WO2020090654A1 - Dispositif de traitement, procédé de commande et programme - Google Patents

Dispositif de traitement, procédé de commande et programme Download PDF

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Publication number
WO2020090654A1
WO2020090654A1 PCT/JP2019/041908 JP2019041908W WO2020090654A1 WO 2020090654 A1 WO2020090654 A1 WO 2020090654A1 JP 2019041908 W JP2019041908 W JP 2019041908W WO 2020090654 A1 WO2020090654 A1 WO 2020090654A1
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Prior art keywords
unit
hole
perforation
laser
cells
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PCT/JP2019/041908
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English (en)
Japanese (ja)
Inventor
元毅 沖仲
孝介 倉知
尚存 柴田
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キヤノン株式会社
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • the disclosure of the present specification relates to a processing device, a control method, and a program.
  • a hair follicle regeneration technique ground hair containing skin tissue pieces is collected, and epithelial stem cells and mesenchymal stem cells obtained from the hair are cultured to form a hair follicle primordia, and the hair follicle primordia is manually prepared in the living body.
  • a method of regenerating a hair follicle by injecting into the dermis is known (Patent Document 1).
  • One of the purposes of the disclosure of the present specification is to efficiently form a hair follicle.
  • the present invention is not limited to the above-mentioned object, and it is also possible to achieve operational effects that are obtained by the respective configurations shown in the modes for carrying out the invention to be described later and that cannot be obtained by conventional techniques. It can be positioned as one of the other purposes.
  • the processing device disclosed in the present specification is provided with a perforation unit that irradiates the skin of a living body with laser light to perforate holes, and an ejection unit that ejects droplets containing cells into the holes.
  • hair follicles can be efficiently formed.
  • the processing apparatus forms a plurality of holes by irradiating the skin of a living body with a laser, and ejects droplets containing cells into the formed holes to form a hair follicle (regeneration).
  • a hair follicle Is a device.
  • regenerating hair follicles and hair by ejecting droplets containing epithelial cells and mesenchymal cells into the holes pierced by irradiating the human scalp with laser.
  • FIG. 1 is a diagram showing an example of the configuration of a processing apparatus.
  • the processing device 100 includes a control device 101, a driving device 102, a punching device 103, a position detector 104, a shape detector 105, a discharge device 106, and a fixing device 108.
  • the control device 101 is a computer for controlling the operation of each part of the processing device 100, and includes a CPU, a ROM, a RAM, an I / O port and the like inside.
  • An operation program of the processing device 100 is stored in the ROM.
  • the program for executing various processing related to the processing may be stored in the ROM like other operation programs, or may be loaded into the RAM from the outside through the network. Alternatively, the program may be loaded into the RAM via a computer-readable recording medium.
  • the I / O port is connected to an external device or a network, and can input / output data and ejection conditions necessary for processing a hole, for example, with an external computer.
  • the data necessary for processing the hole includes shape data of the hole to be manufactured, information on a processing target, laser irradiation conditions, and the like.
  • the ejection conditions include the ejection speed, the amount of ejected droplets, the ejection timing, and the like.
  • the CPU performs overall control of the processing apparatus 100, and has a functional configuration including a position detection unit, a shape detection unit, a position adjustment unit, an intensity adjustment unit, an instruction unit, and a rotation control unit.
  • the position detection unit performs image processing on the image captured by the position detector 104, and converts the position of each device connected to the drive device 102 and the position of the hole drilled in the head 107 into coordinate data. To detect.
  • the shape detection unit performs image processing on the image captured by the shape detector 105, and detects the hole diameter and depth of the hole, the presence or absence of droplets ejected into the hole, and the like.
  • the position adjusting unit and the rotation control unit control the position and posture of each device connected to the drive device 102.
  • the instruction unit issues a discharge instruction to the discharge device 106 when the discharge device 106 whose position and orientation is controlled by the position adjustment unit and the rotation control unit reaches a target position.
  • the instruction unit controls the ejection speed of ejected droplets, the amount of ejected droplets, the ejection timing, and the like.
  • the intensity adjusting unit adjusts the current value of the excitation energy source of the laser oscillation unit in the punching device 103 when the punching device 103 whose position is controlled by the position adjusting unit reaches a target position.
  • the timing for adjusting the current value is not limited to the above.
  • the intensity and pulse number of the laser light emitted from the laser oscillator can be controlled by the current of the excitation energy source. Further, the pulse width and the pulse period can be controlled.
  • a punching device 103, a position detector 104, a shape detector 105, and a discharge device 106 are connected to the driving device 102.
  • the driving device 102 is connected to a hemispherical scan stage, which allows it to move in the X, Y, and Z directions. That is, the driving device 102 is connected to the punching unit, the discharging unit, and the detecting unit, and corresponds to an example of a driving unit that drives each unit.
  • the shape of the scan stage that can drive the driving device 102 is not limited to the above, and it is sufficient that the driving device 102 can be driven in each of the XYZ directions. For example, three-dimensional driving may be possible by connecting to the X scan stage, Y scan stage, and Z scan stage, respectively.
  • the punching device 103 is a pulse laser device including a focusing scanning unit and a laser oscillating unit.
  • the laser oscillating unit emits laser light
  • the focusing scanning unit changes the focusing position and focuses the laser light on the head 107.
  • a hole is drilled in the head 107. That is, it corresponds to an example of a perforation unit that perforates a hole by irradiating the skin of a living body with laser light.
  • the scalp is composed of three layers, the stratum corneum, the epidermis, and the dermis, and it is known that the stratum corneum is several tens of ⁇ m, the epidermis is about 200 ⁇ m, and the dermis is 1 to 3 mm thick.
  • the hair follicle primordium which is the base of the hair follicle, needs to be injected into the dermis where many nerves and blood vessels are present. It is desirable to be able to drill holes of depth. That is, it is desirable that the perforated portion 103 form one hole by removing a part of the epidermis and the dermis of the skin.
  • the depth of the holes is not limited to the above.
  • the opening shape of the holes may be circular or rectangular.
  • the condensing scanning unit is composed of an optical system that condenses the laser light into a minute spot and a robot or stage that can change the position and orientation of the optical system.
  • the condensing scanning unit may have a configuration in which an f ⁇ lens having a condensing function and a scanning function is combined with a galvano scanner, or a configuration in which a galvano scanner and an f ⁇ lens are held by a robot. Since the galvano scanner operates at high speed while reflecting the energy beam, it is desirable that the galvano scanner be made of a material that is lightweight and has a low linear expansion coefficient.
  • the laser beam be narrowed down sufficiently smaller than the target hole diameter and then the laser beam be scanned so as to have a desired shape.
  • the scan pattern of the laser light may be concentric or grid-like.
  • the beam system of the laser beam may be thickened and the laser beam may be perforated without scanning.
  • the laser light is concentrated at one point, the temperature locally rises, so that the laser-irradiated portion is burnt, and the follicle formation efficiency may be reduced. Therefore, in this case, it is preferable that the laser irradiation does not continuously irradiate the adjacent holes, but perforates the skin at a position far from the perforated position to suppress the accumulation of heat damage in the entire scalp.
  • a CO2 laser, an Er: YAG laser, or the like can be used for the laser oscillator.
  • the drive system may be a pulse system or a continuous irradiation system. Note that various effects can be expected in the method of perforation using radiation such as the laser described above, depending on the irradiation conditions (wavelength, pulse period, energy, irradiation time) and the interaction with the skin of the living body.
  • the use of interaction with water allows for efficient drilling.
  • a CO 2 laser having a wavelength of 10.6 ⁇ m and an Er: YAG laser having a wavelength of 2.9 ⁇ m have a water absorption several thousand times larger than that of an Nd: YAG laser having a wavelength of 1.06 ⁇ m. ing.
  • the water in the cells in the skin can be explosively evaporated, and the cells in the skin can be ejected from the inside of the skin to the outside of the skin by the evaporation of the water.
  • an Ar laser, an Nd: YAG laser, a KTP laser, a diode laser or the like, which has a high absorption for hemoglobin may be used.
  • the CO2 laser or the Er: YAG laser may be weakly applied to remove the water without further increasing the depth of the perforations to dry the body fluid. That is, although various effects are obtained depending on the interaction with the skin, the type of laser is not limited to the above, and any laser capable of piercing the head 107 may be used.
  • the pulse period, energy, and irradiation time are controlled, thermal interaction with cells can be expected.
  • thermal interaction with cells can be expected.
  • the irradiated portion of the head 107 reaches a temperature of about 35 to 45 ° C. by irradiating with laser, it has an effect of appropriately warming and activating the skin.
  • the temperature range of 80 to 100 ° C. water easily evaporates, so that perforation using evaporation can be performed as described above.
  • the position detector 104 detects the position of each device connected to the driving device 102 with respect to the head 107.
  • a laser device including a digital camera or a light receiving sensor can be used.
  • the position detection unit in the control device 101 performs image processing on the image captured by the position detector 104, converts the position of each device connected to the drive device 102 into coordinate data, and detects the coordinate data. To do.
  • the head 107 is scanned with a laser beam or the like, and the reflected light is converted into three-dimensional coordinates by the position detection unit of the control device 101 to detect the position of each device connected to the drive device 102. Further, it may be a mechanism that double-checks the position of each device using the coordinates provided in the driving device 102.
  • the shape detector 105 detects the hole diameter and depth of the hole drilled in the head 107 by the punching device 103, and whether or not there is a droplet discharged by the discharging device 106 in the hole.
  • a laser device including a digital camera or a light receiving sensor can be used.
  • the shape detecting unit in the control device 101 When measuring the hole diameter, for example, like the position detector 104, the shape detecting unit in the control device 101 performs image processing on the image captured by the shape detector 105, and the opening diameter of the hole is converted into coordinate data. Detect from the converted value.
  • the reflected light of the laser can be used to detect the depth.
  • the shape detection unit in the control device 101 When detecting whether or not there is a droplet discharged by the discharge device 106 in the hole, the shape detection unit in the control device 101 performs image processing on the image captured by the shape detector 105, and the liquid is discharged. Detect the presence of drops. Specifically, a range of pixel values that can be assumed when the liquid droplets are inside the perforations is designated in advance, and when the pixel values fall within the range as a result of image processing, there are liquid droplets. When the pixel value exceeds the range, it is determined that there is no droplet. In addition, when it is determined that there is no droplet, additional ejection may be performed.
  • the presence or absence of the ejection may be determined by detecting the depth of the hole before and after the ejection of the droplet with a laser. Further, the method of detecting the presence / absence of droplets is not limited to the above. Furthermore, when determining the presence or absence of liquid droplets, it is not a binary value of “Yes” and “No”, but a sufficient amount of liquid droplets ejected to the perforation such as “Sufficiently”, “Slightly insufficient”, and “No”. It may be determined by multi-value according to the amount. In this case, for example, it is determined that there is “sufficiently present”, and it is determined that “somewhat insufficient” and “none” are not present.
  • the processing apparatus 100 may be provided with a detector that detects the position and shape of the hole and whether or not there is a droplet discharged from the discharging device 106 in the hole.
  • the ejection device 106 ejects droplets containing cells into the perforations formed in the head 107. That is, it corresponds to an example of a discharge unit that discharges droplets containing cells to the holes.
  • a thermal inkjet head, a piezoelectric inkjet head, an electrostatic inkjet head, a compressed air jet dispenser, or the like can be used as the ejection device 106, but any device can be used as long as it can eject droplets containing cells.
  • the droplet amount of one droplet discharged by the discharge device 106 is preferably 1 to 500 nl, but the discharge amount is not limited to this.
  • the number of the ejection portions (openings) forming the ejection device 106 may be changed depending on at least one of the type of liquid containing cells to be ejected and the number of droplets containing cells to be ejected. For example, two of a first ejection part that ejects a first droplet containing mesenchymal cells necessary for forming a hair follicle and a second ejection part that ejects a second droplet containing epithelial cells. A configuration including one discharge section may be used.
  • the types of cells to be ejected are not limited to the above, and for example, droplets containing pigment cells that change the color of regenerated hair may be ejected.
  • the positions of the first ejection unit and the second ejection unit may be positions capable of ejecting droplets to the perforations, but when ejecting droplets continuously, scanning of the ejection device 106 is performed. Arrangement arranged in the direction is desirable.
  • the ejection device 106 can eject a plurality of droplets at a speed of 500 droplets / minute or more in consideration of the movement and shape change of the head 107 or the exudation of body fluid.
  • the configuration is not limited to the above.
  • the head 107 is, for example, a human scalp.
  • the head 107 is not limited to the above, and may be skin of various living organisms such as primates of mammals such as monkeys, ungulates such as horses, and rodents of small mammals such as rabbits and mice.
  • the peripheral portion of the treatment is plucked.
  • pretreatment such as moisturizing may be performed in advance. According to the above, it is possible to form a hole having a desired shape and depth regardless of age, sex, external environment, or the like.
  • the fixing device 108 fixes (holds) the head 107 that is the processing target portion. That is, it corresponds to an example of a fixing unit that fixes a living body. For example, as shown in FIG. 1, the head 107 to be processed is fixed.
  • the fixing device 108 is composed of a bed and a fixing belt.
  • a configuration in which a laser displacement meter that detects the shape of the fixed head 107, a contact sensor (not shown), and the like are combined may be used.
  • the configuration of the fixing device 108 is not limited to the above, and may be a configuration in which the head 107 is fixed, for example, by providing a table on which the forehead and the chin are placed. That is, it is sufficient that the head 107 can be fixed.
  • the droplet includes a first droplet containing mesenchymal cells and a second droplet containing epithelial cells.
  • the mesenchymal cells and epithelial cells contained in the two droplets are cells that are at least necessary for forming a hair follicle primordium having a hair regenerating ability.
  • Mesenchymal cells indicate at least one of cells derived from mesenchymal tissue and cells obtained by culturing the cells.
  • mesenchymal cells are obtained from dermal papilla cells, dermal sheath cells, various pluripotent cells, and the like.
  • the epithelial cell indicates at least one of cells derived from epithelial tissue and cells obtained by culturing the cells.
  • epithelial cells are obtained from the outermost layer of the outer root sheath, epithelial cells of the hair matrix, various pluripotent cells, and the like.
  • the hair follicle primordium is a tissue that is a base of hair follicles and is composed of a cell group including the above-mentioned mesenchymal cells and epithelial cells.
  • droplets containing epithelial cells and mesenchymal cells are ejected into the holes perforated in the head 107, and the hair follicle primordium composed of the two cells forms a hair follicle. ..
  • hair having a hair shaft is formed and elongated from the formed hair follicle. That is, the hair follicle primordia form the hair follicle and are the basis for the regenerated hair.
  • the ratio of epithelial cells to mesenchymal cells is preferably 1: 1 from the viewpoint of hair follicle formation, and if the total number of the two cells is about 1000 to 10000, the hair follicle primordium is determined. Can be formed.
  • the ratio of the number of cells and the number of cells are not necessarily the above values.
  • the droplets may also contain a medium for each cell, nutrients necessary for cell survival and growth, and auxiliary substances such as antibiotics and hormones.
  • cell may be a single substance or an aggregate including a plurality of cells such as a cell group.
  • an aggregate including a plurality of cells such as a cell group is referred to as a cell.
  • step S2000 (fix the head with a fixing device)
  • step S2010 in order to detect the position of the head 107, an alignment mark is printed on the scalp of the head 107 outside the treatment area.
  • the alignment mark may be directly marked with a writing instrument such as a pen, or may be marked by the laser of the punching device 103.
  • the shape and size of the alignment mark may be any as long as the resolution of position detection can be performed in units of ⁇ m. That is, the method, shape, and size of marking the alignment mark are not limited to the above.
  • the alignment mark may be marked before the head 107 is fixed by the fixing device 108, or the alignment mark itself may not be marked. If the processing target does not move, this step may be skipped.
  • step S2010 the position detector 104 images the head 107. Then, the position detection unit of the control device 101 converts the captured image into coordinate data, and sets three-dimensional coordinates (x, y, z) on the head 107. At this time, the positions of wrinkles, moles, stains, etc. may be detected from the imaged result, and may be used for position detection supplementarily.
  • the acquired three-dimensional coordinate system is preferably a three-dimensional coordinate system in which the point marked with the alignment mark in step S2010 is the origin (0,0,0).
  • step S2020 (the punches (x m, y m, moved to z m))
  • step S2020 first, the punching device 103 is moved to the initial position (x 1 , y 1 , z 1 ) in order to form a plurality of holes in the head 107.
  • the position adjusting unit of the control device 101 detects the alignment mark marked in step S2000, and when the coordinates are set to (0, 0, 0), the position (x 1 , Y 1 , z 1 ) the perforation device 103 is aligned.
  • the start position of the perforation may be an arbitrary position on the three-dimensional coordinates (x, y, z) acquired in step S2020 as the initial position.
  • the following description will be given on the assumption that the position where the perforation is started is the end point in the treatment area as shown in FIG. That is, aligns to the initial position (x 1, y 1, z 1) First, then, the perforation in the range of (x 1 ⁇ x m ⁇ x n) and (y 1 ⁇ y m ⁇ y n) The procedure is such that a plurality of holes are drilled in the treatment area by moving the device 103 in the XY axis directions.
  • the process is repeated from (x 1 , y 1 ) to (x n , y 1 ), and then the process is repeated from (x 1 , y 2 ) to (x n , y 2 ).
  • the above process is performed until (x 1 , y 1 ) reaches (x n , y n ). That is, the second or subsequent perforation, this step is the step of moving an arbitrary coordinate (x m, y m, z m) to the punching device 103. That is, a plurality of holes are punched in an array.
  • the order in which the plurality of holes are drilled is not limited to the above.
  • the order may be changed such that (x 1 , y 1 ) ⁇ (x 3 , y 1 ) ⁇ (x 2 , y 1 ) ⁇ (x 4 , y 1 ). That is, the processing may be performed while reversing the moving direction in the predetermined axis direction.
  • the array of holes to be perforated does not necessarily have to be an array of equal intervals, and for example, some parts may be perforated to have a high density and some parts may be perforated to have a low density.
  • the processing target portion is damaged, etc., it may be perforated so as to avoid that portion.
  • the punching device 103 is moved to the same XY coordinates as the punching position in step S2030 described later, but in step S2030, the punching target coordinates (x m , y m , z m ) can be punched. If so, the XY coordinates do not necessarily have to be the same.
  • the minimum value and the maximum value in the treatment area are obtained from the Z-axis values detected in step S2010, and a predetermined value is added to the obtained value.
  • the point marked with the alignment mark is outside the treatment area, but if the alignment mark is inside the treatment area, the alignment mark is set to the origin (0, 0, 0). Then, similarly to FIG. 4A, the position (x 1 , y 1 , z 1 ) at which the perforation is to be started in the treatment area with respect to the origin (0, 0, 0) is specified, and the perforation device 103 is located at the coordinates. Align the.
  • the punching device 103 may be moved to a position where light can be collected.
  • the punching device 103 does not have to be moved. That is, the punching device 103 only needs to be in a position capable of punching at desired coordinates.
  • step S2030 the intensity of laser light irradiated from the punching device 103 adjusts the coordinates of performing alignment in the step S2020 (x m, y m, z m) drilling irradiating hole a laser against.
  • the instruction unit instructs the punching device 103 to oscillate the laser light controlled by the current adjusted by the intensity adjusting unit of the control device 101 at a constant oscillation frequency and a desired number of pulses. Is done.
  • the punching device 103 receives the oscillation instruction, and the laser light oscillated from the laser oscillating unit in the punching device 103 is delivered to the condensing scanning unit in the punching device 103 by the delivery fiber or the like and irradiated to the processing point. A hole is drilled.
  • step S2040 (Measure the shape of the hole with the shape detector)
  • the shape detector 105 is used to measure the opening diameter and depth of the hole drilled in step S2030. Then, when the opening diameter and the depth of the hole have not reached the predetermined values, the process is returned to step S2030, and the laser irradiation is performed by the perforation device 103. In the case where the coordinates (x m, y m, z m) are shifted into has occurred, the position adjusting unit to finely adjust the scanned position the driving device 102. Steps S2030 and S2040 are repeated, and when the opening diameter and the depth of the holes satisfy the predetermined values, the process proceeds to step S2050.
  • step S2050 (the discharge device (x m, y m, moved to z m))
  • step S2050 coordinates drilled in step S2040 (x m, y m, z m) to move the ejection device 106.
  • the position of the discharge device 106 is moved, the coordinates drilled in step S2040 (x m, y m, z m) necessarily if droplets are capable of discharging position relative to (x m, y m, z m ) does not have to be above.
  • the ejection device 106 the rotated by controlling the angle (x m, y m, z m) droplets to capable of discharging coordinates pore drilled.
  • step S2060 Cells are discharged by the discharging device
  • the droplet discharged by the discharging device 106 may be one droplet for the hole as long as it is a droplet containing epithelial cells and mesenchymal cells. When the droplet containing the epithelial cells and the droplet containing the mesenchymal cells are different, each droplet is ejected to the hole.
  • the instruction unit issues a discharge instruction to the discharge device 106. ..
  • droplets containing cells are discharged to the holes.
  • a droplet containing epithelial cells and a droplet containing mesenchymal cells are separately ejected into one hole, the droplet containing mesenchymal cells is first discharged. It is desirable to discharge it.
  • step S2070 based on the data acquired from the shape detector 105, the shape detecting unit coordinates (x m, y m, z m) or absence or ejected droplet is in the drilled hole in the To detect.
  • the shape detection unit in the control device 101 performs image processing on the image captured by the shape detector 105 to detect the presence or absence of a droplet. For example, if the range of pixel values that can be assumed when the liquid droplets are inside the hole is specified in advance, and if the pixel values fall within that range as a result of image processing, it is determined that there are liquid droplets. , If the pixel value exceeds the range, it is determined that there is no droplet. Alternatively, it may be determined from the shape of the holes.
  • step S2080 if it is detected that there is a droplet, the process proceeds to step S2080. On the other hand, if it is detected that there is no droplet, the process returns to step S2060.
  • the presence / absence of a droplet is determined not by the binary values of “present” and “absent” but by a multivalued determination in accordance with the amount of droplets such as “sufficiently present”, “somewhat insufficient”, and “absent”, for example, It may be set to return the process to step S2070 when it is determined to be “slightly insufficient” and “not present”.
  • step S2080 judges drilling and coordinates to eject the cell (x m, y m, z m) Whether is the end point coordinates, i.e. whether all the processes in the treatment a preset range has been completed.
  • (x m, y m, z m) of (x m, y m) is a determination on whether or not reached the (x n, y n). When (x n , y n ) is reached, the process ends.
  • the number of times the punching device 103 and / or the discharging device 106 punches or discharges droplets is set in advance, and when the predetermined number of times is completed, the processing of the processing device 100 is ended.
  • the shape detector 105 detects that droplets have been discharged to all the holes, the process ends.
  • the condition for ending the process is not limited to the above.
  • (x n, y n) if not reached, update the value of (x m, y m, z m), the process returns to step S2020.
  • the processing of the processing apparatus 100 is performed as described above.
  • a plurality of holes are perforated at high speed in the skin of the living body with a laser or the like, and droplets containing cells that are the bases of the hair follicles are ejected to the perforated holes, so that efficiency is improved.
  • the processing is performed without contacting the living body, it is possible to reduce the possibility that contamination such as bacteria will occur in the pores.
  • the hair follicle primordia can be cultured in the body, the possibility of cell death can be reduced as compared with the case of culturing the hair follicle primordia outside the body, and efficiency can be improved from this aspect as well.
  • the efficiency of hair follicle formation is improved by repeatedly performing the process in which the perforation device 103 perforates one hole at a specific coordinate and then the ejection device 106 ejects droplets into the hole.
  • a plurality of lasers that the perforation device 103 irradiates and a plurality of ejection units included in the ejection device 106 are respectively provided, so that a plurality of holes are perforated and then a plurality of droplets are ejected to the respective holes.
  • It may be a processing procedure. Further, the procedure may be such that a plurality of holes are punched at the same time and then a plurality of droplets are simultaneously discharged to the respective holes.
  • a procedure of processing may be performed in which all predetermined holes are drilled in the treatment area and then droplets are sequentially discharged to all the holes.
  • the treatment time can be shortened by discharging the droplets containing the cells into the hole at a higher speed, so that the burden on the treatment target can be reduced.
  • the efficiency of hair follicle formation is improved by repeatedly performing the process in which the perforation device 103 perforates one hole at a specific coordinate and then the ejection device 106 ejects droplets into the hole. It was however, in order to make the processing more efficient, the perforation processing by the perforation apparatus 103 and the cell ejection processing by the ejection apparatus 106 may be performed in parallel. Specifically, while the discharging device 106 discharges droplets into the holes punched by the punching device 103 at the coordinates (x 1 , y 1 ), the punching device 103 punches the coordinates (x 2 , y 1 ). To start.
  • the timing of punching by the punching device 103 and the timing of discharging the droplets by the discharging device 106 are not limited to the above. That is, in a series of steps until the treatment is completed, the step of boring a hole and the step of ejecting liquid droplets into the hole may be performed in parallel.
  • the treatment time can be shortened, the burden on the treatment target can be reduced.
  • the skin is collected from the back of the mouse 301 and separated into an epithelial layer and a dermal layer. After that, epithelial stem cells and mesenchymal stem cells are taken out from each layer. After culturing each cell, mix with the basic medium to make a suspension for ejection.
  • the head of the mouse 301 is shaved, the anesthetized mouse 301 is fixed by a fixing device, and an alignment mark is marked by the punching device 103 as shown in FIG.
  • a CO 2 laser (ML-X9650 manufactured by Keyence) is used for the punching device 103.
  • the laser power is 24 W and the working distance is 92 mm.
  • the spot diameter is about 80 ⁇ m.
  • the galvanometer mirror mounted on the CO2 laser is used for laser scanning.
  • the head of the mouse 301 is scanned by the position detector 104 to obtain the shape of the mouse head, and then the perforation position and cell ejection position (xm, ym, zm) are determined and stored in the control device 101. (FIG. 3 (b)).
  • the coordinates with respect to the alignment mark are always checked, and if the indicated values are different, the position is corrected using the driving device 102.
  • the laser is scanned using the galvanomirror so that the opening diameter becomes 0.5 mm (FIG. 3C).
  • the scanning speed of the galvanometer mirror is 500 mm / s.
  • one hole may be formed by changing the laser intensity and irradiating the hole a plurality of times.
  • the shape of the hole is not limited to the example shown in the figure, and may be, for example, a shape whose width increases from the opening toward the inside.
  • the perforated shape of the opening is confirmed by the camera of the shape detector 105 (FIG. 3 (d)). Further, the depth of perforation is confirmed using a laser displacement meter attached to the shape detector 105. At this time, when the shape of the opening is elliptical or the depth of the perforations does not reach the set value, additional laser irradiation is performed. The perforation rate under this condition is 3200 holes / min.
  • the driving device 102 is used to move the ejection device 106 to the ejection position.
  • the cell ejection device 106 Jet Spotter (manufactured by Musashi Engineering) is used. Considering the size of cells, a nozzle having a diameter of 150 ⁇ m is used.
  • the ejection amount 30 nL is ejected as one droplet in consideration of the volume of the perforated portion (FIG. 3 (e)). The concentration of the suspension containing cells is adjusted so that 5000 cells are contained in 30 nL. Further, stirring is performed by bubbling at an appropriate timing so that the cells do not settle in the nozzle.
  • an image of the perforation portion is acquired in advance by the shape detector 105, and the position (x n with respect to the perforation device 103 recorded in the control device 101 is recorded. , Y n , z n ) is confirmed before discharging.
  • the shape detector 105 confirms whether the ejection is properly performed.
  • the ejection speed including alignment is about 3000 holes / min, and it is confirmed that a speed almost equal to the perforation speed can be obtained.
  • Coordinates that are stored in the control unit 101 is the final coordinates (x n, y n, z n) when it reaches the ends of the treatment.
  • the mesenchymal stem cells and the epithelial interstitial cells are cultured within the perforated scalp of the mouse (FIG. 3 (f)).
  • the treated area is observed after 3 weeks, hair growth can be confirmed.
  • the hair cycle can also be confirmed.
  • the punching device 103 is changed to an Er: YAG laser and the same processing as in the first embodiment is performed.
  • the Er: YAG laser has a higher absorption of water and can be expected to improve the drilling speed.
  • the laser irradiation conditions are a laser power of 24 W and a working distance of 92 mm.
  • the scanning speed of the galvanometer mirror is set to 500 mm / s.
  • the perforation speed is 3500 holes / min, which is faster than that of the CO 2 laser, and the damage to the scalp surface and the inside of the perforations can be reduced.
  • the disclosure of the present specification provides a program that implements one or more functions of the above-described embodiments to a system or apparatus via a network or a storage medium, and one or more processors in a computer of the system or apparatus provide the program. Can also be realized by a process of reading and executing. It can also be realized by a circuit (for example, ASIC) that realizes one or more functions.
  • a circuit for example, ASIC
  • the processing device in each of the above-described embodiments may be realized as a single device, or may be a mode in which a plurality of devices are communicably combined with each other to execute the above-described processing. included.
  • the above-described processing may be executed by a common server device or server group. It suffices that the processing device and the plurality of devices constituting the processing system can communicate at a predetermined communication rate, and they do not have to exist in the same facility or in the same country.
  • a software program that realizes the functions of the above-described embodiments is supplied to a system or apparatus, and the computer of the system or apparatus reads out the code of the supplied program. Including the form of executing.
  • the program code itself installed in the computer to implement the processing according to the embodiment by the computer is also one of the embodiments of the present invention. Further, based on the instructions included in the program read by the computer, the OS or the like running on the computer may perform some or all of the actual processing, and the processing may also realize the functions of the above-described embodiments. ..

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Abstract

La présente invention concerne un dispositif d'évacuation qui est caractérisé en ce qu'il comprend : une unité de perforation qui perfore des trous dans la peau d'un corps biologique en projetant une lumière laser; et une unité d'évacuation qui évacue des gouttelettes de liquide contenant des cellules dans les trous.
PCT/JP2019/041908 2018-10-31 2019-10-25 Dispositif de traitement, procédé de commande et programme WO2020090654A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006516006A (ja) * 2003-01-16 2006-06-15 ベクトン・ディキンソン・アンド・カンパニー 細ゲージのマイクロカニューレを用いる皮内細胞の送達
US20110130706A1 (en) * 2009-11-19 2011-06-02 Follica, Inc. Sequential body surface treatment
JP2013523732A (ja) * 2010-03-29 2013-06-17 フォリカ、インク． 併用療法
JP2014500275A (ja) * 2010-12-06 2014-01-09 フォリカ，インコーポレイテッド 禿頭症を治療するため、および毛髪の成長を促進するための方法
WO2016042722A1 (fr) * 2014-09-17 2016-03-24 パナソニックＩｐマネジメント株式会社 Tête à jet d'encre et dispositif d'impression à jet d'encre
WO2017073625A1 (fr) * 2015-10-30 2017-05-04 国立大学法人横浜国立大学 Procédé de préparation d'agrégation de primordium de follicules pileux régénérés, feuille contenant des tissus de follicules pileux, et procédé de préparation de feuille contenant des tissus de follicules pileux

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006516006A (ja) * 2003-01-16 2006-06-15 ベクトン・ディキンソン・アンド・カンパニー 細ゲージのマイクロカニューレを用いる皮内細胞の送達
US20110130706A1 (en) * 2009-11-19 2011-06-02 Follica, Inc. Sequential body surface treatment
JP2013523732A (ja) * 2010-03-29 2013-06-17 フォリカ、インク． 併用療法
JP2014500275A (ja) * 2010-12-06 2014-01-09 フォリカ，インコーポレイテッド 禿頭症を治療するため、および毛髪の成長を促進するための方法
WO2016042722A1 (fr) * 2014-09-17 2016-03-24 パナソニックＩｐマネジメント株式会社 Tête à jet d'encre et dispositif d'impression à jet d'encre
WO2017073625A1 (fr) * 2015-10-30 2017-05-04 国立大学法人横浜国立大学 Procédé de préparation d'agrégation de primordium de follicules pileux régénérés, feuille contenant des tissus de follicules pileux, et procédé de préparation de feuille contenant des tissus de follicules pileux

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