WO2010078214A1

WO2010078214A1 - Automated dewatering apparatus

Info

Publication number: WO2010078214A1
Application number: PCT/US2009/069512
Authority: WO
Inventors: Brian Howard Kram; Ethel R. Macrea
Original assignee: Ventana Medical Systems, Inc.
Priority date: 2008-12-31
Filing date: 2009-12-23
Publication date: 2010-07-08

Abstract

An apparatus is used to dewater microscope slides. The apparatus includes a first dewatering assembly with a first roller and a first sheet dispenser and a second dewatering assembly with a second roller and a second sheet dispenser. The first roller uses an absorbent sheet outputted by the first sheet dispenser and the second roller uses an absorbent sheet outputted by the second sheet dispenser to dewater a microscope slide. The absorbent sheets are moved to avoid carryover or contamination between specimens. Each slide is dewatered using different portions of the sheets. The sheets are automatically moved to bring used regions of the sheets into contact with the slides.

Description

AUTOMATED DEWATERING APPARATUS

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit under 35 U. S. C. § 119(e) of U.S. Provisional Patent Application No. 61/142,129 filed on December 31 , 2008. This provisional application is incorporated herein by reference in its entirety.

BACKGROUND

Technical Field

The present invention relates generally to methods and apparatuses for removing fluids from substrates. More specifically, the invention is related to automated dewatering systems for removing water from specimen-bearing microscope slides.

Description of the Related Art

Tissue sections are often carried by microscope slides. Water is used to facilitate transfer of tissue sections (e.g., thin strips of tissue) to the slides. Cut sections of paraffin-embedded tissue samples are one type of tissue section that can float on a bath of warm water to spread or flatten the sections. Water may be entrained in these sections while the sections float on the water. Slides can be manually inserted into the bath to float the tissue sections onto the slides. The wet slides carrying the sections can be pulled from the bath and dried. Because the slides were submerged in the bath, water may be found on the surfaces of the slides. This residual water may not be compatible with many processing liquids, such as non-polar solvents (e.g., xylene or limonene used in many de-waxing operations). Residual water may lead to unwanted degradation or erosion of the sections. Water may be trapped between a slide and a tissue section such that the section floats on the slide. The floating sections are susceptible to movement along the slide. Additionally, the trapped water may prevent adequate adhesion of the tissue to the slide. Water entrained in the tissue section, water on the surfaces of the slide, and water underneath the tissue section is therefore often removed before staining. Different techniques can be used to remove unwanted water. Drying or baking operations are often performed in order to remove water and to enhance or promote tissue adhesion to the slide. Bake operations typically take between about 30 minutes to about 1 hour, and involve relatively large batch bake ovens with an array of racks for holding slides. To remove significant amounts of water, ovens are often set to relatively high temperatures. Wet slides may also be exposed to ambient air to slowly evaporate unwanted water. Wet slides may be batched into racks and may sit, for example, overnight to allow for evaporation. The slides can be manually un-racked and manually placed into a slide processing platform. Paper-based dewatering operations are often used to rapidly remove water. A freshly mounted wet microscope slide can be placed between two sheets (e.g., two 4" x 6" sheets of absorbent paper). A roller is manually rolled over the upper sheet to compress the wet slide between the two sheets and to push water off of the slide. The two sheets may absorb water during this process. The slide is then separated from the two sheets. The two sheets are discarded to prevent carryover (e.g., carryover of tissue or cells, reagents, etc.) between dewatering operations. Unfortunately, this requires that a user manually process each slide, and it may be difficult for the user to apply the same amount of pressure to each slide resulting in inconstant processing.

BRIEF SUMMARY

Certain embodiments disclosed herein are directed to automated apparatuses for dewatering microscope slides or other types of substrates. The apparatuses include a first dewatering assembly and a second dewatering assembly. The first dewatering assembly includes a first roller and a first sheet dispenser. The second dewatering assembly includes a second roller and a second sheet dispenser. The first roller uses an absorbent sheet outputted by the first sheet dispenser and the second roller uses an absorbent sheet outputted by the second sheet dispenser to dewater a slide. Each slide is dewatered using different portions of the two sheets. The sheets are elongate sheets or strips that are automatically moved to bring unused regions of the sheets into contact with the slides.

In other embodiments, an apparatus is adapted to process a plurality of microscope slides that move along a processing line. The apparatus includes a dewatering assembly that has a roller and an absorbent sheet. The roller is configured to successively contact the microscope slides positioned generally along the processing line with the absorbent sheet so as to dewater the slides. In certain embodiments, the slides are automatically delivered along the processing line through the apparatus.

In some embodiments, an apparatus for processing one or more specimen-bearing microscope slides includes a dewatering system, a processing station, and a conveyor. The dewatering system presses an absorbent sheet against a specimen-bearing microscope slide to remove water from at least one side of the specimen-bearing microscope slide. The processing station modifies a specimen on the specimen-bearing microscope slide. The conveyor transports slides between the dewatering system and the processing station.

In some embodiments, a method of processing a specimen on a wet microscope slide is provided. The method includes removing liquid from a wet microscope slide using an absorbent sheet that is pressed against a front surface of the slide by a first roller. Liquid is removed from the slide using an absorbent sheet that is pressed against a back surface of the slide by a second roller.

In other embodiments, a method of processing one or more specimen-bearing microscope slides is provided. The method includes contacting a specimen-bearing microscope slide with an absorbent sheet as the slide moves alongside a roller that presses the absorbent sheet against the slide. After contacting the slide with the sheet, a conveyor moves the slide to a processing station. In yet other embodiments, a method of processing a specimen- bearing microscope slide includes inserting a specimen-bearing microscope slide between a first dewatering assembly and a second dewatering assembly. A first side of the slide is dewatered using a first sheet of the first dewatering assembly. A second side of the slide is dewatered using a second sheet of the second dewatering assembly.

In other embodiments, a method of processing a plurality of specimen-bearing microscope slides includes sequentially delivering a plurality of specimen-bearing microscope slides to a liquid removal assembly. The liquid removal assembly includes a continuous sheet of absorbent material and a roller. Water is removed from the slides using the continuous sheet, which is pressed against the slides by the roller. In some embodiments, the sheet is sequentially pressed against each of the slides by the roller. The liquid removal assemblies can include one or more sheet dispensers, rollers, receivers, motors, or the like. In some embodiments, an apparatus includes a means for successively dewatering a plurality of microscope slides using at least one sheet of absorbent material. In certain embodiments, the means for successively dewatering the microscope slides includes a means for dewatering upper surfaces of the slides and another means for dewatering lower surfaces of the slides. In certain embodiments, the means for successively dewatering the microscope slides includes a pair of dewatering assemblies that contact an upper and lower surface of the respective slides.

In some embodiments, an automated apparatus has motorized components for dewatering wet microscope slides. The apparatus can receive wet slides and dewater the slides without any significant human intervention. In certain embodiments, the motorized apparatus includes a motorized dewatering system, a transport system, and a processing station.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments are described with reference to the following drawings. The same reference numerals refer to like parts or acts throughout the various views, unless otherwise specified.

Figure 1 is a side elevational view of an apparatus for processing wet microscope slides, in accordance with one embodiment.

Figures 2-5 illustrate one method of dewatering a wet microscope slide.

Figure 6 is a flowchart of one method of processing a specimen. Figure 7 is a side elevational view of an apparatus for processing wet microscope slides, in accordance with another embodiment.

Figure 8 is a side elevational view of an apparatus for processing wet microscope slides, in accordance with yet another embodiment.

Figure 9 is a pictorial view of a multi-station apparatus for processing microscope slides, in accordance with one illustrated embodiment.

Figure 10 is a side elevational view of the apparatus of Figure 9. Figure 11 is a cross-sectional view of the apparatus of Figure 9 taken along a line 11-11 of Figure 10.

DETAILED DESCRIPTION

Figure 1 shows a modular automated apparatus 100 for dewatering wet microscope slides. The apparatus 100 can receive wet slides and dewater the slides without any significant human intervention. The apparatus 100 generally includes a dewatering system 110, a transport system 120, and a processing station 130. The dewatering system 110 can dewater wet slides by using a pair of sheets 140, 150. The transport system 120 feeds wet slides to the dewatering system 110 and delivers the dewatered slides exiting the dewatering system 110 to the processing station 130. Wet specimen-bearing slides can be conveniently inserted through an entrance 170 and placed onto the transport system 120 to begin processing. The illustrated transport system 120 is loading a dewatered specimen-bearing slide 180 into a rack 182 and moving a wet specimen-bearing slide 190 towards an entrance 196 of the dewatering system 110, as indicated by an arrow 194. A housing 160 surrounds and protects the moving components of these systems and can reduce, limit, or substantially eliminate specimen contamination during the dewatering process.

Dewatering processes can be performed to remove water from microscope slides, specimens (e.g., tissue sections or other biological samples) carried on microscope slides, and/or other types of substrates used to transport specimens. Dewatering may involve, without limitation, absorbing water, pushing water, blotting, and/or other techniques for removing water. In some embodiments, including the illustrated embodiment of Figure 1 , the sheets 140, 150 can absorb water (e.g., water entrained in specimens, free water on the surfaces of slides, or the like) and/or push free water (e.g., push water off of surfaces of specimens and/or microscope slides). Wet slides can be substantially dried using dewatering processes. For example, dewatering can be performed to remove most or substantially all of the free water on the front and back surfaces of slides. Water can thus be removed from most of the accessible surfaces (i.e., surfaces not underneath the specimens). In some embodiments, dewatering involves removing a sufficient amount of water from a specimen to allow de- waxing, deparaffinizing, or staining without performing an additional drying operation. In some other embodiments, dewatering can remove a sufficient amount of water to significantly reduce the length of subsequent drying periods. With continued reference to Figure 1 , the dewatering system 110 includes an upper dewatering assembly 200 and a lower dewatering assembly 210. The dewatering assemblies 200, 210 can be generally similar to each other and, accordingly, the following description of one of the assemblies applies equally to the other, unless indicated otherwise.

The dewatering assembly 200 includes a roller device 220, a sheet dispenser 230, and a sheet receiver 240. The roller device 220 can press the upper sheet 140 against microscope slides underneath the roller device 220. The dispenser 230 of Figure 1 is in the form of a roll of absorbent material that can be rotated to dispense the sheet 140. The roller device 220, dispenser 230, and receiver 240 cooperate to tension and move the sheet 140. The roller device 220 includes an actuator 241 , a connector 242, and a roller 246 rotatably coupled to a free end of the connector 242. The actuator 241 can adjust the position of the roller 246 with respect to a processing line 250 (shown in dashed line) generally corresponding to path along which the microscope slides travel. The roller 246 can be a generally cylindrical member configured to roll over a specimen-bearing slide. The roller 246 can firmly press the sheet 140 against the microscope slides and/or specimens while minimizing, limiting, or substantially preventing unwanted damage to the specimens.

The roller 246 can have a one-piece or multi-piece construction. In one-piece embodiments, the roller 246 can be a monolithically formed cylindrical member made of rigid materials, compressible materials, or combinations thereof. Figure 2 shows a multi-piece roller 246 including a main body 260 and a cover 270 surrounding the main body 260. The cover 270 can be made, in whole or in part, of a relatively compressible material capable of deforming when the roller 246 rolls over specimens. Compressible materials include, without limitation, closed cell foam, open cell foam, polymers, rubbers, combinations thereof, or the like. The compressible roller 246 can roll over relatively thick delicate specimens without appreciably damaging the specimens. The cover 270 can also be made of other types of materials. For example, the cover 270 can be made, in whole or in part, of a rigid material (e.g., a hard plastic, metal, composites, or the like). Such a cover is well suited to roll across relatively thin specimens, such as thin paraffin- embedded tissue sections, and is wear resistant for a long working life. The one- piece or multi-piece roller 246 can have texturing, grooves, friction enhancing elements, or other features for reducing relative movement (e.g., slipping) between the sheet 140 and the roller 246.

The sheet dispenser 230 of Figure 1 includes a fixed shaft 280 and an absorbent material 231 , illustrated in the form of a roll of the sheet 140, rotatable about the shaft 280. In some embodiments, the roll of absorbent material 231 has a diameter of about 3 inches and a length of about 3 inches. In some embodiments, the dispenser 230 is biased to tension the sheet 140. After the roll of absorbent material 231 is depleted, a user can install a full roll to continue processing.

The sheet 140 can be a lint-free sheet to avoid depositing a significant amount of lint on microscope slides and/or specimens. Lint may interfere with subsequent processing and/or analyses. In some embodiments, the dispenser 230 includes a roll of lint-free absorbent material, such as a continuous sheet of bibulous paper (e.g., highly-absorbent bibulous paper, fibrous paper, or the like). The sheet 140 can be a monolayer or multilayer absorbent sheet made of natural materials (e.g., cotton, cellulose, or the like), synthetic materials (e.g., plastics, polymers, resins, or the like), or combinations thereof. The thickness of the sheet 140 can be less than the thickness of the slides and greater than the thickness of the specimen such that the sheet 140 can absorb most or substantially all of the available water in the specimen.

The length of the continuous sheet 140 can be selected based on the number and lengths of the slides to be processed. For example, the sheet's length can be equal to or greater than the sum of the lengths of the slides to be processed. In some embodiments, the sheet 140 for process multiple slides has a length equal to or greater than about 2 feet, 4 feet, 10 feet, 20 feet, 50 feet, or ranges encompassing such lengths. Each slide can be dewatered with a different section of the sheet 140 to avoid specimen contamination.

The receiver 240 can receive and accumulate the sheet 140. The receiver 240 can include a spool about which the sheet 140 is wound and a motor 290. The motor 290 can rotate the spool clockwise to pull the sheet 140 from the dispenser 230 and move the sheet 140 in the downstream direction. In other embodiments, the receiver 240 is a container for accumulating the sheet 140 and can be periodically emptied to discard used sheets.

The transport system 120 of Figure 1 includes a feed conveyor 310 positioned upstream of the dewatering assemblies 200, 210 and an output conveyor 320 positioned downstream of the dewatering assemblies 200, 210. The feed conveyor 310 moves a downstream end of a microscope slide into the entrance 196 until the microscope slide is sandwiched between the roller 246 and a roller 330 of the dewatering assembly 210. For example, the feed conveyor 310 can move (e.g., push, carry, or both) a microscope slide lengthwise through the entrance 196. The slide is inserted between the upper and lower sheets 140, 150, which are held against the slide as the slide continues through the dewatering system 110. The output conveyor 320 is operable to move slides that have been processed by the dewatering system 110 towards the processing station 130. The output conveyor 320 of Figure 1 is pushing the slide 180 onto a lowermost shelf 334 of the rack 182.

The conveyors 310, 320 can include, without limitation, one or more rollers, belts, pulleys, drive trains, slide manipulators, slide handlers, or the like. The rollers can be idlers, drive rollers, or the like. The feed conveyor 310 of Figure 1 includes a plurality of idlers, a drive roller, and a continuous belt supported by the idlers and drive roller. The drive roller causes movement of the belt for carrying microscope slides.

The processing station 130 of Figure 1 includes the rack 182 configured to hold and store microscope slides. The slides can be conveniently accessed via a door 351. As used herein, the term "processing station" includes, without limitation, a holding station, a drying station (e.g., baking station, oven, or the like), a material removal station (e.g., a de-waxing station, a deparaffinizing station, or the like), a staining station, a cover-slipping station, or the like. The apparatus 100 can have any number of different and types of processing stations. In some embodiments, the processing station 130 includes a baking station, a deparaffinizing station, and a staining station to provide bake through staining processing.

Figure 1 shows the processing station 130 in the form of an oven capable of heating the slides for a drying period, baking period, or the like. A plurality of heating elements 340a, 340b (collectively 340) are used to heat the slides. The heating elements 340 can be resistive heaters, radiant heaters, convection heaters, or other devices that receive electrical energy and generate heat using the electrical energy. Even though the slides have been dewatered, the slides may be further dried in the station 130.

The illustrated rack 182 includes five vertically spaced horizontally oriented shelves, upon which microscope slides can be placed; however, the rack 182 can have any number of shelves in other orientations. The processing station 130 can also have other types of racks that may include, for example, a framework of bars, wires, shelves, combinations thereof, or the like upon which microscope slides can be arranged and held for a desired length of time.

The door 351 can be used to access the dried microscope slides. A user can manually remove the microscope slides from the rack 182 via an access opening 353. Alternatively, the apparatus 100 can be interfaced with another apparatus that is capable of accessing and removing the microscope slides. For example, the apparatus 100 can be mated to a platform (e.g., an automated staining platform). The slides can be transferred from the apparatus 100 to other equipment without any significant user interaction. The apparatus 100 can be portable for conveniently transporting it between various locations. In a laboratory setting, a user can manually transport it between workstations or between equipment found in a laboratory. The dimensions of the portable apparatus 100 can be relatively small. For example, the apparatus 100 can have a length of about 12 inches, a width of about 4 inches, and a height of about 7 inches. Such an apparatus can be easily grasped and carried to a desired location. Moreover, the apparatus's footprint is relatively small allowing placement near other equipment or locations with minimal installation space. Other dimensions of the apparatus 100 are also possible. Figures 2-5 illustrate one method of removing water from a microscope slide. The dewatering assemblies 200, 210 can successively dewater sides in a relatively short amount of time to ensure that the apparatus 100 is ready to accept a freshly mounted wet slide from a user. Different sections of the sheets 140, 150 are used to contact different slides because specimens may be contaminated if cells, tissues, reagents, or the like are transferred between specimens.

Figure 2 shows the entrance 196 in the form of a relatively narrow gap. A height H of the gap 196 can be generally equal to or less than the thickness of the microscope slide. In some embodiments, the height H of the gap 196 is equal to or less that about 5 millimeters, 2 millimeters, 1 millimeter, 0.5 millimeter, or ranges encompassing such heights. In some embodiments, a slide 171 has a length of about 3 inches (75 mm) and a width of about 1 inch (25 mm) and, in certain embodiments, may include a label, such as a barcode. In some embodiments, the slide 171 has a length of about 75 mm, a width of about 25 mm, and a thickness of about 1 mm. The gap 196 can have a height H that is generally equal to or slightly less than about 1 millimeter. The microscope slide 171 can be in the form of standard microscope slides. In other embodiments, the assemblies 200, 210 can bear against one another prior to receiving a slide. The entrance 196 is the contact interface between the assemblies 210, 210. Figure 3 shows a leading end 350 of the microscope slide 171 after it has been inserted between the rollers 246, 330. Figure 4 shows dewatering of a specimen 370 and the microscope slide 171. The sheet 140 is compressed between the roller 246 and the slide 171 and the sheet 150 is compressed between the roller 330 and the slide 171 in order to absorb free water on the surfaces of the slide 171. The rollers 246, 330 roll along most or substantially all of the longitudinal length of the slide 171. The sheets 140, 150 can continuously contact the slide 171 as the slide 171 moves downstream along the processing line 250. In this manner, the entire longitudinal length of the slide 171 can be automatically dewatered.

In the illustrated embodiment, the upper sheet 140 removes water from an upper surface 360 of the slide 171. The lower sheet 150 removes water from a lower surface 362 of the slide 171. As the specimen 370 is brought into contact with the upper sheet 140, at least a portion of the water 380 surrounding, underneath, and/or proximate to the specimen 370 may be absorbed by the sheet 140. As the roller 246 travels across the specimen 370, the specimen 370 can be compressed to remove entrained water. In some embodiments, the rollers 246, 330 cooperate to push water off of the slide 171 and/or specimen 370. Water 384 in Figure 4 can be pushed by the dewatering assemblies 200, 210 along the slide 171 until the water 384 is ultimately pushed off of the slide 171. This process can be performed without any significant streaking. A wide range of different types of squeeging processes can be performed by the apparatuses 100.

Clean dry regions of the sheets 140, 150 can be continuously brought into contact with the slide 171 and/or specimen 370. As the slide 171 of Figure 4 is moved along the process line 250, the roller 246 rotates clockwise and the roller 330 rotates counterclockwise to move the sheets 140, 150 at generally the same speed as the slide. This can reduce or substantially eliminate relative movement between the slide 171 and one or both sheets 140, 150. In some embodiments, the sheets 140, 150 and slide 171 move together (e.g., in unison) to minimize, limit, or substantially prevent slipping, streaking, or the like. The rollers 246, 330 can thus travel smoothly along the surfaces 360, 362. Additionally, if the specimen 370 is floating on water, the specimen 370 can remain generally stationary with respect to the microscope slide 171 during dewatehng. As shown in Figure 5, the roller 246 can deform to limit or prevent unwanted flattening of the specimen 370. The sheet 140 can be firmly pressed against the specimen 370 and the slide 171 without applying excessive compressive pressures. Such embodiments are well suited for processing relatively thick specimens. The roller 246 can be a rigid roller to roll over relatively thin specimens, such as a section of tissue with a thickness that is less than about 10 microns. A microtome can cut a biological sample into thin sections, for example, slices on the order of about 5 microns to about 6 microns thick. Hard rollers are well suited to dewater these types of thin specimens.

The method shown in Figures 2-5 can be used to remove a substantial portion of the free water disposed on the microscope slide 171. In some embodiments, at least 50%, 70%, 90%, 95%, or 98% of the water by weight on the slide 171 can be removed. The apparatus 100 can also be used to remove other liquids, such as stains, de-waxing fluids (e.g., xylene, limonene, or the like), or other processing liquids. The apparatus 100 can be integrated into staining platforms, de-waxing platforms, and the like. The pressure applied to the slides, the characteristics of the sheets, and dimensions and physical properties of the rollers can be selected based on the liquid to be removed and the characteristics of the specimen. The sheets can be absorbent sheets, lint-free sheets, absorbent lint-free sheets, or other types of sheets depending on the processing criteria. Figure 6 is a flow diagram of one method of preparing and analyzing a specimen. Generally, a specimen can be prepared and placed on a microscope slide. The specimen-bearing microscope slide is loaded into the apparatus 100. The apparatus 100 removes water to prepare the specimen for subsequent processing. This method is discussed in detail below. Specimens in the form of biological samples (e.g., samples of tissue) can be processed to preserve their characteristics, such as the tissue structure, cell structure, or the like. The tissue can be any collection of cells mountable on a substrate including, without limitation, a section of an organ, tumor section, bodily fluid, smear, frozen section, cytology prep, or cell lines. For example, the tissue sample can be a sample obtained using an incisional biopsy, a core biopsy, an excisional biopsy, a needle aspiration biopsy, a core needle biopsy, a stereotactic biopsy, an open biopsy, a surgical biopsy, or the like.

At 410, a fixative is used to fix and preserve the sample. Fixatives can fix and preserve cellular structure, inhibit or substantially stop enzymatic action that may result in the purification or autolysis of the tissue, or the like. The fixation process can increase the rigidity of the tissue, thereby making it more convenient to section, as detailed below. Formaldehyde, ethanol, acetone, paraformaldehyde, or other types of fixatives can be used. The type and number of fixatives can be selected based on the desired processes to be performed, such as staining, cytological staining, immunohistochemistry, or in-situ hybridization. After fixing the tissue sample, the tissue sample can be stored for a desired length of time.

At 420, the sample is embedded in a material that has mechanical properties that may facilitate sectioning. Materials for embedding include, but are not limited to, paraffin, resin (e.g., plastic resins), polymers, agarose, nitrocellulose, gelatin, mixtures thereof, or the like. In some embodiments, the embedding material comprises mostly or entirely of paraffin. Paraffin is a white or generally colorless water insoluble solid substance that is resistant to many reagents. For example, paraffin can be a mixture of hydrocarbons chiefly of the alkaline series obtained from petroleum. A wide range of different mixtures of similar hydrocarbons can be used to make paraffin, and these mixtures can be solid, semi-solid, and/or oily. In some embodiments, the paraffin is a wax.

Different conventional impregnating processes can be used to at least partially embed material in the tissue sample. The tissue sample can be mixed or combined with material that can permeate the tissue sample so as to impart properties that facilitate a cutting process. If the tissue sample is to be sectioned with a microtome or similar device, the tissue sample can be embedded in paraffin or similar material. If the embedding material is paraffin, the paraffin can be heated and melted. The hot liquid paraffin at least partially impregnates the sample and is subsequently solidified.

At 430, the embedded specimen is cut into mountable sections. A microtome can cut the specimen into thin sections, for example, slices on the order of about 5 microns to about 6 microns thick. Each section can include a portion of the tissue sample and some of the embedding material.

At 440, the sections are transferred to microscope slides. In some embodiments, the cut sections are floated on water to spread or flatten the sections. If the sections are pieces of paraffin embedded tissue, the sections can be floated on a warm bath to keep the sections in generally flat configurations. Water may be entrained in the tissue sections while the sections float on the bath. The water may be de-ionized water, double-distilled de-ionized water, purified water, or the like.

A microscope slide can be inserted into the warm bath. A front surface of the slide is used to pick up one or more tissue specimens. To examine multiple tissue samples (e.g., a set of tissue samples, each taken at a different location of a subject) using a single slide, a plurality of the tissue samples may be sequentially floated onto the slide. After floating the specimen(s) onto the slide, the slide is removed from the water. A user can manually prepare slides one at a time. Residual water may be found on many of the surfaces of the specimen- bearing slides. Water can also be trapped between the slide and the thin sections of tissue.

In some embodiments, a droplet of water can be deposited by directly dropping water onto the front surface of a microscope slide and thereafter placing the specimen on top of the droplet. Thus, specimens can be mounted with or without utilizing a bath.

At 450, wet slides are successively delivered into the apparatus 100. A user can manually insert wet slides into the entrance 170 immediately after the specimens are transferred to the slides. The apparatus 100 can have one or more sensors that evaluate whether a loaded slide is ready for dewatehng. Once the apparatus 100 determines that a microscope slide has been fed into the entrance 170, the dewatering system 110 and conveyor system 120 begin to operate. In continuous operation modes, the dewatering system 110 and conveyor system 120 can operate continuously.

The dewatering assemblies 200, 210 can dewater slides in a relatively short amount of time to ensure that the apparatus 100 is ready to accept a freshly mounted wet slide. The mounting process at 440 may take longer than 20 seconds. In some embodiments, the apparatus 100 can dewater a slide in less than about 20 seconds, 10 seconds, or 5 seconds so that the apparatus does not limit throughput. A user can repeatedly transfer specimens to slides and can feed the freshly mounted wet slides into the apparatus 100 without waiting for the apparatus 100 to process any slides.

After dewatering, specimens can be subjected to further processing. In some embodiments, the dewatering process may remove a sufficient amount of water to ready the specimen for staining protocols. In some embodiments, an additional drying process can be performed to remove additional water. The drying process can take less than about 5 minutes, 1 minute, or about 30 seconds. In some embodiments, the apparatus 100 can dewater and dry a wet slide in less than about 2 minutes, 1.5 minutes, 1 minute, or 30 seconds. The dewatering system 110 and the station 130 may cooperate to completely dry the specimen- bearing microscope slide in less than about 4 minutes, 2 minutes, 1 minute, or about 30 seconds. Other processing times are also possible and can be selected based on the type and size of the specimen, amount of water to be removed, or the like.

At 460, the specimen is stained for examination. The specimen can also be baked, de-waxed, deparaffinized, or the like. One or more of these processes can be performed by the modular apparatus 100. Dewatered slides can be dried in the processing station 130 to remove water in the specimen or any residual free water on the surfaces of the slide. In some embodiments, a stain is applied to the specimen after performing a deparaffinizing process using the apparatus 100. In some embodiments, the apparatus 100 can de-wax or deparaffinize the specimen in less than about 2 minutes, 1.5 minutes, 1 minute, or 30 seconds. The microscope slide is then cover slipped for subsequent optical examination.

At 470, the specimen is examined using optical equipment (e.g., a microscope), optical instruments, or the like. Different types of examination processes can be used to perform a wide range of different tissue analyses for obtaining information about pathology, tissue composition, and the tissue architecture. A physician can use this information to diagnose different types of illnesses and to perform medical research.

Figure 7 shows a processing apparatus 500 that includes a dewatehng system 510 for processing one side of a microscope slide 570. A conveyor 520 carries the slide 570 alongside a roller 546. A sheet 540 extends between a sheet dispenser 530 and a sheet receiver 599. The dispenser 530 can include a roll of absorbent material and a housing surrounding the roll of absorbent material. The sheet dispenser 530 may further include, without limitation, one or more motors or other components for controlling movement of the sheet 540. The conveyor 520 includes a plurality of spaced-apart rollers that rotate counterclockwise to move the slide 570 away from an entrance 562 towards an exit 564. The continuous sheet 540 extends about a guide roller 590, the roller 546, a guide roller 598, and into the receiver 599. The roller 546 is a generally cylindrical roller having a one-piece construction and is rotatable about a fixed shaft 548.

Referring to Figure 8, a processing apparatus 571 includes an upper dewatehng assembly 572 and a lower dewatehng assembly 574. The upper dewatehng assembly 572 has a roller 576 that moves across a microscope slide 578 resting on a support member 580 of the assembly 574. The lower surface of the slide 578 rests on a lower sheet 592 between the slide 578 and the support member 580. The illustrated roller 576 moves along a rail 582 from a first position 586 to a second position 587 (shown in dashed line) to contact substantially the entire upper surface of the slide 578. The slide 578 is pressed against the lower sheet 592 as the roller 576 is moved and can remain generally stationary during this process.

In operation, a feed conveyor 594 moves the slide 578 along a processing line 595 until the slide 578 rests on the lower sheet 592. The lower sheet 592 is moved in the downstream direction (indicated by the arrow 596) until the slide 578 is supported by the support member 580. The roller 576 is then moved from the first position 586 to the second position 587. The lower sheet 592 is moved to transfer the dewatered slide 578 to an output conveyor 598 and to position a dry section of the sheet 592 on the support member 580. The upper sheet 590 can be moved in the downstream direction 596 to position a dry section of the sheet 590 above the support member 580. The roller 576 can be returned to the first position 586 before another wet slide is placed on the support member 580.

Figure 9 shows an apparatus 600 that includes a plurality of processing stations 602, 604, 606, 608. A controller 610 controls operation of one or more of the processing stations 602, 604, 606, 608. In some embodiments, the processing station 602 is a dewatering station. The processing stations 604, 606, 608 can be a deparaffinizing station, staining station, and cover-slipping station, respectively. The illustrated controller 610 is communicatively coupled to and commands each of the stations 602, 604, 606, 608. Microscope slides can be automatically processed (e.g., via a process that is substantially free of human intervention) using the apparatus 600.

A transport device 618 transports specimen-bearing microscope slides between the drying station 602 and the other stations 604, 606, 608. The transport device 618 can include, without limitation, one or more conveyor, elevators, slide handlers, slide trays, slide holders, or the like. Slide handlers can include, but are not limited to, slide manipulators, X-Y-Z transport systems, robotic systems, or other automated systems capable of receiving and transporting slides. A robotic system can include, without limitation, one or more pick and place robots, robotic arms, or the like.

Referring to Figures 10 and 11 , the drying station 602 includes a dewatehng apparatus 601 and a slide handler 620, illustrated as a robotic slide handler. The apparatus 601 can remove water from wet microscope slides. The robotic slide handler 620 includes an arm 621 and an end effector 623 capable of picking up and carrying slides between the apparatus 601 and a slide transporter 624, illustrated schematically in Figure 11. The apparatus 601 can be generally similar to the processing apparatuses disclosed herein. Various types of other automated slide processing systems can also have the slide dryers and other features disclosed herein. For example, U.S. Application No. 10/414,804 (U.S. Publication No. 2004/0002163) discloses various types of slide transporters, processing stations, and the like that can be used with or incorporated into the embodiments and features disclosed herein.

Wet microscope slides carrying freshly cut tissue specimens can be processed using the apparatus 600. An access door 630 can be opened, and a user can load specimen-bearing slides into the transport device 618. The transport device 618 can load the slides into the drying station 602. After water removal, the slides are sequentially delivered to the stations 604, 606, 608. The transport device 618 of Figure 11 includes an elevator system 630 and a movable platform 634, shown carrying the slide transporter 624. The elevator system 630 moves the transporter 624 up and down a rail 640.

In some methods of using the apparatus 600, specimen-bearing microscope slides are loaded onto a slide tray, which is placed on the platform 634. The slide handler 620 loads the specimen-bearing microscope slides into the apparatus 601. The apparatus 601 dewaters the specimen-bearing microscope slides. After the specimen-bearing microscope slides are dried a sufficient amount, the slide handler 620 transports the slides back to the transporter 624. The transporter 624 is vertically lowered and positioned adjacent to the processing station 604 for deparaffinizing. The station 604 is capable of removing at least a portion of the embedding material of the specimen. The deparaffinizing station 604 can be a bath-type, deparaffinizing station, or a spray- type, deparaffinizing station. The illustrated deparaffinizing station 604 includes a modular compartment 614 and includes one or more wash dispense nozzles 616 directed downwardly. Deparaffinizing substances are delivered onto the specimens using the nozzles 616. After removing the embedding material (e.g., paraffin), the slides can be rinsed with substances, such as de-ionized water, to remove the deparaffinizing substance and the extra paraffin leaving the bare tissue sample adhered to the microscope slide. Various deparaffinizing substances may be used at the station 604.

For example, the deparaffinizing substances can be fluids, for example, aqueous- based fluids that promote separation of paraffin and tissue specimens, such as those disclosed in U.S. Patent No. 6,855,559, issued February 15, 2005 and U.S. Patent No. 6,544,798, issued April 8, 2003, including de-ionized water, citrate buffer (pH 6.0-8.0), tris-HCI buffer (pH 6-10), phosphate buffer (pH 6.0-8.0), acidic buffers or solutions (pH 1-6.9), basic buffers or solutions (pH 7.1-14), or the like. The substance may also contain one or more ionic or non-ionic surfactants. The deparaffinizing substances can be heated. For example, the substances (e.g., fluids) may be heated to a temperature greater than the melting point of the embedding material, e.g., between 60-70 degrees Celsius. U.S. Patent No. 7,303,725, issued December 4, 2007, discloses various components (e.g., probes, filters, sprayers, etc.) for use with deparaffinizing substances.

After the station 604 has processed the specimen-bearing slides, the transport system 624 delivers the specimen-bearing slides to the station 606 for staining. A desired stain is applied to the tissue samples. The stain can be a biological or chemical substance which, when applied to targeted molecules in tissue, renders the tissue detectable under an instrument. Stains include, without limitation, detectable nucleic acid probes, antibodies, hematoxylin, eosin, and dyes (e.g., iodine, methylene blue, Wright's stain, etc.).

After the specimens are stained, the specimen-bearing slides are transported to the cover-slipping station 608. In other embodiments, the station 608 is a drying station. The station 608 removes stain from the slides and the slides are ready for cover slipping. In some embodiments, the drying station 608 is similar to the apparatus 100 of Figure 1 , apparatus 500 of Figure 7, or the apparatus 571 of Figure 8.

The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments. These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Claims

CLAIMS What is claimed is:

1. An automated apparatus for processing a microscope slide carrying a specimen, the apparatus comprising: a first dewatering assembly including a first roller and a first sheet dispenser; and a second dewatering assembly including a second roller and a second sheet dispenser, the first roller adapted to use a first sheet outputted by the first sheet dispenser and the second roller adapted to use a second sheet outputted by the second sheet dispenser to dewater the microscope slide.

2. The automated apparatus of claim 1 , further comprising a feed conveyor positioned to insert the microscope slide between the first dewatering assembly and the second dewatering assembly.

3. The automated apparatus of claim 1 , further comprising: a rack; and a transport system operable to move a microscope slide that has been processed by the first dewatering assembly and the second dewatering assembly towards the rack.

4. The automated apparatus of claim 1 , wherein the first roller is positioned and configured to roll along a longitudinal length of the microscope slide while the first sheet is between the first roller and the microscope slide.

5. The automated apparatus of claim 1 , wherein the first sheet dispenser is configured to output the first sheet while the first roller presses the first sheet against at least one of the microscope slide and the specimen.

6. The apparatus of claim 1 , wherein the first dewatering assembly and the second dewatering assembly are adapted to simultaneously remove water from a microscope slide having a thickness equal to or less than about 5 mm.

7. An apparatus for processing a plurality of microscope slides that move along a processing line, the apparatus comprising: a dewatering assembly including a roller and an absorbent sheet, the roller positioned to successively contact the plurality of microscope slides located generally along the processing line with the absorbent sheet so as to dewater the plurality of microscope slides.

8. The apparatus of claim 7, wherein the dewatering assembly is operable to contact each of the microscope slides with a different region of the absorbent sheet.

9. The apparatus of claim 7, further comprising another dewatering assembly configured to successively contact the plurality of microscope slides such that the dewatering assemblies remove water on opposite sides of the microscope slides.

10. The apparatus of claim 7, further comprising: a feed conveyor positioned to move the microscope slides towards the dewatering assembly; and an output conveyor positioned to move the microscope slides away from the dewatering assembly.

11. The apparatus of claim 10, further comprising a microscope slide rack positioned to receive the microscope slides from the output conveyor.

12. The apparatus of claim 7, wherein the dewatering assembly includes a sheet dispenser that holds a roll of the absorbent sheet.

13. The apparatus of claim 7, wherein the dewatering assembly and another dewatering assembly cooperate to dewater an upper surface and a lower surface of each of the microscope slides when the respective microscope slides move along the processing line.

14. An apparatus for processing a specimen-bearing microscope slides, the apparatus comprising: a dewatering system adapted to press an absorbent sheet against a specimen-bearing microscope slide to remove water from at least one side of the specimen-bearing microscope slide; a processing station adapted to modify a specimen on the specimen- bearing microscope slide; and a conveyor configured to transport the specimen-bearing microscope slide between the dewatering system and the processing station.

15. The apparatus of claim 14, wherein the dewatering system includes a roller that rolls along most of a longitudinal length of the specimen- bearing microscope slide.

16. The apparatus of claim 14, wherein the dewatering system includes a roller that rolls along the specimen-bearing microscope slide while pressing the absorbent sheet against the specimen-bearing microscope slide.

17. The apparatus of claim 14, wherein the dewatering system and the processing station are operable to dry a wet specimen-bearing microscope slide in less than 2 minutes.

18. The apparatus of claim 14, wherein the dewatering system includes a first roller and a second roller that simultaneously remove water from an upper surface of the specimen-bearing microscope slide using the absorbent sheet and a lower surface of the specimen-bearing microscope slide using another absorbent sheet.

19. The apparatus of claim 14, wherein the conveyor is operable to receive a specimen-bearing microscope slide outputted by the dewatering system and to carry the outputted specimen-bearing microscope slide towards the processing station while the dewatering system removes water from another microscope slide.

20. The apparatus of claim 14, further comprising: a rack in the processing station, the rack configured to hold at least one microscope slide, wherein the processing station generates heat for heating any microscope slides held by the rack for a drying period; and a transfer device positioned to transport microscopes slides between the processing station and another processing station adapted to modify specimens on the microscope slides.

21. The apparatus of claim 14, wherein the processing station is a deparaffinizing station configured to deliver at least one deparaffinizing fluid towards the specimen.

22. A method for processing a specimen on a wet microscope slide, the method comprising: removing liquid from a wet microscope slide using an absorbent sheet that is pressed against a front surface of the microscope slide by a first roller; and removing liquid from the wet microscope slide using an absorbent sheet that is pressed against a back surface of the microscope slide by a second roller.

23. The method of claim 22, further comprising contacting the microscope slide with the absorbent sheets while the first roller and the second roller rotate.

24. The method of claim 22, further comprising: delivering a plurality of microscope slides successively contacted by the absorbent sheets to a rack; and drying the plurality of microscope slides held by the rack.

25. The method of claim 22, wherein each of the microscope slides is contacted by different regions of each of the absorbent sheets.

26. A method of processing a wet microscope slide, the method comprising: contacting a microscope slide with an absorbent sheet as the microscope slide moves alongside a roller that presses the absorbent sheet against the microscope slide; and after contacting the microscope slide, moving the microscope slide to a processing station using a transport device.

27. The method of claim 26, wherein contacting the microscope slide with the absorbent sheet includes rolling the roller along the microscope slide while the roller presses the absorbent sheet against the microscope slide.

28. The method of claim 26, further comprising: drying a tissue section on the microscope slide using the processing station.

29. The method of claim 28, wherein contacting the microscope slide and drying of the tissue section are completed in less than about 2 minutes.

30. A method of processing a specimen-bearing microscope slide, comprising: inserting a specimen-bearing microscope slide between a first dewatehng assembly and a second dewatering assembly; dewatering a first side of the specimen-bearing microscope slide using a first sheet of the first dewatering assembly; and dewatering a second side of the specimen-bearing microscope slide using a second sheet of the second dewatering assembly.

31. The method of claim 30, further comprising: rotating a first roller of the first dewatering assembly to press the first sheet against the first side of the specimen-bearing microscope slide; and rotating a second roller of the second dewatering assembly to press the second sheet against the second side of the specimen-bearing microscope slide.

32. The method of claim 30, further comprising: moving the first sheet towards the first roller as the first roller rotates; and moving the second sheet towards the second roller as the second roller rotates.

33. The method of claim 30, wherein the first side and the second side of the specimen-bearing microscope slide are simultaneously dewatered.

34. The method of claim 30, further comprising: delivering the first sheet from a first dispenser while dewatehng the first side; and delivering the second sheet from a second dispenser while dewatehng the second side.

35. A method of processing a plurality of wet microscope slides, the method comprising: sequentially delivering a plurality of microscope slides to a liquid removal assembly, the liquid removal assembly including an continuous sheet of absorbent material; and removing water from each of the microscope slides by contacting each of the microscope slides with the continuous sheet.

36. The method of claim 35, further comprising pressing the continuous sheet against each of the microscope slides using a roller.

37. The method of claim 35, wherein removing water from each of the microscope slides includes contacting each of the microscope slides with a different section of the continuous sheet.

38. The method of claim 35, further comprising: processing at least one specimen on one of the microscope slides using a deparaffination station after sequentially delivering one of the microscope slides to the liquid removal assembly.

39. The method of claim 35, further comprising: moving the microscope slides from the liquid removal assembly to a rack using a conveyor.