JP2019024343A - Culture scaffold and method of producing same - Google Patents

Abstract

To reduce disordering of aligned fibers in a culture scaffold provided with a fiber assembly comprising a plurality of aligned fibers.SOLUTION: A fiber scaffold comprises a substrate, a fiber assembly arranged on the substrate, and a weld formed in one part of the fiber assembly. The fiber assembly comprises a plurality of aligned fibers and is fixed to the substrate by the weld.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a culture scaffold comprising a plurality of arranged fibers and a method for producing the same.

  In recent years, fiber base materials have attracted attention as a culture scaffold for culturing biological tissues and microorganisms (see Patent Document 1). The fiber substrate is, for example, a woven fabric, a knitted fabric, or a non-woven fabric, and has a three-dimensional structure. Therefore, biological tissues and microorganisms can be cultured in a state close to a physiological environment in vitro.

Special table 2010-517590

  When a fiber aggregate in which a plurality of fibers are arranged is used as a culture scaffold, a certain degree of rigidity can be secured in the fiber arrangement direction. However, the rigidity is low in the thickness direction of the fiber assembly and the direction perpendicular to the fiber arrangement direction, and the fiber arrangement tends to be disturbed.

One aspect of the present invention includes a substrate, a fiber assembly disposed on the substrate, and a weld portion formed on a part of the fiber assembly,
The said fiber assembly is related with the scaffold for culture | cultivation containing the arranged some fiber and being fixed on the said board | substrate by the said welding part.

Another aspect of the present invention includes a step of preparing a substrate;
Disposing a fiber assembly including a plurality of arranged fibers on the substrate;
A step of welding a part of the fiber assembly to the substrate to form a welded portion, and a fiber fixing step of fixing the fiber assembly to the substrate by the welded portion. It relates to a manufacturing method.

  In a culture scaffold provided with a fiber assembly including a plurality of arranged fibers, disorder of the arrangement of fibers can be reduced.

It is a top view which shows typically the scaffold for culture | cultivation which concerns on one Embodiment of this invention. It is a top view which shows typically the fiber assembly of the state exposed from the through-hole of FIG. It is a top view which shows typically other embodiment of a welding part. It is a side view which shows typically the winding rotary body in the deposition process of the manufacturing method which concerns on this invention. It is a side view which shows typically the winding rotary body in the transfer process of the manufacturing method which concerns on this invention, a frame, and a fiber assembly. It is a side view which shows typically the frame, the board | substrate, and fiber assembly in the arrangement | positioning process of the fiber assembly of the manufacturing method which concerns on this invention. It is sectional drawing which shows typically the frame, the board | substrate, and fiber assembly in the fiber fixing process of the manufacturing method which concerns on this invention. It is a perspective view which shows the winding rotary body of Fig.4 (a) and FIG.4 (b). It is a schematic top view of the one part area | region of the fiber assembly for demonstrating the arrangement | sequence of a fiber.

  Hereinafter, the culture scaffold and the production method thereof according to the embodiment of the present invention will be described in more detail with reference to the drawings as necessary.

[Culture scaffold]
FIG. 1 is a top view schematically showing a culture scaffold according to an embodiment of the present invention. The culture scaffold 100 includes a substrate 110, a fiber assembly 130 disposed on the substrate 110, and a welded portion 140 formed on a part of the fiber assembly 130. The fiber assembly 130 includes a plurality of arranged fibers 131 and is fixed on the substrate 110 by the welded portion 140.

  In general, the arrangement of the fibers tends to be disturbed only by placing a plurality of arranged fibers on the substrate. For example, when the culture scaffold is immersed in a liquid culture medium or when a liquid culture medium is poured into the culture scaffold, the fibers are disturbed. For this reason, even in culture applications, when high fiber alignment is required, it is required to reduce the disturbance of the fiber alignment. According to the present embodiment, the fiber assembly 130 is fixed on the substrate 110 by the welded portion 140, so that the disorder of the arrangement of the fibers 131 can be reduced or suppressed.

  More specifically, the illustrated scaffold 100 includes a frame body 120 mounted on the substrate 110. The frame 120 includes one main surface (first main surface) 120X and the other main surface (second main surface) 120Y opposite to the first main surface 120X. It is mounted on the substrate 110 such that the surface 120X faces the substrate 110. The frame body 120 includes a through hole 121 that penetrates from the first surface 120X to the second surface 120Y. When the through-hole 121 penetrates the frame body 120 in the thickness direction, a first opening 121a is formed on the first surface 120X, and a second opening 121b is formed on the second surface 120Y. In the illustrated example, the frame body 120 includes four through holes 121, but is not limited to this case, and may have one or more through holes 121.

  The fiber assembly 130 is interposed between the substrate 110 and the frame body 120. The plurality of fibers 131 are arranged along one direction, and the plurality of arranged fibers 131 constitutes a fiber assembly 130. At least a part of the fiber assembly 130 and the welded portion 140 are exposed from the first opening 121a formed in the first surface 120X by the through hole 121, respectively. In the illustrated example, the fiber assembly 130 is not within the entire surface of the substrate 110 on which the frame body 120 is mounted, but within a range facing one main surface (first surface 120X) of the frame body 120. Has been placed.

  FIG. 2 is a top view schematically showing the fiber assembly 130 exposed from the first opening 121a of one through hole 121 in FIG. In the illustrated example, in the portion exposed from the first opening 121 a of the fiber assembly 130, the welded portions 140 are formed in spots at four locations, and the fiber assembly 130 is fixed on the substrate 110 by the welded portions 140. Has been. The position and number of the welded portions 140 and the shape of the welded portions 140 are not particularly limited. However, in consideration of placing biological tissues and cells on the culture scaffold 100, the welded portion 140 may be a resistance to growth of biological tissues and cells. Therefore, it is preferable to form the welded portion 140 so as to avoid the position where the biological tissue or cells are arranged. From this viewpoint, the position, number, shape, and the like may be selected. For example, when a biological tissue or cell is placed near the center of the first opening 121a, as shown in FIG. 2, the welding portion 140 is formed around the center of the first opening 121a, avoiding the vicinity. Is preferred.

  FIG. 3 is a top view schematically showing another embodiment of the welded portion. 3 also shows the fiber assembly 130 exposed from the first opening 121a of one through-hole 121, as in FIG.

In FIG. 3, the welding part 240 is formed in a line shape. In the illustrated example, two line-shaped welded portions 240 are formed, and each welded portion 240 extends in a direction intersecting with the plurality of arranged fibers 131. Also in FIG. 3, as in the case of FIG. 2, two welds 140 are formed around the center of the first opening 121a, avoiding the vicinity.
However, not only in the case of FIGS. 2 and 3, the welded portions 140 and 240 can be formed at desired positions on the fiber assembly 130 (and the substrate 110) according to the purpose.

  From the viewpoint of high effect of reducing the disorder of the arrangement of the plurality of fibers 131, it is preferable to form the welded portion 240 in a line shape as shown in FIG. From the viewpoint of hardly inhibiting the growth of biological tissues and cells, it is preferable to form the welded portion 140 in a spot shape as shown in FIG.

  The culture scaffold 100 is used, for example, as a holding body that holds a medium for culturing biological tissues and microorganisms and supports the biological tissues and microorganisms. Further, the culture scaffold 100 may be used in a potential measuring device or the like for measuring these potentials in a state where biological tissue or microorganisms are held. The culture scaffold 100 may be used for each application while being accommodated in a holder or the like as necessary.

  In this specification, “biological tissue” refers to a biological tissue or a part thereof, a cell constituting a biological tissue or an organ, a cell that can differentiate into a biological tissue or organ such as an iPS cell or an ES cell (and its cells). Tissue or organs cultured from cells, or a part thereof).

(Fiber assembly 130)
The fiber aggregate 130 is an aggregate of a plurality of arranged fibers 131. In the fiber assembly 130, the plurality of fibers 131 are preferably arranged in one direction. That the plurality of fibers 131 are arranged in one direction means that in the fiber assembly 130, the fibers 131 do not intersect with each other or the average angle (acute angle) at which the fibers 131 intersect each other is 0 °. It means exceeding 60 ° or less. In this way, when the plurality of fibers 131 are arranged, the fibers 131 are likely to extend along the arrangement direction of the fibers 131, so that stress on the biological tissue and microorganisms is reduced. Therefore, it becomes easy for biological tissues and microorganisms to grow along the arrangement direction of the fibers 131.

  Here, the average angle (acute angle) at which the fibers 131 intersect can be determined from the intersection of the fibers 131 in the average length direction. The average length direction of the fibers 131 can be determined based on, for example, a scanning electron microscope (SEM) photograph when the fiber assembly 130 is viewed from the normal direction. FIG. 6 is a schematic top view of the fiber assembly for explaining the arrangement of the fibers. In FIG. 6, the state of the fiber assembly 130 in the SEM photograph which image | photographed the fiber assembly 130 from the normal line direction is imitated. A square region R having a predetermined size (for example, 100 μm × 100 μm) is set when the fiber assembly 130 composed of a plurality of fibers 131 is viewed from the normal direction. At this time, the region R is determined so that eight or more fibers 131 are included in the region R, and 50% or more of the fibers 131 located in the region R intersect two opposite sides of the region R. In this region R, the direction of a straight line (dotted line in FIG. 6) connecting a point where a certain fiber 131 intersects the two opposite sides is the average length direction of the fiber 131.

  For example, in the region R, the average angle at which the fibers 131 intersect with each other is selected by arbitrarily selecting two fibers 131 from a plurality of (for example, twelve) fibers 131 arbitrarily selected. An angle at which the average length direction intersects (for example, θ1 in FIG. 6) is obtained. Another two fibers 131 are selected, and an angle (for example, θ2 in FIG. 6) at which the average length direction of each fiber 131 intersects is obtained. Such an operation is performed on the remaining selected fibers 131 (for example, eight). And the average of each angle is calculated and it is set as the average angle which the fibers 131 cross.

  The ratio of the area of the fiber 131 to the unit area of the fiber assembly 130 can be selected from 10 to 90%. The fiber assembly 130 may be formed very thin. In this case, the ratio of the fibers 131 per unit area is 20 to 50%, and preferably 30 to 40% is uniformly dispersed and deposited. The ratio of the area of the fibers 131 is a region of a predetermined area (for example, an ellipse having a minor axis of 3 mm and a major axis of 6 mm) on one main surface (for example, the upper surface) of the fiber assembly 130. Can be obtained by binarizing an image obtained with an optical microscope or the like, calculating the area occupied by the fibers 131, and converting the area to a ratio (%) per unit area.

  The material of the fiber 131 is not particularly limited as long as it can be used for a biological tissue or a scaffold for culturing microorganisms. Among these, the fiber 131 preferably contains a rubber-containing styrene resin in that it has a high affinity for biological tissues and microorganisms and is difficult to give stress to the biological tissues and microorganisms when culturing. As the rubber-containing styrene resin, a block polymer (including a hydrogenated product thereof) containing a polystyrene block and a polybutadiene block is preferable. The fiber 131 may contain one kind of rubber-containing styrene resin, or may contain two or more kinds. The fiber 131 may include a rubber-containing styrene resin (first resin) and another resin (second resin). The second resin is preferably a styrene resin from the viewpoint of high affinity with the rubber-containing styrene resin. If necessary, the fiber 131 may contain various additives.

  The block polymer may be, for example, a diblock body in which a polybutadiene (PB) block and a polystyrene (PS) block are connected, or may be a polyblock body or more in which a PB block and a PS block are alternately connected. Good. The block polymer preferably contains a PS block at least at the end from the viewpoint of ensuring affinity with the styrene resin. The PB block increases the flexibility and elongation of the resulting fiber 131.

  The content of the PB block in the block polymer is, for example, 10 to 50% by mass, preferably 10 to 30% by mass or 15 to 30% by mass, and more preferably 20 to 30% by mass. When the content of the PB block is in such a range, the affinity with the styrene resin is increased, and the homogeneous fibers 131 are easily generated. Further, the obtained fiber 131 has high flexibility and elongation. Further, when the fiber 131 is generated by the electrospinning method, high spinnability is ensured.

  When the fiber 131 includes two or more kinds of rubber-containing styrene resins, examples of the rubber-containing styrene resins include those having different rubber contents and / or block structures.

  As the styrene resin, a polymer different from the above block polymer is used. Examples of the styrene resin include polystyrene (styrene homopolymer), and a copolymer of styrene and another copolymerizable monomer. A styrene resin may be used alone or in combination of two or more. The ratio of the rubber-containing styrene resin to the styrene resin may be adjusted according to the rubber content in the rubber-containing styrene resin, the spinning method, and / or the use.

  The mass ratio of the rubber-containing styrene resin and the styrene resin (= rubber-containing styrene resin: styrene resin) can be selected from 90:10 to 3:97, for example. For example, when the solution spinning method or the electrospinning method is adopted, the mass ratio of the rubber-containing styrene resin and the styrene resin is preferably 70:30 to 3:97, and may be 50:50 to 3:97. In the melt spinning method, the degree of freedom of resin combination, mixing ratio, rubber content and the like can be increased as compared with the solution spinning method and the electrospinning method. For example, the mass ratio of the rubber-containing styrene resin and the styrene resin can be 90:10 to 50:50 or 90:10 to 70:30.

  For example, the average fiber diameter of the fibers 131 is preferably 0.5 to 20 μm, more preferably 1 to 8 μm, and particularly preferably 1.5 to 4 μm.

  The average fiber diameter is an average value of the diameters of the fibers 131. The diameter of the fiber 131 is a diameter of a cross section perpendicular to the length direction of the fiber 131. If such a cross section is not circular, the maximum diameter may be considered as the diameter. Further, the width in the direction perpendicular to the length direction of the fibers 131 when viewed from the normal direction of one main surface of the fiber assembly 130 may be regarded as the fiber diameter. The average fiber diameter is, for example, an average value of the diameters of arbitrary portions of arbitrary 10 fibers included in the fiber assembly 130.

(Welded portion 140, 240)
The welding parts 140 and 240 are formed by thermally welding the fibers 131. Since the fiber aggregate 130 is at least partially fixed to the substrate 110 by the welded portions 140 and 240, the arrangement disorder of the plurality of fibers 131 can be reduced.

The number, position, and shape of the welded portions 140, 240 may be selected according to the usage and application of the culture scaffold 100, the shape of the frame 120, and the like.
The welding parts 140 and 240 should just be formed in at least one place, and may be formed in two or more places.
2 and 3 show a spot shape or a line shape, but the present invention is not limited to these cases, and the welded portions 140 and 240 may be formed in, for example, an arc shape or a ring shape.

  Although the example which formed the welding parts 140 and 240 in the part exposed from the 1st opening 121a of the through-hole 121 of the frame 120 was shown in FIGS. 1-3, it is not restricted to these cases. For example, in FIG. 1, the welded portions 140 and 240 may be formed so as to be hidden by the frame body 120 between the adjacent through holes 121. That is, the welding parts 140 and 240 may not be exposed from the first opening 121a.

  One welded portion 140, 240 may be formed by welding one fiber 131 of the plurality of fibers 131 to the substrate 110. From the viewpoint of easily reducing the disorder of the arrangement of the plurality of fibers 131, as shown in FIGS. 2 and 3, two or more fibers 131 of the plurality of fibers 131 are welded by one welding portion 140,240. The substrate 110 is preferably fixed to the substrate 110. That is, it is preferable that one welded portion 140, 240 is formed so as to intersect (or straddle) two or more fibers 131 among the plurality of fibers 131.

(Substrate 110)
The substrate 110 is not particularly limited and may be appropriately selected depending on the application. Examples of the material of the substrate include glass, quartz, resin, and combinations thereof. The substrate may be a plate shape, a film shape, or a porous shape. Examples of the substrate include a glass plate, a quartz plate, an acrylic plate, a porous substrate (such as a nonwoven fabric), or a combination thereof.

  The board | substrate 110 may be equipped with the electrode as needed. Examples of such electrodes include a plurality of electrodes (first electrodes) insulated from each other. The plurality of first electrodes are arranged so as not to contact the fiber assembly 130. The substrate 110 may further include a plurality of micro electrodes (second electrodes) electrically connected to the first electrode and insulated from each other. The plurality of second electrodes are arranged in contact with at least a part of the fiber assembly 130.

  What is necessary is just to select suitably the kind and size of a 1st electrode and a 2nd electrode, the distance between adjacent electrodes, etc. according to a use, respectively. Examples of the first electrode and the second electrode include an ITO (indium tin oxide) electrode and a platinum electrode.

(Frame)
The frame 120 includes a first surface 120X, a second surface 120Y opposite to the first surface 120X, and one or more through holes 121 penetrating from the first surface 120X to the second surface 120Y. The fiber assembly 130 is disposed on the surface of the first surface 120X so as to cover at least a part of the through hole 121. That is, the fiber assembly 130 (fiber 131) is exposed from the opening (first opening 121a) on the first surface 120X side of the through hole 121.

  When the frame body 120 is mounted on the substrate 110, the first opening 121 a is closed by the substrate 110 via the fiber assembly 130, and a recess is formed on the substrate 110 by the through hole 121. A culture solution containing biological tissue or microorganisms is injected into the recess from the opening (second opening) on the second surface 120Y side of the through hole 121. The injected biological tissue or microorganism grows using the fiber assembly 130 as a scaffold. Since the plurality of fibers 131 constituting the fiber assembly 130 are arranged, a biological tissue or a microorganism can be grown along the length direction of the fibers 131.

  The material of the frame 120 is not particularly limited, and may be made of glass or resin (including elastomer). The size of the frame 120 is not particularly limited as long as the entire first surface 120X can face the substrate 110. When electrodes are arranged on the substrate 110, the size of the frame 120 may be adjusted so as not to hinder the wiring of the electrodes.

  The number of through holes 121 is not particularly limited, and may be set as appropriate according to the size and use of the frame body 120. The shape and size of the first opening 121a and the second opening 121b are not particularly limited, and may be set as appropriate according to the application. The shape and size of the first opening 121a and the second opening 121b may be the same or different. The shape of the depression formed by the through hole 121 is not particularly limited. For example, when both the first opening 121a and the second opening 121b are circular, the shape of the recess may be a cylindrical shape or a mortar shape. From the viewpoint of easily injecting the culture solution, it is preferable that the depression has a mortar shape in which the second opening 121b is larger than the first opening 121a as shown in the drawing.

(Other)
The board | substrate 110, the frame 120, and the fiber assembly 130 may be adhere | attached by the adhesion part as needed. The adhesive part is formed of an adhesive (including an adhesive). Examples of the adhesive include a pressure sensitive adhesive, a hot melt adhesive, and a curable adhesive.

[Method for producing culture scaffold 100]
The culture scaffold 100 according to the present embodiment includes a step of preparing a substrate 110, a step of arranging a fiber assembly 130 including a plurality of arranged fibers 131 on the substrate 110, and a fiber assembly with respect to the substrate 110. A part of the body 130 is welded to form a welded part 140, and the welded part 140 can be manufactured by a manufacturing method including a fiber fixing step of fixing the fiber assembly 130 to the substrate 110. In the culture scaffold 100 obtained by such a manufacturing method, the disorder of the arrangement of the fibers 131 can be reduced.

  The manufacturing method according to the present embodiment further includes a first surface 120X, a second surface 120Y opposite to the first surface 120X, and one or more through holes 121 penetrating from the first surface 120X to the second surface 120Y. And a step of preparing the frame body 120, and by discharging a raw material liquid of the fiber 131 from the nozzle to generate the fiber 131 and depositing the fiber 131 so as to circulate on the peripheral surface of the winding rotary body. It is preferable to include a deposition step for forming the fiber assembly 130 and a transfer step for transferring the fiber assembly 130 to the first surface 120X of the frame body 120 while rotating the winding rotary body. In the step of arranging the fiber assembly 130, the frame body 120 onto which the fiber assembly 130 obtained in the transfer step has been transferred is mounted on the substrate 110 so that the first surface 120X faces the substrate 110. Thus, it is preferable to dispose the fiber assembly 130 on the substrate 110.

  In this method, the fiber 131 is wound by the winding rotary body while spinning the fibers 131, so that the fiber assembly 130 formed on the peripheral surface of the winding rotary body has high alignment in one direction. Then, by transferring the fiber assembly 130 together with the frame body 120 to the substrate 110, the fiber assembly 130 that retains high alignment when wound up by the winding rotary body is replaced with the substrate 110 and the frame body. The fiber assembly 130 having high alignment can be fixed to the substrate 110 in a subsequent welding process.

  Hereinafter, the manufacturing method of this embodiment is demonstrated, referring drawings. Fig.4 (a) is a side view which shows typically the winding rotary body 10 grade | etc., In the deposition process of the manufacturing method which concerns on this embodiment. FIG. 4B is a side view schematically showing the winding rotary body 10, the frame body 120, the fiber assembly 130, and the like in the transfer process of the manufacturing method according to the present embodiment. FIG. 4C is a side view schematically showing the frame body 120, the substrate 110, the fiber assembly 130, and the like in the arrangement step of the fiber assembly 130 of the manufacturing method according to the present embodiment. FIG. 4D is a schematic cross-sectional view schematically showing the frame 120, the substrate 110, the fiber aggregate 130, and the like in the fiber fixing step.

(1) Preparatory process of the board | substrate 110 First, the board | substrate 110 with which the fiber assembly 130 is arrange | positioned is prepared. As shown in FIG. 4C, the substrate 110 includes a mounting surface 110X on which the fiber assembly 130 is disposed (or mounted). When the frame body 120 is used, the frame body 120 is mounted on the mounting surface 110X in a subsequent process.

  In FIG. 4C, an adhesive portion 150 is formed on at least a part of the mounting surface 110X. The adhesion part 150 is formed in a part other than the part facing the first opening 121a of the mounting surface 110X, for example, by printing, a dispenser, or the like. The adhesive portion 150 is not necessarily provided on the mounting surface 110 </ b> X, and may be formed on the fiber assembly 130 or the first surface 120 </ b> X of the frame body 120.

(2) Preparation Step of Frame 120 When using the frame 120, the first surface 120X, the second surface 120Y opposite to the first surface 120X, and the second surface 120Y penetrate from the first surface 120X. A frame body 120 including one or more through holes 121 is prepared.
In the case of forming the adhesive portion on the first surface 120X, the adhesive portion may be formed in accordance with the description of the case of forming it on the mounting surface 110X.

(3) Deposition step (FIG. 4 (a))
The fibers 131 are generated from the raw material liquid 132, and the fibers 131 are deposited while rotating around the circumferential surface of the winding rotary body 10 one or more times. Thereby, the fiber assembly 130 in which the fibers 131 are arranged in one direction is formed on the peripheral surface of the winding rotary body 10.

  When the winding rotary body 10 is not used, the fibers 131 may be deposited by spinning directly on the mounting surface 110X of the substrate 110 and the first surface 120X of the frame body 120. From the viewpoint of obtaining high alignment, it is preferable to use the winding rotary member 10.

  The method (spinning method) for producing the fibers 131 from the raw material liquid 132 is not particularly limited, and may be appropriately selected according to the type of the fibers 131 to be produced. Examples of the spinning method include a solution spinning method, a melt spinning method, and an electrospinning method.

  The solution spinning method is a method in which a solution obtained by dissolving the raw material of the fiber 131 in a solvent is used as the raw material liquid 132. The solution spinning method includes a wet spinning method and a dry spinning method. In the wet spinning method, the raw material liquid 132 is discharged into the coagulating liquid, and the fiber 131 is formed by a chemical reaction between the raw material of the fiber 131 and the coagulating liquid, or by replacing the solvent with the coagulating liquid. In the dry spinning method, the fiber 131 is formed by discharging the raw material liquid 132 into the air and then removing the solvent by heating or the like. The dry spinning method is preferable in that the fibers 131 are easily deposited in a state of being arranged in one direction.

  The melt spinning method is a method in which a melt obtained by heating and melting the raw material of the fiber 131 is used as the raw material liquid 132. The obtained raw material liquid 132 is solidified into a fiber shape by being discharged into the air and then cooled. In this case, normally, a solvent for dissolving the raw material of the fiber 131 is not used. Therefore, the melt spinning method is preferable in that the solvent removal operation can be omitted.

  The electrospinning method is common to the solution spinning method in that a solution obtained by dissolving the raw material of the fiber 131 in a solvent is used as the raw material liquid 132. However, in the electrospinning method, the raw material liquid 132 is discharged into the air while applying a high voltage. It is preferable to volatilize the solvent contained in the raw material liquid 132 in the process until it reaches the peripheral surface of the winding rotary body 10.

  In the electrospinning method, in order to apply a high voltage to the raw material liquid 132, the raw material liquid 132 is charged positively or negatively. At this time, the winding rotary member 10 is grounded or charged to a polarity opposite to that of the raw material liquid 132. Thereby, the discharge end of the raw material liquid 132 discharged in the air is attracted to the winding rotary body 10 and adheres to the peripheral surface. Then, by rotating the winding rotary body 10 while discharging the raw material liquid 132, the fibers 131 are deposited while circling around the circumferential surface of the winding rotary body 10, as in the solution spinning method and the melt spinning method. A fiber assembly 130 including fibers 131 that cover at least a part of the circumferential surface of the winding rotary body 10 and are arranged in one direction is formed.

(Raw material liquid)
The raw material liquid 132 used in the solution spinning method or the electrospinning method includes the raw material of the fiber 131 and a solvent. The raw material liquid 132 used in the melt spinning method includes a raw material of the melted fiber 131. As a raw material, the material which comprises the fiber 131 can be used. The raw material liquid 132 may further contain an additive as necessary.

  The solvent used in the raw material liquid 132 in the solution spinning method or the electrospinning method is not particularly limited as long as it dissolves the raw material of the fiber 131 and can be removed by volatilization or the like, and depends on the type of raw material and the manufacturing conditions. Thus, water and an organic solvent can be appropriately selected and used. As the solvent, an aprotic polar organic solvent is preferable. Examples of such a solvent include amides such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc), and N-methyl-2-pyrrolidone (NMP) (chain or cyclic amide). A sulfoxide such as dimethyl sulfoxide; These solvent may be used individually by 1 type, and may be used in combination of 2 or more type.

  The solid content concentration of the raw material liquid 132 used in the solution spinning method or the electrospinning method can be adjusted according to the type of the solvent, but is, for example, 5 to 50% by mass, even if it is 10 to 30% by mass. Good.

  In the melt spinning method, since the raw material melt of the fiber 131 is used as the raw material liquid 132, it is not necessary to consider the solubility of the raw material in the solvent as in the case of the solution spinning method or the electrospinning method. Therefore, the selection range of the raw material of the fiber 131 is expanded.

(Winding rotary body)
An example of the winding rotary body 10 is shown in FIG. FIG. 5 is a perspective view of the winding rotary body 10.
The configuration of the winding rotary body 10 is not particularly limited as long as it can rotate, and may be a drum shape or a belt stretched by a plurality of rolls. In the latter case, the belt is rotated by rotating at least one roll. Examples of the material of the winding rotary body 10 include metal materials, various resins, various rubbers, ceramics, and combinations thereof. When the winding rotary body 10 is a belt, the belt may be a metal belt or a resin belt. When the fiber 131 is spun by the electrospinning method, the resin belt preferably has conductivity. The outer shape of the winding rotary body 10 may be, for example, a cylinder or a prism.

The fibers 131 are deposited on the circumferential surface of the winding rotator 10 while being arranged in a direction that circulates around the circumferential surface of the winding rotator 10 (hereinafter, array direction D _F ). The arrangement direction _DF is, for example, a direction along the rotation direction of the winding rotator 10 (that is, the direction perpendicular to the rotation axis of the winding rotator 10). The angle θ _F (where θ _F ≦ 90 °) formed by the arrangement direction D _F and the rotation axis may be, for example, 60 ° or more and 90 ° or less. The arrangement direction _DF is the longitudinal direction of the fibers 131 when the fibers 131 are viewed from the normal direction of the peripheral surface of the winding rotary body 10. The longitudinal direction of the fiber 131 may be obtained by taking an approximate straight line of the fiber 131 when viewed from the normal direction of the peripheral surface of the winding rotary body 10. Angle theta _F is the average value of the angle formed between the arrangement direction D _F of a plurality of fibers 131 and the rotary shaft. The arrangement direction _DF of the plurality of fibers 131 deposited on the winding rotary body 10 may be different from each other within the above range.

A plurality of belt-like convex portions 10 </ b> P extending in the direction along the rotation axis of the winding rotator 10 may be disposed on the circumferential surface of the winding rotator 10. Thereby, the aggregate (fiber aggregate 130) of the fibers 131 arranged so as to circulate around the circumferential surface of the winding rotary body 10 is easily peeled off from the winding rotary body 10. As a result, the fiber assembly 130 can be easily transferred to the substrate 110 and the frame body 120 while maintaining the arrangement of the fibers 131. The ends of the plurality of convex portions 10P may be connected by ribs 10R that extend in a direction intersecting the rotation axis.
The material of the convex part 10P is not specifically limited, Various resin materials are mentioned.

  As will be described later, prior to the transfer process of the fiber assembly 130 to the frame body 120 (see FIG. 4B), the fiber assembly 130 is cut in a state of being wound around the winding rotary body 10. In the case where the fiber assembly 130 is cut, the fiber assembly 130 is placed between the protrusions 10P, for example, a planned cutting point C (FIG. 4A) so that at least a part of the cut fiber assembly 130 is in contact with the protrusions 10P. ). Like the example of illustration, you may make the space | interval of the convex parts 10P adjacent to the cutting plan location C smaller than the space | interval of the convex parts 10P of another part.

(4) Heating step A heating step of heating at least one of the fiber assembly 130 and the frame body 120 may be performed after the deposition step and before the transfer step. Since the fiber assembly 130 is heated directly and indirectly through the frame body 120 and is softened by the heating process, the adhesion between the fiber assembly 130 and the frame body 120 is improved.

  The heating method is not particularly limited, but is preferably a non-contact type in that the arrangement of the fibers 131 can be maintained. Examples of the non-contact type heating device include known devices such as a halogen lamp. The heating temperature may be appropriately set in consideration of the softening point or melting point of the fiber 131.

(5) Transfer process (FIG. 4B)
The fiber assembly 130 is transferred to the frame body 120 while rotating the winding rotary body 10.
Prior to the transfer step, the fiber assembly 130 may be cut at the planned cutting position C in a state of being wound around the winding rotary body 10. For example, the planned cutting position C is set according to the shape and size of the frame 120 (or the first opening 121a). The fiber assembly 130 is cut in a direction along the rotation axis of the winding rotary body 10, for example. The fiber assembly 130 is transferred to the frame 120 by using the cut portion as a trigger.

  The frame body 120 is placed on a stage 53 supported by, for example, the XZ stage 52 and is transported. The XZ stage 52 conveys the stage 53, that is, the frame body 120 placed on the stage 53, in a direction perpendicular to the rotation axis of the winding rotary body 10 (X-axis direction) and an up-down direction (Z-axis direction). Can do.

  From the viewpoint of further improving productivity, it is preferable that the transfer process is performed on the plurality of frames 120 collectively or continuously. In this case, the plurality of frame bodies 120 may be arranged on the stage 53 along the Y-axis direction (direction along the rotation axis of the winding rotary body 10), or may be arranged along the X-axis direction. Good. In addition, a transfer process may be performed on an aggregate of a plurality of integrally formed frame bodies 120. In this case, the assembly of the frame bodies 120 is separated into individual frame bodies 120 after the transfer process and before the fiber assembly arrangement process. According to this method, the fiber assembly 130 can be transferred to a plurality of frames 120 at the same time, and most of the fibers 131 accumulated on the winding rotary member 10 are used for transferring the frame 120. , Productivity further improves.

(6) Fiber assembly placement step (FIG. 4C)
The fiber assembly 130 is disposed on the substrate 110 by mounting the frame body 120 onto which the fiber assembly 130 has been transferred, on the substrate 110 so that the first surface 120X is opposed to the frame body 120. At this time, the fiber assembly 130 is interposed between the frame body 120 and the substrate 110. Even when the transfer process is performed on the plurality of frame bodies 120 at once or continuously, one frame body 120 is mounted on one substrate 110.

  When the frame body 120 is not used, the fiber assembly 130 is placed on the substrate 110 by transferring the fiber assembly 130 to the mounting surface 110X of the substrate 110 in the transfer step according to the above case. Is done.

(7) Fiber fixing step (FIG. 4 (d))
After the step of placing the fiber assembly 130 on the substrate 110, a part of the fiber assembly 130 is welded to form the welded portion 140. The fiber assembly 130 is fixed to the substrate 110 by the welded portion 140. The welding is preferably performed by heat welding.

  More specifically, as shown in FIG. 4 (d), heating is performed by bringing a welding instrument 160 into contact with a part of the fiber assembly 130 to melt or soften the fibers 131, while Press against the mounting surface 110X. Thereby, the melted or softened fiber 131 adheres to the mounting surface 110X of the substrate 110, and the welded portions 140 and 240 are formed. And the fiber 131 adhering to the board | substrate 110 solidifies in the welding parts 140 and 240, and the fiber assembly 130 is fixed to the board | substrate 110 via the welding parts 140 and 240. FIG.

  The welding instrument 160 includes a metal member 160a, a heater 160b for heating the metal member 160a, and a silicone rubber portion 160c attached to the tip of the metal member 160a (the contact portion with the fiber assembly 130). The welding instrument 160 is heated by the heater 160b so that the silicone rubber portion 160c reaches a predetermined temperature. By providing the silicone rubber portion 160c at the tip of the metal member 160a, the welding instrument 160 can be brought into contact with the fiber assembly 130 via the silicone rubber portion 160c. Thereby, while being able to contact the welding instrument 160 and the fiber assembly 130 at the time of contact | abutting stably, the releasability at the time of separating the welding instrument 160 from the fiber assembly 130 after welding can be improved.

  For example, when the spot-like welded portion 140 is formed, a welding instrument 160 having a hemisphere or similar shape to the tip end portion (silicone rubber portion 160c in the illustrated example) that contacts the fiber assembly 130 is used. The tip of the welding instrument 160 may be brought into contact with the fiber assembly 130. Using a welding device 160 having a similar shape to this, the tip of the welding device 160 (silicone rubber portion 160c in the illustrated example) is brought into contact with the fiber assembly 130 and moved so as to intersect the arrangement of the fibers 131. A line-shaped weld 240 may be formed. Further, the end of the plate-shaped metal member 160a (or end face) is covered with the silicone rubber portion 160c so that the tip of the welding device 160 crosses the fiber assembly 130 so that it intersects the array of the fibers 131 of the fiber assembly 130. The line-shaped welded portion 240 may be formed by abutting. Thus, what is necessary is just to determine the shape of the welding instrument 160 according to the shape of a welding part.

  In the illustrated example, the silicone rubber portion 160c is provided at the tip of the metal member 160a. However, the silicone rubber portion 160c is not necessarily provided, and the tip of the metal member 160a may be covered with a material other than silicone rubber. Good. As such a material, it is preferable to use a material that can withstand the welding temperature and has flexibility and / or releasability.

  Although the temperature of welding is determined according to the kind of material of the fiber 131 and / or the degree of welding of the fiber 131, etc., it is 70-150 degreeC, for example, and it is good also as 90-130 degreeC.

  The scaffold for culturing according to one embodiment of the present invention is suitable as a substrate for culturing microorganisms or biological tissues or for measuring the potential of microorganisms or biological tissues.

DESCRIPTION OF SYMBOLS 10: Winding rotary body 10P: Convex part 10R: Rib 51: Nozzle 52: XZ stage 53: Stage 100: Culture scaffold 110: Board | substrate 110X: Mounting surface 120: Frame 120X: 1st surface 120Y: 2nd Surface 121: Through hole 121a: 1st opening 121b: 2nd opening 130: Fiber assembly 131: Fiber 132: Raw material liquid 140,240: Welding part 150: Adhesion part 160: Welding instrument 160a: Metal member 160b: Heater 160c: Silicone rubber part

Claims (7)

A substrate, a fiber assembly disposed on the substrate, and a weld portion formed on a part of the fiber assembly,
The said fiber assembly is a scaffold for culture | cultivation containing the arranged some fiber and being fixed on the said board | substrate by the said welding part.   The culture scaffold according to claim 1, wherein the welded portion is formed in a spot shape or a line shape.   The culture scaffold according to claim 1 or 2, wherein the fiber assembly has the plurality of fibers arranged in one direction.   The culture scaffold according to claim 3, wherein, in the plurality of fibers, an average angle at which the fibers intersect is 0 ° or more and 60 ° or less. And a first surface, a second surface opposite to the first surface, and one or more through holes penetrating from the first surface to the second surface. A frame body mounted on the substrate so as to be opposed,
The fiber assembly is interposed between the substrate and the first surface,
At least a part of the fiber assembly is exposed from the first opening formed in the first surface by the through hole,
The culture scaffold according to any one of claims 1 to 4, wherein the welded portion is exposed from the first opening. Preparing a substrate;
Disposing a fiber assembly including a plurality of arranged fibers on the substrate;
A step of welding a part of the fiber assembly to the substrate to form a welded portion, and a fiber fixing step of fixing the fiber assembly to the substrate by the welded portion. Production method. further,
Preparing a frame including a first surface, a second surface opposite to the first surface, and one or more through holes penetrating from the first surface to the second surface;
A deposition step of forming a fiber assembly by discharging a fiber raw material liquid from a nozzle to generate the fiber, and depositing the fiber so as to circulate on a peripheral surface of a winding rotary body,
A transfer step of transferring the fiber assembly to the first surface of the frame while rotating the winding rotary body,
In the step of arranging the fiber assembly, the frame body onto which the fiber assembly obtained in the transfer step is transferred is mounted on the substrate such that the first surface faces the substrate. The manufacturing method of the scaffold for culture | cultivation of Claim 6 which arrange | positions the said fiber assembly on the said board | substrate by.

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