JP4880381B2 - Microscope cover film and method for producing the same - Google Patents

Description

  The present invention relates to a microscope cover film suitable for automatic encapsulation and a method for manufacturing the same.

  Transmission illumination optical microscopes (hereinafter referred to as “microscopes”) are used in various fields. For example, in the case of cytology or histology in the medical industry, a cell as a sample is placed on a slide glass that is a sample holding member, and is covered with a cover glass that is a transparent member for protection. The sample with the cover glass overlapped is observed with a microscope as a specimen. In recent years, preparation of specimens has been automated in order to respond to high-speed processing such as cytodiagnosis. Automation of specimen preparation is realized by overlaying a cover glass coated with an adhesive and a glass slide on which a few drops of an organic solvent that swells or dissolves the adhesive is dropped. This superposition is called “encapsulation”.

  Furthermore, a polymer film such as cellulose triacetate has come to be used as a protective transparent member in place of the above cover glass. A film in which an adhesive is applied to this polymer film is called a cover film. The polymer film is rich in flexibility as compared with the cover glass, and the polymer film is curled to the side where the adhesive is applied by utilizing the shrinkage force of the applied adhesive. At the time of encapsulation, the curl of the polymer film is used to closely contact the slide glass. Thereby, it can prevent that a bubble mixes between a cover film and a slide glass.

  However, while polymer cover films have many advantages, several problems have also emerged. For example, the thickness of a normal polymer film is 0.1 mm, and even if the thickness of the adhesive is added to the thickness, the thickness is only about 0.12 mm, which is larger than the standard thickness of 0.17 mm for the cover glass. It gets smaller. For this reason, the spherical aberration due to the objective lens of the microscope cannot be sufficiently corrected, and defocusing occurs. The spherical aberration referred to here is a phenomenon in which light passing near the center of the spherical surface of the objective lens and light passing through the peripheral edge thereof are not collected at one point on the optical axis.

In response to this problem, the invention described in Patent Document 1 eliminates out-of-focus blur by adjusting the numerical aperture and magnification of the objective lens. The inventions of Patent Documents 2 to 4 attempt to solve the problem caused by the cover film adhesive such as blocking that causes the films to adhere to each other when the cover film is stored in a roll.
JP 2001-242384 A JP-A-62-38408 JP-A-1-203940 JP 11-101943 A

  However, the invention described in Patent Document 1 requires the use of a correction objective lens when using a microscope. This type of correction objective lens is expensive and requires a correction operation, so that improvement has been desired.

  Also, the problem of defocusing is solved by bringing the thickness of the polymer film closer to the thickness of the cover glass. However, increasing the thickness of the polymer film improves its rigidity and makes it difficult for the polymer film to curl on the adhesive side. Become. By making it difficult to curl, the adhesion between the cover film and the slide glass is weakened, and bubbles are easily mixed. When bubbles enter, film peeling occurs from the bubble components, which causes a problem in specimen storage.

  SUMMARY OF THE INVENTION An object of the present invention is to provide a microscope cover film that can eliminate out-of-focus blur without changing the setting of an optical system of a microscope and can be brought into close contact with a slide glass, and a method for manufacturing the same.

  In order to solve the above problems, the present invention comprises a transparent support and an adhesive layer formed on the transparent support, and is placed so as to cover a specimen on a slide glass, In the cover film for a microscope which is fixed to the slide glass by swelling or dissolving an adhesive layer, the transparent support is a cellulose acylate having a thickness of 110 μm or more and 130 μm or less, and the cellulose acylate includes a plasticizer. 14 wt% or more and 16 wt% or less is added, and the adhesive layer is formed so that the total thickness after drying with the addition of the transparent support is 130 μm or more and 170 μm or less, and when the adhesive layer is dried A toy curl is imparted by contraction, and the toy curl is fixed to the slide glass when the adhesive layer of the encapsulating liquid is used. Characterized in that it is a curl amount exceeding reverse curl amount generated by Jun or dissolved.

  The curl amount exceeding the reverse curl amount is preferably a curl amount having a maximum height of 1 mm to 10 mm when a rectangular sample of 45 mm × 300 mm is placed on a flat surface. When the adhesive layer is formed by applying the adhesive layer to the transparent support, the viscosity of the adhesive is 85 cp or more and 115 cp or less. It is preferable to dry the adhesive layer.

  The method for producing a cover film for a microscope according to the present invention uses a cellulose acylate having a plasticizer added in an amount of 14% by weight or more and 16% by weight or less and having a thickness of 110 μm or more and 130 μm or less as the transparent support. The step of coating and forming the adhesive layer on one surface of the transparent support so that the total thickness after drying is 130 μm or more and 170 μm or less, and the drying temperature after coating the adhesive layer is 100 ° C. or more and 150 ° C. The adhesive layer is dried within 5 seconds at a temperature of ℃ or less, and a toy curl is imparted by the adhesive layer. When the toy curl is fixed to the slide glass, The amount of curl is greater than the amount of reverse curl generated by swelling or dissolution of the adhesive layer by the sealing liquid.

  The toy curl preferably has a curl amount such that the maximum height when a 45 mm × 300 mm rectangular sample is placed on a flat surface is 1 mm or more and 10 mm or less. It is preferable that the viscosity of the adhesive in the step of applying and forming the adhesive layer is 85 cp or more and 115 cp or less.

  According to the present invention, the transparent support and the adhesive layer formed on the transparent support are placed so as to cover the specimen on the slide glass, and the adhesive layer is swollen or filled with the sealing liquid. In the microscope cover film which is dissolved and fixed to the slide glass, the transparent support is cellulose acylate having a thickness of 110 μm or more and 130 μm or less, and the cellulose acylate contains a plasticizer of 14% by weight or more and 16% by weight. The adhesive layer is formed so that the total thickness after drying with the addition of the transparent support is 130 μm or more and 170 μm or less, and the toy curl is formed by shrinkage when the adhesive layer is dried. When the toy curl is fixed to the slide glass, the toy curl is caused by swelling or dissolution of the adhesive layer by the sealing liquid. By a curl amount in excess of the reverse curling amount of raw, as well as eliminate the defocusing, it is possible to close contact with the slide glass without mixing air bubbles at the time of inclusion.

  As shown in FIG. 1, a microscope cover film 10 of the present invention (hereinafter simply referred to as “cover film”) includes a triacetyl cellulose film 11 (hereinafter referred to as “TAC film”) which is a transparent support, and the TAC film 11. It consists of the adhesive layer 12 formed on top. In addition, about a transparent support body, it is not necessary to limit only to a TAC film, and a transparent and flexible polymer film is used. In particular, a cellulose acetate film is preferably used.

  The TAC film 11 is manufactured by a known solution casting method. The solution casting method comprises a dope preparation process and a film manufacturing process. In the dope preparation process, polymer triacetyl cellulose is dissolved in a solvent, and a dope is prepared by adding a plasticizer or the like, and in the film manufacturing process, the dope is cast on a traveling endless support to cast a film. The cast film is peeled off from the support to obtain a wet film, and the wet film is stretched and dried to obtain the TAC film 11.

  As shown in FIG. 2, the thickness T1 of the manufactured TAC film 11 is preferably 110 μm or more and 130 μm or less. If it is less than 110 μm, as described above, the spherical aberration cannot be sufficiently corrected, and defocusing occurs. On the other hand, by setting the thickness T1 to 110 μm or more, it is possible to eliminate defocusing, but the rigidity of the TAC film 11 is improved and curling is difficult. Therefore, the amount of plasticizer added to the dope in the dope preparation process is increased from 14% by weight to 15% by weight to make it easy to curl. The weight% here refers to the weight percentage with respect to TAC. In addition, it is preferable that the addition amount of a plasticizer is 14 to 16 weight%, and it is more preferable that it is 14.5 to 15.5 weight%. Examples of the plasticizer include triphenyl phosphate and diphenyl phosphate.

  The adhesive of the adhesive layer 12 is preferably a polymer adhesive having a glass transition temperature of 50 ° C. Examples of the polymer adhesive include acrylic adhesives and polyester adhesives. Use Aron S-1017 and Aron S-1030C (both manufactured by Toagosei Chemical Industry Co., Ltd.) for acrylic adhesives, and Byron 200 (manufactured by Toyobo Co., Ltd.) for polyester adhesives. Is preferred. The thickness T2 of the adhesive layer 12 is preferably 10 μm or more and 30 μm or less. The total thickness T3 obtained by adding the thickness T1 of the TAC film 11 to the thickness T2 of the adhesive layer 12, that is, the thickness T3 of the cover film is preferably 130 μm or more and 170 μm or less.

  The viscosity of the adhesive is preferably 85 cp or more and 115 cp or less, and more preferably 100 cp or more and 115 cp or less. When it is less than 85 cp, when the adhesive swells or dissolves in the sealing liquid described later, the shrinkage force of the TAC film 11 caused by the adhesive is reduced, and the cover film 10 is difficult to curl. The adhesion between the cover film 10 and the slide glass 13 (see FIG. 3) is weakened. For this reason, a gap is formed between the side edge of the cover film 10 and the slide glass 13, and bubbles are mixed.

  As shown in FIG. 3, the cover film 10 is placed by an automatic enclosing machine (not shown) on a slide glass 13 on which a subject (not shown) is placed and a few drops of a sealing solution for swelling or dissolving the adhesive is dropped. , Automatically superimposed. The filling liquid is preferably an organic solvent, for example, xylene.

  As shown in FIG. 4, the degree of curl of the cover film 10 is represented by the height H of the sample 14 of the cover film 10 from the flat surface. This degree of curling is called the toy curl amount. Sample 14 is obtained by cutting an original film obtained by applying an adhesive layer 12 to a TAC film 11 with a length L of 300 mm and a width of 45 mm in the casting direction. Curling to the adhesive layer 12 side is called plus curl, and curling to the side opposite to the adhesive layer 12 side is called minus curl. Hereinafter, the difference between when the cover film 10 is curled and when it is not curled will be described with reference to FIGS. 5 and 6.

  FIG. 5 (A) shows a state before the cover film 16 that has been subjected to a plus curl to some extent is placed on the slide glass 13 on which the subject is placed and the sealing liquid 15 is dripped, and FIG. The state where the cover film 16 is superimposed on the slide glass 13 is shown. On the other hand, FIG. 6 (A) shows a state before the uncurled cover film 17 is superimposed on the slide glass 13 on which the subject is placed and the sealing liquid 15 is dropped, and (B) is The cover film 17 is shown superimposed on the slide glass.

  As shown in FIG. 5 (B), the cover film 16 that has been slightly curled to some extent is in intimate contact with the slide glass 13. However, as shown in FIG. The adhesive curls due to shrinkage when it swells or dissolves. Therefore, the side edge part of the cover film 16 floats and air bubbles are mixed between the side edge part and the slide glass 13. Therefore, in order to bring the cover film 10 and the slide glass 13 into close contact with each other, the cover film 10 is preliminarily applied to the cover film 10 in anticipation of the negative curl so that the cover film 10 does not negatively curl when the sealing liquid 15 is contracted. Leave a little plus curl. The amount of toy curl at this time is preferably 1 mm or more and 10 mm or less. By using the cover film 10 having a toy curl amount in this range, even if the cover film 10 is negatively curled due to swelling or dissolution of the adhesive at the time of sealing, the cover film as a whole can be held in the positive curl and air bubbles are mixed in. Can be prevented.

  As shown in FIG. 7, the cover film production line 20 for producing the cover film 10 includes a coating device 21, a blower device 22, and a winding device 23. The roll-shaped TAC film 11 is sent to a coating device 21, and the coating device 21 applies an adhesive to one surface of the TAC film 11 to form an adhesive layer 12. The thickness of the TAC film is preferably 110 μm or more and 130 μm or less. The viscosity of the adhesive is preferably 85 cp or more and 115 cp or less. The thickness of the adhesive layer is preferably such that the total thickness including the thickness of the TAC film is 130 μm or more and 170 μm or less. The cover film 10 on which the adhesive layer 12 is formed exits the coating device 21 and is conveyed to the winding device 23 by the pass roller 25.

  During the conveyance by the pass roller 25, the drying air 27 is sent from the blower 22 to the cover film 10. The temperature at which the cover film 10 is dried by the drying air 27 is preferably 100 ° C. or higher and 150 ° C. or lower, and more preferably 105 ° C. or higher and 130 ° C. or lower. This temperature is set higher than the conventional drying temperature, and by raising the temperature, the evaporation of the solvent in the adhesive is activated, and the cover film 10 is positively curled. The toy curl amount of the cover film 10 is preferably 1 mm or more and 10 mm or less. The drying time by the drying air 27 is preferably 1 second or longer and 10 seconds or shorter, more preferably 5 seconds or longer and 8 seconds or shorter after the cover film 10 leaves the coating device 21. In addition, although drying after application | coating was performed with the drying wind from the air blower 22, it does not need to restrict to this.

  Hereinafter, the present invention will be specifically described with reference to examples. In addition, this invention is not limited to a following example.

In Examples 1 to 3 and Comparative Examples 1 to 3, the following five conditions were changed.
T1; TAC film 11 thickness (μm)
P1: Amount of plasticizer added (weight percent with respect to TAC film)
D1: Drying temperature after application of adhesive (° C)
DT1: Drying time after application by drying air 27 (seconds)
V1: Viscosity of adhesive at the time of adhesive application (cp)
In each example, whether or not bubbles are mixed between the side edge of the cover film 10 and the slide glass 13 after sealing (“bubbles” in Table 1 below) and whether or not defocusing occurs ( In Table 1 below, “Focus”) was evaluated. The thickness of the adhesive layer was 19 μm. The adhesive was a solution of Aron S-1030C dissolved in a 4: 6 (volume ratio) mixed solvent of ethyl acetate and toluene. This adhesive was applied to TAC film 11 at 190 g / m ² . At this time, the coating amount of toluene was 86 g / m ² , and the coating amount of ethyl acetate was 58 g / m ² . Xylene was used as the sealing liquid. The viscosity of the adhesive was measured using a Brookfield analog clay meter manufactured by Brookfield.

  Table 1 shows the conditions in each example and the results of that example. In the “bubble” column, “◯” indicates that bubbles are not mixed, and “x” indicates that bubbles are mixed. In the “focus” column, ○ indicates that no out-of-focus has occurred, and x indicates that out-of-focus has occurred.

It is a perspective view of a cover film. It is sectional drawing of a cover film. It is a perspective view which shows the state with which the cover film was piled up on the slide glass. It is a perspective view which shows the sample of a cover film. (A) It is explanatory drawing which shows the state before superimposing the cover film which carried out the plus curl to some extent on a slide glass, and (B). (A) It is explanatory drawing which shows the state before superimposing the cover film which is not curled on a slide glass, (B) is the state on which they were superimposed. It is the schematic which shows a cover film manufacturing line.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Cover film 11 TAC film 12 Adhesive layer 13 Slide glass 14 Sample 15 Filling liquid 16 Cover film 17 Cover film 20 Cover film production line 21 Coating apparatus 22 Blower 27 Drying air

Claims (6)

The slide glass comprises a transparent support and an adhesive layer formed on the transparent support, and is placed so as to cover the specimen on the slide glass, and the adhesive layer is swollen or dissolved by an encapsulating liquid. In the microscope cover film fixed to
The transparent support is a cellulose acylate having a thickness of 110 μm or more and 130 μm or less, and a plasticizer is added to the cellulose acylate by 14 wt% or more and 16 wt% or less,
The adhesive layer is formed so that the total thickness after drying with the addition of the transparent support is 130 μm or more and 170 μm or less,
A toy curl is imparted by shrinkage during drying of the adhesive layer, and the toy curl is generated by swelling or dissolution of the adhesive layer by the sealing liquid when being fixed to the slide glass. A microscope cover film characterized by having a curl amount exceeding a reverse curl amount.   2. The curl amount exceeding the reverse curl amount is a curl amount having a maximum height of 1 mm or more and 10 mm or less when a rectangular sample of 45 mm × 300 mm is placed on a flat surface. Cover film for microscope.   When the adhesive layer is formed by applying the adhesive layer to the transparent support, the viscosity of the adhesive is 85 cp or more and 115 cp or less, and after the application of the adhesive layer, the drying temperature is 100 ° C. or more and 150 ° C. or less within 5 seconds. 3. The cover film for a microscope according to claim 1, wherein the adhesive layer is dried. The slide glass comprises a transparent support and an adhesive layer formed on the transparent support, and is placed so as to cover the specimen on the slide glass, and the adhesive layer is swollen or dissolved by an encapsulating liquid. In the manufacturing method of the cover film for microscopes to be fixed to
A cellulose acylate having a plasticizer added of 14 wt% or more and 16 wt% or less and having a thickness of 110 μm or more and 130 μm or less is used as the transparent support, and the total thickness after drying with the addition of the transparent support is 130 μm or more and 170 μm or less. Applying and forming the adhesive layer on one surface of the transparent support so that
A drying step of drying the adhesive layer within 5 seconds with a drying temperature of 100 ° C. or higher and 150 ° C. or lower after applying the adhesive layer, and providing a toy curl with the adhesive layer;
The toy curl has a curl amount exceeding a reverse curl amount generated by swelling or dissolution of the adhesive layer by the sealing liquid when being fixed to the slide glass. Manufacturing method.   5. The microscope cover film according to claim 4, wherein the toy curl has a curl amount with a maximum height of 1 mm to 10 mm when a rectangular sample of 45 mm × 300 mm is placed on a flat surface. Production method.   6. The method for producing a microscope cover film according to claim 4, wherein the adhesive has a viscosity of 85 cp to 115 cp in the step of applying and forming the adhesive layer.

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