JP2003220322A - Liquid mixing mechanism - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid mixing mechanism capable of efficiently conducting diffusing and mixing in a micro-region. <P>SOLUTION: The mechanism has micro first and second flow channels 31a and 31b which are crossed at a cross section 37 or joined at a joint section 38. A first liquid which flows through the first flow channel 31a and a second liquid which flows through the second flow channel 31b are crossed at the cross section 37 or joined at the joint section 38 then mixed. At least one side of the first and second liquids is sent to the cross section 37 or the joint section 38 while being pulsated. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid mixing mechanism, and more particularly to a liquid mixing mechanism for mixing a small amount of liquid.

[0002]

2. Description of the Related Art μ-TAS (μ-Total Anal)
The ysis System) is much smaller than the conventionally used instruments such as flasks and test tubes. Therefore, it is noted that one of the features is that the amounts and costs of reagents and specimens to be used and disposal can be suppressed, and minute amounts can be synthesized and detected. μ-TAS is
Clinical analysis chip, environmental analysis chip, gene analysis chip
(DNA chip), hygiene analysis chip, chemical / biochemical synthesis chip, etc.

For example, Japanese Patent Publication No. 2000-512541 discloses an extraction device having a flow passage of about 10 μm to about 100 μm.

[0004] In addition, "LIQUID-SHEET BREAKU" in "Current status and prospect of microreactor technology" (supervised by Kinki Chemical Society Robot Synthesis Research Group)
P IN MICROMIXERS "is disclosed. In this system, a liquid and a gas are made to flow in opposite directions to each other on the same plane, and they are merged and taken out directly above.

[0005]

In the world of minute flow channels having microscale channels, both the size and the flow velocity are small and the Reynolds number is 200 or less. For example, the average 200 used in microchannels
When water is flown through a channel having a width of μm at a flow rate of 2 mm / s, the Reynolds number is 0.4. Therefore, in the world of minute flow paths (for example, in water, the flow path width is about 500 μm or less), the world of laminar flow control is not the turbulent flow control of the conventional reactor.

The microscale space has a large specific interfacial area, which is advantageous for diffusive mixing at the interface where 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 the mixing is W ² / W where W is the channel width and D is the diffusion coefficient.
Since it is proportional to D, the smaller the flow channel width, the faster the mixing (diffusion) time. The diffusion coefficient D is given by the following equation. D = Kb × T / 6 × π × μ × r (1) (where T: liquid temperature, μ: viscosity, r: particle radius, Kb:
(Boltzmann constant)

For example, the relationship between the flow channel width (channel width), the specific interfacial area (S / V) and the diffusion time (t) when particles having a particle diameter of 10 nm (0.01 μm) are used is shown in FIG. It becomes as shown. In addition, S is a boundary area and V is a volume.

That is, in the microscale space, molecular transport, reaction and separation can be carried out without using mechanical stirring.
It is performed promptly only by the spontaneous behavior of molecules and particles.

Recently, research on a type of diffusing in the width direction of the flow channel has been announced. However, the flow channel width of up to about 200 μm can be produced relatively easily, and even if a pump is combined, the flow channel resistance is reduced. Rise is not a problem level. However, depending on the application, there is a problem that it takes too much time when mixing is performed by spontaneous diffusion with a channel width of 200 μm level.

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

[0012] Plasma is a component excluding blood cells, all 100
It is assumed that the particles are nm or less, and the viscosity is also assumed to be 2 cps on average. The reagent to be mixed is considered to be about 45 nm or less. The febrinogen associated with coagulation in plasma is approximately 45 nm.
It is a molecule, the diffusion coefficient is D = 5 × 10 ⁻⁸ cm ² / sec, and the diffusion time for moving 100 μm is 2000.
Calculated as seconds. With a movement of 25 μm, the diffusion time is 12
It will be 5 seconds.

However, in reality, many proteins and molecules are contained in plasma, interact with each other, and depending on the type (solvent, concentration) of the reagent to be mixed with plasma, the difference in concentration (promoting diffusion) ( It is necessary to calculate by correcting the mole fraction), the mutual diffusion coefficient, etc. Moreover, the viscosity may be high depending on the sample. For example, if the viscosity is 20 cps, the diffusion time will be 10 times as long as the above result.

As for the 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.
If the mixing takes 2000 seconds as in the above calculation result, it is detected with a viscosity gradient of 2000 seconds in the width direction. From a detection perspective, it's a challenge.

Further, the biggest problem is that in the case of an inspection in which the coagulation is completed within a short time, for example, within 10 seconds, the coagulation occurs at the interface between the two liquids while the diffusion hardly progresses in the minute flow path. , It becomes a barrier and the diffusion does not proceed. In the case of a blood coagulation test that needs to be mixed instantaneously in this way, in the flow path with a width of 100 μm,
The inspection doesn't work. Also, other than blood coagulation,
Mixing for a very short time is generally required in many fields and has many uses.

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

Therefore, a technical problem to be solved by the present invention is to provide a liquid mixing mechanism capable of efficiently diffusing and mixing in a minute region.

[0018]

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

The liquid mixing mechanism comprises minute first and second flow paths that intersect or merge at an intersection or a confluence, and the first liquid and the second flow channel that flow through the first flow channel. The second liquid flowing through the above-mentioned liquid is of a type that intersects or merges at the intersection or the junction to mix. At least one of the first and second liquids is sent to the intersecting portion or the merging portion while pulsating.

In the above configuration, the pulsating first and second
At least one of the liquids is intermittently supplied to the intersection or the confluence. As a result, the first liquid mass and the second liquid mass are alternately arranged at the intersecting portion or the merging portion and the downstream side thereof, and the first liquid mass and the second liquid mass are adjacent to each other. There may be diffusive mixing between.

According to the above construction, by appropriate pulsation,
The distance in the direction perpendicular to the interface between the adjacent first liquid mass and the second liquid mass can be reduced, and the first and second liquids can be uniformly mixed in a short time.

Therefore, the diffusive mixing can be efficiently performed in the minute area.

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

According to the above construction, the cross-sectional area of the intersecting portion or the merging portion is small, so that the distance between the adjacent first and second liquid masses in the direction perpendicular to the interface can be reduced to shorten the mixing time. it can. By partially reducing only the cross-sectional area of the intersecting portion or the merging portion, it is possible to minimize the increase of the flow path resistance due to the reduction of the cross-section. Further, since the cross-section becomes larger in the flow path on the downstream side of the intersection or the confluence, the liquid mass spreads, for example, in an umbrella shape, 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 lumps becomes smaller, and it is possible to mix them in a shorter time.

Preferably, at least one of the first and second liquids is at least ⅕ times the volume of the intersecting portion or the merging portion per one time, and is sufficiently smaller than the flow channel width before and after that. Pulsates.

In the above structure, the flow rate per pulsation is approximately the same as the volume of the intersection or the confluence. According to the above configuration, at the intersecting portion or the merging portion, the first and second liquid masses having the same volume as the volume of the intersecting portion or the merging portion can be formed and efficiently mixed.

Preferably, the first and second liquids are
At the intersecting portion or the merging portion, the intersecting portions or the merging portions have substantially opposite phases.

According to the above construction, the first liquid mass and the second liquid mass are alternately formed at the intersecting portion or the merging portion, and the first and second liquids are efficiently mixed. You can

Preferably, one of the first and second liquids is pulsated and the other is rectified and fed to the intersecting portion or the joining portion.

According to the above structure, only one of the first and second liquids needs to be pulsed, and the timing adjustment with the other liquid is not required, so that the liquids can be mixed by simple control.

Preferably, the first and second flow paths are
Merge after crossing.

In the above structure, the first and second flow paths once intersect at the intersection, the downstream sides of the intersection are separated, and the first and second flow paths join again at the junction. Between the intersection of the first and second flow paths and the confluence, both the first and second liquids are mixed. The first and second liquids can be mixed more uniformly by merging them in the merging section.

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

According to the above construction, the liquid can be sent while pulsating the liquid by the micropump. If a micropump is used, the whole structure can be simplified and the size can be easily reduced. For example, it is suitable when the liquid mixing mechanism is configured in the microchip.

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

According to the above construction, the pulsation can be given to the liquid supply by driving the diaphragm while the liquid is supplied by the appropriate means. Since the diaphragm only gives pulsation, it has a small load capacity, has a simple structure, and can be easily miniaturized. For example, it is suitable when the liquid mixing mechanism is configured in the microchip.

[0037]

BEST MODE FOR CARRYING OUT THE INVENTION A liquid mixing mechanism according to each embodiment of the present invention will be described below with reference to FIGS.

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

As shown in the configuration diagram of FIG. 2, in the liquid mixing mechanism 30, the first and second flow passages 31a and 31b generally intersect at an intersection 37 in an X-shape, and the downstream side thereof. Part 3
6 joins in a Y shape at the joining portion 38, and the joining passage 31x is connected to the downstream side thereof.

The first and second flow paths 31a and 31b are provided at their ends with liquid introduction ports 32a and 32b for introducing a liquid such as a sample or a reagent. Also,
Micro pumps 34a and 34b are provided between the liquid introduction ports 32a and 32b and the intersection 37, respectively. The width of the intersection portion 37 and the confluence portion 38 is smaller than the width of the flow channels 31a, 31b, 31x before and after the intersection portion 37 and the confluence portion 37.
The cross section in the direction perpendicular to the flow path in the vicinity of the merging portion 38 is narrower than the cross sections in the direction perpendicular to the flow path of the flow paths 31a, 31b, 31x before and after the flow path.

As the micropumps 34a and 34b, for example, diffuser type pumps are used as shown in the sectional views of FIGS. Micro pumps 34a, 34b
PZT [Pb (Zr, Ti) O ₃ ] 3, which is a ceramic piezoelectric material, is attached to the vibration plate 320 facing the pump chamber 35b.
5s is attached. The PZT35s has a drive unit 3
When a drive voltage is applied by 40, it is curved toward the pump chamber 35b, and the volume of the pump chamber 35b is changed. At this time, the front and rear diffusers 35a, 35c
The liquid is sent due to the difference in the flow path impedance.

In the diffuser 35c on the downstream side, even if the pressure change in the pump chamber 35b is rapid or gradual, since the liquid flows in a laminar flow state, the change in the flow path impedance is relatively small.

On the other hand, the diffuser 35 on the upstream side
In a, the change in the flow path impedance is relatively large. That is, the diffuser 35a on the upstream side is connected to the pump chamber 3
When the pressure change in 5b is rapid, turbulent flow occurs, so that the diffuser 35 having the flow path impedance on the downstream side is generated.
It becomes larger than c. On the other hand, when the pressure change in the pump chamber 35b is gentle, turbulent flow does not occur, so the flow path impedance becomes smaller than that of the diffuser 35c on the downstream side.

For example, when a sawtooth drive voltage that repeats a sharp rise and a gentle fall is applied to the PZT 35s, the volume of the pump chamber 35b sharply decreases due to the abrupt change of the voltage, and an arrow 364 in FIG. As shown by, the liquid is ejected from the diffuser 35c on the downstream side. Next, due to the gradual change in voltage, the pump chamber 3
The volume of 5b slowly returns to its original position, and in FIG.
As indicated by 62, the liquid is sucked into the pump chamber 35b from the diffuser 35a on the upstream side. At this time, the diffuser 35c on the downstream side is also slightly affected by the pump chamber 3
The liquid is sucked back into 5b. By repeating this, the liquid is sent forward as a whole.

When mixing is performed using the liquid mixing mechanism 30,
By supplying the first and second liquids, for example, a liquid sample and a reagent to the liquid inlets 32a and 32b, respectively, and driving the micropumps 34a and 34b, the first and second liquids are introduced into the confluent channel 31x. Alternately send the liquid toward.

For example, as shown in FIG. 5, the micropumps 34a and 34b (indicated as "pump 1" and "pump 2") are cyclically driven in antiphase to pulsate the first and second liquids. The amplitude W of is alternately given. As a result, the first and second liquids flow into the intersecting portion 37 approximately alternately, and the first and second liquids are located on the downstream side 36 of the intersecting portion 37 of the first and second flow channels 31a and 31b. The lumps of are arranged alternately in the flow direction. At this time, spontaneous diffusion occurs between the first and second liquid masses (liquid layers).

The liquids on the downstream side 36 join again at the joining portion 38. Then, 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 in the merging portion 38 enters the merging passage 31x, the cross-sectional area of the merging passage 31x in the direction perpendicular to the passage is larger than that of the merging portion 38 in the direction perpendicular to the passage. , The lump of liquid spreads almost like an umbrella, and the liquid layer becomes thin.

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, each flow path 31
The micro pumps 32a and 32b are required for a and 31b, and it is necessary to drive the micro pumps in consideration of the phase difference of their pulsations. However, according to the following second and third embodiments, a simpler method can be used. Can be mixed with.

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

The liquid mixing mechanism 40 has a structure similar to that of the first embodiment, and has the first and second flow paths 41a and 41b.
Intersect at an intersection 47 in an X-shape, and a portion 46 on the downstream side merges at a junction 48 into a Y-shape and is connected to the merge channel 41x.

On the other hand, unlike the first embodiment, the liquid introduction port 42 and the micro pump 44 are provided only in the first flow path 41a.
Is provided so that the first liquid supplied to the liquid introduction port 42 can be supplied with pulsation.

The second liquid can be injected into the second flow path 41b at a constant flow rate as shown by an arrow 49. For example, an external pump or syringe (not shown) is connected to the second channel 41b, or a deformable diaphragm is connected to an appropriate means (for example, pushing by an external actuator, or shape memory in which the diaphragm is attached to the diaphragm). Deformation with a bimetal deformation of an alloy thin plate) and pushing in, the liquid is sent at a constant flow rate.

Mixing of the liquid is performed by intermittently interrupting the first liquid pulsating by the micropump 44 into the flow of the second liquid which constantly flows. That is, in the crossing portion 47, the first liquid mass and the second liquid mass are arranged alternately in the flow path advancing 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 has a structure similar to that of the first embodiment. That is, the first and second flow paths 5
1a and 51b intersect at an intersection 57 in an X shape, and the downstream side 56 merges in a Y shape at a junction 58 and is connected to the merge flow path 51x. At the ends of the first and second flow paths 51a and 51b, liquid introduction ports 52a and 52a are provided.
b are provided respectively.

On the other hand, unlike the first embodiment, as shown by an arrow 59, the first and second liquids supplied to the liquid introduction ports 52a and 52b are liquid-sucked by suction from the merging flow path 51x side. It is supposed to do. For example, a syringe or a pump (not shown) is connected to the confluent flow path 51x to suck. The suction may be performed using vacuum suction or capillary force.

A diaphragm 54 is provided in the first flow path 51a, and is vibrated by an appropriate means to give a pulsation to the liquid supply. The diaphragm 54 gives a pulsation to the liquid feeding by, for example, attaching a piezoelectric element to the diaphragm to deform it, deforming it by electrostatic attraction force, or attaching an external vibration mechanism. Since the diaphragm 54 does not need to give a propulsive force to the liquid and only needs to cause pulsation, it can have a simpler shape and configuration than a micropump.

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

Further, instead of sucking from the merging flow path 51x side, the liquid may be pushed out from the liquid introducing 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 structure in which the intersection 37 is eliminated from the first embodiment. That is, the liquid inlet 6
2a, 62b and the first and second flow paths 61a, 61b provided with the micro pumps 64a, 64b, respectively,
The merging portion 66 merges in a Y shape and is connected to the merging flow path 61x.

When mixing using the liquid mixing mechanism 60,
Similarly to the first embodiment, the first and second liquids supplied to the liquid introduction ports 62a and 62b are supplied to the micro pumps 64a and 6a.
The merging portion 66 merges by driving 4b. At this time, for example, the first and second liquids are supplied to the merging portion 66 in opposite phases, so that the first liquid mass and the second liquid mass are alternately arranged in the flow path advancing direction. Allow to mix and mix by spontaneous diffusion.

Although the liquid mixing mechanism 60 cannot obtain the effect of remixing, it has a simple shape and is easy to process.
The problem of bubbles remaining is unlikely to occur.

Also in the second and third embodiments, the intersecting portions 47 and 57 can be eliminated and the mixing can be performed only at the merging portions 48 and 58.

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

The liquid mixing mechanism 70 is a combination of the fourth embodiment and has first, second and third flow paths 71.
The a, 71b, and 71c are designed to merge in sequence. That is, the first and second flow paths 71a and 71b join in a Y shape at the joining portion 76a and are connected to the front joining passage 71s. The front merging flow path 71s joins the third flow path 71c in a Y shape at the merging portion 76b and is connected to the merging flow path 71x. First, second and third flow paths 71a, 7
The liquid introduction ports 72a, 72b, 7 are provided at the ends of 1b, 71c.
3c and micro pumps 74a, 74b, 74c are provided respectively.

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

The liquid mixing mechanism 80 includes the first, second and third liquid mixing mechanisms.
The flow channels 81a, 81b, 81c of the above are merged at one time at the merging portion 86 and are connected to the merged flow channel 81x.
Liquid introduction ports 82a, 82b, 83c and micropumps 84a, 84b, 84c are provided in the first, second and third flow paths 81a, 81b, 81c, respectively.

The liquid mixing mechanism 80 includes the liquid inlets 82a and 82a.
First, second and third supplied respectively to 2b and 83c
The liquid of (1), (2), and (3) are driven by the micropumps 84a, 84b, and 84c, and the phases of the liquids are gradually shifted to the merging portion 86, thereby arranging the first, second, and third liquid masses in the flow passage advancing direction. It can be mixed by dynamic diffusion.

In the case of arranging the flow passages in a plane, when the number of flow passages increases, the vicinity of the merging portion becomes overcrowded. Therefore, by stacking a plurality of substrates each having a flow channel formed therein and connecting each flow channel with a through hole, it is possible to send more kinds of liquids to one place and mix them.

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 2 shown in the perspective view of FIG.
For 0, the blood component obtained by blood cell separation can be tested by mixing it with a reagent on the microchip 20 and reacting them.

The microchip 20 has a transparent glass plate 2 on the upper and lower surfaces of the silicon substrate 20a in which the channel 21 is formed.
0b is joined. The microchip 20 is
It 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 each other at the intersection 21x, and then merge with the third flow channel 21c. Although not shown, the flow passage width in the vicinity of the intersection portion 21x and the confluence portion with the third flow passage 21c may be narrower than the width of the flow passages before and after the same as in the first embodiment. .

A filter receiving portion 23a is formed at an end of the second flow path 21b, and a diaphragm 23b is provided at an intermediate position.
Are formed. Water-repellent valves 24a and 24b each having a partially reduced flow passage cross section are formed near the intersection 21x in the first flow passage 21a and the second flow passage 21b, respectively. A liquid storage portion 23c is formed on the end side of the third flow path 21c.

The first flow path 21 is formed in the upper glass plate 20b.
reagent inlet 25a communicating with the end of a, blood receiver 25b communicating with filter receiver 23a, and third flow path 21
A suction hole 25c communicating with the end of c, an atmosphere communication port 22a communicating with the first flow path 21a and the outside, and an atmosphere communication port 22b communicating with the second flow path 21b with the outside are provided. .

An appropriate reagent is introduced into the reagent introducing port 25a. The introduced reagent is transferred to the first flow path 2 due to the capillary phenomenon.
1a is advanced and stopped 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 on this filter, the blood component from which blood cells have been removed by the filter progresses in the first flow path 21b due to the capillary phenomenon, fills the diaphragm 23b, and stops when the tip reaches the water repellent valve 24b.

The reagent and the blood component stopped at the water repellent valves 24a and 24b can be sucked from the suction hole 25c with an appropriate pressure by a syringe or the like while the atmosphere communication ports 22a and 22b are closed. , To the third flow path 21c and mixed. At this time, the diaphragm 23b is pushed in at an appropriate cycle to give pulsation to the blood component.

Then, the change in the mixed liquid in the third 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,
The transmitted light transmitted through c or the scattered light from the third flow path 21c is detected by a photodetector (not shown) (for example, a photodiode). Thus, tests such as biochemical tests and blood coagulation tests (APTT, PT, complex factor T, febrinogen, etc.) can be performed.

For example, the external dimensions of the microchip 20 are approximately 20 mm × 40 mm × 0.5 mm, the width of the flow channel 21 is 200 μm, and the depth thereof is approximately 100 μm. However, the size and shape are not limited to this. The smaller the micro-channel 21 is, the smaller the amount of the specimen and the reagent to be used, 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. For the silicon substrate 400, for example, a 200 μm thick silicon wafer 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 so that each of them has a thickness of 1.0 μm.

Next, as shown in FIG. 14C, a polysilicon film 420 is formed on the lower surface. Polysilicon film 4
The film 20 is formed by epitaxial growth to have a thickness of 30 μm, for example.

Next, a resist is applied on the upper surface, a predetermined mask pattern is exposed and 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, the oxide film 410
Is removed to form a portion 416 and a portion 414 that is partially removed in the thickness direction. For resist application, for example, a resist such as OFPR800 is used and spin coating is performed with a spin coater, and the thickness of the resist film is, for example, 1 μm. Exposure is performed by an aligner, and development is performed by a developer. For example, RIE is used for etching the oxide film. A stripping solution such as sulfuric acid / hydrogen peroxide is used for stripping the resist.

Next, after the silicon etching is performed halfway on the upper surface, the oxide film 414 is completely removed by etching, and the silicon etching is performed again.
As shown in (e), a portion 404 that penetrates the silicon substrate 400 and a portion 402 that is partially removed are formed. For silicon etching, for example, ICP (high frequency inductively coupled plasma, Inductive Co) is used.
upd Plasma) is used.

Next, the oxide film 410 on the upper surface is formed by, for example, BH.
Completely remove with F. Then, as shown in FIG. 14F, the glass plate 43 is formed on the upper surface of the silicon substrate 400.
Paste 0. For example, anodic bonding is performed at 900V and 400 ° C.

When equipped with a micropump, FIG.
As shown in (g), PZ is attached to the diaphragm of the pump chamber.
Glue T.

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

FIG. 12 shows a simulation result in the case of mixing only at the merging portion. In the simulation model, the first flow channel 100 and the second flow channel 102 join together at the narrow flow channels 104 and 106 at the merging portion, and then the merge flow channel 108.
Connect to. The narrow channel 106 has a width of 20 μm, and the confluent channel 108 has a width of 200 μm. In the second channel 102,
The second liquid is supplied at a constant pressure of 500 Pa. The first flow path 100 is filled with the first liquid 130 at 2000 Pa, 5
Pulsates by turning on / off at 00 Hz.
The confluent channel 108 is filled with a buffer solution in advance. FIGS. 12A to 12H show the state of the flow every 1 ms. Reference numeral 122 is a boundary between the buffer liquid and the second liquid. When the liquid enters the confluent flow passage 108 from the narrow flow passage 106, it spreads out in a generally umbrella shape, and the thin first liquid layers 132, 134, 136 and the second liquid layers 142, 144,
146 are alternately formed in the flow path advancing direction.

FIG. 11 shows a simulation result when mixing is performed using the intersecting portion and the merging portion. The simulation model is such that after the thin channel 204 connected to the first channel 200 and the thin channel 202 connected to the second channel (not shown) intersect at the intersection 206, It is bent in a letter shape and joins at the joining portion 208 to form a wide joining channel 210.
Connect to. The confluence channel 210 is filled with a buffer solution in advance. FIGS. 11A to 11D show the state of the flow every 5 ms. When the first and second liquids pass through the intersecting portion 206 and the merging portion 208 and flow into the merging passage 210, their respective liquid layers are too thin and already mixed.

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

Further, since diffusion in the direction of flow passage is used, there is no need to narrow the width of the flow passage, and the burden of liquid transfer due to an increase in flow resistance is reduced. That is, it is not necessary to increase the pressure generated by the pump or increase the size of the structure to withstand high pressure.

Further, the structure of the liquid mixing mechanism is relatively simple, it can be formed in a plane on one substrate, and the number of parts 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, FIG. 15 (a)
As shown in FIG.
Pulse trains Pb are alternately applied to drive. 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 pulse number. By performing such drive control, it is possible to increase the accuracy of liquid supply and increase the degree of freedom.

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

Further, as shown in FIG. 15B, by pulsating the pump A with the pulse train Pa and using the pump B as a rectifying pump, mixing of the two liquids by pulsation and rectification can be realized.

Further, by appropriately controlling the feed amount of the liquid, the concentration gradient and the pH can be provided on the downstream side of the intersection or the junction.
It is possible to make a solution with a gradient. This allows
For example, it is efficient because it is possible to carry out chemical reactions with different conditions such as concentration and pH at the same time.

The present invention is not limited to the above embodiments, but can be implemented in various other modes.

For example, the liquid mixing mechanism is not limited to the microchip, but can be configured in various ways.

The specific embodiments described above include the following inventions. (1) The first step of flowing the first and second liquids into the minute first and second flow paths intersecting or merging at the intersecting portion or the merging portion, respectively, and in the intersecting portion or the merging portion,
A second liquid which intersects or merges the first liquid and the second liquid
And a step of pulsating at least one of the first and second liquids in the first step. (2) In the second step, the cross-sectional area of the part where the first liquid and the second liquid intersect or merge with each other is greater than the cross-sectional area of the flow path before and after that part in the direction perpendicular to the flow path. The liquid mixing method according to (1) above, characterized in that (3) In the first step, the first and second
At least one of the liquids is ⅕ or more times the volume of the intersecting portion or the merging portion per one time, and pulsates a sufficiently small amount with respect to the flow channel width before and after that. The liquid mixing method according to (1). (4) In the first step, the first and second
2. The liquid mixing method according to (1) above, characterized in that the liquid intersects or merges in substantially the opposite phase at the intersecting portion or the merging portion. (5) In the first step, one of the first and second liquids pulsates, and the other rectifies, the liquid mixing method according to (1). (6) In the second step, the first and second steps
The liquid mixing method according to (1) above, characterized in that the liquids of (1) are crossed and then merged again. (7) In the first step, the first and second steps
The first and second micropumps provided on the upstream side of the intersecting portion or the merging portion of at least one of the flow paths of
The liquid mixing method according to (1) above, characterized in that at least one of the liquids described in 1) is pulsated. (8) In the first step, the first and second steps
At least one of the first and second liquids is pulsated by a diaphragm provided on the upstream side of at least one of the intersecting portion or the merging portion of the flow path of
The liquid mixing method according to (1) above.

[Brief description of drawings]

FIG. 1 is a graph showing the relationship between channel width, diffusion time, and specific boundary area.

FIG. 2 is a configuration diagram of a liquid mixing mechanism according to the first embodiment of the present invention.

FIG. 3 is a configuration diagram of a micropump.

4 is a cross-sectional view of the micropump taken along line IV-IV in FIG.

FIG. 5 is a graph showing a drive flow rate of a micro pump.

FIG. 6 is a configuration diagram of a liquid mixing mechanism according to a second embodiment of the present invention.

FIG. 7 is a configuration diagram of a liquid mixing mechanism according to a third embodiment of the present invention.

FIG. 8 is a configuration diagram of a liquid mixing mechanism according to a fourth embodiment of the present invention.

FIG. 9 is a configuration diagram of a liquid mixing mechanism according to a fifth embodiment of the present invention.

FIG. 10 is a configuration diagram of a liquid mixing mechanism according to a sixth embodiment of the present invention.

FIG. 11 is a simulation result of the flow of the liquid mixing mechanism.

FIG. 12 is a simulation result of the flow of the liquid mixing mechanism.

FIG. 13 is a perspective view of a microchip including a liquid mixing mechanism.

FIG. 14 is a manufacturing process diagram of a microchip.

FIG. 15 is a drive waveform diagram of the micro pump.

[Explanation of symbols]

20 microchips 21a First flow path 21b Second flow path 21c Third flow path (merging portion) 21x intersection 30 Liquid mixing mechanism 31a First flow path 31b Second flow path 34a, 34b Micro pump 37 intersection 38 Junction 40 Liquid mixing mechanism 41a First flow path 41b Second flow path 44 micro pump 47 intersection 48 Confluence part 50 Liquid mixing mechanism 51a First flow path 51b Second flow path 54 diaphragm 57 intersection 58 Confluence part 60 Liquid mixing mechanism 61a First flow path 61b Second flow path 64a, 64b Micro pump 66 Confluence section 70 Liquid mixing mechanism 71a, 71b, 71c Flow path 74a, 74b, 74c Micro pump 76a, 76b Confluence part 80 Liquid mixing mechanism 81a, 81b, 81c channels 84a, 84b, 84c Micro pump 86 Confluence part

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Claims (5)

[Claims] 1. A microfluidic first and second flow path that intersects or merges at an intersecting portion or a merging portion, and a first liquid flowing through the first flow passage and a minute liquid flowing through the second flow passage. In a liquid mixing mechanism in which the second liquid intersects or merges with the intersecting portion or the merging portion to mix, at least one of the first and second liquids is pulsated to the intersecting portion or the merging portion to deliver the liquid. And a liquid mixing mechanism. 2. The liquid mixture according to claim 1, wherein the cross-sectional area of the intersecting portion or the merging portion in the direction perpendicular to the flow passage is smaller than the cross-sectional area of the flow passages before and after the intersecting portion in the direction perpendicular to the flow passage. mechanism. 3. The liquid mixing mechanism according to claim 1, wherein the first and second liquids intersect or merge in substantially the opposite phase at the intersecting portion or the merging portion. 4. The liquid mixing mechanism according to claim 1, wherein the first and second flow paths merge after intersecting each other. 5. The liquid mixing mechanism according to claim 1, wherein a diaphragm is provided on the upstream side of the intersecting portion or the joining portion of at least one of the first and second flow paths.