JP4640017B2 - Emulsifying device - Google Patents

Description

The present invention relates to an emulsifying apparatus that produces an emulsion in which a dispersed phase of water or oil is uniformly dispersed in a continuous phase of water or oil.

  An emulsion is an oil droplet (dispersed phase) produced by adding a surfactant (emulsifier) to two liquids that do not mix with each other, such as water and oil, and adding mechanical operations such as stirring. An O / W (oil in water) type dispersion in water (continuous phase) and a W / O (water in oil) type emulsion in which water droplets (dispersed phase) are dispersed in oil (continuous phase).

  As a conventional general emulsion production method, batch production using a dispersion method is known. This is a production method in which oil, an aqueous phase, and a surfactant are introduced into a large container and a large amount of emulsion is produced at once using a rotation / stirring mechanism.

  However, this production method has a problem in that the oil droplets or droplets are not uniform in size because the shearing force applied during rotation and stirring is not uniformly applied to the entire liquid. In addition, in order to stabilize this particle size distribution to a constant value, rotation and stirring for 20 minutes or more are required.

  In the state where the particle size of the emulsion is not uniform, the effect and performance vary and cause quality degradation.

  As a method of solving the above problem, there is a method of generating an emulsion using a microfluidic chip. A microfluidic chip supplies liquid to a microchannel having a width and a depth of several μm to several hundreds of μm, and emulsification is performed in the microchannel.

  Specifically, as disclosed in Patent Document 1 below, the ratio of the contact area of each liquid to the total volume of the liquid is divided by dividing oil and water into a number of flows and arranging them alternately. A method of advancing emulsification using a fluid shear rate generated between the flow path wall surface by forming a flow with increased flow and narrowing the flow path in stages, or as disclosed in Patent Document 2 below In addition, there are known ones that are produced by press-fitting a dispersed phase (oil) into a continuous phase (water) through a microchannel (microfluidic passage) having a width and height of about 10 μm.

JP 2004-81924 A JP 2004-267837 A

  In the above prior art, when a liquid is flowed at a high speed to a microfluidic chip to perform emulsification at a flow rate of, for example, several tens to several hundred ml / min, the microchannel is too small or the channel wall surface occupies the liquid volume. Since the contact area is large, the internal pressure loss becomes excessive, and it is difficult to flow a desired flow rate.

  In order to perform reliable emulsification by supplying a desired flow rate, it is necessary to prepare a pump that can withstand high pressure, or to perform parallel processing using a plurality of microfluidic chips called numbering up. Even if it is removed, the entire device becomes larger.

  Furthermore, emulsions not only change in particle size due to temperature fluctuations due to seasonal changes, but also have a property called phase inversion that changes from oil droplets to water droplets or from water droplets to oil droplets at a certain temperature. Strongly received.

  Even if a large amount of emulsion can be produced at one time by the batch method, a temperature distribution is likely to occur in the stirring vessel, and not only a dispersed phase having a uniform particle size of the dispersed phase but also an O / W type can be obtained. And W / O type may coexist, and in order to avoid this, much labor is required for temperature adjustment.

  Therefore, an object of the present invention is to provide an emulsification method capable of producing a large amount of an emulsion in which the particle size of a dispersed phase is fine and uniform.

  Another object of the present invention is to provide a compact emulsifying apparatus capable of producing a large amount of emulsion in which the dispersed phase has a fine and uniform particle size.

  Still another object of the present invention is to provide a small-sized emulsifying apparatus that can easily adjust the temperature and can produce a large amount of an emulsion having a fine and uniform dispersed phase particle size.

  Further, the device of the present invention that achieves the above object is characterized in that two types of liquids, which are a continuous phase and a dispersed phase of an emulsion, are supplied to a microchannel in a microfluidic chip and emulsified in the microchannel. In an emulsifying apparatus for obtaining an emulsion, a flat flow path is provided so as to be dispersed and supplied so as to be orthogonal to the flow of a liquid that is a wide planar continuous phase. A microfluidic chip for obtaining a primary emulsion and a Venturi tube for passing a primary emulsion discharged from the microfluidic chip to obtain a secondary emulsion having a fine dispersed phase are provided.

  In addition, a feature of the device of the present invention that achieves the above object is that temperature adjusting means is provided in the microfluidic chip.

  In the present invention, a large amount of a primary emulsion having a large diameter but a uniform dispersed phase in a microfluidic chip is produced under a low pressure loss, and then the emulsion is refined in a venturi tube with a uniform dispersed phase. A large amount of emulsion can be stably obtained with a simple structure by the generation divided into two stages.

  Hereinafter, an embodiment shown in the drawings will be described.

  In FIG. 1, the structure of the emulsification apparatus 1 which becomes this invention is shown. In this example, an O / W emulsion in which oil droplets are dispersed in water using a mixture of water and a surfactant for the continuous phase and edible oil for the dispersed phase will be described.

  A continuous phase (water, surfactant) serving as a solvent for the emulsion and a dispersed phase (edible oil) serving as a solute are contained in separate liquid tanks 91A and 91B. The liquids stored in the liquid tanks 91A and 91B are fed to the microfluidic chip 10 by the pumps 92A and 92B via the liquid feeding tubes 93A and 93B and the check valves 94A and 94B for preventing the backflow, as will be described later. First, a primary emulsion is produced in the microfluidic chip 10.

  The pumps 92A and 92B use a syringe pump when the liquid feeding conditions are frequently changed and liquid feeding accuracy is required, and when the liquid feeding conditions are fixed and long-time continuous liquid feeding is required. It is preferable to use a gear pump or a rotary pump. These pumps 92A and 92B may be low-pressure pumps having a discharge pressure of about several atmospheres for reasons described later. Moreover, it is preferable that the liquid feeding tubes 93A and 93B are made of a fluororesin tube that has high corrosion resistance and is hard to expand (hard).

  The microfluidic chip 10 is adjusted to an arbitrary temperature by a temperature control device (temperature control device) 95 attached to the adapter member 30 (FIG. 2) constituting the microfluidic chip 10 and a temperature controller 96 that controls the temperature control device 95. The liquid (solvent and solute) that has been adjusted and sent to the microchannel in the microfluidic chip 10 has high reactivity with respect to temperature and is maintained at an arbitrary temperature in a short time for the reason described later. This makes it possible to adjust the liquid viscosity and stabilize the emulsion particle size.

  Since the temperature control device 95 preferably has both heating and cooling functions in order to cope with various conditions, in this embodiment, the Peltier element is used to control the direction of current so that heating and cooling can be performed. did.

  The primary emulsion generated by the microfluidic chip 10 is sent to the venturi tube 40 through the liquid feeding tube 97, and a secondary emulsion in which the dispersed phase is refined is generated in the venturi tube 40 as described later. It is stored in the tank 98.

  As described above, in the apparatus of the present invention, it is possible to generate an emulsion in a flow type simply by feeding a liquid with the liquid feed pumps 92A and 92B, and a liquid dispensing mechanism and a stirring mechanism as in batch production. There is no need to separately provide the device, and the device can be reduced in size and simplified.

  In this embodiment, the Venturi tube 40 is a separate part from the microfluidic chip 10, but this is to remove the Venturi tube 40 and use it when there is no need to make the emulsion fine. When only the emulsion is generated, a flow path similar to that of the venturi tube 40 may be provided in the microfluidic chip 10 and the both may be integrated.

Details of each part will be described below.
2 is an exploded perspective view of the microfluidic chip 10 viewed from the front side, and FIG. 3 is an exploded perspective view of the microfluidic chip 10 viewed from the back side (the opposite side of FIG. 2).

  2 and 3, the microfluidic chip 10 includes a microfluidic chip body 11 formed of a plate material having a thickness of several millimeters such as metal, glass, silicon, and resin according to the type of liquid to be fed, and the microfluidic chip body. 11 is a main surface on the back side of the microfluidic chip body 11 on the opposite side of the lid member 20 disposed on one main surface on the front side of the microfluidic chip body 11 and constituting the ceiling portion of the flow path in the microfluidic chip main body 11. And an adapter member 30 that connects the liquid feeding mechanism such as the liquid feeding pumps 92A and 92B and the microfluidic chip 10 and a seal member (not shown) arranged between these three members. -30) prevents the liquid from leaking by screw fastening.

  As the seal member, a material having a thickness of 0.5 mm and excellent in corrosion resistance is punched so as to be fitted in the packing member 12 and 21 provided on the back surface of the lid member 20 and the microfluidic chip body 11.

  In this embodiment, a seal member is used to enable disassembly and cleaning. However, the lid member 20 and the adapter member 30 are directly fixed to the front and back of the microfluidic chip body 11 using other methods such as laser bonding or adhesive. You may do it. 2 and 3, the ellipses drawn along the outer periphery of the microfluidic chip body 11, the lid member 20, and the adapter member 30 are screw holes.

  4 and 5 are a front view of one main surface side (front side) of the microfluidic chip body 11 and a longitudinal sectional view taken along the line AA in FIG.

  The microfluidic chip body 11 is provided with channels having various shapes of grooves and holes extending from the liquid supply unit to the liquid discharge unit, which will be described in detail below, and is closely fixed to the surface of the microfluidic chip body 11. The lid member 20 and the adapter member 30 function as a lid that seals the grooves.

  The microfluidic chip body 11 includes a micro flow channel 16 on the main surface on the front side, a continuous phase supply unit 14 and a dispersed phase supply unit 15 on the main surface on the back side, and an emulsion discharge unit 17 on both main surfaces. . The continuous phase supply unit 14, the dispersed phase supply unit 15, and the emulsion discharge unit 17 connect the continuous phase liquid supply tube 93A, the dispersed phase 93B, and the primary emulsion liquid supply tube 97, as will be described later. Are connected to screw holes 31, 32, 33 (see FIGS. 2 and 3) provided in the adapter member 30.

  As shown in FIGS. 2 and 4, the microchannel 16 is rectangular and has a planar shape in which one short side is a semi-elliptical shape, the straight short side is the upstream side, and the semi-elliptical short side is The side is the downstream side.

  As shown in FIG. 3, the continuous phase supply unit 14 is provided at the position of a continuous phase buffer 14 a having a planar shape of a baseball home base shape and a side of the base shape corresponding to the pitcher side of the baseball. It is comprised from the phase nozzle 14b. The apex portion of the triangular-shaped continuous phase buffer 14a that increases in width toward the continuous phase nozzle 14b opens the continuous phase discharge port 34 that communicates with the connection screw hole 31 of the continuous phase liquid supply tube 93A in the adapter member 30. As a hole position.

  As shown in the enlarged circle on the left side in FIG. 4, the continuous phase nozzle 14 b is configured by an opening (oval shape) that is continuous in the width direction of the microfluidic chip body 11 from the back of the microfluidic chip body 11 to the front. The width of the continuous phase buffer 14a is equal to the nozzle width at the position of the continuous phase nozzle 14b. The opening position on the front side of the continuous phase nozzle 14 b is the upstream end of the microchannel 16.

  The continuous phase supplied from the continuous phase discharge port 34 flows as shown by an arrow (1) in FIG. 5 (indicated by a dotted line in FIG. 4), and after filling the continuous phase buffer 14a, a micro flow channel is supplied from the continuous phase nozzle 14b. 16 is discharged to form a thin sheet-like flow equal to the entire width of the microchannel 16 shown in FIG.

  In producing the emulsion, the sheet-like flow discharged from the continuous phase nozzle 14b preferably has a uniform flow rate in the width direction. Therefore, the discharge amount in the width direction is averaged by sufficiently increasing the pressure loss in the continuous phase nozzle 14b with respect to the pressure loss in the continuous phase buffer 14a. In this embodiment, the continuous phase nozzle 14b is an oval nozzle having a high aspect ratio of 26 mm in width and 0.2 mm in length, and generates a pressure loss 100 times that of the continuous phase buffer 14a, resulting in a uniform flow rate. Realized sheet-like flow.

  As shown in FIGS. 3 and 4, the disperse phase supply unit 15 corresponds to the disperse phase buffer 15 a having a base shape like a base of a baseball as in the continuous phase supply unit 14 and the baseball pitcher side. It is composed of a number of dispersed phase nozzles 15b provided at the positions of the sides of the home base shape.

  The apex portion of the triangular dispersed phase buffer 15a that increases in width toward the dispersed phase nozzle 15b opens the dispersed phase discharge port 35 that communicates with the connection screw hole 32 of the dispersed phase feeding tube 93B in the adapter member 30. As a hole position. In the dispersed phase buffer 15a, the opening position side of the dispersed phase discharge port 35 is the upstream side, and the dispersed phase nozzle 15b side is the downstream side.

  The dispersed phase supplied from the dispersed phase discharge port 35 as indicated by the arrow indicated by (3) in the drawing is discharged from a number of dispersed phase nozzles 15b into the continuous phase flow of the microchannel 16 after filling the dispersed phase buffer 15a. It is.

  FIG. 6 is an enlarged perspective cross-sectional view of the disperse phase nozzle 15b portion along the BB cutting line shown in the right circle in FIG.

  Each of the dispersed phase nozzles 15b is a Mt. Fuji, barnacle or truncated cone-shaped projection having a minute opening in the center, and these are arranged in a row at a certain interval in the width direction of the microfluidic chip body 11 and are minute. A total of 126 protrusions projecting toward the flow path 16 are provided in a staggered arrangement in four stages. The number of stages of each dispersed phase nozzle 15b and the number of projections arranged in one stage may be determined from the particle size of the emulsion to be produced, the amount of treatment, the ratio between the continuous phase and the dispersed phase, and the like.

  The dispersed phase nozzle 15b is formed by cutting the bottom surface of the micro flow channel 16 with an extremely fine end mill. Since the angle of the dispersed phase nozzle 15b is matched to the tip end angle of the end mill, the nozzle can be easily formed simply by cutting in a circle with the end mill, and the productivity is excellent.

  Since the discharge amount from each dispersed phase nozzle 15b is desirably uniform, each dispersed phase nozzle 15b has a diameter of 0.1 mm as in the above-described continuous phase nozzle 14b, and the pressure loss is increased compared to the dispersed phase buffer.

  As indicated by (3) in FIG. 6, the dispersed phase discharged from each dispersed phase nozzle 15b is sheared into droplets by the continuous phase indicated by (2) in the figure flowing in an orthogonal manner. The particle size of the droplet can be adjusted by changing the flow rate ratio between the continuous phase and the dispersed phase. Further, since the dispersed phase nozzle 15b is a truncated conical protrusion, the dispersed phase is easily sheared and the particle diameter is easily stabilized as compared with a nozzle having a hole in a plane.

  As described above, droplets are generated in each dispersed phase nozzle 15b. As described above, the continuous phase has a uniform flow rate in the width direction of the flow path, and the flow rate discharged from each dispersed phase nozzle 15b is also uniform. Therefore, droplets having the same diameter are generated in all the dispersed phase nozzles 15b, and as a result, a primary emulsion having a uniform particle size can be generated.

  The primary emulsion generated in the microfluidic chip body 11 passes through the emulsion discharge portion 17 provided downstream of the microchannel 16 and then passes through the emulsion discharge portion provided in the adapter member 30 so as to communicate with the emulsion discharge portion 17. From the outlet 36, the screw hole 33 (see FIGS. 2 and 3) is reached and discharged out of the chip.

  As described above, a primary emulsion having a uniform particle size is generated in the microfluidic chip 10. The smallest dimension of the flow path in the chip is 0.1 mm of the dispersed phase nozzle 15b, which is larger than the conventional chip. In this way, by increasing the size of the flow path in the chip, the increase in pressure loss is suppressed, and in the case of a low-viscosity liquid, even if a liquid amount of about several tens to 100 ml / min is processed, the pressure loss is reduced to several atmospheric pressures It becomes possible to suppress.

  However, since the nozzle diameter is large, the primary emulsion at this stage has a dispersed phase particle size of around 100 μm, depending on the conditions. Therefore, in order to obtain a finer emulsion, in this embodiment, the emulsion is refined using the Venturi tube 40.

  A temperature sensor groove 13 for installing a temperature sensor is provided in the center of the back surface of the microfluidic chip body 11 as shown in FIG. A temperature sensor such as a thermocouple or a platinum resistor is installed in the groove 13 to measure the temperature, and the temperature controller 96 shown in FIG.

  Since the microchannel 16 provided in the microfluidic chip 10 has a planar shape and the volume is sufficiently smaller than the volume of the chip 10, the liquid fed into the chip 10 by adjusting the temperature of the chip 10. Can be made equal to the chip temperature in a short time.

FIG. 7 is an exploded perspective view of the venturi tube 40.
The venturi tube 40 is a cylinder made up of two parts, a venturi tube lid 41 and a venturi tube body 42. The venturi tube lid 41 is provided with a female screw, and the venturi tube main body 42 is provided with a male screw corresponding thereto. An O-ring groove 43 is provided on the surface of the venturi main body 42 that contacts the lid portion, and the Venturi tube 40 with no liquid leakage is obtained by screwing the lid portion into the main body with the O-ring inserted into the groove.

  Notches 44A and 44B are provided at both ends of the venturi tube 40, and can be easily assembled or disassembled using a tool such as a wrench. The reason why the venturi tube 40 is divided is to improve the workability when processing the in-tube flow path using wire electric discharge machining.

FIG. 8 is a longitudinal sectional view of the venturi tube 40 taken along the line CC shown in FIG.
The primary emulsion produced by the microfluidic chip 10 is fed to the venturi tube 40 in the direction indicated by the arrow in the drawing. For this reason, female screws for connecting pipe joints are provided at both upper and lower ends of the venturi tube 40, the upper side being the supply side screw hole 45 and the lower side being the discharge side screw hole 46.

  A circular flow path is provided inside the venturi tube 40, a throat portion (diaphragm) 47 having a minimum diameter provided immediately after the supply-side screw hole 45, and a taper shape in which the diameter gradually increases thereafter. Of the enlarged portion 48.

  The primary emulsion sent to the Venturi tube 40 has a small flow passage cross-sectional area, and the pressure drops in the throat 47 in inverse proportion to the increase in the flow velocity, and suddenly moves to an enlarged portion where the flow passage cross-sectional area increases. To restore pressure.

  Due to this steep pressure fluctuation, the primary emulsion is disintegrated, and the dispersed phase is refined to become a secondary emulsion. Since the fineness of the dispersed phase is more remarkable as the pressure fluctuation is larger, it is desirable to increase the flow rate of the emulsion or to reduce the diameter of the throat 47 in order to produce a fine dispersed phase emulsion.

  In this embodiment, the Venturi tube 40 is divided and wire electric discharge machining is used to realize a throat 47 having a diameter of 0.3 mm.

  As a result, a fine emulsion having a uniform dispersed phase diameter and a few μm could be obtained in a large amount such as an emulsion flow rate of about 50 ml / min.

  In the above explanation, an example of producing an O / W type emulsion in which oil droplets are dispersed in water was introduced. However, the continuous phase and the dispersed phase were exchanged to produce a W / O type emulsion in which water droplets were dispersed in oil. You can also

  As an alternative to the venturi tube 40 of FIG. 1, an orifice or capillary with a restriction may be used.

It is a block diagram of the emulsification apparatus which shows one Embodiment of this invention. It is the disassembled perspective view which looked at the microfluidic chip shown in FIG. 1 from the front side. It is the disassembled perspective view which looked at the microfluidic chip shown in FIG. 1 from the back side. FIG. 3 is a front view of the microfluidic chip body shown in FIG. 2. FIG. 5 is a longitudinal sectional view of the microfluidic chip body taken along the line AA in FIG. 4. FIG. 5 is an enlarged perspective cross-sectional view of a dispersed phase nozzle portion taken along the line BB in FIG. 4. FIG. 2 is an exploded perspective view of the venturi tube shown in FIG. 1. It is a longitudinal cross-sectional view of a venturi pipe along the CC cutting line of FIG.

Explanation of symbols

1 ... Emulsifying device
10 ... Microfluidic chip
11 ... Microfluidic chip body
14 ... Continuous phase supply section
14b ... Continuous phase nozzle
15 ... Dispersed phase supply section
15b ... Dispersed phase nozzle
16 ... microchannel
17 ... Emulsion discharge part
20 ... Lid member
30 ... Adapter member
40 ... Venturi tube
42 ... Venturi tube body
47 ... Throat (aperture)
48 ... Enlarged part
91A ... Liquid (continuous phase) tank
91B ... Liquid (dispersed phase) tank
98 ... Emulsion tank
95 ... Temperature controller

Claims (3)

In an emulsification apparatus that supplies two liquids that are a continuous phase and a dispersed phase of an emulsion to a microchannel in a microfluidic chip, emulsifies in the microchannel, and obtains an emulsion.
A micro that obtains the primary emulsion from the discharge port with a micro-channel of a planar channel that supplies the dispersed phase so as to be orthogonal to the flow of the liquid that becomes a wide planar continuous phase. A fluidic chip and a Venturi tube that passes through the primary emulsion discharged from the microfluidic chip to obtain a secondary emulsion in a fine dispersed phase, the microfluidic chip having a width of the microchannel and A continuous-phase nozzle that supplies a continuous phase from an opening having substantially the same length and at least one line in the width direction of the micro-channel and projecting in a truncated cone shape toward the micro-channel and opening the center An emulsifying apparatus comprising a plurality of dispersed phase nozzles having holes . 2. The emulsifying apparatus according to claim 1, wherein the microfluidic chip is provided with temperature adjusting means . 2. The emulsifying apparatus according to claim 1, wherein an orifice or a capillary is used in place of the venturi tube .

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