JP5563322B2 - Process device with microbubble generator - Google Patents

Description

The present invention, [hereinafter abbreviated as "CT"] Taylor Couette (Couette-Taylor) reactor, or, where that is referred to as STT (Spinning Tube in a Tube) reactor, rotate coaxially within the fixed outer cylinder An apparatus for performing various processes by arranging an inner cylinder to be pressed and press-fitting a reaction material into a narrow gap between an inner cylinder inner wall and an inner cylinder side wall at a substantially constant flow rate, that is, such a reactor And a device system combining a device for generating microbubbles called microbubbles and nanobubbles.

Its purpose is
1 To increase the efficiency of chemical reaction, that is, to realize a highly efficient process.

  2 CT (Couette-Taylor) sterilization and / or cleaning operation of a CT (Couette-Taylor) reactor having a narrow gap that forms a spiral pseudo-micro reaction channel in a flow, especially the narrow gap sterilization and / or To reduce and increase the efficiency of cleaning work.

  3 Extracting and / or generating nano-sized bubbles from micro-sized bubbles.

  4. To provide a biological process apparatus (bioprocess apparatus) such as cell culture using an apparatus that forms a material flow without contamination.

CT (Couette-Taylor) reactor or STT (Spinning
For the tube in a tube reactor, see Patent Document 1 and Patent Document 2, or Non-Patent Document 1.

  The present inventors have proposed improvements and applications as disclosed in Patent Documents 3 to 8 for devices that generate microbubbles called microbubbles and nanobubbles. Further, Takahashi et al. Of the National Institute of Advanced Industrial Science and Technology and Chiba et al. Of the Leo Research Institute have proposed Patent Documents 9 to 25 prior to the proposal of the present inventor. Refer to Non-Patent Document 2 to Non-Patent Document 4 as materials supplementing these.

  On the other hand, in biological process equipment (bioprocess equipment) such as cell culture, contamination (foreign matter contamination) is a major problem, and great attention has been paid to sterilization and washing before the start of the process and elimination of contamination during the process. I have to. Here, it is significant to continue the biological process.

  That is, if a continuous flow is formed, even if foreign matter is mixed (contamination) only for a certain period of time, it is only necessary to eliminate the process part due to the flow, and as a result, the amount of mixed foreign matter can be extremely reduced. Refer to Patent Document 26 to Patent Document 28 for the technology conscious of continuous flow.

The present invention is based on these known techniques and proposes improvements and improvements that meet the objects 1 to 4 described above.
US Pat. No. 6,471,392 Japanese Patent No. 3309093 Japanese Patent Application No. 2009-234683 “Composition containing microbubbles for promoting cell change, and ... Method for promoting cell change” Japanese Patent Application No. 2009-243940 “Composition of microbubbles and microbubble generator” Japanese Patent Application No. 2009-249900 “Apparatus for generating microbubbles in liquid” Japanese Patent Application No. 2009-265832 “Apparatus and method for generating heat by generating microbubbles in liquid” Japanese Patent Application No. 2009-282840 "A device for promoting cell change with a liquid composition containing microbubbles, ... Method for promoting" Japanese Patent Application No. 2010-000569 “Microbubble generator with variable microbubble diameter and microbubble concentration, design method” JP 2009-189307 A “Sterilization or Inactivation Method of Spore Bacteria” JP 2009-131770 “Method for producing carbon dioxide nanobubble water” JP 2009-131769 A “Method for Producing Nitrogen Nanobubble Water” JP 2009-084258 A "Drug for treatment or prevention of cancer containing nanobubbles" Japanese Unexamined Patent Publication No. 2009-039600 “Ultrafine Bubble Generation Device” JP 2008-259456 A “Method for Preserving Seafood” JP 2008-237950 A “Method for producing water containing hydroxyl radicals and water containing hydroxyl radicals” JP 2008-093612 A "Method for producing water containing reactive active species and water containing reactive active species" JP 2008-093611 A "Method for producing water containing extremely fine bubbles and water containing extremely fine bubbles" JP 2008-063258 A "Tissue preservation solution" JP 2007-275089 A "Long-lasting ozone water, environmental sterilization / deodorizing purification method using long-lasting ozone water" Japanese Patent Application Laid-Open No. 2006-223239 “A method for extracting active ingredients of roasted seafood using oxygen nanobubbles and a processed fish meat material to which active ingredients obtained by the extraction method are added” Japanese Patent Application Laid-Open No. 2005-246294 “Oxygen Nano Bubble Water and Method for Producing the Same” Japanese Patent Application Laid-Open No. 2005-246293 “Ozone water and method for producing the same” JP 2005-245817 A “Method for producing nanobubbles” Japanese Patent Application Laid-Open No. 2005-110552 “Pressurized Multilayer Micro-Ozone Sterilization / Purification / Animal Sterilization System” No. 2005/030649 publication "Crushing of microbubbles" JP 2009-291097 A "Cell culture device" National University Corporation Gunma University Olympus Japanese Patent Application Laid-Open No. 07-075549 “Biological cell culture device” Hitachi, Ltd. Japanese Laid-Open Patent Publication No. 06-261736 “Cell culture device for living organisms” Space Development Corporation, Mitsubishi Heavy Industries, Ltd. Michael A. Gonzalez and James T. Cizewski, “High Conversion, Solvent Free, Continuous Synthesis of Imidazolium Ionic Liquids in Spinning Tube-in-Tube Reactors.” Process Res. Dev. , 2009, 13 1, p64-66 2005 New Energy and Industrial Technology Development Organization Commissioned Research Study Survey on Industrial Use of Nano Bubble Water in Biotechnology Results Report 38-40 “Evaluation Research on Preservation of Living Tissue Using Nano Bubble Water” Hojo Y, et al. “Anti-inflammability Property of Oxygen Nano-bubbles” Circulation Journal vol. 70, supplement I, p276 (The 70th Annual Meeting of the Japanese Circulation Society) 2005 New Energy and Industrial Technology Development Organization Commissioned Research Study on Industrial Use of Nano Bubble Water in Biotechnology Results Report 40-45 “Evaluation of Nano Bubble Water Effects on Cell Physiology”

  As described above, the issues are as follows (reprinted).

  1 To increase the efficiency of chemical reaction, that is, to realize a highly efficient process.

  2 CT (Couette-Taylor) sterilization and / or cleaning operation of a CT (Couette-Taylor) reactor having a narrow gap that forms a spiral pseudo-micro reaction channel in a flow, especially the narrow gap sterilization and / or To reduce and increase the efficiency of cleaning work.

  3 Extracting and / or generating nano-sized bubbles from micro-sized bubbles.

  4. To provide a biological process apparatus (bioprocess apparatus) such as cell culture using an apparatus that forms a material flow without contamination.

The structure that forms the basis of the present invention (see claim 1 and FIG. 1) is a fixed hollow outer cylinder, an inner cylinder that rotates coaxially with a substantially constant gap from the inner wall of the outer cylinder, a rotating means for the inner cylinder, and the gap Means C1 for supplying a liquid to one end of the gas and means C2 for extracting the liquid from the other end of the gap, and the liquid is supplied to the gap by the supply means while the inner cylinder is rotating. A process apparatus in which a process related to a liquid is executed while the liquid forms a spiral CT (Couette-Taylor) flow pattern in the gap by being supplied at a substantially constant flow rate. And means C21 for switching the liquid supplied by the liquid supply means C1 between A1: liquid outside the apparatus and B1: liquid extracted by means C2 for extracting the liquid from the other end of the gap. CT (Couette-Taylor) reactor process It is a device.

  1 is a process apparatus using a circulation type CT (Couette-Taylor) reactor. When B1 is selected, the liquid to be processed circulates in the CT (Couette-Taylor) reactor. Therefore, it is suitable for a process that takes a long time such as several days in an extreme case, such as a crystallization process or a cell culture process.

  The flow pattern of the reaction material flowing in the gap of the reaction apparatus is induced by the press-fitting pressure of the supply means of the reaction material related to the liquid and the shearing force due to the rotation of the inner cylinder. This is a traveling Taylor vortex (Taylar_Vortex) flow pattern having a spiral tube inside and a secondary swirl flow vector in the spiral tube.

  This flow forms a continuous pseudo-microreaction channel (generally the same as the microreactor channel because the gap scale is sufficiently small), making it suitable for biological processes such as ideal cell culture with low contamination. is there.

Further, the present invention (see claim 1 and FIG. 2) includes a fixed hollow outer cylinder, an inner cylinder that rotates coaxially with a substantially constant gap from the inner wall of the outer cylinder, a rotating means for the inner cylinder, and a liquid at one end of the gap. Means C1 and means C2 for extracting the liquid from the other end of the gap, and the liquid is supplied to the gap by the supply means while the inner cylinder is rotating. A CT (Couette-Taylor) reactor in which a process involving the liquid is performed while the liquid flows in a spiral CT (Couette-Taylor) flow pattern in the gap by supplying at a rate; And a process apparatus comprising a microbubble generator (microbubble or nanobubble generator) for generating microbubbles in the liquid stored in the liquid storage tank MR, wherein the liquid supplied by the liquid supply means C1 A2: Liquid outside the device If, B2: were combine means CM1 to switch to the liquid stored in the liquid reservoir MR, a process device that combines the CT (Couette-Taylor) reactor and microbubble generator.

  In FIG. 1 and FIG. 2, fixed flow means such as an electromagnetic pump / syringe pump for pressurizing liquid may be interposed in the middle of the line indicating the pipe. The description of the quantitative flow means is omitted in the figure. The electromagnetic pump employs a solenoid in the drive, and the electromagnetic pump that reciprocates the diaphragm by the electromagnetic force generated in the solenoid in conjunction with the pulse signal. The syringe pump is a fixed amount by moving the syringe like a cylinder. It is a transport means.

  By introducing microbubbles or nanobubbles into the gap of a CT (Couette-Taylor) reactor, it is considered that the progress of the chemical process as in Non-Patent Document 1 is promoted.

  Further, since microbubbles generate radicals by crushing, introduction of nanobubbles into the gap of a CT (Couette-Taylor) reactor enables sterilization and / or washing, which is preferable because it eliminates the need for conventional decomposition cleaning.

  On the other hand, a configuration as shown in FIG. 3 is conceivable. That is, a fixed hollow outer cylinder, an inner cylinder that rotates coaxially with an inner surface of the outer cylinder while maintaining a substantially constant gap, a rotating means for the inner cylinder, a supply means for press-fitting a reaction material into one end of the gap, and An extraction means for extracting a post-reaction material from the other end of the gap, and while the inner cylinder is rotating, pressurizing the reaction material into the gap with the supply means at an approximately constant flow rate; In a flow-type continuous reaction apparatus in which a physical and / or chemical reaction is induced while a material to be reacted flows through the gap, one electrode E1 for electrochemical reaction is provided on the inner surface of the hollow outer cylinder, and the outer surface of the inner cylinder The other electrode E2, the external terminals E10 and E20 electrically connected to the one and the other electrodes, respectively, and a means for applying a voltage between the external terminals, and the reaction material has the gap therebetween. During flow, one and the other through the external terminal Continuous electrochemical process that induces an electrochemical reaction in a reaction material by forming an annular electrochemical cell between concentric double cylinders sandwiched between the one and the other electrode by applying a voltage between the two electrodes It is a reactor.

Furthermore, the present invention has an improved structure incorporating the above-described continuous electrochemical reaction apparatus.

That is, (Claim 1 ), one electrode of electrochemical reaction on the inner surface of the fixed hollow outer cylinder, the other electrode of electrochemical reaction on the outer surface of the coaxially rotating inner cylinder, and the one and the other A process apparatus further comprising an external terminal electrically connected to each electrode and means for applying a voltage between the external terminals.

  With such a configuration, the reactant in the process related to the liquid is sandwiched between the one and the other electrode by applying a voltage between the one and the other electrode through the external terminal while flowing in the gap. An annular electrochemical cell between concentric double cylinders is formed to induce an electrochemical reaction in a reaction material related to a liquid.

The apparatus of the present invention is a technique in which the characteristic of continuous and narrow reaction field formation of a known CT reaction apparatus (STT reaction apparatus) is applied to an electrochemical reaction.

  In the conventional electrochemical reaction apparatus, the reaction field formed between the electrodes is relatively wide with respect to the present invention, and the spatial uniformity of the reaction cannot be maintained. The drawback is that the use of various rotating electrodes that rotate the electrode and various stirring means improve the spatial uniformity of the reaction field and attempt to achieve uniform reaction, but this is not possible. Sufficient and reaction efficiency was not high compared to other common reaction efficiencies.

In the apparatus of the present invention , a counter electrode is provided on the inner surface of the stationary outer cylinder and the outer surface (side surface) of the rotating inner cylinder of the CT reactor, and a continuous and narrow electrochemical reaction field is formed by applying a voltage between them. This improves the spatial uniformity of the reaction and provides unprecedented process efficiency.

  Next, the formation of a spiral CT (Couette-Taylor) flow in a CT (Couette-Taylor) reactor is somewhat affected by gravity. Therefore, in the horizontal (horizontal) CT (Couette-Taylor) described in Patent Document 1 and Patent Document 2 and the vertical (vertical) CT (Couette-Taylor) obtained by rotating these by 90 degrees, The flow pattern is slightly different. The same applies to a state in which the vehicle is rotated at an angle other than 90 degrees.

  There are practically effective positioning (placement methods) in these horizontal type (horizontal placement), vertical type (vertical placement), and skewed state (oblique placement). Therefore, as a practical improvement, it is convenient if the positioning of the CT (Couette-Taylor) reactor can be freely changed.

  That is, in the CT (Couette-Taylor) reactor, common to the fixed hollow outer cylinder and the inner cylinder rotating coaxially while maintaining a substantially constant gap with the inner wall of the outer cylinder. It is preferable to further include means ROT for freely changing an angle formed by the rotation axis of the horizontal axis and a horizontal plane or a vertical line.

  In the apparatus of the present invention, the process may be a process of sterilizing and / or cleaning the gap of its own CT (Couette-Taylor) reactor.

In addition, according to some descriptions in Patent Document 9 to Patent Document 25 by Takahashi et al. Of the National Institute of Advanced Industrial Science and Technology, Chiba et al. Of the Leo Research Laboratories, the microbubble-containing liquid generated by the microbubble generator is discharged or When an electrochemical reaction such as electrolysis is performed to generate or stabilize nanobubbles, such an electrochemical reaction such as discharge or electrolysis may be performed by the apparatus of the present invention .

In other words, in the process apparatus of the present invention, the process may be a process for generating and / or separating nanobubbles from a liquid containing microbubbles and stabilizing them.

The apparatus of the present invention can be expected to improve the efficiency of chemical reaction by introducing micro / nano bubbles. This is an effect that depends on the action of the micro / nano bubble itself on the chemical reaction.

In addition, the apparatus of the present invention can efficiently sterilize and / or wash a CT (Couette-Taylor) reactor having a narrow gap that forms a spiral pseudo-micro reaction channel with a CT (Couette-Taylor) flow. First, CM1 is set to B2, and micro / nano bubbles flow into the apparatus. Micro-nano bubbles generate radicals by their crushing. This radical sterilization and / or cleaning effect is preferable because it can be sufficiently sterilized and cleaned without the work conventionally performed by disassembly and cleaning. After the micro / nano bubble sterilization / cleaning operation mode, CM1 is set to A2, and a reaction process is introduced from the outside of the apparatus to perform a desired process reaction. Thus, it is possible to instantaneously switch between the cleaning / sterilization mode and the process reaction mode, which is preferable.

In addition, the apparatus of the present invention in which a microbubble generator and a CT (Couette-Taylor) reactor with electrodes are combined is used to extract and / or generate nanosized bubbles from microsized bubbles and to suspend them in an ion group. The turbidity stabilization process can be performed continuously in an electrode-equipped CT (Couette-Taylor) reactor. In other words, it is possible to realize a cascade process in which the microbubble generator is a microbubble raw material supplier and the subsequent nano-size bubble extraction and / or generation process is performed by an electroded CT (Couette-Taylor) reactor. It is an aspect. Here, since an electrochemical reaction is performed in a CT (Couette-Taylor) reactor with electrodes, it is necessary to supply an electrolyte such as salt at a port of the reactor, for example, in order to make the liquid conductive. Of course, it means for supplying the electrolyte, such as salt is not limited to a port of CT (Couette-Taylor) reactor, storage tank and the supply means C1 microbubble generator, disposed in the vicinity and pipes switching means C21 May be.

  Further, in the configuration of the third aspect of the present invention, a spiral CT (Couette-Taylor) flow which is difficult to stabilize is caused by a rotation axis common to the fixed hollow outer cylinder and the inner cylinder rotating coaxially and a horizontal plane or a vertical line. It can be easily stabilized by adjusting the angle formed. This leads to improved efficiency.

As described above, with the apparatus of the present invention, when the gap of its own CT (Couette-Taylor) reactor is sterilized and / or washed, nanobubbles are generated and / or separated from a liquid containing microbubbles and stabilized. In some cases, improvement in operability and efficiency can be expected.

In the present invention, since a CT (Couette-Taylor) reactor that forms a spiral pseudo-micro continuous flow is used, an ideal biological process such as cell culture with less contamination can be realized. In other words, since it is a continuous flow, even if foreign matter is contaminated (contamination) only for a certain period of time, it is sufficient to eliminate the process part due to the flow, and as a result, the amount of foreign matter can be extremely reduced.

FIG. 2 is a schematic diagram showing the basic configuration of the present invention, in which liquid supplied by the liquid supply means C1 is extracted by A1: liquid outside the apparatus and B1: means C2 for extracting the liquid from the other end of the gap. The structure provided with the means C21 which switches to the made liquid is shown. Here, C22 is a switching means for extracting the extracted liquid to the outside of the apparatus by means C2 for extracting the liquid and setting it as B1, that is, the supply liquid of the liquid supply means C1. It is a schematic diagram showing the configuration of the apparatus of the present invention, CM1, that is, the liquid supplied by the liquid supply means C1, A2: liquid outside the apparatus, B2: liquid stored in the liquid storage tank MR, The structure which comprises the means to switch to is shown. FIG. 2 is a schematic view showing a CT (Couette-Taylor) reactor with electrodes, which is a component of the apparatus of the present invention, and one electrode E1 for electrochemical reaction on the inner surface of a fixed hollow outer cylinder, The other electrode E2 of the electrochemical reaction on the outer surface of the cylinder, the external terminals E10 and E20 electrically connected to E1 and E2, and means for applying a voltage between the external terminals (not shown) It has. FIG. 4 is a schematic diagram showing components of claim 3 of the present invention, and is a ROT, that is, a rotation axis (z) common to a fixed hollow outer cylinder and a coaxially rotating inner cylinder of a CT (Couette-Taylor) reactor; Means for freely changing the angle between the horizontal plane and the vertical line is provided. The ROT is a mechanism that grips and rotates a CT (Couette-Taylor) reactor as shown, for example. It is explanatory drawing of the mechanism which hold | grips and rotates CT (Couette-Taylor) reactor of FIG.

DESCRIPTION OF SYMBOLS 1 Fixed hollow outer cylinder 2 The liquid supplied from gap | interval A1 C1 of the inner wall 32 of the inner cylinder 32 rotating coaxially, maintaining the substantially constant gap | interval 4 with the inner wall of 1, and the side wall of 2 The liquid outside an apparatus The switching mode A2 C1 uses the liquid supplied from the outside as the switching mode B1 C1 uses the liquid supplied by the extraction means C2 as the liquid supplied from the extraction mode C2. Switching mode C1 for introducing microbubbles as liquid containing microbubbles stored in the liquid storage tank MR of the bubble generator C1 Means for supplying liquid to one end of the gap 4 Extracting the liquid from the other end of the gap 4 the liquid supplied by means C 21 liquid supply means C1, A1: device outside of the liquid, and, B1: extracted by means C2 for extracting the liquid from the other end of the gap the liquid, The means C22 for switching to the liquid supply means C1 supplies the liquid extracted by the liquid extraction means C2 to B1, that is, the supply liquid for the liquid supply means C1. Means E1 for switching the liquid to A2: liquid outside the apparatus, and B2: liquid stored in the liquid storage tank MR. Recessed curved surface electrode E2 disposed on the inner surface of the fixed hollow outer cylinder 1. External terminal M1 electrically connected to the external terminal E20 E2 electrically connected to the convex curved electrode E10 E1 disposed on the outer surface of the inner cylinder 2 Liquid M4 Gas suction means M10 Eddy current pump M11 Eddy current pump Built-in impeller M14 Liquid suction means (front end)
M15 Liquid discharge means (front end)
MR Liquid storage tank ROT A means for freely changing an angle formed by a rotation axis common to the fixed hollow outer cylinder and the coaxially rotating inner cylinder and a horizontal plane or a vertical line. For example, a rotation mechanism.
z Common rotation axis for fixed hollow outer cylinder and coaxially rotating inner cylinder

Claims (3)

A fixed hollow outer cylinder, an inner cylinder that rotates coaxially while maintaining a substantially constant gap with the inner wall of the outer cylinder, means for rotating the inner cylinder,
Means C1 for supplying liquid to one end of the gap; and
Means C2 for extracting the liquid from the other end of the gap,
While the inner cylinder is rotating, supplying the liquid to the gap with the supply means at a substantially constant flow rate,
Taylor Couette the process liquid is involved in spiral Taylor Couette (Couette-Taylor) while being fluidized with a flow pattern liquid among the gap is performed (Couette-Taylor) reactor, and,
A process apparatus comprising a microbubble or nanobubble generator for generating microbubbles in a liquid stored in a liquid storage tank MR,
The liquid supplied by the liquid supply means C1 is
A2: Liquid outside the device,
B2: to immediately Bei means CM1 to switch to the liquid stored in the liquid reservoir MR, and,
One electrode of electrochemical reaction on the inner surface of the fixed hollow outer cylinder, and
The other electrode of the electrochemical reaction on the outer surface of the coaxially rotating inner cylinder, and
An external terminal electrically connected to each of the one and other electrodes; and
Means for applying a voltage between the external terminals, and
The liquid supplied by the liquid supply means C1 is
A1: liquid outside the device,
B1: Liquid extracted by means C2 for extracting the liquid from the other end of the gap,
And means C21 for switching to
A process apparatus comprising an electromagnetic pump or a syringe pump in the pipe from C2 to C21.   2. The process apparatus according to claim 1, wherein an electrolyte supply means is provided in the pipe extending from C2 to C21. In the Taylor -Taylor reactor of the apparatus of claim 1 or 2,
A rotation axis common to the fixed hollow outer cylinder and the inner cylinder rotating coaxially while maintaining a substantially constant gap with the inner wall of the outer cylinder;
A process apparatus further comprising means for freely changing an angle formed with a horizontal plane or a vertical line.