JP5821559B2 - Functional film transfer device - Google Patents

Description

  The present invention relates to a transfer device for transferring a functional film into a cell culture container.

  Patent Document 1 discloses a cell culture support (a cell culture container such as a petri dish) having a surface coated with a layer of a hydrophilic polymer (temperature-responsive polymer) to be cultured. By using this cell culture support, it can be easily detached from the cell support and recovered without destroying the cultured / proliferated cells simply by changing the temperature. However, as described in Patent Document 1, it is necessary to perform surface treatment separately by batch treatment on a cell culture container such as a petri dish to provide a functional compound layer. There is still room for improvement.

JP-A-2-21865

  As a technique for solving the inconvenience due to the batch processing of the cell culture support described in Patent Document 1, a raw material in which a large number of functional compound layers are arranged on a strip-shaped release film is prepared in advance, and a labeling technique is used. The functional compound layer is continuously peeled from the original fabric using the cell culture container, and each peeled functional compound layer is removed from the cell culture container by using an adsorption head that has been conventionally used as a conveying means such as a sheet material. Then, the negative pressure is released and the functional compound layer is arranged at the bottom of the cell culture container.

  On the other hand, when a functional film is placed on the bottom surface of a cell culture container to culture and proliferate cells, both are in close contact with each other with no air bubbles between the bottom surface of the cell culture container and the back surface of the functional film. Is required. If bubbles are present, they may be transferred to a microscopic observation image at the time of cell culture.

  The present inventors have used an adsorption head that has been used for pasting seals and transferred it onto the cell culture vessel with the functional film adsorbed on the adsorption surface of the adsorption head, where the negative pressure is released. Many processes are performed to drop the functional film onto the bottom surface of the cell culture container. In many cases, however, avoid the presence of bubbles between the dropped functional film and the bottom surface of the cell culture container. I couldn't. When bubbles are present, it is necessary to remove the bubbles by autoclaving with high-temperature and high-pressure steam. In addition to the extra work required, some types of functional films are equipped with a hydrophilic polymer. In the case of a functional film, the functional film may be damaged by autoclaving.

  The present invention has been made in view of the above circumstances, and when the functional film is transferred from the initial position to the cell culture container by using the adsorption head, the functional film and the bottom surface of the cell culture container (functional film receiving). It is an object of the present invention to provide a functional film transfer device capable of dropping a functional film onto the bottom surface (functional film receiving surface) of a cell culture container in a state where no air bubbles are present between the functional film and the surface). .

  The present inventors have conducted a number of experiments to solve the above-described problems, and thereby have a suction head 1 having a planar suction surface having a plurality of negative pressure suction holes 2 as shown in FIG. When the functional film 3 is adsorbed and the negative pressure is released with the adsorption surface of the adsorption head 1 and the bottom surface 5 of the cell culture container 4 in parallel posture, the functional film 3 is shown in FIG. As shown in FIG. 10 (c), it falls toward the bottom surface 5 of the cell culture container 4 while maintaining a posture substantially parallel to the bottom surface 5 of the cell culture container 4, and the air escape path is limited. Thus, it has been found that bubbles 6 remain between the two.

  The present invention is based on the above findings, and the functional film transfer device according to the present invention is a transfer device for transferring a functional film into a cell culture vessel, and the functional film is adsorbed on the adsorption surface by negative pressure. An adsorbing head that can be used, and a second position that is an upper position of the cell culture container that receives the functional film falling from the adsorbing head from a first position where the adsorbing head is negatively adsorbed to the functional film. A suction head moving means for moving, and a cell culture container support means for supporting the cell culture container at a position for receiving the functional film falling from the suction head, and further, the suction surface of the suction head is in a horizontal posture And a second tilting hand for tilting the functional film receiving surface of the cell culture container from a horizontal position to a tilted position. Characterized in that it comprises one or both of.

  In the functional film transfer apparatus according to the present invention, the adsorption head that has negatively adsorbed the functional film at the first position, which is an appropriate place, is moved to the second position, which is the upper position of the cell culture container, by the adsorption head moving means. Move to. At that position, the functional film drops toward the functional film receiving surface of the cell culture container by releasing the negative pressure and, if necessary, blowing out a small amount of air.

  When the adsorption surface of the adsorption head and the functional film receiving surface of the cell culture container are held in a horizontal and parallel posture in which one is not inclined with respect to the other by the first and second inclined means First, the functional film falls on the functional film receiving surface while maintaining a posture parallel to the functional film receiving surface of the cell culture container. In that case, bubbles may be formed between the functional film and the receiving surface after dropping.

  By operating both or any one of the first and second tilting means, the suction surface of the suction head and the functional film receiving surface of the cell culture container are in a posture in which one is slightly tilted with respect to the other, In the state, the functional film is dropped toward the functional film receiving surface of the cell culture container. In this case, the functional film falls in a posture slightly inclined rather than parallel to the functional film receiving surface of the cell culture container. Therefore, the falling functional film landed on the functional film receiving surface of the cell culture container earlier than the other part, the part closest to the functional film receiving surface of the cell culture container, Thereafter, the remaining area of the functional film lands on the functional film receiving surface with a time difference. In the process, air that exists between the back surface of the functional film and the bottom surface of the cell culture container (functional film receiving surface) is discharged sequentially and continuously outside, so there is no air bubble between them. Thus, the entire functional film is arranged on the functional film receiving surface of the cell culture container.

  In the present invention, the shape of the suction surface of the suction head in plan view is preferably a shape that matches the shape of the functional film to be transferred. In the case of a circular functional film, a suction head having a circular suction surface in plan view is used, and in the case of a rectangular functional film, a suction head having a rectangular suction surface in plan view is used.

  In one aspect of the functional film transfer device according to the present invention, the adsorption head and the cell culture container are rectangular in a plan view, and the first inclination means and / or the second inclination means are the adsorption head and / or cell. It is a means for inclining the adsorption head and / or the cell culture vessel with an axis parallel to the side of the culture vessel as a rotation axis. In this embodiment, any side edge of the rectangular functional film can be landed on the functional film receiving surface of the cell culture container first.

  In another aspect of the functional film transfer apparatus according to the present invention, the suction head and the cell culture container are rectangular in a plan view, and the first tilting means and / or the second tilting means are the suction head and / or The suction head and / or the cell culture container are inclined with the diagonal line of the cell culture container as a rotation axis. In this embodiment, any corner of the rectangular functional film can be landed on the functional film receiving surface of the cell culture container first.

  The present invention further provides, as a method for producing a cell culture container, a functional film having a functional organic compound layer on one side and an adhesive layer on the other side, and a release film that supports the pressure-sensitive adhesive layer side of the functional film A step of preparing an original fabric having: a step of conveying the original fabric with the functional organic compound layer of the functional film as an upper surface; and a step of peeling the functional film from the release film. A step of separating the functional film, a step of adsorbing and supporting the separated functional film from above by negative pressure adsorption, and the functional film so that a cell culture container is positioned below the functional film. A step of aligning the cell culture vessel, a step of relatively lowering the lower surface of the functional film supported by adsorption and the bottom surface of the cell culture vessel, and relative A step of stopping negative pressure adsorption in an inclined posture, dropping the functional film onto the cell culture container, and integrating the functional film and the cell culture container via the adhesive layer; Disclosed is a method for producing a cell culture container.

  By using this manufacturing method, it is possible to dispose the functional film on the functional film receiving surface of the cell culture container in a state where generation of bubbles is suppressed between the back surface of the functional film and the bottom surface of the cell culture container. This makes it possible to simplify or omit the defoaming process in the autoclave, which has been conventionally required.

  By using the functional film transfer device according to the present invention, the functional film is transferred to the cell while suppressing the generation of bubbles between the back surface of the functional film and the bottom surface of the cell culture container (functional film receiving surface). It becomes possible to arrange | position to the functional film receiving surface of a culture container.

The schematic diagram explaining an example of the functional film transferred by the functional film transfer apparatus by this invention. The schematic diagram explaining the original fabric which temporarily bonded many functional films to the strip | belt-shaped peeling film. The schematic diagram explaining an example of the functional film transfer apparatus by this invention. The figure explaining an example of a suction head. The figure for demonstrating a state when a functional film falls on the functional film receiving surface of a cell culture container. The 2nd figure for demonstrating a state when a functional film falls on the functional film receiving surface of a cell culture container. The figure which shows the flask type cell culture container which is an example of the cell culture container which has arrange | positioned the functional film. The figure which shows the manufacturing procedure of the flask type cell culture container shown in FIG. The figure which shows the other manufacturing procedure of the flask type cell culture container shown in FIG. The figure explaining the fall state of the sheet | seat sheet in the case of using the conventional suction head.

  Hereinafter, the present invention will be described based on embodiments. FIG. 1 is a cross-sectional view schematically showing an example of a functional film transferred by the functional film transfer apparatus according to the present invention. In the present invention, the functional film as a target is particularly a film having a pressure-sensitive adhesive layer having flexibility and having a desired function suitable for cell culture on the surface. It is not limited. In a preferred embodiment, like the functional film 10 shown in FIG. 1, the functional compound layer 12 is laminated on one surface of the film base layer 11, and the pressure-sensitive adhesive layer 13 is laminated on the other surface. In addition, in FIG. 1, 14 is a peeling film which makes the strip | belt shape mentioned later.

<Film base material layer 11>
Although not limited, the film base material layer 11 should just contain the material which can form the said functional compound layer 12 in one surface, and the kind of material is not specifically limited. Typically, as a material for the film base layer 11, polyethylene terephthalate (PET), polystyrene (PS), polycarbonate (PC), TAC (triacetyl cellulose), polyimide (PI), nylon (Ny), low density polyethylene (LDPE), medium density polyethylene (MDPE), vinyl chloride, vinylidene chloride, polyphenylene sulfide, polyether sulfone, polyethylene naphthalate, polypropylene, acrylic and the like.

  The surface of the film base material layer 11 on the side where the functional compound layer 12 is formed can be a surface subjected to an easy adhesion treatment. “Easy adhesion treatment” refers to treatment with an easy adhesive such as polyester, acrylic ester, polyurethane, polyethyleneimine, silane coupling agent, perfluorooctane sulfonic acid (PFOS), and the like.

  The thickness of the film base material layer 11 (when the film base material layer 11 includes an easy adhesion layer in addition to the base material layer, it refers to the entire thickness of the film base material layer including the easy adhesion layer) is particularly Although there is no restriction | limiting, It is preferable that it is the thickness which provides flexibility, for example, is 5 micrometers-400 micrometers, Preferably it is 50 micrometers-250 micrometers.

<Functional compound layer 12>
The functional compound constituting the functional compound layer 12 includes an organic compound or an inorganic compound, and more preferably has a surface that can be changed from cell adhesiveness to cell nonadhesiveness by a predetermined stimulus. Examples thereof include hydrophilic compounds such as a stimulus-responsive polymer and an ethylene glycol chain composed of one or more ethylene glycol units (CH ₂ —CH ₂ —O).

The film thickness of the functional compound layer is, for example, preferably in the range of 0.5 nm to 300 nm, and more preferably in the range of 1 nm to 100 nm.
Hereinafter, preferred embodiments of the “stimulus responsive polymer layer” and the “hydrophilic compound layer” will be described.

<Stimulus responsive polymer layer>
The functional organic compound layer is particularly preferably a stimulus-responsive polymer layer. The stimulus-responsive polymer layer is a layer containing a polymer in which the degree of cell adhesion on the surface is changed by a predetermined stimulus. Examples of the stimulus responsive polymer include a temperature responsive polymer, a pH responsive polymer, an ion responsive polymer, and a photoresponsive polymer. Among these, a temperature-responsive polymer is preferable because it is easy to give a stimulus.

  As the temperature-responsive polymer, for example, a polymer that exhibits cell adhesion at a temperature at which cells are cultured and exhibits cell non-adhesion at a temperature at which the produced cell sheet is peeled may be used. For example, a temperature-responsive polymer has improved affinity to surrounding water at temperatures below the critical dissolution temperature, and the polymer takes up water and swells to make it difficult for cells to adhere to the surface (cell non-adhesiveness). It is preferable to use a material exhibiting a property (cell adhesiveness) that makes the polymer shrink and easily adheres cells to the surface when water is desorbed from the polymer at a temperature equal to or higher than the same temperature. Such a critical solution temperature is called a lower critical solution temperature. A temperature-responsive polymer having a lower critical solution temperature T of 0 ° C. to 80 ° C., more preferably 0 ° C. to 50 ° C. may be used. This is because the cells can be stably cultured when T is 0 ° C to 80 ° C.

  Suitable temperature-responsive polymers include acrylic polymers or methacrylic polymers. Specific examples of suitable temperature-responsive polymers include poly-N-isopropylacrylamide (T = 32 ° C.), poly-Nn-propyl acrylamide (T = 21 ° C.), and poly-Nn-propyl methacrylamide. (T = 32 ° C.), poly-N-ethoxyethyl acrylamide (T = about 35 ° C.), poly-N-tetrahydrofurfuryl acrylamide (T = about 28 ° C.), poly-N-tetrahydrofurfuryl methacrylamide (T = About 35 ° C.), and poly-N, N-diethylacrylamide (T = 32 ° C.).

  As the pH responsive polymer and the ion responsive polymer, those suitable for the cell sheet to be prepared can be appropriately selected.

  The stimulus-responsive polymer layer is prepared by preparing a coating composition containing a monomer that is polymerized to form a target stimulus-responsive polymer and an organic solvent that can dissolve the monomer. The film is coated on the surface of the material to form a coating film, and then the monomer in the coating film is polymerized by an appropriate means such as radiation irradiation to form a polymer. And a grafting reaction between them.

<Hydrophilic compound layer>
As another embodiment of the functional organic compound layer, hydrophilicity such as an ethylene glycol chain composed of one or more ethylene glycol units (an ethylene glycol chain composed of a plurality of ethylene glycol units can be referred to as a “polyethylene glycol chain”). A layer of a functional compound.

  The terminal of the ethylene glycol chain may be in a form blocked with a hydroxyl group, or the terminal of the ethylene glycol chain may be in a form in which another substance such as a biological substance is linked by a covalent bond.

  A layer containing an ethylene glycol chain whose end is blocked with a hydroxyl group can provide a hydrophilic surface to which cells are difficult to adhere.

  Bio-related substances that can be covalently bonded to the end of ethylene glycol chain include antigens, antibodies, DNA, RNA, peptides, hormones, enzymes, cytokines, sugar chains, lipids, coenzymes, enzyme inhibitors, cells, and other functions. The protein which has is included. Furthermore, the low molecular weight compound which has affinity with such a biological substance, and a high molecular compound are also contained in the range of a biological substance.

  In order to immobilize a hydrophilic compound layer such as an ethylene glycol chain on the surface of a resin film base layer, it can be physically adsorbed on the surface of the film base layer in advance. A primer layer containing a polysiloxane containing a functional group in a side chain that can form a covalent bond by reacting with a hydroxyl group at the end of the chain is provided. The functional group on the side chain of the polysiloxane is preferably a glycidyl group or an epoxy group. The primer layer can be formed by applying a silanol compound having a desired side chain to the surface of the film substrate layer, and performing condensation polymerization on the surface to convert it into polysiloxane.

Next, the functional group of the primer layer and the hydroxyl group of polyethylene glycol in which two or more ethylene glycol or ethylene glycol units are repeated are reacted to form a covalent bond, thereby immobilizing the ethylene glycol chain. At this time, ethylene glycol or polyethylene glycol containing a catalytic amount of concentrated sulfuric acid is brought into contact with the primer layer.
A layer containing ethylene glycol chains whose ends are blocked with hydroxyl groups is formed in this way.

  Furthermore, if necessary, at least one functional group capable of forming a covalent bond with another substance is directly or indirectly linked to one end of the ethylene glycol chain. The method for introducing the functional group is not particularly limited.

<Adhesive layer 13>
Examples of the pressure-sensitive adhesive constituting the pressure-sensitive adhesive layer 13 include polyester resin, acrylic ester resin, polyurethane resin, polyethyleneimine resin, silane coupling agent, and perfluorooctane sulfonic acid (PFOS). Among them, acrylic ester Resins, polyurethane resins and the like can be preferably used.

  Although the thickness of an adhesive layer is not specifically limited, It is preferable that they are 10 micrometers-300 micrometers, and it is more preferable that they are 20 micrometers-200 micrometers.

  The functional film 10 having the layer structure shown in FIG. 1 can be produced by an arbitrary method. In the present embodiment, the functional film 10 is produced as follows. That is, the pressure-sensitive adhesive layer 13 is applied to the entire surface of the strip-shaped release film 14, and the strip-shaped film base material layer 11 and the functional film 10 having the same width are laminated thereon. Thereby, as shown in the figure, a long object 20 (see FIG. 2) is formed, which is composed of a four-layer structure of the release film 14, the pressure-sensitive adhesive layer 13, the film base material layer 11, and the functional film 10. . The release film 14 is not particularly limited as long as it has the required strength and flexibility. For example, a release treatment such as a silicone release agent is applied to a film made of a resin such as polyethylene terephthalate or a foamed film thereof. Can be mentioned.

  A form (not shown) having an outer shape of the functional film 10 to be obtained is pushed down from the surface opposite to the release film 14 of the long object 20 so as to reach the surface of the release film 14. Thereby, in the functional film 10, the film base material layer 11, and the pressure-sensitive adhesive layer 13, a cut line 21 that forms an outer shape of the functional film 10 is formed. By performing the stamping operation on the long object 20 continuously at a predetermined interval, a long object 20 having a plurality of cut lines 21 as shown in FIG. 2 is obtained. The long object 20 is wound into a roll so that the functional film 10 side is on the inside, and is made into a raw fabric 22 (see FIG. 3) and stored.

  In addition, there is no restriction | limiting in the shape in planar view of the functional film 10, It can take arbitrary shapes, The formwork according to it is used. In the example shown in FIG. 2, the functional film 10 intended to be placed on the bottom surface 51 </ b> A of the cell culture vessel 50 </ b> A having a tapered shape as shown in FIG. 7 is obtained. Is substantially the same shape as the shape of the inner peripheral contour of the bottom surface 51A of the cell culture vessel 50A.

  FIG. 3 shows an example of a functional film transfer device according to the present invention. The functional film transfer device 30 shown in the figure includes an air cylinder 31, and a suction head 40 as shown in FIG. 4 is detachably attached to the lower end of the air cylinder 31. The air cylinder 31 and the suction head 40 are supported by a robot arm 60, and the robot arm 60 can be moved in the XY axis direction which is a surface direction and the Z axis direction which is a vertical direction by a control device 61. ing. Further, the control device 61 performs control to slightly tilt the central axis L of the air cylinder 31 and the suction head 40 in an arbitrary direction a of 360 ° with the vertical direction as the center. The control device 61 makes the air cylinder 31 and the suction head 40 slightly inclined (for example, about 1 to 3 ° C.) from the vertical posture, so that the suction surface of the suction head 40 is slightly changed from the horizontal posture. It becomes a posture inclined to. In this example, the means comprising the robot arm 60 and the control device 61 are the “suction head moving means” and “first tilting means for tilting the suction surface of the suction head from the horizontal posture to the tilted posture” in the present invention. It is a device that doubles as

  In the vicinity of the air cylinder 31, a guide base 32 extending in the horizontal direction or in a slightly inclined direction is located, and the long object 20 unwound from the raw fabric 22 is provided with a guide roll 33. Is moved along the upper surface of the guide table 32, made a U-turn at the tip, and then taken up by the take-up roll 34. When the long object 20 makes a U-turn at the tip of the guide base 32, the inner region defined by the cut line 21 is peeled off from the release film 14 and sent out in the direction of the extended line on the upper surface of the guide base 32. That is, the functional film 10 having a three-layer structure of the functional film 10, the film base layer 11, and the pressure-sensitive adhesive layer 13 is continuously peeled from the release film 14 with the pressure-sensitive adhesive layer 13 side as the lower surface side. , Sent out in a horizontal direction or a slightly inclined downward direction.

  The functional film transfer device 30 further includes cell culture container support means 35 that can be repeatedly moved and stopped intermittently with the cell culture container 50 placed in a horizontal posture. The cell culture container support means 35 is provided with a cell culture container attitude control means 70 capable of controlling the attitude of the cell culture container 50 to be supported and conveyed from a horizontal attitude to a slightly inclined attitude. Specifically, the cell culture container posture control means 70 has an arm 72 whose posture is controlled by the control device 71, and the arm 72 gives an inclination to an appropriate position of the cell culture container support means 35, The cell culture container 50 located on the inclined region is inclined from the horizontal posture. The cell culture container attitude control means 70 including the control device 71 corresponds to the “second inclination means for inclining the functional film receiving surface of the cell culture container from the horizontal attitude to the inclined attitude” in the present invention.

  Preferably, an air nozzle 37 having a lateral width substantially equal to the lateral width of the functional film 10 is directed obliquely upward in the vicinity of the front end of the guide table 32 and below the functional film 10 to be delivered. It can be installed in a different posture. By receiving the air jet from the air nozzle 37 from below, the functional film 10 peeled from the release film 14 and sent out can maintain a substantially horizontal posture thereafter.

  4A and 4B, the suction head 40 includes a suction surface 41 that is a substantially flat surface and an air chamber on the back side of the suction surface 41, as shown in a sectional view and a plan view viewed from below. 42, and the air chamber 42 is connected to the air passage 36 of the air cylinder 31. The air passage 36 is connected to appropriate air suction and exhaust means (not shown). In the illustrated example, the shape of the suction surface 41 is circular in plan view, and a number of negative pressure suction holes 44 are formed in the suction surface 41.

  Unlike the one shown in FIG. 2, circular cut lines 21 having substantially the same size as the suction surface 41 are provided on the original fabric 22 used in the functional film transfer device 30 provided with the suction head 40 at regular intervals. As described above, the circular functional film 10 is continuously peeled from the release film 14 in a posture in which the pressure-sensitive adhesive layer 13 side is the lower surface side, and is sent out in the horizontal direction.

  The operation of the functional film transfer device 30 will be described. First, while guiding the original fabric 22 by guide rolls 33..., The original fabric 22 is routed so as to pass through the upper surface of the guide table 32 and its front end, and the U 22 is turned at the front end of the guide table 32. Is wound on the winding roll 34. In this state, when the raw fabric 22 is wound up, as described above, the functional film 10 peeled from the release film 14 from the front end of the guide stand 32 is in a posture with the adhesive layer 13 side as the lower surface side. It is sent out in the horizontal direction continuously at regular intervals.

  The control device 61 positions the air cylinder 31 and the suction head 40 at a position where the delivered functional film 10 can be sucked by the suction head 40 with negative pressure. At this time, the control device 61 operates the robot arm 60 to control the posture so that the central axis L of the air cylinder 31 and the suction head 40 is in a vertical posture. In that posture, the air in the air chamber 42 is sucked by the suction means, whereby a negative pressure is generated on the suction surface 41, whereby the functional film 10 is sucked by the suction surface 41 with a negative pressure.

  In a state where the vertical posture is maintained, the control device 61 operates the robot arm 60 to bring the air cylinder 31 and the adsorption head 40 to a position directly above the cell culture vessel 50 supported and transported by the cell culture vessel support means 35. Move. After the movement, the air cylinder 31 and the suction head 40 are lowered until the distance between the bottom surface 51 which is the functional film receiving surface of the cell culture container 50 and the functional film 10 is about 0.1 mm to 10 mm, and negative at the lowered position. Release pressure. Here, it is assumed that the control device 71 controls the posture of the arm 72 so that the cell culture vessel 50 supported on the cell culture vessel support means 35 takes a horizontal posture.

  When the negative pressure is released at the lowered position as described above, the suction force of the adsorption surface 41 disappears, so that the functional film 10 adsorbed on the adsorption surface 41 is directed toward the bottom surface 51 of the cell culture vessel 50 by its own weight. Fall. In the above example, the adsorption surface 41 of the adsorption head 40 and the bottom surface 51 of the cell culture vessel 50 supported on the cell culture vessel support means 35 are both in a horizontal and parallel posture. As shown in FIG. 10B, the functional film 10 tends to be parallel to the bottom surface of the cell culture vessel 50, and tends to embrace the bubbles 6 after dropping.

  In order to solve this problem, in the functional film transfer device 30 according to the present invention, the suction surface 41 of the suction head 40 and the bottom surface of the cell culture vessel 50 supported on the cell culture vessel support means 35 (functional film receiving surface). ) 51 and the control device 61 functioning as the “first tilting means for tilting the suction surface of the suction head from the horizontal posture to the tilted posture”, and “the function of the cell culture vessel” Both or either of the control devices 71 functioning as “second tilting means for tilting the photosensitive film receiving surface from the horizontal posture to the tilted posture” are appropriately operated.

  Hereinafter, an example of the operation will be described with reference to FIGS. 5A, the control means 61 is operated so that the central axis L of the air cylinder 31 and the suction head 40 is slightly inclined from the vertical posture, and the support surface of the cell culture vessel 50 remains in a horizontal posture. It is in the state. When the negative pressure is released in this state, the functional film 10 falls toward the cell culture vessel 50 in a posture inclined diagonally to the left in the figure, and the leftmost region in the figure of the functional film 10 is the cell first. After landing on the bottom surface 51 of the culture vessel 50, the region on the right side is sequentially landed on the bottom surface 51 of the cell culture vessel 50.

  FIG. 5 (b) shows that the center axis L of the air cylinder 31 and the suction head 40 remains in a vertical posture, and the control means 71 is operated to give the cell culture container support means 35 a required inclination, thereby In this state, 50 is in an inclined posture. When the negative pressure of the suction head 40 is released in this state, the functional film 10 falls toward the cell culture container 50 in a posture in which the horizontal posture is maintained, but the cell culture vessel 50 is inclined downward in the drawing. In this case as well, in this case, the leftmost region of the functional film 10 first lands on the bottom surface 51 of the cell culture container 50, and then the right region sequentially from there to the cell culture container 50. Landing on the bottom of the.

  5C, the control means 61 is operated so that the central axis L of the air cylinder 31 and the suction head 40 is slightly inclined to the left in the figure from the vertical attitude, and further, the control means 71 is operated. In this state, the cell culture container support means 35 is provided with a required downward slant to make the cell culture container 50 slant downward. In this case, when the negative pressure of the suction head 40 is released, the functional film 10 falls toward the cell culture container 50 in a posture inclined downward to the left, and the functional film 10 has a leftmost region in the drawing. First, it lands on the bottom surface 51 of the cell culture container 50. Thereafter, the region on the right side is landed on the bottom surface of the cell culture vessel 50 sequentially. However, here, since the cell culture vessel 50 is also inclined to the right, the same air expelling effect at a smaller inclination angle than in the case of FIG. 5 (a) or FIG. 5 (b). Can be raised.

  When the adsorption head 40 and the cell culture vessel 50 are rectangular in plan view, the adsorption head 40 or the cell culture vessel 50 is inclined with the axis parallel to the side of the rectangle as the rotation axis. As shown in the side sectional view of FIG. 5D and the plan view of FIG. 5E, any one side 10x of the functional film 10 is first landed on the bottom surface of the cell culture vessel 50. it can. Further, as shown in the plan view of FIG. 6A, the suction head 40 or the cell culture vessel 50 is inclined with the rectangular diagonal line P as the rotation axis, so that the plan view of FIG. Any corner 10y of the functional film 10 can be landed on the bottom surface of the cell culture vessel 50 first. An optimum method may be selected according to the shape of the functional film 10 or the shape of the bottom surface of the cell culture vessel 50.

  In the above description, the air cylinder 31 and the suction head 40 are integrated with each other and the posture is adjusted by the control device 61. However, a flexible means such as a universal joint is provided between the air cylinder 31 and the suction head 40. By interposing, an inclined posture can be given only to the suction head 40 by an appropriate control device.

  In addition, the shape of the adsorption surface 41 in the adsorption head 40 is not limited to the circular or rectangular shape described above, but is determined depending on the shape of the bottom surface 51 of the cell culture container 50 that transfers the adsorbed functional film 10. Further, as the cell culture container 50, in addition to a dish-shaped or bowl-shaped container with an open top, a flask-shaped container 50A as shown in FIG.

  As shown in FIG. 7A, the flask-type cell culture container 50A includes a container part 100 and a lid 110. The container unit 100 includes at least a bottom surface 51A, a side wall portion 102 erected on the periphery of the bottom surface 51A, and a top surface portion 103 that is joined to the upper end portion of the side wall portion 102 and is opposed to the bottom surface 51A. The bottom surface 51A has a shape in which one end side of a rectangular flat plate is narrowed, and a through hole 104 is formed in the side wall portion 102 corresponding to the narrowed tip. And the neck part 105 extended to the container part outer side from the periphery of the through-hole 104 is provided, and the lid | cover 110 is mounted | worn detachably there. By combining the container part 100 and the lid 110, a flask-type cell culture container 50A is formed.

  FIG. 7B shows a cross section along the line bb in FIG. 7A, and FIG. 7C shows a cross section along the line cc. In the internal space surrounded by the bottom surface 51 </ b> A, the side wall portion 102, and the top surface portion 103 of the container portion 100, an inner chamber 130 for containing cells and a culture medium is formed. The functional film 10 described above is fixed to a part of the bottom surface 51 </ b> A facing the inner chamber 130.

  The functional film 10 can be fixed when the surface to which the functional film 10 is fixed is not opened and is located in a closed container like the flask type cell culture container 50A. What is necessary is just to complete the target cell culture container by fixing the functional film 10 to a shape-shaped member, and combining the member after film fixation with another member.

  For example, as shown in FIG. 8, a first member 201 having a bottom surface 51A and a side wall portion 102, the side opposite to the fixing surface of the functional film 10 on the bottom surface 51A being opened, and the top surface portion on the opened surface The container part 100 is formed by joining the second member 202 corresponding to 103. At this time, before joining the second member 202, the functional film 10 is fixed to the inner surface of the bottom surface 51A of the first member 201 using the functional film transfer device 30 according to the present invention. The first member 201 and the second member 202 are joined together in a liquid-tight manner by an appropriate method so that the culture solution does not leak out according to the purpose of cell culture.

  In the embodiment shown in FIG. 9, the first member 301 corresponding to the bottom surface 51 </ b> A, the second member 302 corresponding to the side wall portion 102 including the neck portion 105, and the third member 303 corresponding to the top surface portion 103 are joined. Thereby, the container part 100 is formed. In this aspect, the functional film 10 is fixed to the portion of the first member 301 corresponding to the inner surface of the bottom surface 51A by the method described above.

  When the functional film 10 is transferred to the flask-type cell culture vessel 50A having the shape of the bottom surface 51A shown in FIGS. 7 to 9, one end side as shown in FIG. While using the long object 20 with the cut line 21 having a narrowed shape, the shape of the suction surface 41 of the suction head 40 is also a shape corresponding to it.

  In the case of such a shape, in the case of the cell culture container 50A shown in FIGS. 7 to 9 in one end side of the bottom surface 50A, in the region 54 on the end portion side opposite to the neck portion 105 of the bottom surface 51A, It is desirable that one end side of the falling functional film 10 can be brought into contact most quickly. For this purpose, the first tilting means or the second tilting means is configured to tilt the adsorption head 40 or the cell culture vessel 50 about an axis parallel to the side of the end region 54. By doing so, the intended purpose can be achieved.

  In this invention, the material which comprises the cell culture container 50 is not specifically limited, The material generally used in cell culture can be used. For example, polystyrene resin, polyester resin, polyethylene resin, polyethylene terephthalate resin, polypropylene resin, ABS resin, nylon, acrylic resin, fluorine resin, polycarbonate resin, polyurethane resin, methylpentene resin, phenol resin, melamine resin, epoxy resin, vinyl chloride A resin material such as a resin, a resin material containing at least one of the above-described surface hydrophilized treatment, and an inorganic material such as glass or quartz are preferable, but a resin material is preferable. The resin material is preferably a polystyrene resin or a polyethylene terephthalate resin.

10 ... functional film,
11 ... film base material layer,
12 ... Functional compound layer,
13 ... adhesive layer,
14 ... stripping release film,
20 ... long object composed of four layers,
21 ... a score line forming the outer shape of the functional film,
22 ... roll-shaped original fabric,
30 ... Functional film transfer device,
31 ... Air cylinder,
32 ... Information desk,
33 ... Guide roll,
34 ... take-up roll,
35 ... Cell culture vessel support means,
36 ... Airway,
40: Suction head,
41 ... adsorption surface,
42 ... Air chamber,
44 ... negative pressure adsorption hole,
50, 50A ... cell culture vessel,
51, 51A ... bottom of cell culture vessel,
60 ... Robot arm 61 ... Control device (first tilting means for tilting the suction surface of the suction head from the horizontal posture to the inclined posture),
70: Cell culture container posture control means,
71... Control device (second tilting means for tilting the functional film receiving surface of the cell culture container from the horizontal posture to the inclined posture)
72 ... arm,
L: Center axis of air cylinder and suction head.

Claims (3)

A transfer device for transferring a functional film into a rectangular cell culture vessel in plan view, the transfer device comprising:
A rectangular suction head in a plan view capable of negative pressure suction of the functional film on the suction surface;
An adsorption head moving means for moving the adsorption head from a first position for negatively adsorbing the functional film to a second position which is an upper position of the cell culture container for receiving the functional film falling from the adsorption head;
Cell culture container support means for supporting the cell culture container at a position for receiving the functional film falling from the adsorption head, and
First tilting means for tilting the suction surface of the suction head from a horizontal posture to an inclined posture;
Either or both of the second tilting means for tilting the functional film receiving surface of the cell culture container from a horizontal position to an inclined position ;
The first tilting means and / or the second tilting means are means for tilting the adsorption head and / or the cell culture container about an axis parallel to the side of the adsorption head and / or the cell culture container. A functional film transfer device. A transfer device for transferring a functional film into a rectangular cell culture vessel in plan view, the transfer device comprising:
A rectangular suction head in a plan view capable of negative pressure suction of the functional film on the suction surface;
An adsorption head moving means for moving the adsorption head from a first position for negatively adsorbing the functional film to a second position which is an upper position of the cell culture container for receiving the functional film falling from the adsorption head;
Cell culture container support means for supporting the cell culture container at a position for receiving the functional film falling from the adsorption head, and
First tilting means for tilting the suction surface of the suction head from a horizontal posture to an inclined posture;
Bei example either or both of the second tilting means for tilting the functional film receiving surface of the cell culture vessel from a horizontal position to the inclined position,
The first tilting means and / or the second tilting means are means for tilting the adsorption head and / or the cell culture container about the diagonal line of the adsorption head and / or the cell culture container as a rotation axis. Film transfer device. Preparing a raw material having a functional film having a functional organic compound layer on one side and a pressure-sensitive adhesive layer on the other side, and a release film supporting the pressure-sensitive adhesive layer side of the functional film;
Transporting the original fabric with the functional organic compound layer of the functional film as an upper surface;
Separating the functional film from the original fabric by peeling the functional film from the release film;
A step of adsorbing and supporting the separated functional film from above by negative pressure adsorption;
Aligning the functional film and the cell culture container so that the cell culture container comes below the functional film;
A step of relatively tilting the lower surface of the functional film supported by adsorption and the bottom surface of the cell culture vessel;
The negative pressure adsorption is stopped in a relatively inclined posture, the functional film is dropped onto the cell culture container, and the functional film and the cell culture container are integrated via the adhesive layer. method for producing a cell culture vessel, wherein the Ru and a step.

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