WO2017069085A1 - 気泡噴出チップ、局所アブレーション装置及び局所アブレーション方法、並びにインジェクション装置及びインジェクション方法 - Google Patents
気泡噴出チップ、局所アブレーション装置及び局所アブレーション方法、並びにインジェクション装置及びインジェクション方法 Download PDFInfo
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- WO2017069085A1 WO2017069085A1 PCT/JP2016/080692 JP2016080692W WO2017069085A1 WO 2017069085 A1 WO2017069085 A1 WO 2017069085A1 JP 2016080692 W JP2016080692 W JP 2016080692W WO 2017069085 A1 WO2017069085 A1 WO 2017069085A1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/02—Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
- C12M3/006—Cell injection or fusion devices
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/89—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microinjection
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/004—Photosensitive materials
- G03F7/038—Macromolecular compounds which are rendered insoluble or differentially wettable
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/16—Coating processes; Apparatus therefor
- G03F7/162—Coating on a rotating support, e.g. using a whirler or a spinner
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/16—Coating processes; Apparatus therefor
- G03F7/168—Finishing the coated layer, e.g. drying, baking, soaking
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/20—Exposure; Apparatus therefor
- G03F7/2002—Exposure; Apparatus therefor with visible light or UV light, through an original having an opaque pattern on a transparent support, e.g. film printing, projection printing; by reflection of visible or UV light from an original such as a printed image
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/26—Processing photosensitive materials; Apparatus therefor
- G03F7/30—Imagewise removal using liquid means
- G03F7/32—Liquid compositions therefor, e.g. developers
- G03F7/322—Aqueous alkaline compositions
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/16—Coating processes; Apparatus therefor
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/26—Processing photosensitive materials; Apparatus therefor
Definitions
- the present application relates to a bubble ejection tip, a local ablation device, a local ablation method, an injection device, and an injection method.
- a bubble ejection tip capable of ejecting bubbles upward, a local ablation device and a local ablation method including the bubble ejection tip, and an injection device and an injection method.
- local processing technique examples include a contact processing technique using a probe such as an electric knife or a non-contact ablation technique using a laser or the like. Widely known.
- a technique for improving the resolution by suppressing the heat invasive region has been devised by recently suppressing the contact processing technique of the electric knife to a sintered surface on the order of several micrometers (see Non-Patent Document 1).
- Non-Patent Document 2 a technology for performing cell processing (see Non-Patent Document 2) and a laser processing technology that suppresses bubble generation in the liquid phase have been devised.
- the conventional contact processing technique using a probe such as an electric scalpel has the property of burning an object by Joule heat generated by continuous high frequency. There was a problem that the influence was great. Further, even in a non-contact processing technique using a laser such as a femtosecond laser, there is a problem of a thermal invasion effect on a tissue around a cut surface due to a high density energy being locally applied.
- injection method for introducing a nucleic acid substance or the like into a cell or the like
- electroporation, ultrasonic sonopo And the like are widely known.
- the conventional electroporation technique there is a limit in improving the permeability of the cell membrane due to the electric field strength, and it is difficult to inject an object having a hard cell membrane or cell wall instead of a flexible lipid bilayer membrane.
- the sonoporation technique using ultrasonic waves it is difficult to focus the ultrasonic waves, and it is difficult to increase the resolution by generating local bubble cavitation.
- the injection method based on the particle gun method also has a problem that the introduction efficiency is low because a substance adhered to the particle surface is detached from the surface when the particle is driven.
- the electroporation method, the sonoporation method, and the particle gun method have a problem that it is difficult to inject a valuable substance because the amount of the substance to be injected is large.
- the present inventors have formed a core material made of a conductive material, an insulating material, covered the core material, and the tip of the core material.
- a bubble ejecting member including an outer portion including a stretched portion, and a gap formed between the stretched portion of the outer portion and the tip of the core, and immersing the bubble ejecting member in a solution;
- a patent application has been filed for finding that bubbles are generated by applying a high-frequency voltage in a solution, and that the workpiece can be cut (local ablation) by continuously discharging the bubbles to the workpiece (patent) Reference 1).
- an outer shell portion is provided outside the outer shell portion of the bubble ejection member so as to have a shell portion and a space, and the injection material is dissolved by introducing a solution in which the injection material is dissolved and / or dispersed in the space. And / or the dispersed solution can generate bubbles adsorbed on the interface, and the injection target contained in the solution covering the bubbles while cutting the workpiece by continuously releasing the bubbles to the workpiece.
- Patent Document 1 has been found to be capable of being injected into a workpiece, and a patent application has been filed (see Patent Document 1).
- the bubble ejection part is formed by providing an electrode between the photosensitive resin laminated on the substrate and the top surface of the bubble ejection chip to prevent leakage.
- the present inventors have developed a bubble ejection chip (hereinafter sometimes referred to as “multi-cylinder chip 1 ′”) packaged with PDMS (Yoko Yamanishi et al., “Multi-cylinder injection with microarray electrodes”). “, No. 15-2, Proceedings of the 2015, JSME Conference on Robotics and Mechatronics, Kyoto, Japan, May 17-19, 2015, hereinafter referred to as“ Non-Patent Document 3 ”).
- the bubble ejection part shown in FIG. 1 (1) is formed in parallel with the substrate.
- the multi-cylinder chip 1 'shown in FIG. 1 (1) is immersed in a solution in a petri dish or the like
- the thin-plate substrate of the multi-cylinder chip 1' is used.
- the multi-cylinder tip 1 ′ is generally used by immersing it in a petri dish or the like from the horizontal or diagonal direction, not the vertical direction.
- the said nonpatent literature 3 also describes forming the location which hold
- the place to do is the structure which intends to eject a bubble in a horizontal direction.
- An energization part is formed on a substrate using a photolithography technique, and the bubble ejection part is formed upward so that the electrode is connected to the energization part formed on the substrate.
- the bubble jet port faces upward when placed on the surface, and the bubble can be jetted in a direction substantially perpendicular to the substrate plane,
- the photosensitive resin constituting the bubble ejection portion is formed into a cylindrical shape from above with respect to the substrate, a bubble ejection chip having an arbitrary number and an arbitrary position of the bubble ejection portions is manufactured. What you can do, Newly found
- an object of the present application is to provide a bubble ejection tip, a local ablation device, a local ablation method, an injection device, and an injection method.
- the present application relates to a bubble ejection tip, a local ablation apparatus, a local ablation method, an injection apparatus, and an injection method described below.
- the energization part is formed on the substrate
- the bubble ejecting portion includes an electrode formed of a conductive material, an outer portion formed of an insulating photosensitive resin, and an extending portion extending from the outer portion, and the outer portion covers the electrode and extends.
- the part extends from the tip of the electrode, and the bubble ejection part includes a gap formed between the extension part and the tip of the electrode,
- the electrode of the bubble ejection part is formed on the energization part, Bubble ejection tip.
- the bubble ejection tip according to (2) wherein the height of the bubble ejection portion is different.
- the above (1) to (5) can further include an outer shell portion formed around the bubble jetting portion, and a solution containing an injection substance can be stored in a space between the bubble jetting portion and the outer shell portion.
- the bubble ejection tip according to (6) wherein a flow path for feeding a solution containing an injection substance and / or a solution for forming an assist flow is formed in the space.
- a local ablation apparatus including the bubble ejection tip according to any one of (1) to (7).
- An injection device including the bubble ejection tip described in any one of (1) to (7) above.
- (10) Fill at least the voids of the bubble ejection tip of the local ablation device according to (8) above with a solution, By applying a high frequency pulse to the electrode pair composed of the electrode of the local ablation device and the counter electrode, bubbles are released from the tip of the bubble ejection part, A local ablation method for processing a workpiece with the bubbles.
- the bubble ejection tip of the present application forms the bubble ejection portion so that the bubble ejection opening opens above the substrate. Therefore, since the bubbles can be ejected upward in the solution, the change in the traveling direction due to buoyancy is reduced when the bubbles advance in the solution. Further, the bubbles do not adhere to the members constituting the bubble ejection tip 1 or the like. Further, when the bubble ejection tip is disposed at the bottom of a container such as a petri dish, the bubble ejection portion faces upward, so that the workpiece can be locally ablated or injected from below.
- FIG. 1 (1) and (2) are diagrams showing an outline of a multi-cylinder chip 1 '.
- FIG. 2 is a diagram showing an outline of the multi-cylinder tip 1 '.
- FIG. 3 is a diagram showing an outline of an example of the embodiment of the bubble ejection tip 1.
- 4 (1) to 4 (4) are diagrams showing another embodiment of the bubble ejection tip 1.
- FIG. 5A is a diagram illustrating an example of a manufacturing process of the bubble ejection tip 1.
- FIG. 5B is a diagram illustrating an example of a manufacturing process of the bubble ejection tip 1.
- FIG. 5C is a diagram illustrating an example of the manufacturing process of the bubble ejection tip 1.
- 6 (1) to 6 (4) are diagrams showing another embodiment of the bubble ejection tip 1.
- FIG. 7 is a diagram illustrating an overall configuration of an example of the embodiment of the local ablation apparatus 6 using the bubble ejection tip 1.
- FIG. 8 is a diagram showing an outline of an example of the embodiment of the bubble ejection tip 1 that is more suitable for the injection device.
- FIG. 9 is a cross-sectional view taken along the line A-A ′ of FIG.
- FIGS. 10 (1) to 10 (6) are diagrams for explaining an example of an embodiment in which the bubble ejection tip 1 is used as a needleless injection.
- FIG. 11 (1) is a drawing substitute photograph, a photograph of the bubble ejection tip 1 produced in Example 1
- FIG. 11 (2) is a drawing substitution photograph, which is an enlarged photograph of the vicinity of the bubble ejection portion 3.
- FIG. 11 (1) is a drawing substitute photograph, a photograph of the bubble ejection tip 1 produced in Example 1
- FIG. 11 (2) is a drawing substitution photograph, which is an enlarged photograph of the vicinity of the bubble ejection portion 3.
- FIG. 11 (1)
- FIG. 11 (3) is a diagram for illustrating the dimensions in the vicinity of the produced bubble ejection portion 3.
- FIG. 11 (4) is a drawing-substituting photograph in which the bubble ejection part 3 and at least a part of the counter electrode 5 are arranged in the frame body 41.
- FIG. 12 is a drawing-substituting photograph in which the generation of bubbles 36 is photographed with a high-speed camera.
- FIG. 13 is a drawing-substituting photograph showing a discharge from the electrode 31 in addition to the ejection of bubbles in Example 3.
- FIG. 3 is a diagram schematically showing an example of the embodiment of the bubble ejection tip 1.
- the bubble ejection tip 1 includes at least a substrate 2, a bubble ejection portion 3, and an energization portion 4.
- the energization unit 4 is formed on the substrate 2.
- the bubble ejection part 3 includes an electrode 31 made of a conductive material, an outer part 32, an extending part 33, and a gap 34. More specifically, the outer portion 32 covers the periphery of the electrode 31, and the extending portion 33 extends further from the outer portion 32 than the tip of the electrode 31.
- the air gap 34 is formed between the extending portion 33 and the tip of the electrode 31, and a bubble outlet 35 is formed on the side opposite to the electrode 31. As shown in FIG.
- the gap 34 is covered with the electrode 31 and the extending portion 33 except for the bubble ejection port 35. That is, a space (channel) for sending liquid or the like is not formed between the electrode 31 and the outer portion 32, and the gap 34 communicates with the outside only through the bubble jet port 35.
- a voltage to the counter electrode 5 and the electrode 31 (not shown in FIG. 3)
- the bubbles 36 can be continuously ejected.
- the counter electrode 5 may be formed on the substrate 2 or may be separate from the bubble ejection tip 1.
- the material for forming the substrate 2 is not particularly limited as long as the current-carrying portion 4 can be laminated, and examples thereof include glass, quartz, PMMA, and silicon.
- the material for forming the electrode 31 is not particularly limited as long as it is a material that can be energized and can be deposited on the energizing portion 4 by a method such as electroplating or electroless plating.
- a method such as electroplating or electroless plating.
- the outer portion 32 and the extending portion 33 are produced using a photolithography technique. Therefore, the material forming the outer portion 32 and the extending portion 33 is not particularly limited as long as it is an insulating photosensitive resin. Examples thereof include commercially available positive photoresists such as TSMR V50 and PMER, and negative photoresists such as SU-8 and KMPR. Since the bubble 36 is ejected by energizing the electrode 31 and the counter electrode 5, a load is likely to be applied to the bubble outlet 35, which is a fine part, particularly when a high voltage is applied. Since negative photoresists such as SU-8 and KMPR are harder than positive photoresists, it is preferable to use a negative photoresist as the photosensitive resin when a high voltage is applied to the bubble ejection portion 3.
- the energization unit 4 and the counter electrode 5 are not particularly limited as long as electricity from an external power source can be passed to the electrode 31, and the same material as the electrode 31 can be used. In the case where the counter electrode 5 is a separate body, it is sufficient that the electrode 31 can be energized. When the counter electrode 5 is formed on the substrate 2, the counter electrode 5 may be stacked on the substrate 2 in the same manner as the energization unit 4.
- the depth of the gap 34 (the length from the tip of the electrode 31 to the bubble ejection port 35.
- L is a size at which bubbles can be generated at least in the gap 34. It is necessary that L / D is at least 1 or more.
- the upper limit of L / D is not particularly limited as long as the bubbles 36 can be continuously ejected. L / D can be adjusted by the thickness of the laminated photosensitive resin and the height of the electrode 31 to be deposited.
- the size of the bubble 36 to be ejected can be adjusted by changing the diameter D of the bubble ejection port 35, and may be adjusted by the shape of the photomask at the time of manufacture.
- the embodiment of the bubble ejection tip 1 shown in FIG. 3 shows an example in which a plurality of bubble ejection portions 3 are formed for the sake of explanation, but the number of bubble ejection portions 3 may be one. Further, as shown in the manufacturing method described later, the bubble ejection tip 1 is formed by etching the outer portion 32 and the extending portion 33 constituting the bubble ejection portion 3 into the cylindrical shape from above with respect to the substrate 2, A bubble ejection tip in which an arbitrary number and an arbitrary position of the bubble ejection portions 3 can be produced.
- FIG. 4 is a diagram showing another embodiment of the bubble ejection tip 1, for example, an equal interval shown in FIG. 4 (1), a circle shown in FIG. 4 (2), a x shape shown in FIG.
- the ejection portions 3 can be formed in an arbitrary number and arrangement. Further, by repeating exposure and etching in which the thickness of the photosensitive resin to be laminated and the shape of the photomask are repeated, in addition to arranging at any number and at any position, for example, as shown in FIG. Moreover, the height of the bubble ejection part 3 can also be changed.
- a plurality of locations such as a line shape or a planar shape, are injected at a time instead of a single location.
- the multi-cylinder chip 1 ' in addition to the line-shaped injection, it is possible to inject in a planar shape by stacking a plurality of multi-cylinder chips 1'.
- the bubble outlets can be formed in a planar shape.
- the bubble ejection tip 1 of the present application the bubble ejection portions can be arranged at an arbitrary number and an arbitrary position.
- FIG. 4 (4) when the height of the bubble ejection portion 3 is changed, the distance between the bubble ejection port and the workpiece can be made constant even if the workpiece is a three-dimensional shape. it can.
- FIGS. 5A to 5C are diagrams showing an example of the manufacturing process of the bubble ejection tip 1 of the present application. Note that FIGS. 5A to 5C illustrate an example in which the bubble jetting part 3 is provided for the purpose of illustration. However, when a plurality of bubble jetting parts 3 are formed, the shape of the photomask can be changed. Good. (1) The material for forming the energizing portion 4 is laminated on the substrate 2 by sputtering. (2) Photoresist 8 is applied, and exposure and development are performed using a mask so that the photoresist 8 is finally left in a portion where the energization portion 4 is finally formed.
- the material other than the portion where the energizing portion 4 is formed is removed by a method such as wet etching.
- the energization part 4 is formed by removing the photoresist 8.
- the counter electrode 5 may be formed simultaneously with the energization unit 4 by changing the shape of the photomask.
- a photoresist is applied, and exposure and development are performed using a mask so that the photoresist remains on an unnecessary portion of the energizing portion 4 (a portion where the bubble ejection portion 3 is not formed). Since the photoresist is cured by exposure and development, the insulating layer 37 is formed without being removed in the following steps.
- Exposure and development are performed using a photomask that is coated with a photoresist and designed to have a shape in which the outer portion 32 and the stretched portion 33 remain.
- the photoresist cured by exposure and development becomes the outer portion 32 and the extending portion 33.
- the size of the electrode 31 of the bubble jetting part 3 may be adjusted by the size of the photomask.
- the bubble ejection tip 1 shown in the embodiment can be manufactured. As shown in (6) and (7), the entire periphery of the electrode 31 is covered with a cylindrical photosensitive resin (the outer shell portion 32 and the extending portion 33). Different from the cylindrical tip 1 ′.
- the bubble ejection port 35 can be directed above the substrate 2.
- “above the substrate” means a direction substantially perpendicular to the plane of the substrate 2 on which the energization unit 4 is formed, or a direction in which the energization unit 4 is stacked as viewed from the substrate 2. Both have the same meaning, although their expressions are different. Therefore, by immersing the bubble ejection tip 1 in the petri dish or the like with the surface of the bubble ejection tip 1 on which the bubble ejection part 3 is not formed facing down, the bubble ejection port 35 can be arranged upward in the petri dish or the like, Can be erupted.
- the bubble ejection tip 1 since the bubble ejection tip 1 is only required that the counter electrode 5 and the electrode 31 are electrically connected, for example, a frame body including the bubble ejection portion 3 and at least a part of the counter electrode 5 is formed on the bubble ejection tip 1,
- the frame body may be filled with a conductive solution.
- the electrode 31 is grown to the same height as the outer portion 32.
- Photoresist is applied, and exposure and development are performed using a photomask designed to have a shape in which the stretched portion 33 remains.
- the extending portion 33 may be formed so as to straddle the outer portion 32 and the electrode 31.
- the exposed electrode 31 may be masked with a photoresist, PDMS, or the like after the extending portion 33 is formed.
- the stretched portion 33 is produced by photolithography.
- the stretched portion 33 may be separately produced by a three-dimensional modeling / processing technique and bonded with an adhesive or the like. Examples of the separately prepared stretched portion 33 include tapered shapes shown in (8-1) and (8-2), but other shapes may be used.
- the size, speed, invasiveness, directivity, and the like of the bubbles can be adjusted by making the extending portion 33 smaller than the outer portion 32.
- the upper electrode 31 may be grown by electroplating after the procedure (8). In the case of (9), the size, speed, invasiveness, directivity, etc. of the bubbles can be adjusted by adjusting the height of the electrodes.
- the thickness and the inner diameter of the cylindrical photosensitive resin can be arbitrarily set, so that even if the applied voltage is increased, the stretched portion 33 is hardly damaged. Therefore, the electrode can be enlarged, and as a result, it is possible to discharge from the electrode in addition to the ejection of bubbles by increasing the voltage applied to the electrode. Therefore, in addition to local ablation or injection by bubbles, the object to be processed can be subjected to electric discharge machining, and can be used as a treatment apparatus for cancer or the like.
- holes can be made in a wide variety of hard materials such as biomaterials such as plant cells, metals, and polymers, and genes, reagents, and the like can be introduced as necessary.
- the heights of the bubble ejection portions 3 are all the same.
- the procedure (6) may be repeated after the procedure (6), and at this time, the height of the photoresist to be applied is increased. What is necessary is just to make it differ from the height of the outline part 32 shown to (6).
- FIG. 6 is a diagram showing another example of the embodiment of the bubble ejection tip 1.
- all the bubble ejection portions 3 may be formed on a single energization portion 4, but the energization portions 4 may be divided into a plurality of portions.
- 6A shows an example in which the energization unit 4 is divided into blocks
- FIG. 6B shows an example in which the energization unit 4 is divided into units
- FIG. 6C shows an example in which the energization unit 4 is divided into an inner part and an outer part.
- the division unit is not particularly limited.
- the voltage applied to the bubble ejection section 3 can be changed for each divided unit when local ablation and local injection are performed.
- the voltage of the outer portion where the distance between the bubble ejection port and the workpiece is separated is set to the inner side.
- FIG. 7 is a diagram showing an overall configuration of an example of an embodiment of the local ablation apparatus 6 using the bubble ejection tip 1.
- the local ablation device 6 shown in FIG. 7 includes an electrical output means, and the electrical output means is for forming a circuit with the general commercial AC power supply device 61 and the electrode 31 and the counter electrode 5 of the bubble ejection tip 1.
- the electric wire 62 is included at least, and a non-inductive resistor 63, a voltage amplification circuit 64, a DIO (Digital Input Output) port (not shown), and the like may be provided as necessary.
- the electric output means can be easily created by incorporating a non-inductive resistor 63, a DIO port or the like into a conventional electric knife electric circuit and setting the output configuration for a minute object.
- the electric current, voltage, and frequency output to the electrode 31 and the counter electrode 5 can eject bubbles, and can be discharged from the electrode 31 as needed, and do not damage the bubble ejection portion 3.
- the current is preferably 10 mA to 10 A, and more preferably 25 mA to 800 mA. If the current is smaller than 10 mA, the bubbles 36 may not be generated well. If the current is larger than 10 A, electrode wear occurs, which is not preferable.
- the voltage is preferably 100 V to 100 kV, more preferably 200 V to 8.0 kV.
- the electrode 31 may be worn and the stretched portion 33 may be damaged.
- the frequency is preferably 1 kHz to 1 GHz, more preferably 5 kHz to 1 MHz, and particularly preferably 10 kHz to 60 kHz. If the frequency is less than 1 kHz, the stretched portion 33 may be damaged, and if it is greater than 1 GHz, the bubbles 36 may not be generated, which is not preferable. Note that the above numerical values are approximate numerical values and can be changed depending on the size of the electrode 31.
- the bubble ejection tip 1 and the counter electrode 5 of the local ablation device 6 are immersed in a conductive solution. Then, the object to be processed is locally ablated by disposing the object to be processed above the bubble ejection part 3 of the bubble ejection tip 1 and causing the bubbles 36 ejected from the bubble ejection part 3 to collide with the object to be processed. Can do.
- the processing object is not particularly limited as long as it can be ablated by bubbles, and examples thereof include cells and proteins.
- cells include stem cells, skin cells, mucosal cells, hepatocytes, pancreatic islet cells, nerve cells, chondrocytes, endothelial cells, epithelial cells, bone cells, muscle cells, egg cells and the like isolated from human or non-human animal tissues.
- examples include cells such as animal cells, plant cells, insect cells, microbial cells such as Escherichia coli, yeast and mold. Further, when discharging from the electrode 31, in addition to processing by bubbles, the effect of electric discharge processing can be obtained, so that a harder object to be processed may be used.
- machining in the present application means that bubbles are ejected to the object to be processed, and if necessary, holes are made in the object or a part of the object is cut by electric discharge.
- Patent Document 1 the present inventors have revealed that bubbles ejected from a bubble ejecting member can adsorb an injection substance.
- the bubbles generated by energizing the core material are charged with electricity, and it is considered that the injection substance is adsorbed by the bubbles. Therefore, when performing the local ablation using the bubble ejection tip 1 shown in FIG. 3 or FIG. 4, if an injection substance is included in the conductive solution in which the bubble ejection tip 1 is immersed, the air bubbles 36 around which the injection substance is adsorbed. Can be erupted. Therefore, the injection substance can be introduced while locally ablating the workpiece.
- FIG. 8 is a diagram showing an outline of an example of an embodiment of a bubble ejection tip 1 (hereinafter, sometimes referred to as “injection bubble ejection tip”) more suitable for an injection device.
- FIG. 9 is a cross-sectional view taken along the line A-A ′ of FIG.
- an outer outer portion 7 that can fill a solution containing an injection substance is formed on the outer periphery of the bubble ejection portion 3.
- the first injection substance can be adsorbed around the bubbles 36 ejected from the bubble ejection port 35.
- the outer shell portion 7 may be formed separately from the bubble ejection tip 1 and disposed around the bubble ejection portion 3.
- a flow channel 71 for feeding a conductive solution may be formed so as to be connected to the outer shell 7. Through the channel 71, a solution containing the first injection substance can be sent between the outer shell portion 7 and the bubble ejection portion 3.
- the conductive liquid forms a liquid flow in the extension line direction of the bubble ejection portion 3 as shown by the white arrow in FIG.
- This liquid flow serves as an assist flow, and assists the movement of the bubbles 36, whereby the force of the bubbles 36 contacting the workpiece can be increased.
- the outer shell 7 and the flow path 71 can be manufactured by photolithography, nanoimprinting, etching technology, three-dimensional modeling, three-dimensional processing technology, ultraviolet curing technology, stereolithography technology, two-photon absorption stereolithography, and the like.
- the material for forming the outer shell 7 and the flow path 71 is preferably an insulating material, and known insulating materials such as polydimethylsiloxane (PDMS), parylene, epoxy resin, polyimide, polyethylene, glass, quartz, PMMA, and silicon.
- PDMS polydimethylsiloxane
- parylene epoxy resin
- polyimide polyimide
- polyethylene polyethylene
- glass glass
- quartz quartz
- PMMA polymethylsiloxane
- silicon silicon
- An injection device can be manufactured by using the bubble ejection portion tip 1 for injection instead of the bubble ejection portion tip 1 of the local ablation device 6 described above.
- the injection substance can be introduced while locally ablating the object to be processed in the same procedure as the local ablation method except that the solution containing the injection substance is filled between the outer shell part 7 and the bubble ejection part 3.
- the injection substance is not particularly limited as long as it can be dissolved and / or dispersed in a liquid regardless of whether it is a gas, a solid, or a liquid.
- the gas include air, nitrogen, helium, carbon dioxide, carbon monoxide, argon, oxygen, and the like.
- the solid include DNA, RNA, protein, amino acid, and inorganic substance, and examples of the liquid include a drug solution and an amino acid solution.
- the solution for dissolving and / or dispersing the injection substance include physiological saline, a culture medium, and the like.
- the bubble ejection portion chip 1 for injection shown in FIGS. 8 and 9 can be used for local ablation or injection in the air, that is, as needleless injection.
- the bubble ejection tip 1 shown in FIGS. 8 and 9 may be brought into direct contact with the workpiece in the air.
- FIGS. 10 (1) to (6) are diagrams for explaining an example of an embodiment when used as needleless injection.
- a solution 50 hereinafter sometimes referred to as “filled solution”
- FIG. 10 (1) shows an example in which a cap 51 is provided around the bubble ejection tip 1. Further, a support 52 may be attached to the substrate 2 of the bubble ejection tip 1 in order to make the bubble ejection tip 1 easily contact the workpiece.
- the support body 52 may be produced in a solid shape, it may be formed in a hollow shape, and an electric wire for applying a voltage to the energizing portion 4 and the counter electrode 5 may be passed through the inside. Further, in the case of a hollow shape, a filling channel may be continuously supplied by forming a channel inside and connecting it to the channel 71 shown in FIG. In that case, the cap 51 may be omitted. The same applies to the following embodiments.
- FIGS. 10 (2) and 10 (3) are diagrams for explaining another embodiment of needleless injection.
- the distance between the air bubble outlet and the object to be processed be finely adjusted.
- FIGS. 10 (2) and 10 (3) show an embodiment in which fine adjustment of the distance is facilitated.
- a movable frame 53 slidable with respect to the bubble ejection tip 1 is provided around the bubble ejection tip 1, and the support body 52 is slidably inserted into a hole formed in the movable frame 53 and supported. The body 52 is fixed to the bubble ejection tip 1.
- an urging means 54 such as a spring is provided between the substrate 2 of the bubble ejection tip 1 and the movable frame 53 so that the movable frame 53 protrudes from the bubble ejection tip 1.
- 10 (4) and 10 (5) are diagrams for explaining another embodiment of needleless injection.
- the variable frame 56 is formed around the bubble ejection tip 1 with a flexible material such as silicon instead of the movable frame 53. As shown in FIG. 10 (4), the tip of the variable frame 56 protrudes from the bubble ejection tip 1 before use.
- the variable frame 56 is deformed by removing the cap and pushing the tip of the variable frame 56 against the workpiece 10, so that the bubble outlet and the workpiece 10 You can fine-tune the distance.
- FIGS. 10 (1) to (5) show examples in which needleless injection is used from below the object to be processed.
- the filling solution 50 has surface tension, as shown in FIG. 10 (6).
- the bubble outlet may be used downward.
- Example 1 [Production of bubble ejection tip 1]
- a sputtering apparatus (Vacuum Device MSP-30T, Inc.) was used to deposit Au on the glass substrate for 1 minute with a plasma current value (80 mA).
- OFPR-800 LB 200CP was spin-coated on a glass substrate at 2000 rpm for 30 seconds and 7000 rpm for 2 seconds, and prebaked at 90 ° C. for 30 minutes in an oven.
- development was performed using NMD-3. After the development, rinsing was performed using ultrapure water, and moisture was removed with a spin dryer or the like to dry.
- SU-8 3050 was spin-coated on a glass substrate at 1000 rpm for 30 seconds and 4000 rpm for 2 seconds, and prebaked on a hot plate at 95 ° C. for 50 minutes. Thereafter, exposure was performed using a chromium mask, and post-exposure baking was performed on a hot plate at 95 ° C. for 5 minutes.
- PGMEA 3-Methoxy-1-methylethyl acetate
- CAS Number: 142300-82-1 moisture is removed by a spin dryer, and the outer portion 32 which is a cylindrical structure of SU-8 is dried.
- An electrode was connected to the Au patterning portion, and Ni plating was grown to the height (100 ⁇ m) of the SU-8 pattern along the inside of the outer portion 32 of SU-8.
- SU-8 3050 was spin-coated on a glass substrate at 800 rpm for 30 seconds and 4000 rpm for 2 seconds, and prebaked on a hot plate at 95 ° C. for 50 minutes.
- FIG. 11 (1) is a photograph of the bubble ejection tip 1 produced in Example 1
- FIG. 11 (2) is an enlarged photograph of the vicinity of the bubble ejection portion 3.
- FIG. 11 (3) is a figure for showing the dimension of the produced bubble ejection part 3 vicinity.
- the thickness of the lower shell portion 32 was about 65 ⁇ m
- the diameter of the electrode 31 was about 50 ⁇ m
- the height of the bubble ejection portion 3 was about 150 ⁇ m
- the diameter of the bubble ejection port was about 40 ⁇ m.
- Example 2 [Production of local ablation device and injection device and bubble ejection experiment]
- the bubble ejection tip 1 produced in Example 1 is incorporated, and further, a non-inductive resistor and a DIO port are incorporated in the electric output means, and a local ablation apparatus and injection apparatus are incorporated.
- a frame body 41 having a size capable of disposing the bubble ejection portion 3 and at least a part of the counter electrode 5 in the frame is manufactured by PDMS and attached to the bubble ejection chip 1. It was.
- the frame 41 was filled with a 2.5 M NaCl solution 42.
- FIG. 12 is a photograph of the occurrence of bubbles 36 with a high speed camera. As is clear from the photograph, it was confirmed that the bubbles 36 could be ejected upward from the bubble ejection port 35 by using the bubble ejection tip 1 produced in Example 1. Further, no bubbles remained in the vicinity of the bubble ejection port. This is thought to be because the bubble outlets face upward and move smoothly upward due to buoyancy in addition to the jetting power of bubbles.
- Example 3 [Blowing out bubbles containing plasma]
- the solution of the local ablation device and the injection device prepared in Example 2 is a 0.15 M NaCl solution, the electrical output conditions are a current of 5.0 A, a voltage of 6.2 kV, an output frequency of 450 kHz, and a sampling frequency for impedance matching.
- the jetted bubbles were photographed at a frame rate of 230,000 fps using VW600M (manufactured by KEYENCE).
- FIG. 13 is a photograph taken. As is apparent from FIG. 13, in Example 3, it was confirmed that the electrode 31 was discharged in addition to the ejection of bubbles. Further, since the discharge was confirmed, it is considered that the bubble contains plasma in principle.
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Abstract
Description
(1)フォトリソグラフィ技術を用いて基板上に通電部を形成し、基板上に形成した通電部に電極が接続するように気泡噴出部を上方に向けて形成することで、気泡噴出チップをシャーレ等に置いた際に気泡噴出口が上方を向き、気泡を基板平面に対して略垂直方向に噴出できること、
(2)気泡噴出部を構成する感光性樹脂を、基板に対して上方から筒状にエッチングして形成することで、気泡噴出部を任意の個数及び任意の位置に配置した気泡噴出チップを作製できること、
を新たに見出した
前記通電部は、前記基板上に形成され、
前記気泡噴出部は、導電材料で形成された電極、絶縁性の感光性樹脂で形成された外郭部及び外郭部から延伸した延伸部を含み、前記外郭部は前記電極の周囲を覆い且つ前記延伸部は前記電極の先端より延伸し、更に、前記気泡噴出部は前記延伸部及び前記電極の先端との間に形成された空隙を含み、
前記気泡噴出部の電極は前記通電部上に形成されている、
気泡噴出チップ。
(2)前記気泡噴出部が2以上形成されている上記(1)に記載の気泡噴出チップ。
(3)前記気泡噴出部の高さが異なる上記(2)に記載の気泡噴出チップ。
(4)前記感光性樹脂が、ネガティブ型フォトレジストである上記(1)~(3)の何れか一に記載の気泡噴出チップ。
(5)前記気泡噴出部の電極とで電極対を構成する対向電極が、前記基板上に形成されている上記(1)~(4)の何れか一に記載の気泡噴出チップ。
(6)前記気泡噴出部の周りに形成された外側外郭部を更に含み、前記気泡噴出部と前記外側外郭部との空間にインジェクション物質を含む溶液を貯めることができる上記(1)~(5)の何れか一に記載の気泡噴出チップ。
(7)前記空間にインジェクション物質を含む溶液及び/又はアシスト流を形成するための溶液を送液するための流路が形成されている上記(6)に記載の気泡噴出チップ。
(8)上記(1)~(7)の何れか一に記載の気泡噴出チップを含む局所アブレーション装置。
(9)上記(1)~(7)の何れか一に記載された気泡噴出チップを含むインジェクション装置。
(10)上記(8)に記載の局所アブレーション装置の気泡噴出チップの少なくとも空隙を溶液で満たし、
前記局所アブレーション装置の電極と対向電極とで構成される電極対に高周波パルスを印加することで、気泡噴出部の先端から気泡を放出させ、
該気泡で加工対象物を加工する局所アブレーション方法。
(11)前記高周波パルスを印加した際に、前記電極から放電する上記(10)に記載の局所アブレーション方法。
(12)上記(9)に記載のインジェクション装置の気泡噴出チップの少なくとも空隙を、インジェクション物質を含む溶液で満たし、
前記インジェクション装置の電極と対向電極とで構成される電極対に高周波パルスを印加することで、前記インジェクション物質を含む溶液が吸着した気泡を放出し、
該気泡で加工対象物を局所アブレーションしながら、加工対象物にインジェクション物質を導入するインジェクション方法。
(13)前記高周波パルスを印加した際に、前記電極から放電する上記(12)に記載のインジェクション方法。
(1)通電部4を形成する材料をスパッタリングにより基板2上に積層する。
(2)フォトレジスト8を塗布し、最終的に通電部4を形成する部分にフォトレジスト8が残るように、マスクを用いて露光・現像する。
(3)ウェットエッチング等の方法により、通電部4を形成する部分以外の材料を除去する。
(4)フォトレジスト8を除去することで、通電部4を形成する。なお、図示していないが、対向電極5を基板2上に形成する場合は、フォトマスクの形状を変えることで、通電部4と同時に対向電極5を形成すればよい。
(5)フォトレジストを塗布し、通電部4の不要部分(気泡噴出部3を形成しない部分)の上にフォトレジストが残るようにマスクを用いて露光・現像する。露光・現像によりフォトレジストは硬化することから、以下の工程で除去されず絶縁層37を形成する。
(6)フォトレジストを塗布し外郭部32及び延伸部33が残るような形状に設計したフォトマスクを用いて露光・現像する。露光・現像により硬化したフォトレジストが外郭部32及び延伸部33となる。気泡噴出部3の電極31の大きさは、フォトマスクの大きさを調整すればよい。
(7)通電部4の上に、電気めっきにより電極31を成長させることで、実施形態に示す気泡噴出チップ1を作製することができる。(6)及び(7)に示すように、電極31の周囲の全てが筒状の感光性樹脂(外郭部32、延伸部33)で覆われている点で、図1及び図2に示す多筒式チップ1’と異なる。そして、通電部4上で電極31を成長させることで、基板2の上方に気泡噴出口35を向かせることができる。なお、「基板の上方」とは、通電部4を形成した基板2の平面に対し略鉛直方向、または、基板2からみて通電部4を積層した方向を意味する。両者は、表現は異なるが同じ意味である。したがって、気泡噴出チップ1の気泡噴出部3を形成していない面を下側にしてシャーレ等に浸漬することで、気泡噴出口35をシャーレ等内で上方に向けて配置でき、気泡36を上方に噴出することができる。そのため、溶液中で気泡36が進む際に、浮力による進行方向の変化が少なくなると同時に、気泡36の噴出方向と進行方向が同じであるため、気泡噴出口35の周囲で気泡が滞留することがない。なお、気泡噴出チップ1は、対向電極5と電極31が導通すればよいので、例えば、気泡噴出部3及び少なくとも対向電極5の一部を含む枠体を気泡噴出チップ1上に形成し、当該枠体の中に導電性の溶液を満たしてもよい。
(7-1)上記(7)の手順に代え、電極31を外郭部32と同じ高さまで成長させる。
(8)フォトレジストを塗布し、延伸部33が残るような形状に設計したフォトマスクを用いて露光・現像する。(8)において、電極31が露出すると漏電のおそれがある。そのため、延伸部33は、外郭部32と電極31にまたがるように形成すればよい。なお、延伸部33の外径を電極31の外径より小さくする場合は、延伸部33を形成した後に、露出している電極31をフォトレジストやPDMS等でマスクをすればよい。また、上記の手順はフォトリソグラフィにより延伸部33を作製しているが、三次元造形・加工技術で別途延伸部33を作製し、接着剤等で接着してもよい。別途作製する延伸部33としては、(8-1)、(8-2)に示すテーパー形状が挙げられるがその他の形状であってもよい。上記のとおり、延伸部33を外郭部32より小さくすることで、気泡の大きさ、速度、侵襲性、指向性等を調整することができる。
(9)なお、必要に応じて、上記(8)の手順に後に、電気めっきにより上段電極31を成長させてもよい。(9)の場合、電極の高さを調整することで気泡の大きさ、速度、侵襲性、指向性等を調整することができる。
〔気泡噴出チップ1の作製〕
(1)ガラス基板上にスパッタリング装置((株)真空デバイスMSP-30T)を用いて、Auをプラズマ電流値(80mA)、1分間成膜した。
(2)ガラス基板上にOFPR-800 LB(200CP)を2000rpmで30秒間、及び7000rpmで2秒間スピンコートし、オーブン内で90℃で30分間プリベイクした。次いで、クロムマスクを用いて露光後、NMD-3を用いて現像した。現像後は、超純水を用いてリンスをし、スピンドライヤー等で水分を飛ばし乾燥させた。
(3)パターニングされたOFPR以外の領域にAuエッチャント(AURUM-302、関東化学(株)を浸漬させてAuをエッチングし、超純水でリンスした。
(4)ガラス基板をアセトンにつけて残りのOFPR膜を除去して、Au電極部のパターニング、及び対向電極5を完成した。
(5)ガラス基板にSU-8 3005を2000rpmで30秒間スピンコートし、ホットプレート上で95℃で3分間、プリベイクした。その後クロムマスクを用いて露光を行い、ホットプレートの上で95℃で3分間、ポストエクスポージャベイクを行った。最後にPGMEA(2-Methoxy-1-methylethyl acetate;CAS Number:142300-82-1)を用いて現像し、スピンドライヤーで水分をとばし乾燥させSU-8の絶縁層を作製した。
(6)ガラス基板にSU-8 3050を1000rpmで30秒間及び4000rpmで2秒間スピンコートし、ホットプレート上で95℃で50分間、プリベイクした。その後クロムマスクを用いて露光を行い、ホットプレートの上で95℃で5分間、ポストエクスポージャベイクを行った。最後にPGMEA(2-Methoxy-1-methylethyl acetate; CAS Number:142300-82-1)を用いて現像し、スピンドライヤーで水分をとばし乾燥させSU-8の筒状構造物である外郭部32を作製した。
(7)Auパターニング部に電極を接続し、SU-8の外郭部32の内側に沿ってNiめっきをSU-8パターンの高さ(100μm)まで成長させた。
(8)ガラス基板にSU-8 3050を800rpmで30秒間及び4000rpmで2秒間スピンコートし、ホットプレート上で95℃で50分間、プリベイクした。その後クロムマスクを用いて露光を行い、ホットプレートの上で95℃で5分間、ポストエクスポージャベイクを行った。最後にPGMEA(2-Methoxy-1-methylethyl acetate;CAS Number:142300-82-1)を用いて現像し、スピンドライヤー等で水分をとばし乾燥させ、(6)で作製した外郭部32の上にSU-8の筒状構造物(外郭部32及び延伸部33)を作製した。
(9)Auパターニング部に電極を接続し、SU-8の筒状構造物の内側に沿ってNiめっきをSU-8の筒状構造物の上から30μmまで成長させた。
〔局所アブレーション装置及びインジェクション装置の作製及び気泡噴出実験〕
医療用電気メス(ConMed社製、Hyfrecator2000)のメスに換え、実施例1で作製した気泡噴出チップ1を組み込み、更に、無誘導抵抗及びDIOポートを電気出力手段に組み込み、局所アブレーション装置及びインジェクション装置を作製した。
次に、図11(4)に示すように、気泡噴出部3と少なくとも対向電極5の一部を枠内に配置できる大きさの枠体41をPDMSで作製し、気泡噴出チップ1に貼り付けた。枠体41の枠内には、2.5MのNaCl溶液42を満たした。そして、電流27.7mA、電圧309V、アウトプット周波数は450kHz、インピーダンスマッチングのためのサンプリング周波数は450kHz、3.5kHzでフィードバックを行い、電極31と対向電極5に電気を出力した。気泡の形成は、ハイスピードカメラ(VW-9000,Keyence社製)を用いて、枠体41の側面から撮影を行った。
〔プラズマを含む気泡の噴出〕
実施例2で作製した局所アブレーション装置及びインジェクション装置の溶液を0.15MのNaCl溶液とし、電気出力条件を電流5.0A、電圧6.2kV、アウトプット周波数は450kHz、インピーダンスマッチングのためのサンプリング周波数は450kHz、3.5kHzでフィードバックした以外は、実施例2と同様に気泡を噴出した。噴出した気泡を、VW600M(KEYENCE社製)を用い、フレームレート:230,000fpsで撮影した。図13は撮影した写真である。図13から明らかなように、実施例3では、気泡の噴出に加え、電極31から放電していることが確認できた。また、放電が確認できたことから、原理的に気泡にはプラズマが含まれていると考えられる。
Claims (13)
- 基板、通電部、気泡噴出部を少なくとも含み、
前記通電部は、前記基板上に形成され、
前記気泡噴出部は、導電材料で形成された電極、絶縁性の感光性樹脂で形成された外郭部及び外郭部から延伸した延伸部を含み、前記外郭部は前記電極の周囲を覆い且つ前記延伸部は前記電極の先端より延伸し、更に、前記気泡噴出部は前記延伸部及び前記電極の先端との間に形成された空隙を含み、
前記気泡噴出部の電極は前記通電部上に形成されている、
気泡噴出チップ。 - 前記気泡噴出部が2以上形成されている請求項1に記載の気泡噴出チップ。
- 前記気泡噴出部の高さが異なる請求項2に記載の気泡噴出チップ。
- 前記感光性樹脂が、ネガティブ型フォトレジストである請求項1~3の何れか一項に記載の気泡噴出チップ。
- 前記気泡噴出部の電極とで電極対を構成する対向電極が、前記基板上に形成されている請求項1~4の何れか一項に記載の気泡噴出チップ。
- 前記気泡噴出部の周りに形成された外側外郭部を更に含み、前記気泡噴出部と前記外側外郭部との空間にインジェクション物質を含む溶液を貯めることができる請求項1~5の何れか一項に記載の気泡噴出チップ。
- 前記空間にインジェクション物質を含む溶液及び/又はアシスト流を形成するための溶液を送液するための流路が形成されている請求項6に記載の気泡噴出チップ。
- 請求項1~7の何れか一項に記載の気泡噴出チップを含む局所アブレーション装置。
- 請求項1~7の何れか一項に記載された気泡噴出チップを含むインジェクション装置。
- 請求項8に記載の局所アブレーション装置の気泡噴出チップの少なくとも空隙を溶液で満たし、
前記局所アブレーション装置の電極と対向電極とで構成される電極対に高周波パルスを印加することで、気泡噴出部の先端から気泡を放出させ、
該気泡で加工対象物を加工する局所アブレーション方法。 - 前記高周波パルスを印加した際に、前記電極から放電する請求項10に記載の局所アブレーション方法。
- 請求項9に記載のインジェクション装置の気泡噴出チップの少なくとも空隙を、インジェクション物質を含む溶液で満たし、
前記インジェクション装置の電極と対向電極とで構成される電極対に高周波パルスを印加することで、前記インジェクション物質を含む溶液が吸着した気泡を放出し、
該気泡で加工対象物を局所アブレーションしながら、加工対象物にインジェクション物質を導入するインジェクション方法。 - 前記高周波パルスを印加した際に、前記電極から放電する請求項12に記載のインジェクション方法。
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US15/769,259 US20180305654A1 (en) | 2015-10-19 | 2016-10-17 | Bubble-jetting chip, local ablation device and local ablation method, and injection device and injection method |
AU2016343077A AU2016343077A1 (en) | 2015-10-19 | 2016-10-17 | Bubble ejection chip, local ablation device, local ablation method, injection device, and injection method |
JP2017546540A JP6670507B2 (ja) | 2015-10-19 | 2016-10-17 | 気泡噴出チップ、局所アブレーション装置及び局所アブレーション方法、並びにインジェクション装置及びインジェクション方法 |
EP16857400.2A EP3366757A4 (en) | 2015-10-19 | 2016-10-17 | BUBBLE EXTRACTION, LOCAL ABLATION DEVICE, LOCAL ABLATION METHOD, INJECTION DEVICE AND INJECTION METHOD |
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WO2020085281A1 (ja) * | 2018-10-26 | 2020-04-30 | 国立大学法人九州大学 | 気泡噴出方法、気泡噴出用デバイス、および、気泡噴出装置 |
JP2020080704A (ja) * | 2018-11-22 | 2020-06-04 | 国立大学法人 大分大学 | 三次元細胞培養装置および三次元細胞培養方法並びに薬物評価装置 |
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