Specimen slide and method for producing a specimen slide

Abstract

To provide an improved system and method for coverslipping a pathology sample.SOLUTION: Automated coverslipping is simplified by reducing or eliminating xylene and other toxic solvents, reducing the number of mechanical manipulations and eliminating the dispensing of liquid mounting agents and coverslipping manipulations, improving the reliability of automated coverslipping of coverslipped slides by reducing or eliminating smearing or coating of slide edges with mounting agents, improving processing speed by eliminating the need for solvent drying prior to handling, and accelerating IHC processing by allowing or enabling the use of aqueous wet samples.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to the preparation of slides for analysis, and more particularly to the preparation of samples on slides. Mounting and coverslipping are also involved.

[0002] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application is a continuation of U.S. Provisional Patent Application No. 63 / 038,264, filed June 12, 2020. The benefit of this application is claimed and is incorporated herein in its entirety. [Background technology]

[0003] Preparation of tissue samples for histological analysis generally involves several steps (e.g., Fixation of the sample (e.g., using formalin), embedding the sample in paraffin, The embedded samples were sectioned using a microtome and the tissue sections were mounted on slides. The paraffin is then removed, usually by treatment with a solvent, and the tissue specimen is The material may be treated with dyes, stains, or other reagents. After such treatment, the material is usually mounted. A liquid is applied to the sample and a coverslip is applied to the sample and slide. A mountant is deposited on the sample, a coverslip is applied, and then The solvent is dried.

[0004] Tissue slides are typically prepared using either xylene-based or aqueous-based methods. Xylene-based methods are used to mount coverslips. Clinical pathologists have been increasingly interested in MRI-based methods because they are considered more reliable and durable than MRI-based methods. generally prefer xylene-based methods.

[0005] Mounting media can serve one or more purposes in preparing coverslipped specimens. The mounting agent helps to hold the sample in place during imaging and may prevent the sample from drying out. It is desirable for the mounting medium to have a refractive index that is desired for the objective lens used for imaging. It may also help preserve samples over time for long-term storage. Exemplary mounting media include: Dako Mounting Medium manufactured by Agilent Technologies, Inc. Ako Mounting Medium contains toluene and xylene. Designed for use with automated glass coverslippers It is a low viscosity, fast drying encapsulant.

[0006] The method of coverslipping using liquid mounting media has several drawbacks. Yes, the mounting medium may coat the edges of the slides and interfere with automated handling. Dispensing some mountants requires fluid handling of viscous materials, which can clog piping. This can leave a residual chemical film on the instrument. Cover guards manually loaded by the user The glass may become clogged or break, causing interruptions to the process. If there is too little, voids or bubbles may remain, and if there is too much, it may leak out from the sides. This is very important and requires a long drying step after application.

[0007] An alternative method for coverslipping is to use cellulose acetate coated with mounting medium. Use tape (Sakura Tissue Tek, Sakura Finetek Japan Co., Ltd. Tokyo, Japan). However, this tape is activated using xylene.

[0008] The use of xylene is prohibited by many existing regulations, as xylene is considered toxic and flammable. This is a significant drawback to most coverslipping techniques. - Coverslipping instrumentation is carried out in a ventilated chemical safety hood. This increases complexity and operational costs. Xylene has been designated as a potential carcinogen by the European Union and is used in various Eliminating xylene from the coverslipping process is recommended because it is not recommended by certain authorities. It is hoped that this will happen.

[0009] Another drawback of some existing methods is that they do not tolerate the presence of water in coverslip samples. However, some techniques such as immunohistochemistry (IHC) In some specimen processing, the final staining step is aqueous, so the samples should be prepared before coverslipping. The specimen must be dehydrated with a solvent. If the cover slip mounting technique allows for specimens in water, Advantageously, this step can be eliminated or automated.

[0010] Some existing aqueous coverslip mounting methods do not fix the coverslip to the slide. (requiring an additional adhesive step), the sample dries out within a few days and is not suitable for long-term storage. For these reasons, it is considered unreliable for clinical use. Summary of the Invention [Problem to be solved by the invention]

[0011] The present disclosure provides improved systems and methods for coverslipping pathology specimens. . [Means for solving the problem]

[0012] The present system and method may provide one or more advantages over existing systems and methods. The advantages include, for example, the reduction or elimination of xylene and other toxic solvents and mechanical Reduces the number of manipulations, eliminating dispensing of liquid mountant and handling of coverslips This simplifies automated coverslipping and prevents contamination of the mounting medium on the slide edges. Automated cover slipping of slides by reducing or eliminating damage or coating. Improved handling reliability and elimination of the need for solvent drying before handling This improves processing speed and allows or enables the use of aqueous wet samples. and accelerating IHC processing by using a chromatographic method.

[0013] In some embodiments of the method, the adhesive penetrates and / or bonds to the sample (i.e., permeation and / or binding), thereby providing longer storage stability . [Brief explanation of the drawings]

[0014] [Figure 1] 1A-1D illustrate an exemplary embodiment of a coverslipping system and process. [Figure 2] FIG. 1 illustrates one embodiment of a slide carrier. [Figure 3A] 1A-1C illustrate an exemplary embodiment of a slide carrier module. [Figure 3B] 1A-1C illustrate an exemplary embodiment of a slide carrier module. [Figure 4A] 1A-1D illustrate views and aspects of an exemplary embodiment of a coverslipping module. [Figure 4B] 1A-1D illustrate views and aspects of an exemplary embodiment of a coverslipping module. [Figure 4C] 1A-1D illustrate views and aspects of an exemplary embodiment of a coverslipping module. [Figure 4D] 1A-1D illustrate views and aspects of an exemplary embodiment of a coverslipping module. [Figure 4E] 1A-1D illustrate views and aspects of an exemplary embodiment of a coverslipping module. [Figure 5] FIG. 1 illustrates an exemplary embodiment of a solvent exchange module. [Figure 6] FIG. 1 illustrates another exemplary embodiment of a solvent exchange module. [Figure 7A] FIG. 1 illustrates another exemplary embodiment of a solvent exchange module. [Figure 7B] FIG. 1 illustrates another exemplary embodiment of a solvent exchange module. [Figure 8] FIG. 1 illustrates an exemplary embodiment of a coverslip mounting protocol. [Figure 9] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 10] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 11A] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 11B] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 12] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 13] 1A-1C illustrate exemplary embodiments of cover glass strips and dispensers. [Figure 14] FIG. 1 illustrates an exemplary embodiment of a system architecture for the coverglass mounting system described herein. [Figure 15] FIG. 1 illustrates an exemplary embodiment of a system architecture for the coverglass mounting system described herein. [Figure 16] FIG. 1 shows an image of a coverslip-mounted specimen on a slide as described herein. [Figure 17] FIG. 1 shows an image of a coverslip-mounted specimen on a slide as described herein. [Figure 18] FIG. 1 shows an image of a coverslip-mounted specimen on a slide as described herein. [Figure 19A] FIG. 1 shows an image of a coverslip-mounted specimen on a slide as described herein. [Figure 19B] FIG. 1 shows an image of a coverslip-mounted specimen on a slide as described herein. [Figure 20] FIG. 1 illustrates another exemplary embodiment of a solvent exchange module. [Figure 21A] FIG. 1 shows one embodiment of a capillary head for solvent exchange. [Figure 21B] FIG. 1 shows one embodiment of a capillary head for solvent exchange. [Figure 21C] FIG. 1 shows one embodiment of a capillary head for solvent exchange. [Figure 21D] FIG. 1 shows one embodiment of a capillary head for solvent exchange. [Figure 22] FIG. 1 illustrates one embodiment of a method for using a capillary head for solvent exchange. [Figure 23] 10A-10C show images and heat map analysis of unstained tissue sections processed using an embodiment of the device. [Figure 24] FIG. 1 shows images of specimens processed as described in Example 9. DETAILED DESCRIPTION OF THE INVENTION

[0015] Before describing various embodiments, it is to be understood that the teachings of the present disclosure are limited to the specific embodiments described. It is understood that the term is not limited to the above. All technical and scientific terms are commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications referenced herein are incorporated by reference in their entirety. and is hereby expressly incorporated by reference in its entirety.

[0016] As used herein, the terms "approximately" and "about" The term "amount" means, in addition to its ordinary meaning, a limit or amount that is acceptable to a person skilled in the art. The term "about" generally refers to ±15% of the indicated number. For example, "about 10 " can indicate a range of 8.5 to 11.5. For example, "almost the same" means that a person skilled in the art would means that the compared items are considered to be the same. The terms include the numbers defining the range. The terms "value" and "values" are interchangeable. Each subrange between any stated value or values ​​within a stated range is also intended to be disclosed. Where a stated range is inclusive of any limit, ranges excluding either or both of those included limits are also included herein. Included in the disclosure.

[0017] As used herein, the terms "a," "an," and "the" shall mean any combination of the terms "a," "an," and "the" that is appropriate to the context. Therefore, unless otherwise specified, both singular and plural referents are included. For example, "a fluid" includes one fluid and multiple fluids. The terms "second," "third," and other ordinal numbers are used herein to refer to the present system and It is used to distinguish between different elements of the method and is not intended to impose numerical limitations. When referring to a first layer and a second layer, it is meant that the component has only two layers. A component having a first element and a second element should not be construed as being a single element unless otherwise indicated. It may also include a third element, a fourth element, a fifth element (and so on), unless otherwise specified.

[0018] Generally, it is understood that the drawings and the various elements shown therein are not drawn to scale. Furthermore, "upper", "lower", "top", "bottom", "upper side", "lower", "left", Relative terms such as "right," "vertical," and "horizontal" are used in various contexts as may be shown in the accompanying drawings. These relative terms are used to describe the relationship of elements to one another. In addition to the orientation shown, the device and / or element (i.e., the device or element or both) It is understood that the present invention is intended to encompass different orientations (e.g., capillary treatment model). If a module is inverted relative to the perspective of the drawing, for example, it may be described as "above" another element. Similarly, if the device is 90 degrees to the viewpoint of the drawing, the element "below" it will be considered "below" the device. For example, an element described as "vertical" would become "horizontal" if rotated by 10 degrees. .

[0019] As used herein, a "slide" refers to a biological or chemical sample. Any sample holder, support or substrate having at least one substantially flat surface for A slide is a carrier capable of supporting at least one sample, a microscope slide, a specimen, or a The slide may be a test tube, a chip, an array, or a disc. The slide is usually the first main slide. The major slide surface typically has a major axis and a minor axis, e.g. It has a rectangular major axis and a minor axis.

[0020] The sample can be disposed on the slide in a variety of ways. In some embodiments, the sample A sample is a biological sample such as a layer or slice of tissue or cells. Often the sample is a histological specimen. tissue sections or cell smears or pellets for analysis. The tissue can be preserved in an embedding medium such as paraffin or aldehyde. The sample in the embedding medium may be subjected to steps such as deparaffinization. and thereby covering and / or infiltrating (i.e., covering or wetting) the sample. The paraffin or other embedding medium (or both) is removed.

[0021] The method and system of the present invention can use a cover glass, such as a cover glass tape. This tape is the coverslip for the sample. In this case, the term "tape" includes tapes, strips, bands, patches, and other comparable As an adhesive for attaching a cover glass to a tissue section, It is desirable for the adhesive to provide a sufficiently strong bond to the specimen and slide.

[0022] As used herein, "automatic" or "automated" refers to a mechanical device. devices, computers, and / or electronic controls (i.e., mechanical devices, computers, or Multiple stages substantially performed by (electronic control or all of them) or signals Although this refers to a step-by-step process, some modifications may be possible, such as manually replacing one of the features or steps described. As used herein, automated coverage does not exclude a step of human intervention. The glass mounting system also includes an automated solvent exchange system or may include other automated devices.

[0023] Description of the illustrated embodiment The present disclosure provides improved methods and systems for preparing coated specimen slides.

[0024] In some embodiments, the coverslip tape is provided on a first reel. The cover glass tape is wound from the first reel to the cover glass. The cover glass extends across the glass mounting area to a second reel or is unwound. The tape is applied to the area of ​​the slide after the first piece of cover glass tape has been applied (the first (by unwinding a portion from one reel and winding a portion onto a second reel, etc.) The cover glass can then be advanced across the area where the cover glass is attached. A second section of tape can be positioned on the next slide.

[0025] In some embodiments, the present disclosure provides a slide carrier module comprising the following components: module 200, an optional solvent exchange module 500, and a cover glass tape or other cover glass. Dispense a glass burr and apply it to the specimen and slide, pressing it firmly into place A coverslipping system (100) comprising a coverslipping module (400). do.

[0026] An exemplary general process for coverslipping slides is shown in FIG. In the setup sub-process or area, the user slides the slide 10 on which the sample is placed. The user provides the slide 10 in the slide carrier 20. The slide carrier 20 can then be immersed in a solvent tank 30. The sample 12 is disposed on the slide 10. The slide 10 includes a sample area 14 and a slide It may contain a bar code 16. In one embodiment, the solvent tank contains an input solvent that is water. An example of a slide carrier is shown in FIG. 2. The slide carrier 20 is a solvent tank. The slide carrier handle 21 is integral with the slide carrier 20. The slide carrier 20 may be integrated into the slide holder 22 or may lock on and off the slide carrier 20. The slide carrier handle 21 is used for immersion of the slide carrier 20 in the solvent tank and for removing the solvent from the solvent tank. The slide carrier handle 21 facilitates removal of the slide carrier 20 from the The slide carrier may include a flange 22, which may be configured to move the slide carrier. The slide 10 can be engaged by a robot arm. Solvents are used for one or more purposes, such as to remove the solvent or to apply fresh solvent to the sample. In some embodiments, the solvent tank 30 may be used as an encapsulant. In another embodiment, the solvent tank 30 contains an assay solvent. The input solvent may be for purposes other than mounting, such as water or solvent, and the input solvent may then be pre-wetted. After a desired period of time, the slide carrier 20 is returned to the solvent tank. 30, placed in the slide carrier module 200, and coverslipped. During the setup, the user can also select the cover glass to be applied to the slide 10. Enter the protocol for mounting the coverslip, including the length of the tape. Figures 3A and 3B show the procedure. B shows the slide carrier 20 being removed from the solvent tank by the slide carrier module 200. The slides 10 are then removed and transferred sequentially to the cover slip mounting module 400. The slide 10 is held vertically within the slide carrier module 200. The slide remover engages with the short side of the single slide 10 and pushes the slide 10 upward. The size is such that it can be lifted up and removed from the slide carrier 20. One or more of the parts may be automated rather than performed by a user. will be understood.

[0027] In the coverslipping subprocess or area, the slide 10 is mounted on a slide carrier. 20 and transferred to a support for processing. The support is then transferred to a solvent exchange module and / or the coverslipping module (i.e., the solvent exchange module or the coverslipper) the mounting module, or both), which are described in more detail below. In some embodiments, the slide 10 has a cover slip tape applied. In other embodiments, the slide 10 is already subjected to solvent exchange before cover slipping. After the coverslip is applied to the slide, the coverslip mounting slide The slide carrier 20 (either the same slide carrier as before or a different slide carrier) One or more of the above parts of the procedure may be automated. It will be appreciated that this may be done by the user or by the user.

[0028] 4A-4E illustrate an exemplary embodiment of a coverslipping module 400. The slides are then loaded into the coverslipper module 400 as shown in Figures 4 and 5A. The slide is positioned on a slide mount table 402. Generally, the slide has a major axis extending along the , the direction in which the slide mount table 402 moves, and / or the cover glass tape disc The direction in which the spacer moves relative to the slide mount table (i.e., the slide mount The direction in which the table 402 moves or the cover glass tape dispenser slides the direction of movement relative to the table (or both) The slide mount table 402 can be moved manually or automatically. For example, the slide mount table 402 can be attached to a linear stage 403. The linear stage 403 provides automated linear motion. In this position, the slide is oriented with its long axis facing the direction in which the cover slip tape unwinds from the reel. The cover glass mounting module 400 is positioned to align the cover glass tray. a cover glass tape dispenser assembly 404, The assembly 404 includes a reel 406 on which a supply of cover glass tape is wound. The release liner motor drives the release liner on the release liner assembly 408. The liner is rolled to secure the source tape 410 in the source tape assembly 416 to the cover tape. The release liner 412 is drawn through the tape dispenser assembly 418. The separated material is separated from the peeled tape 414 passing through the slot 420 and over the extrusion guide 422. When the peeled tape triggers the position sensor 424, the release liner motor stops. Stop.

[0029] In some embodiments, the system applies pressure to the cover glass tape on the slide. The laminator assembly 430 is provided for laminating the , desired or predetermined pressure and / or velocity (i.e., pressure or velocity or both) The laminator roller 434 may include a laminator roller 434 that rolls the cover glass tape horizontally. The laminator assembly 430 also mounts the laminator roller 434 to the slide-mount table 402. and / or pressure applied to the cover glass tape 414 To increase or decrease the laminator roller 434 (i.e., to move the laminator roller 434 to the slide mount table), pressure applied to the cover glass tape 414 to move it vertically relative to the tape 402 laminator actuator 432 (for increasing or decreasing or both) In some embodiments, the slide mount table 402 may include a The stage is configured for horizontal movement along an axis. As shown in the exemplary embodiment of FIGS. 4C-4E, the slide mount table 40 2 is moved to the laminator start position 436, and the laminator actuator 432 When the guide 10 is positioned by the laminator actuator 432, the laminator roller Use the tape 434 to press the peeled tape 414 onto the slide 10. After the coverslip tape 414 is applied to the slide 10, the applied coverslip tape The tape can be cut from the source tape using a knife, as shown in the exemplary embodiment of FIG. The actuator 442 extends the knife 444 through the cutting slot 446 to perform the peeling. The linear stage ensures that the laminated tape 414 is cut to the appropriate length. The laminator moves at a controlled speed from a laminator start position 436 to a laminator end position 438 and is peeled off. The coated cover glass tape 414 is pressed onto the slide 10 .

[0030] The coverslipping module 400 is configured so that the laminator roller 434 is flush with the slide. The laminator force and lamination speed are also controlled by the cover. Controlled by the glass mounting module 400. In some embodiments, 10 Newtons Roller laminator force of 1 / inch to 300 Newtons / inch, or roller contact force of 1 / inch to 300 Newtons / inch It has been found that a roller force of 150 Newtons / inch to 250 Newtons / inch is suitable. In some embodiments, the ASTM D2240 Type A or Type D scale is used. It has a Shore durometer hardness of 10 to 80, especially 20 to 30, as determined by In some embodiments, a laminator roller with a speed of 0.01 mm / sec to 10 m / sec has been useful. m / sec, especially 0.1mm / sec to 0.5mm / sec lamination speed is useful. The slide mount table moves between the laminator start position and laminator end position. Lamination of the coverslip tape to the slide is done in multiple passes due to multiple moves. In some embodiments, the lamination may be performed in 1 to 10 lamination passes, or in 2 to 4 lamination passes. It has been found that the sintered body is suitable.

[0031] After lamination is complete, the laminator actuator 432 retracts the laminator roller 434. The linear stage 403 moves the slide mount table to the unload position. The slide carrier module moves the slides to the slide carrier (usually The slides are then transferred to the output slide carrier.

[0032] In some embodiments of the method, the solvent on the sample is exchanged before applying the cover slip tape. FIG. 5 shows a typical example of a solvent exchange (i.e., a cover slip device according to the present invention). An exemplary novel method for removing an undesired solvent and applying a desired solvent in a deposition process 5 shows a solvent exchange module 500. For example, an undesired solvent may be a dye that is The pre-wetting solvent may be the input solvent used to apply the encapsulant. Conventional techniques use xylene as a pre-wetting solvent. However, as mentioned above, xylene is not desirable. Other useful pre-wet solvents include Contains water, hexane, ethanol, isopropyl alcohol, Clearify® ) and other solvents. Also, mixtures of these solvents, as well as surfactants and protons, The addition of other substances to enhance wetting, including pyrene glycol, was also useful. (which may be the solvent used in the solvent tank to process the sample) as a pre-wet solvent. A solvent that provides a process route for changing the input solvent into a pre-wet solvent if it is not suitable for A solvent exchange module 500 can be included in the system. To ensure the conversion, it may be useful to use one or more intermediate solvents in succession. do.

[0033] In an exemplary embodiment, as shown in FIG. 5, the slide 10 is disposed on a support, The support in this case includes a solvent return 550 ( For example, a vacuum chuck). To achieve this, a vacuum chuck or other solvent return unit 5 50 may be connected to a solvent return pump 551 through a solvent trap 552. The rack 550 may be disposed on a slide-mount table or may be attached to a slide-mount table. In FIG. 5, the slide mount table is integrated with the first air knife. Starting at 510, a first dispenser 522 dispenses a first solvent from a first solvent source 522. 20, a second air knife 530, and a second solvent dispenser 542 for dispensing a second solvent from a second solvent source 542. The first air knife 510 and the second air knife 53 move to the dispenser 540. 0 is fluidly connected to flow meters 511, 531, which in turn are connected to air knives 5 The flow meters 511, 531 control, determine, or measure the gas supplied to the gas supply pipes 10, 530. Air or other gas is received from an air supply 514 or other gas source. 510, 530 directly, or pressure regulator 513, air flow valve 512, and flow meter 511, 531.

[0034] In one embodiment of the method, the input solvent on the slide is water, and the solvent exchange module The solvent exchange module 500 uses an alcohol solvent. The alcohol solvent may be an ethanol-containing solvent, such as 100% ethanol, or at least It can be an aqueous solution containing 92% ethanol or at least 96% ethanol. In some embodiments, the first solvent source 522, the first air knife 510, and the first Only the dispenser 520 is used, and the alcohol solvent acts as a pre-wetting solvent. It is also contemplated that additional air knives, dispensers, and solvents may be added to the solvent exchange module. The solvent dispenser may be an atomizer having various shapes as known to those skilled in the art. , brush, stamp, or drip tube.

[0035] FIG. 6 illustrates a solvent exchange module 60 in which a sprayer 602 is used as the first dispenser. 6 shows another exemplary embodiment of the slide 10. The slide 10 is disposed on a support 604. The air flow 606 is directed at the leading edge of the slide 10 by a first air knife 608. The sprayer 602 is operated to deposit the input solvent 610 at the trailing end of the slide 10. When slide 10 is moved from left to right by a vacuum chuck in support 604, A pre-wetting solvent 612 is sprayed onto the tip of the nozzle.

[0036] FIG. 7A shows a solvent exchange head that dispenses an exchange fluid to remove water or other undesired solvents from the sample. 7 shows another embodiment of a solvent exchange module 700 for removing capillary forces. The capillary gap formed by the slide and the solvent exchange head is filled with the solvent. This keeps the dispensed exchange liquid in place and prevents the solvent from running off the slide. In the embodiment shown in A, a capillary gap is formed between the slide 10 and the solvent exchange head 702. The solvent exchange head 702 has at least one distribution hole and at least one exhaust hole. It is provided with an outlet hole through which the replacement fluid can be dispensed onto the slide 10 and an outlet hole through which the replacement fluid can be dispensed onto the slide 10. The solvent exchange module 700 can remove the bleeding liquid from the slide. configured to position the solvent exchange head 702 at a distance from it, the distance being such that a capillary gap is formed between the slide and the solvent exchange surface of the solvent exchange head 702, which is extremely small. For example, this distance can be less than 1600 μm, or less than 800 μm, or less than 400 μm, or less than 200 μm, or less than 100 μm, or less than 50 μm. In some embodiments, the solvent exchange head 702 includes a distribution hole at the center of the solvent exchange head and two discharge holes, one at each end of the solvent exchange head near the edge of the slide. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than 2.6 mL / s when the flow rate through the distribution hole is more than 2.4 mL / s (or a flow rate of more than 1.3 mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. μm, or less than <0000ID=200>μm, or less than <0000ID=100>μm, or less than <0000ID=50>μm. In some embodiments, the solvent exchange head 702 includes a distribution hole at the center of the solvent exchange head and two discharge holes, one at each end of the solvent exchange head near the edge of the slide. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than 2.6 mL / s when the flow rate through the distribution hole is more than 2.4 mL / s (or a flow rate of more than 1.3 mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. μm, or less than <0000ID=200>μm, or less than <0000ID=100>μm, or less than <0000ID=50>μm. In some embodiments, the solvent exchange head 702 includes a distribution hole at the center of the solvent exchange head and two discharge holes, one at each end of the solvent exchange head near the edge of the slide. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than 2.6 mL / s when the flow rate through the distribution hole is more than 2.4 mL / s (or a flow rate of more than 1.3 mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the solvent exchange head 702 includes a distribution hole at the center of the solvent exchange head and two discharge holes, one at each end of the solvent exchange head near the edge of the slide. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than 2.6 mL / s when the flow rate through the distribution hole is more than 2.4 mL / s (or a flow rate of more than 1.3 mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the solvent exchange head 702 includes a distribution hole at the center of the solvent exchange head and two discharge holes, one at each end of the solvent exchange head near the edge of the slide. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than 2.6 mL / s when the flow rate through the distribution hole is more than 2.4 mL / s (or a flow rate of more than 1.3 mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the discharge hole(s), if any, is larger than the distribution hole(s) so that the exchange solvent is maintained under the solvent exchange head. The solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. [[ID=,,15]] In some embodiments, the solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the solvent exchange head 702 can be moved along the slide 10 in one direction or back and forth one or more times so that the exchange liquid flows substantially over the entire sample and staining area of the slide. For example, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. In some embodiments, the solvent exchange head can pass over the sample at least once, twice, three times, four times, five times, or more. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move to the slide edge but should not extend beyond the edge to prevent leakage. By multiple reciprocating motions, the efficiency of solvent exchange can be increased. The velocity of the liquid flow through the distribution hole and the discharge hole(s), if any, should be selected to provide a laminar flow of liquid in the capillary gap. For example, in some embodiments, the flow rate through the discharge hole(s), if any, can be less than <0000ID=2.6>mL / s when the flow rate through the distribution hole is more than <0000ID=I2.4>mL / s (or a flow rate of more than <0000ID=1.3>mL / s passes through each of the two discharge holes). The flow rate can be set by a pump connected to the distribution line and the return line. To maximize the staining area, the head needs to be able to move​​​​​​​​​​​​ A replacement fluid containing a replacement solvent (such as ethanol) is delivered through a dispense line 706 from a reservoir 704. onto the slide 10, and the effluent is removed from the slide and passed through return lines 708, 71 0 and back to the reservoir 704. The delivery line 706 and return lines 708, 710 The flow of liquid through the exchange solvent is provided by pumps 707, 709, 711. The capillary force keeps the solvent exchange head 702 under pressure, and the design of the device allows for This limits leakage or wicking from the top of the slide. The amount of solvent exchange can be controlled during the final pass of the slide under the solvent exchange head 702. This allows for more consistent results when coverslipping slides. In this embodiment, gas from an exchange solvent such as ethanol is passed through a refrigerant containing a coal filter 712. The gas is collected by using a fume hood 713 or the like, which allows the gas to The majority of the exchange solvent is removed from the slide 10. The solvent passes through and is removed along with the unwanted solvent through the drain hole and then returned to the reservoir 704. As a result, the exchange fluid in the reservoir is filled as more slides are transferred to the solvent exchange head 702. As the replacement fluid is processed by the For example, the replacement fluid in the reservoir must first be replenished with ethanol. The user may have a 96% v / v concentration of an exchange solvent such as ethanol. The reservoir may be replaced or refilled when it reaches 90% v / v or another predetermined limit. To reduce the amount of water that dilutes the exchange solvent in reservoir 704, users should consider using this solvent exchange method. An additional step may be taken to remove any water on the slide before use.

[0038] Figure 7B shows the solvent exchange head 702 in the device of Figure 7A. In the solvent exchange head 702, the width is substantially the same as the width of the slide. The capillary 702 has one central distribution hole 714 and two discharge holes 716, 717. This reduces the flow resistance to the gap and shortens the exchange time of the volume under the head. Suitable solvent exchange heads may be any desired number, e.g., 1, 2, 3, 4, 5, 6, The flow of replacement fluid and removal fluid may be directed through one or more distribution holes and drain holes. In some embodiments, the solvent exchange module can be controlled by a pump. Alternatively, some implementations may provide separate pumps for the delivery and return lines. In an embodiment, the module has one pump for the delivery line and one pump for the return line. In FIG. 7B, the discharge holes 716, 717 have a raised surface 71 around the discharge holes. 8, 719, or the like, to form a capillary smaller than the area around the distribution hole 714. It is positioned in an area having a gap.

[0039] Figure 8 shows the slide loading, solvent exchange, coverslipping, and slide extraction steps described above. Implementing the activities and modules of the overall method for preparing coated specimen slides 8 shows an exemplary embodiment of an instrument protocol for coating a coated sample. Various embodiments of the present method for preparing slides are shown. One or more subroutines containing instructions are input into the controller. is provided in a slide carrier, the slide carrier comprising a solvent exchange module and a cover The slide carrier is loaded into the instrument with a glass mounting module. Select a slide from the slide list. The barcode reader in the instrument identifies the slide and the identification information is stored in the The controller provides signals to direct the slide to a location for processing. If the instructions for the slide require solvent removal, the slide should be The slides are then transferred to a solvent removal module such as the module according to FIG. The support is arranged on a support such as a magazine or conveyor, which is moved along one axis, preferably The slide is moved along its long axis. The air knife is activated to remove the input melt on the slide. In some embodiments, the module also applies a solvent, such as a pre-wet solvent. The slides are transferred to the coverslipping module. In some embodiments, the same support (e.g., stage) can be used for both the solvent exchange module and the The cover slip tape is transferred from the dispenser assembly to the cover slip module. The stage is pushed out of the assembly so that the rear edge of the slide is under the leading edge of the cover glass tape. Position the slide as shown in Figure 1. that is, the stage and / or dispenser assembly is aligned with the long axis of the slide. (preferably substantially the same as the direction in which the cover glass tape is extruded) The laminator assembly moves linearly. The laminator assembly stretches the laminator (roller, etc.). Cover - The glass tape is cut to the appropriate length to cover the sample on the slide. Then, pressure is applied to the cover glass tape to adhere it to the slide. The laminator assembly retracts the laminator. The stage then extracts the slide. to an unloading location where the actuator ejects the slide; The slide is placed in an output slide carrier.

[0040] In order to use clean cover glass tape in any form in the present system and method, In some embodiments, the clean cover glass tape can be applied to the cover glass. The cover glass source tape is supplied as a cover glass tape. To keep the cap clean and / or to facilitate its application to the slide (i.e., cover - To keep the glass tape clean or to facilitate its application to the slide or The cover glass source tape 902 has one or more of the following characteristics: The structure is shown in Figure 9. The cover glass source tape 902 generally comprises a backing layer 904 and In some configurations, the cover glass source tape 902 also includes a peel-off layer 906. The release layer 908 prevents the cover glass source tape 902 from being wound on a reel. This is particularly desirable when provided as a

[0041] In some embodiments, the coverglass source tape includes a kiss cut portion. The kiss-cut portion has a lightly cut portion within the boundary of the portion used as the cover glass tape. When cover slips are kiss-cut, they are removed from the backing. Multiple kiss-cut sections can be positioned linearly on a strip of release layer, etc. This can be done.

[0042] 10, 11A and 11B, 12 and 13 show various cover glasses that may be advantageous. 10 shows an exemplary embodiment of a cover glass source tape. The tape 1002 is a release liner 100 that is drawn through the tape dispenser assembly. 4, the peeled tape 1006 is pushed onto a guide surface 1008 and 11A and 11B, the kiss-cut source tape 1102 The optically transparent backing and pressure sensitive adhesive are provided. The adhesive is provided as a series of kiss-cut areas on a continuous release liner 1106. The kiss-cut coverglass source tape 1102 is a series of kiss-cut coverglasses 1 104 are fabricated to be uniformly positioned along the length of the release liner 1106 The tape dispenser assembly 1108 uses a position sensor for movement control. Each kiss-cut cover glass is extruded as shown on the right. The coated coverglass source tape 1202 is used to define the coverglass 1206. It has perforations 1204 and uses a tape reel to advance the tape over the slide. The annular punch 1208 peels off the frame-cut cover glass 1206, Attach the tape to the slide. After the coverslip is peeled off, the slides can be collected on a tape reel 1210. In 13, the cover glass source tape 1302 does not have a release liner. The moving mechanism 1304 pushes out each length of tape cut by the knife 1306, Applies to slide 10. Other items include a barcode reader, air knife, and cover glass tape. Dispensers, laminators, and cover glass tape cutters or knives, etc. There are several components.

[0043] Some conventional approaches to slide processing involve the slides in water being washed with a series of alcohol baths ( alcohol bath, and ensure dehydration before immersion in a xylene bath. Thus, in some exemplary embodiments of the system, as shown in FIG. The automatic basket mover can be used to select 70% ethanol, 95% ethanol, 100% ethanol, and between a series of slide baths or tanks, such as slide baths containing Clearify® FIG. 14 also illustrates the slide preparation system described herein. 15 shows the placement of the stem in one embodiment of the slide preparation system shown in FIG. In the second configuration, a slide-mounted table provides a space between the air knife and the solvent dispenser. The slide moves.

[0044] In some embodiments, the system includes a storage unit for the slide carriers. For example, the system may have one, two, three, four, five, or more slide carriers. In some embodiments, the system may include an input repository and an output repository for the software. The slides are retrieved from the slide carrier using the The slides are then returned to the same slide carrier. For example, the process may involve first performing a solvent exchange. Then, apply a coverslip and then return the slide to the slide carrier from which it was collected. This allows a new slide carrier to be prepared to receive the processed slides. This simplifies the equipment and reduces the need for handling slide carriers. This reduces the need for basket handling within the device. In this case, the basket is loaded underwater and removed from the water when slide processing begins. In some embodiments, slide processing is performed to reduce artifacts resulting from drying of tissue samples. For example, in some embodiments, Slide processing takes approximately 15 seconds, and a basket of 20 slides can be processed in 5 minutes. This allows the slide to stay out of the water for a maximum of 4 minutes and 45 seconds, Artifacts resulting from drying of tissue samples can be reduced or eliminated. In some embodiments, the solvent exchange process is completed in about 5 seconds or less. The glass mounting process can be completed in about 5 seconds or less. The process of returning to the carrier takes approximately 5 seconds or less.

[0045] In some embodiments, the system includes in situ hybridization. Assays other than immunohistochemistry assays such as immunohistochemistry (immunohistochemistry) It can be used for automated coverslipping of slides subjected to sieving. In embodiments, the system provides the option to dry load slide carriers and exchange solvents. Instead of applying a mounting medium for the assay (e.g., FISH mounting medium and a dispenser for applying the

[0046] [material] In some embodiments, the cover slip tape is 3M™ Microfluidic Diagnostic It can be made from materials such as Tape 9795R or other transparent adhesive tape. In the case of the cover glass tape, it is single-sided (i.e., adhesive is provided on only one side). In some embodiments, the cover glass tape comprises a delayed tack adhesive. The thickness of the tape is 50 microns to 500 microns, preferably 100 microns to 300 microns. The thickness of the adhesive may be between 5 microns and 200 microns, preferably 15 microns. It can be up to 30 microns.

[0047] The cover glass tape comprises a pressure sensitive adhesive, which in some embodiments comprises a plurality of silicone Available in polyurethane and acrylic formulations. Currently available from 3M Company (Minnesota, Maplewood, IN), Polymer Science, Inc. (Monticello, IN), and Adh Consumer-grade products are being developed by companies such as Resives Research, Inc. (Glen Rock, PA). Transparent and optically clear backing materials and adhesives for electronic device displays and other applications Examples of suitable adhesives include acrylonitrile copolymers (e.g., Butadiene-acrylonitrile polymer (BACN polymer), butadiene-acrylonitrile tolyl-isoprene polymers (BACNI polymers), styrene copolymers (e.g., Styrene / butadiene / styrene (SBS polymer), styrene / isoprene / styrene (SIS polymer), and styrene / ethylene / butylene / styrene (SEBS polymer) )), as well as low tack pressure sensitive adhesives such as acrylate copolymers. For example, blends and mixtures of polymeric materials may be used. Pressure sensitive adhesives also have sufficient acidity. It may also contain antioxidants, UV stabilizers and crosslinkers.

[0048] The coverglass tape also includes a backing, which is usually an optically clear polymeric film. Suitable polymer film materials include cellulose diacetate, cellulose triacetate, polyethylene Polyethylene terephthalate, styrene-acrylonitrile, and polymethyl methacrylate filler In some embodiments, the backing is a cyclic olefin polymer or a cyclic olefin. In some embodiments, the backing is a polyimide copolymer. In some embodiments, the cover glass tape also has a thickness of 0.05 to 0.05 mm. A tie layer may be included between the pressure-sensitive adhesive. The selection of an appropriate tie layer material will depend on the pressure-sensitive adhesive used. The adhesive layer may be applied based on the type of adhesive and backing. Many materials are useful, such as polyvinyl chloride, vinyl chloride / vinyl acetate copolymers, and polymers, chlorine-containing polymers such as polyvinylidene chloride, polycarbodiimides and ethylene vinyl acetate polymers and copolymers, acid or anhydride modified polyethylene, propylene and Ethylene vinyl acetate polymers and copolymers can be used.

[0049] [Parameters] In some embodiments, the entire coverglass tape and / or its individual components (i.e. , the refractive index of the cover glass tape as a whole and / or its individual components) is It can be 1 to 2, or 1.2 to 1.8, or 1.45 to 1.65. , the refractive index is selected to substantially match the refractive index of the slide.

[0050] In some embodiments, the luminous transmittance of the cover glass tape (ASTM D1003- 95) is at least about 85% or at least 75%.

[0051] In some embodiments, the adhesive has a strength of about 0.1 N / 25 mm width to about 3.0 N / 25 mm width. 180° peel adhesion values ​​can be shown.

[0052] In some embodiments, the adhesive has a strength of at least about 2 kN / m 2 , or at least about 4 kN / m 2 It can exhibit a dynamic shear strength of

[0053] [Sample preparation method before and after cover glass mounting] The method may be used to prepare a sample for analysis and / or to stabilize the sample after processing. (i.e., to prepare samples for analysis or to stabilize samples after processing or Both of these methods may include additional steps before or after coverslipping. The sample may be analyzed and / or stored (i.e., analyzed or stored or In some embodiments, the sample may be prepared for either (or both) embedding medium. The embedding medium is removed after placement on the slide. The step(s) are used for most samples, such as tissue sections from FFPE blocks. Since they are embedded in paraffin, they are generally deparaffinized. Deparaffinization is any technique that removes the embedding medium from the specimen on the slide. For histochemical analysis, in some embodiments, the target recovery process involves with a suitable buffer solution such as MES buffer or citrate buffer adjusted to a high or low pH. This is done by contacting the two and heating them to a suitable temperature (about 95°C) or higher. This is called heat-induced epitope retrieval (HIER). The sample is purified by applying pepsin, proteinase K, or another digestive enzyme. The cells are subjected to either proteolytic digestion or acid-based antigen retrieval with an acid such as formic acid, followed by Incubating it to facilitate access by assay reagents such as antibodies The method and system of the present invention also allows for the sample to be immersed in water prior to applying the cover glass tape. In situ hybridization (ISH) based on The method may include one or more processes for performing molecular analysis using assays of the source. is the denaturation of nucleic acids by heating in the presence of a buffer, and the fluorescence in situ For fluorescence in-situ hybridization (FISH) Hybridization of fluorescently labeled nucleic acid probes or chromogenic in situ hybridization Application of chromogens for chromogenic in-situ hybridization (CISH) The ISH sample is allowed to dry before application of mounting medium and coverslip.

[0054] The following examples are illustrative of the present disclosure and are not to be construed as limiting the disclosure in any way. It should not be. [Example]

[0055] [Example 1] In this example, a transparent tape containing a pressure-sensitive adhesive (3M9795R) was applied to the cover glass tape. The suitability of the uterine tissue for use as a template was evaluated. The tissue was processed for embedding (FFPE: formalin fixation and paraffin embedding) and then embedded at 5 μm. Sections were cut and mounted on slides. The sections were degreased and stained with hematoxylin and eosin. Staining with Clearif as a pre-wetting solvent followed by dehydration in ethanol. y (registered trademark).

[0056] Tape 3M9795R, manufactured by 3M Company (Maplewood, Minnesota), has a release liner. The adhesive includes a clear polypropylene backing coated with a silicone adhesive having a Load a roll of 4 mm wide tape onto the cover slip mounting module as shown in Figure 4A. The cover slip mounting module was designed to dispense adhesive tape, as shown in Figure 10. The slides were manually removed from the Clearify® pre-wet solvent bath. The device was then taken out, placed on the slide table 402, and the device was operated using a computer. Bar glass tape was applied to each slide followed by lamination. Laminator Actuator Pressure The force was 80 psi and the linear stage speed was 10 mm / s. An example of a scanned image of a sample is shown in FIG.

[0057] [Example 2] In this example, after the cover glass tape of the present invention is attached to the specimen and slide, The ability of the sample from Example 1 to remove the cover glass tape was evaluated. Attempts were made to remove the coverslip after the first test. The tissue sample was easily removed from the tissue and was intact, as well as washed away with Clearify®. For the second sample, the cover glass tape was removed. When the slides were removed after one week, many of the tissue samples had lifted off the slides. For the sample, when the cover glass tape was peeled off after storing it at 60°C for one month, The sample was completely lifted from the slide. Solvents such as Clearify® It is believed that the adhesive interacts with the adhesive, softening it and causing it to swell into the tissue. Over time, the Clearify® evaporated and the tissue was filled with adhesive. It becomes a state.

[0058] [Example 3] In this example, an accelerated aging protocol was used to etch the cover glass prepared in Example 1. Coverslip-mounted specimen slides were evaluated. The specimen slides were stored at 60°C for several weeks. The potential fading of the dye over 2.3, 3.3, and 4.3 years was assessed. provides images of cover-slipped samples at various time points. In the coverslip-mounted specimens, fading of the hematoxylin dye was observed. However, the 3M9795R cover glass-mounted sample was relatively stable.

[0059] [Example 4] This example evaluates the cover slip mounting technique of the present invention using an alcohol pre-wetting solvent. As in Example 1, a sample of uterine tissue was placed on a slide and stained with hematoxylin. As described in Example 1, the coverslip was attached using a 3M9795R cover slip module. A cover glass was attached. PA), and different pre-wetting solutions, each of which contained 1% propylene glycol. Excellent cover glass performance was achieved. Figure 17 shows the performance of the cover glass mounted sample. The image shows:

[0060] [Example 5] This example evaluates the coverslipping technique of the present invention on IHC stained samples. The materials were then mixed with various pre-wet solvents, namely Clearify® and alcohol and polysorbate. The effect of micro-dewetting and the construction of good IHC images were investigated. The multiblock samples were evaluated for their ability to build antibodies against 3,3'-diaminobenzidine. Except for staining using IHC, where the cells are stained with DAB and the nuclei are counterstained with hematoxylin. The glass was prepared in the same manner as in Example 1. 3M9795R was used as the cover glass. Using Clearify® pre-wetting solvent, panel (a) of Figure 18 This was found to result in areas of micro-dry-out, as shown in panel 18 of Figure 18. As shown in (b) and (c), pre-wet solutions of ethanol and 1% propylene glycol were used. By using the solution, we were able to improve the cover glass attachment. The mounted sample showed no solvent voids.

[0061] [Example 6] This example evaluates the use of the coverslipping technique of the present invention on FISH samples. Samples were prepared as in Example 1 and stained for FISH. The Fluorescence Mounting Medium was applied to the sample as a pre-wetting solvent. The samples were then coated with 3M8211 acrylic resin from 3M Company (Maplewood, Minnesota). Covered with transfer tape and coverslip. Fluorescence microscopy on coverslip-mounted slides. The examination revealed a focus of nucleic acid staining and cellular counterstaining. (Figure 19B) had a higher fluorescent background than the control (Figure 19A).

[0062] [Example 7] In some embodiments, a solvent exchange module (as illustrated in FIGS. 5, 7A, and 7B) 20, the linear stage 403 can be used to move the surface of the slide 10. The capillary head may include a capillary head 360 that is swept across the surface. The surface of the slide is close to the surface at a distance of 0.2 mm to 3 mm, preferably 0.5 mm to 2 mm. The capillary head 360 also includes a capillary surface 362 positioned in the a solvent supply port (Solv) fluidly connected to a dispenser (such as the first dispenser 520 in FIG. 5); a solvent supply port 364 fluidly connected to a solvent return (such as solvent return 550); and a solvent return port 366. The flow rate of the solvent return port is The flow rate of the dispenser 320 is adjusted to exceed that of the capillary surface and the slurry. Ensure excess solvent is removed between the feed and the solvent return port. Optionally, for return flow over the supply flow, air is drawn in. An air vent 368 is provided on the capillary head.

[0063] [Example 8] As shown in Figures 21A-21D, various capillary designs were used to improve performance. A significant design variation is the use of a solvent supply port 364. and various shapes of the solvent return port 366, as well as the capillary surface 362. The capillary surface is contoured to allow for the capillary to be positioned relative to the surface. It is also possible to influence the flow characteristics of the Pillai head.

[0064] In Example 8, FIG. 21A, the solvent supply port 364 and the solvent return port 366 are both Both ports are shaped as slots that span the width of the slide. The substrate 362 is positioned on the substrate surface 362.

[0065] In Example 8, FIG. 21B, the solvent return port is positioned away from the capillary surface 363. This design ensures that only spilled solvent is removed from the capillary surface. It has advantages.

[0066] In Example 8, FIG. 21C, the solvent supply port 364 and the solvent return port 366 are both This design has the advantage of being simpler to manufacture and providing good flow sweep. It has points.

[0067] In Example 8, Figure 21D, two solvent return ports are positioned at the end of the capillary surface. This design allows for a more efficient path between the solvent supply and return ports. It has the advantage of being short.

[0068] [Example 9] A capillary head 360 of the design of FIG. 21B was used. The capillary surface 362 is the same as that of FIG. 2, the gap 363 between the capillary surface and the slide is 0.5 mm. The first dispenser (the first dispenser in FIG. 5) was positioned above the slide 10. The first solvent (e.g., Sensor 520) was delivered at a rate of 1.5 ml / s, 95% ethanol. The medium return pump was a vacuum trap set at 50 kPa. Table 1 was performed using the system shown in Figures 4A and 5 and described above.

[0069] [Table 1]

[0070] This protocol is applicable to multiblock tissue sections with unstained tissue, as shown in Figure 23. The tissue sections were prepared without solvent exchange. Panel a of Figure 23 shows the images. Panel c of Figure 23 shows a heat map of the intercepts. The second section was processed with this protocol, which involved shifting the slide and processing only the top half of the slide ( Image in panel b of Figure 23 and absorbance heatmap in panel d of Figure 23).

[0071] This protocol was also performed on ovarian tissue sections stained with KI67 and hematoxylin. Control sections treated by immersion in 100% ethanol for 2 minutes are shown in Figure 24. Experimental sections processed using this protocol are shown in panel a of Figure 24. The figure shows the results of the experiment.

[0072] Exemplary Embodiments Exemplary embodiments provided by the presently disclosed subject matter include, but are not limited to: Not limited to:

[0073] Embodiment 1. A method for preparing coated sample slides for optical analysis, such as optical microscopy. The specimen (such as a tissue section) on the slide is brought into contact with a mounting medium, which is The absence of silica gel and the covering of the sample on the slide with a cover glass, The cover glass has a first major surface and a second major surface, and has a first major surface facing the sample. The tape may be provided with a pressure sensitive adhesive and a suitable pressure may be applied to the tape, thereby securing the cover glass tape. and adhering the tape to the slide.

[0074] Embodiment 2. The method of embodiment 1, wherein the cover glass comprises a cover glass tape. .

[0075] Embodiment 3. A clean cover glass tape is wound on a tape reel, and the method Unroll a section of clean cover slip tape and apply the unrolled section to the slide. 3. The method of embodiment 2, further comprising:

[0076] Embodiment 4. A clean cover glass tape is on the release layer, and the method comprises: 4. The method of claim 2 or 3, comprising separating the tape from the release layer. In the release layer, the release layer has a release layer end, and the release layer end is wound on a release layer reel. Rotation of the wheel can advance or drive the cover glass tape.

[0077] Embodiment 5. The sample is placed on a slide and the solvent is removed from the specimen before coating the sample. 5. The method of any one of embodiments 1 to 4, further comprising:

[0078] Embodiment 6. The method further comprises partially or completely dehydrating the sample after placement on the slide. The method according to any one of embodiments 1 to 5, comprising: It can be partially dehydrated to a moisture content of less than 15%.

[0079] Embodiment 7. The method of embodiment 6, wherein the sample is partially or completely dehydrated by solvent exchange. The method described.

[0080] Embodiment 8. The method of embodiment 7, wherein the exchange solvent is applied to the sample by spraying.

[0081] Embodiment 9. Blow a line of gas onto the sample (e.g., using an air knife to blow air) 9. The method of embodiment 8, further comprising evaporating the solvent (by spraying).

[0082] Embodiment 10. The exchange solvent is passed through a capillary gap across the sample. 8. The method of embodiment 7, wherein the slide is applied to the sample. For example, the slide is to treat a larger surface area.

[0083] Embodiment 11. A piezoelectric transducer is applied to the slide to induce high frequency pressure waves to effect solvent exchange. 8. The method of embodiment 7, wherein the method accelerates

[0084] Embodiment 12. Remove the slide from the slide carrier and place the slide on the slide table. 12. The method of any one of embodiments 1 to 11, further comprising disposing the In this configuration, the slide table is designed to hold the slide and prevent movement by the slide. The slide table surface is substantially horizontal. It may be present or may have an angle.

[0085] Embodiment 13. The method of any one of embodiments 1 to 12, wherein the pressure-sensitive adhesive penetrates the pores of the sample. How to post.

[0086] Embodiment 14. By rolling a roller on the cover glass tape, for example, 60 ps 14. Any one of embodiments 1 to 13, wherein pressure is applied to the cover glass tape at a pressure of i. The roller can move in one direction on the tape, or it can move in the first direction. It can then move in a second direction (e.g., back and forth along the tape). The roller can roll over the tape more than once, applying the same pressure each time but with different It may be possible.

[0087] Embodiment 15. A coverslipping module having a surface for slides. A slide mount table that prevents the slide from moving on the slide mount table. a slide-mounted table having one or more slide stops for preventing or reducing A lever that moves the slide mount table along the longitudinal axis of the slide on the slide table. The near actuator and the slide mount table are located above the feed end and the extrusion end. A cover glass tape dispenser for providing a cover glass tape, the cover glass tape dispenser comprising: The feed end receives the cover glass tape and places it on the slide on the slide mounting table. A cover glass tape is configured to be extruded from an extrusion tip at an angle. tape dispenser and a slide positioned after the extrusion end of the tape dispenser The tape is configured to roll over the cover glass and apply pressure to the cover glass tape. and a roller.

[0088] Embodiment 16. A release liner that receives a release liner from a coverglass tape dispenser 16. The apparatus of embodiment 15, further comprising a reel. The reel can be positioned by the feed end.

[0089] Embodiment 17. The tape dispenser separates the release liner from the cover glass tape. 15 or 16, wherein a release liner separator, such as a wedge or roller, is provided for The device described in

[0090] Embodiment 18. A solvent exchange module for a sample on a slide, comprising: The slide support includes a gas flow sensor located above the slide support and a gas flow sensor located above the slide support. and a gas supply device configured to spray ink onto the support and one of the gas supply devices. one or both of the solvent exchange modules are configured for linear motion.

[0091] Embodiment 19. The module of embodiment 18, wherein the support is a conveyor.

[0092] Embodiment 20. The support includes a heater (such as a resistive heater embedded in the support). The module according to embodiment 18.

[0093] Embodiment 21. An apparatus for preparing coated specimen slides, comprising a solvent exchange module and a and a bar glass loading module.

[0094] Embodiment 22. The apparatus of embodiment 21, further comprising a slide handler module. .

[0095] Embodiment 23. A substantially xylene-free coverslipped specimen slide, comprising: A slide having a sample on its surface and a cover glass tape attached to the sample. a cover glass tape, the cover glass tape being substantially entirely covered by the cover glass tape; A mounting medium in contact with the specimen between the cover slip tape and the slide. Coverslip the sample slide with mounting medium, but not with xylene.

[0096] Embodiment 24. The mounting agent comprises one or more C 1-4 Alcohol or C 1-4 glycol 24. The slide of embodiment 23, comprising:

[0097] Embodiment 25. The method of embodiment 23 or 24, wherein the sample comprises one or more dyes, such as fluorescent dyes. The slide described.

[0098] Embodiment 26. The sample containing the dye is stable for at least 10 years, as described in embodiments 23-2. 5. A slide according to any one of the preceding paragraphs.

[0099] Embodiment 27. The adhesive side of the cover glass tape is configured to be applied to a sample on a slide. A coverslipping apparatus comprising a coverslip tape dispenser.

[0100] Embodiment 28. A solvent exchange module for a sample on a slide, comprising: The slide holder was a support for the slides and a solvent exchange head that dispensed the exchange fluid and removed the waste fluid. The solvent exchange head can be positioned at a distance from the slide, and the support and and a solvent exchange head configured for linear motion. Solvent exchange module.

[0101] Embodiment 29. The solvent exchange head comprises an exchange surface facing the slide, the exchange surface having a drain hole. 29. The solvent exchange module of embodiment 28, comprising a raised portion surrounding

[0102] Embodiment 30. The exchange surface has a length and a width, the width being substantially the same as the slide width. 30. The solvent exchange module according to embodiment 28 or 29.

[0103] Embodiment 31. A reservoir containing an exchange fluid and a solvent exchange head connecting the reservoir. One or more delivery lines and one or more return lines connecting the reservoir and the solvent exchange head 31. The solvent exchange module according to any one of embodiments 28 to 30, further comprising:

[0104] Embodiment 32. The distance between the exchange head and the slide forms a capillary gap. 32. The solvent exchange module according to embodiment 31, further comprising: It can move across the surface to treat a larger area than the solvent exchange head.

[0105] Embodiment 33. Configured to induce high frequency pressure waves to accelerate solvent exchange on a slide. 33. The solvent exchange module of any of embodiments 28-32, further comprising a piezoelectric transducer. Rule.

[0106] Embodiment 34. A dispense pump fluidly connected to a dispense line and connected to one or more return lines. 34. Any of embodiments 28 to 33, further comprising at least one return pump connected to the The solvent exchange module according to claim 1.

[0107] Embodiment 35. A method of preparing a sample slide for analysis, comprising: wherein the sample comprises a first solvent; and forming a capillary gap between the tissue section and the solvent exchange head; Dispensing an exchange liquid containing a second solvent from a dispensing hole in the exchange head and dispensing the second solvent from the capillary gap. and removing the effluent from the

[0108] Embodiment 36. The first solvent comprises water and the second solvent comprises an alcohol (e.g., ethanol). 36. The method of embodiment 35, comprising:

[0109] Embodiment 37. The method of embodiment 35 or 36, wherein the effluent comprises a mixture of the first solvent and the second solvent. is the method described in 36.

[0110] Embodiment 38. The method further comprising passing the effluent through a reservoir, the reservoir containing a second solvent. 38. The method of any one of embodiments 35 to 37, wherein the replacement fluid contains

[0111] Embodiment 39. The replacement fluid is held under the replacement head during the dispensing and removal steps. The method according to any one of embodiments 35 to 38, wherein

[0112] Embodiment 40. The solvent exchange head includes a second solvent exchange head, the second solvent exchange head being configured to dispense a second solvent through a distribution hole in the middle portion of the solvent exchange head. 40. The method of any one of embodiments 35 to 39, wherein the solvent is partitioned.

[0113] Embodiment 41. The first solvent is partially or completely removed from the sample after placement on the slide. 41. The method of any one of embodiments 35 to 40, further comprising removing the sample. For example, the sample is When the first solvent contains water, the sample has a water content of 0% to 20%, preferably less than 15%. It can be partially dehydrated up to

[0114] Embodiment 42. The sample is partially or completely dehydrated by solvent exchange. The method described in 1.

[0115] Embodiment 43. One or more delivery lines provide replacement fluid to the slides and one or more return lines. 43. The method of embodiment 42, wherein the line removes drainage fluid from the slide.

[0116] Embodiment 44. The path from the delivery line to the return line is a capillary for solvent transfer. 44. The method of embodiment 43, wherein a gap is formed.

[0117] Embodiment 45. A piezoelectric transducer is applied to the slide to induce high frequency pressure waves to effect solvent exchange. 45. The method of any one of embodiments 35 to 44, wherein the method accelerates the

[0118] Embodiment 46. The exchange liquid is applied to the sample for 60 seconds or less for solvent exchange. 46. ​​The method according to any one of aspects 35 to 45.

[0119] Embodiment 47. The method of any one of embodiments 35 to 46, wherein the replacement liquid is applied to the sample for about 5 seconds or less. Any of the methods described above.

[0120] Embodiment 48. The method of claim 48, further comprising covering the sample on the slide with a coverslip. The lath has a first major surface and a second major surface, and has a pressure-sensitive adhesive on the first major surface facing the sample. 48. The method of any one of embodiments 35-47, comprising administering to a subject a therapeutically effective amount of an anti-inflammatory drug.

[0121] Embodiment 49. A method for carrying out the method of embodiment 49, wherein the process of covering the sample with a coverslip takes about 5 seconds or less. 49. The method according to any one of aspects 35 to 48.

[0122] Embodiment 50. The slide is mounted on a slide carrier after the sample has been covered with a coverslip. 50. The method of embodiment 49, wherein the endothelial cell is disposed within the endothelial cell.

[0123] Embodiment 51. The process of placing a slide in a slide carrier takes about 5 seconds or less. The method of embodiment 50, wherein

[0124] The terminology used herein is for the purpose of describing particular embodiments and is not intended to be limiting. It is understood that the scope of the invention is not intended to be limiting. In addition to the technical and scientific meaning, the present teachings are generally understood and accepted in the art. This is what is being done.

[0125] [Cited documents] International Publication No. 1999 / 053357 International Publication No. 2002 / 012857 International Publication No. 2014071959 International Publication No. 0212857 U.S. Patent No. 6,589,650 UK Patent Publication No. 2482726 International Publication No. 9953357 U.S. Patent No. 4,203,797 U.S. Patent No. 4,853,262 U.S. Patent Application Publication No. 2010081579 U.S. Patent Application Publication No. 2002037269 U.S. Patent Application Publication No. 2007166197 U.S. Patent No. 5,569,527 International Publication No. 2005085799 European Patent Application Publication No. 1438585 European Patent Application Publication No. 1309847 U.S. Patent Application Publication No. 2010069259

[0126] In view of the present disclosure, it is understood that methods and apparatus can be implemented in accordance with the present teachings. Additionally, the various components, materials, structures, and parameters are provided merely as examples and examples. In light of this disclosure, the present teachings may be implemented in other applications, including, but not limited to, The components, materials, structures, and devices that implement these applications are also described in the accompanying patents. It can be determined while remaining within the scope of the claims.

Claims

1. A slide mount table having a surface for a slide, the slide mount one or more slide stops for preventing or reducing movement of said slide on the support table; a slide mount table having a slide; The slide mount table is moved in the longitudinal direction of the slide on the slide table. a linear actuator for a cover glass over the slide mount table, the cover glass having a feed end and an extrusion end; a cover glass tape dispenser, the cover glass tape dispenser comprising: a cover glass tape dispenser; - Receives glass tape and mounts it at an angle to the slide on the slide mount table a cover glass tape extruding section configured to extrude the cover glass tape from the extrusion end with a predetermined angle; -Glass tape dispenser, The tape dispenser is positioned behind the extrusion end and rolls to a roller configured to apply pressure to the cover glass tape on the A cover glass mounting module comprising:

2. a release liner reel that receives a release liner from the cover glass tape dispenser; The apparatus of claim 1 , comprising:

3. The tape dispenser separates the release liner from the cover glass tape.

3. The apparatus of claim 1 or 2, comprising a liner separator.

4. a support for the slide; A gas line is provided above the support to blow onto the slide on the support. One or both of the support and the gas supply device are a gas supply device configured to move linearly; A solvent exchange module for samples on slides, comprising:

5. The module of claim 4 , wherein the support is a conveyor.

6. The module of claim 4 , wherein the support comprises a heater.

7. contacting the sample on the slide with a xylene-free mounting medium; covering the sample on the slide with a coverslip, has a first major surface and a second major surface, and a pressure-sensitive element on the first major surface facing the sample. coating with an adhesive; Apply a suitable pressure to the cover glass, thereby pressing the cover glass against the slide. Attaching it to the 1. A method for preparing a coated sample slide for optical analysis, comprising:

8. The method of claim 7 , wherein the coverglass comprises a coverglass tape.

9. A clean cover glass tape is wound on a tape reel, and the method includes: Unwind the cleaned section of cover glass tape and place the unwound section on the slide. Apply to The method of claim 8 further comprising:

10. The clean cover glass tape is on a release layer, and the method comprises:

10. The method of claim 8 or 9, further comprising separating the cap from the release layer.

11. The sample is placed on the slide and solvent is removed from the specimen before coating the sample. The method of any one of claims 7 to 10, further comprising:

12. further comprising partially or completely dehydrating the sample after placement on the slide. The method according to any one of claims 7 to 11.

13. 13. The method of claim 12, wherein the sample is partially or completely dehydrated by solvent exchange. 。

14. 14. The method of claim 13, wherein the exchange solvent is applied to the sample by spraying.

15. 15. The method of claim 14, further comprising blowing a line of gas over the sample to evaporate the solvent. The method described below.

16. The exchange solvent flows across the sample through the capillary gap, thereby The method of claim 12 applied to

17. The slide moves relative to the capillary gap to treat a larger surface area.

17. The method of claim 16.

18. A piezoelectric transducer is applied to the slide to induce high frequency pressure waves to accelerate the solvent exchange. The method of claim 13 .

19. Remove the slide from the slide carrier and place the slide on a slide table. The method of any one of claims 7 to 18, further comprising disposing.

20. The method according to any one of claims 7 to 19, wherein the pressure sensitive adhesive penetrates the pores of the sample. Law.

21. The pressure is applied to the cover glass by rolling a roller on the cover glass tape. The method according to any one of claims 7 to 20, applied to a bar glass tape.

22. a solvent exchange module; Cover glass mounting module and 1. An apparatus for preparing coated specimen slides, comprising:

23. 23. The apparatus of claim 22, further comprising a slide carrier module.

24. a slide having a sample thereon; a cover glass tape attached to the sample, wherein substantially all of the sample is covered by the cover glass tape; a cover glass tape covered by a bar glass tape; The xylene in contact with the sample between the cover glass tape and the slide No mounting agent A substantially xylene-free coverslip-mounted sample slide.

25. The mounting agent may be one or more of １－４ Alcohol or C １－４ Contains glycol, claims Item 25. The slide according to item 24.

26. 26. The slide of claim 24 or 25, wherein the sample comprises one or more dyes.

27. 27. A method according to claim 24, wherein the sample containing the dye is stable for at least 10 years. The slides described in paragraph .

28. A coverglass tape configured to apply the adhesive side of the coverglass tape to a sample on a slide. A coverslipper equipped with a rust tape dispenser.

29. a support for the slide; a solvent exchange head for dispensing exchange fluid and removing waste fluid, said solvent exchange head comprising: The support and the solvent exchange can be positioned at a distance from the slide. or both are configured for linear motion; A solvent exchange module for samples on slides, comprising:

30. The solvent exchange head has an exchange surface facing the slide, the exchange surface having the drain hole.

30. The solvent exchange module of claim 29, comprising a surrounding raised portion.

31. 3. The exchange surface according to claim 2, wherein the exchange surface has a length and a width, the width being substantially the same as the slide width.

31. The solvent exchange module according to claim 9 or 30.

32. a reservoir for storing the exchange liquid; and a connector for connecting the reservoir to the solvent exchange head. one or more delivery lines and one or more return lines connecting the reservoir and the solvent exchange head; 32. The solvent exchange module of claim 29, further comprising a line.

33. The distance between the interchangeable head and the slide defines a capillary gap.

33. The solvent exchange module of claim 32.

34. The solvent exchange module moves across the slide and 34. The solvent exchange module of claim 33, wherein the solvent exchange module is capable of treating an area as large as 100 MPa.

35. configured to induce high frequency pressure waves to accelerate the solvent exchange on the slide. The solvent exchange module of any one of claims 29 to 34, further comprising a piezoelectric transducer. 。

36. a distribution pump fluidly connected to the distribution line; and a and at least one return pump. Solvent exchange module.

37. providing a sample on a slide, the sample comprising a first solvent; And, forming a capillary gap between the sample on the slide and a solvent exchange head; 、 dispensing a replacement fluid comprising a second solvent from a dispensing orifice in the solvent exchange head; removing effluent from the capillary gap; 1. A method of preparing a specimen slide for analysis, comprising:

38. 38. The method of claim 37, wherein the first solvent comprises water and the second solvent comprises an alcohol. method.

39. 38. The method of claim 37, wherein the effluent comprises a mixture of the first solvent and the second solvent. The method described below.

40. The method further includes passing the effluent through a reservoir, the reservoir containing the second solvent.

40. The method of any one of claims 37 to 39, comprising containing a replacement fluid.

41. The replacement fluid is held under the replacement head during the dispensing and removing steps. The method according to any one of claims 37 to 40, wherein the

42. The solvent exchange head distributes the second solvent through a distribution hole in a middle portion of the solvent exchange head.

42. The method of any one of claims 37 to 41, wherein a medium is dispensed.

43. Partially or completely removing the first solvent from the sample after placement on the slide.

43. The method of any one of claims 37 to 42, further comprising:

44. 44. The method of claim 43, wherein the sample is partially or completely dehydrated by solvent exchange. 。

45. One or more delivery lines provide replacement fluid to the slides, and one or more return lines provide replacement fluid to the slides.

45. The method of claim 44, further comprising removing the effluent from the slide.

46. A path from the delivery line to the return line is provided between capillaries for the solvent to travel.

46. ​​The method of claim 45, further comprising forming a gap.

47. A piezoelectric transducer is applied to the slide to induce high frequency pressure waves to accelerate the solvent exchange. The method according to any one of claims 37 to 46,

48. 38. The method of claim 37, wherein the exchange fluid is applied to the sample for 60 seconds or less for solvent exchange.

48. The method according to any one of claims 1 to 47.

49. 49. Any of claims 37 to 48, wherein the replacement liquid is applied to the sample for about 5 seconds or less.

10. The method according to claim 1.

50. and covering the sample on the slide with a coverslip, The device has a first major surface and a second major surface, and a pressure-sensitive element on the first major surface facing the sample. The method of any one of claims 37 to 49, comprising providing an adhesive.

51. Claims 37-50, wherein the process of covering the sample with a coverslip takes about 5 seconds or less.

10. The method according to any one of the preceding claims.

52. The slide is placed in a slide carrier after the sample is covered with the cover slip.

52. The method of claim 51 , wherein the

53. the process of placing the slide in the slide carrier takes about 5 seconds or less. Item 53. The method according to item 52.

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