient, or the like can be made downstream of the intersection or the merging portion by appropriately controlling the liquid feed amount. Thereby, for example, chemical reactions in which conditions such as concentration and pH are changed can be performed at a time, which is efficient.

  In addition, this invention is not limited to said each embodiment, It can implement in another various aspect.

  For example, the liquid mixing mechanism is not limited to a microchip and can be configured in various forms.

The specific embodiments described above include the following inventions.
(1) a first step of causing the first and second liquids to flow into the minute first and second flow paths that intersect or merge at the intersection or the junction, respectively;
A second step of crossing or merging the first liquid and the second liquid at the intersection or merging section;
In the first step, at least one of the first and second liquids is pulsated.
(2) In the second step, the cross-sectional area in the direction perpendicular to the flow path of the portion where the first liquid and the second liquid intersect or merge is greater than the cross-sectional area in the direction perpendicular to the flow path of the flow path before and after The liquid mixing method according to (1) above, wherein the liquid mixing method is also small.
(3) In the first step, at least one of the first and second liquids is not less than 1/5 times the volume of the intersecting portion or merging portion, and the flow width before and after the first and second liquids. The liquid mixing method according to the above (1), wherein a sufficiently small amount is pulsated.
(4) The liquid mixing method according to (1), wherein, in the first step, the first and second liquids intersect or merge at a substantially opposite phase at the intersecting part or the joining part. .
(5) The liquid mixing method according to the above (1), wherein in the first step, one of the first and second liquids pulsates and the other is rectification.
(6) The liquid mixing method according to (1), wherein in the second step, the first and second liquids are crossed and then merged again.
(7) In the first step, at least one of the first and second liquids is caused by a micro pump provided upstream of at least one of the intersecting portion or the merging portion of the first and second flow paths. The liquid mixing method according to the above (1), wherein the liquid is pulsated.
(8) In the first step, at least one of the first and second liquids is pulsated by a diaphragm provided upstream of at least one of the intersecting part or the joining part of the first and second flow paths. The liquid mixing method as described in (1) above, wherein

It is a graph which shows the relationship between channel width, diffusion time, and a specific interface area. It is a block diagram of the liquid mixing mechanism which concerns on 1st Embodiment of this invention. It is a block diagram of a micropump. FIG. 4 is a cross-sectional view of the micropump cut along line IV-IV in FIG. 3. It is a graph which shows the drive flow rate of a micro pump. It is a block diagram of the liquid mixing mechanism which concerns on 2nd Embodiment of this invention. It is a block diagram of the liquid mixing mechanism which concerns on 3rd Embodiment of this invention. It is a block diagram of the liquid mixing mechanism which concerns on 4th Embodiment of this invention. It is a block diagram of the liquid mixing mechanism which concerns on 5th Embodiment of this invention. It is a block diagram of the liquid mixing mechanism which concerns on 6th Embodiment of this invention. It is a simulation result of the flow of a liquid mixing mechanism. It is a simulation result of the flow of a liquid mixing mechanism. It is a perspective view of the microchip containing a liquid mixing mechanism. It is a manufacturing process figure of a microchip. It is a drive waveform figure of a micro pump.

Explanation of symbols

20 microchip 21a 1st flow path 21b 2nd flow path 21c 3rd flow path (merging part)
21x intersection 30 liquid mixing mechanism 31a first flow path 31b second flow path 34a, 34b micropump 37 crossing section 38 confluence section 40 liquid mixing mechanism 41a first flow path 41b second flow path 44 micropump 47 Intersection 48 Merge section 50 Liquid mixing mechanism 51a First flow path 51b Second flow path 54 Diaphragm 57 Intersection 58 Merge section 60 Liquid mixing mechanism 61a First flow path 61b Second flow path 64a, 64b Micro pump 66 Junction part 70 Liquid mixing mechanism 71a, 71b, 71c Flow path 74a, 74b, 74c Micropump 76a, 76b Junction part 80 Liquid mixing mechanism 81a, 81b, 81c Channel 84a, 84b, 84c Micropump 86 Junction part

Claims (4)

A first liquid flowing in the first flow path and a second liquid flowing in the second flow path, each having a minute first and second flow path each having a narrow width portion and a wide width portion; In the liquid mixing mechanism that crosses or joins at the narrow part and mixes,
A liquid mixing mechanism, wherein at least one of the first and second liquids is sent to the narrow portion while pulsating.   The liquid mixing mechanism according to claim 1, wherein a cross-sectional area of the narrow width portion in a direction perpendicular to the flow path is smaller than a cross-sectional area of the wide width portion in the direction perpendicular to the flow path.   2. The liquid mixing mechanism according to claim 1, wherein the first and second liquids intersect or merge with each other in a substantially opposite phase in the narrow portion.   The liquid mixing mechanism according to claim 1, further comprising a diaphragm upstream of the narrow portion of at least one of the first and second flow paths.

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