Xylene-free tissue processing apparatus and method for processing tissue - Patents.com

Abstract

A tissue processing device and a method for tissue processing performed by the tissue processing device are provided. [Solution] An improved method for tissue processing or tissue processing device is capable of supporting xylene-free processing and is capable of effectively removing substitutes for xylene (isopropanol, IPA, etc.) without the addition of additional protective chemical reagents to remove isopropanol, thereby simplifying tissue processing methods and significantly reducing costs.

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates to the field of tissue processing, and in particular to tissue processing devices and methods for tissue processing with a tissue processing device. [Background technology]

[0002] Biological tissue samples are very important for biological research, pathological detection or other related fields. Tissue processing methods usually include the steps of fixing tissue samples, dehydrating the fixed tissue samples with a dehydration reagent, cleaning the dehydrated tissue samples with a cleaning reagent to remove the dehydration reagent, and infiltrating the cleared (cleaned) tissue samples with a carrier material. Xylene, a colorless and transparent liquid that has strong irritation and is harmful to the human body as a carcinogen, is commonly used to remove dehydration reagents such as ethanol in tissue sump in tissue processing methods. It is necessary to remove xylene to ensure a good working environment.

[0003] It has been proposed to use a substitute for xylene, such as isopropanol, abbreviated as IPA, in tissue processing methods. CN101929927B discloses a xylene-free method for processing tissue samples, which includes the addition of a carrier material protection reagent, such as PARALAST, to remove isopropanol in the tissue sample and reactor after cleaning the dehydrated tissue sample with isopropanol, so as to reduce the amount of isopropanol mixed into the carrier material, such as paraffin. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Chinese Patent No. 101929927 Summary of the Invention [Problem to be solved by the invention]

[0005] However, this xylene-free method requires the use of additional reagents (such as PARALAST), resulting in expensive costs and complicated processes due in part to the disposal of waste chemical reagents such as PARALAST. Furthermore, other existing tissue processing methods or devices that support xylene-free processing often experience ingress of carrier material into the air system, which results in increased maintenance costs and reduced device lifespan due to blocking of the air system.

[0006] Thus, there is an urgent need for improved xylene-free processing devices and tissue processing methods using same, particularly those capable of removing isopropanol in an effective, low cost and simple manner. [Means for solving the problem]

[0007] SUMMARY OF THE DISCLOSURE The present disclosure seeks to alleviate, at least in part, at least one of the problems existing in the related art. Accordingly, a tissue processing device and a method for tissue processing performed by the tissue processing device are provided.

[0008] In a first aspect, in an embodiment, configured to receive a tissue sample and allow the tissue sample to be processed; a first carrier material inlet (101), a first carrier material outlet (102), a processing reagent inlet (103), a processing reagent outlet (104) and a first gas outlet (105); A reactor (100); a second carrier material outlet (201) configured to receive a carrier material and connected to the first carrier material inlet (101) of the reactor (100) and a second gas outlet (202); A carrier material container (200); a second heater (300) configured to heat the carrier material in the carrier material container (200); The reactor (100) has a first air inlet (401) and a first liquid outlet (402) connected to a first gas outlet (105), configured to condense at least a portion of the gas from the reactor (100) into a liquid; A first capacitor (400); a first liquid container (500) connected to the first liquid outlet (402) of the first condenser (400) and configured to receive condensate from the first condenser (400); A tissue processing device (1) is provided, comprising:

[0009] According to the embodiment(s), the tissue processing device provided in the present disclosure is capable of supporting xylene-free processing and allows for effective removal of xylene substitutes (or alternatives, such as isopropanol, IPA, etc.) during processing without the further addition of protective chemical reagents (such as PARALAST) to remove isopropanol, significantly reducing costs while simplifying tissue processing methods.

[0010] In one embodiment, the tissue processor (1) comprises an on-off valve (600) disposed in a pipe connecting the first carrier material inlet (101) of the reactor (100) and the second carrier material outlet (201) of the carrier material container (200); Preferably, the on-off valve (600) is configured to operate in a cycle each including an open time of 1-10 seconds, preferably 1.5 seconds, and a close time of 0.2-5 seconds, preferably 1.0 second.

[0011] According to this embodiment, the supply speed of carrier material such as molten paraffin from the carrier material container 200 to the reactor 100 can be slowed down, and the isopropanol in the molten paraffin can be properly separated from the paraffin under the operating condition (i.e., high temperature and negative pressure), thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short period of time when the molten paraffin is filled into the reactor 100 under the operating condition, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0012] In another embodiment, the tissue processing apparatus (1) further comprises a first pressure control device (700) configured to control the reactor (100) to be operated under a pressure as follows: First stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes, preferably 15 minutes; Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes.

[0013] According to this embodiment, the pressure in the reactor is gradually reduced so that isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, which prevents the isopropanol in the paraffin from generating a large amount of foam in a short time when filling the molten paraffin into the reactor under operating conditions, and further avoids the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0014] In another embodiment, the tissue processing device (1) further comprises a first heater (800) configured to heat the processing reagents and / or carrier material in the reactor (100), preferably the first heater (800) is a heated lid; Optionally, the first heater (800) is configured to control the reactor (100) to operate at a temperature of: The temperature is increased from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and then maintained at 75-90°C, preferably 85°C, for 30-40 minutes.

[0015] According to this embodiment, the temperature of the reactor is gradually increased so that isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under operating conditions, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0016] In another embodiment, the tissue processor (1) comprises a second condenser (900) having a second air inlet (901) and a second liquid outlet (902) connected to the second gas outlet (202) of the carrier material container (200) and configured to condense at least a portion of the gas from the carrier material container (200) into a liquid; a second liquid container (1000) connected to the second liquid outlet (902) of the second condenser (900) and configured to receive condensate from the second condenser (900); Further includes.

[0017] In this embodiment, the first condenser (400) and the second condenser (900) each include a cooling coil (403), and optionally further include a cooling fan (404) and a cooling channel (405) surrounding the cooling coil (403).

[0018] According to this embodiment, the isopropanol in the carrier material can be completely removed.

[0019] In another embodiment, the tissue processor (1) comprises a pressure of -20 to -75 kPa, preferably -40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds; Optionally, atmospheric pressure for 5 seconds to 15 seconds, preferably 6 seconds; and a second pressure control device (1100) configured to control the carrier material container (200) to be operated under pressure in cycles each including:

[0020] According to this embodiment, the isopropanol in the carrier material can be completely removed.

[0021] In another embodiment, the tissue processing device (1) further comprises a processing reagent container (1200) having an outlet (1201) and a return inlet (1202), the outlet (1201) is connected to a processing reagent inlet (103) of the reactor (100), and the recovery inlet (1202) is connected to a processing reagent outlet (104) of the reactor (100); Preferably, the outlet (1201) and the recovery inlet (1202) are provided separately or combined into the same arrangement; Preferably, the processing reagent vessels (1200) include a fixation reagent vessel, a dehydration reagent vessel, a cleaning reagent vessel and optionally a carrier material protection reagent vessel.

[0022] In another embodiment, The first carrier material inlet (101) and the first carrier material outlet (102) of the reactor (100) are arranged separately or combined into the same arrangement; Optionally, the second carrier material inlet and the second carrier material outlet (201) of the carrier material container (200) are arranged separately or combined into the same arrangement, and optionally, the processing reagent inlet (103) and the processing reagent outlet (104) of the reactor (100) are arranged separately or combined into the same arrangement.

[0023] In a second aspect, in an embodiment A method for tissue processing performed by the tissue processing device (1) according to the first aspect, comprising: Providing a tissue sample to be processed into a reactor; Fixing the tissue sample with a fixative; dehydrating the fixed tissue sample with a dehydration reagent; cleaning the dehydrated tissue sample and the reactor with a cleaning reagent to remove the dehydration reagent; providing a carrier material from a carrier material container to the reactor to infiltrate the cleared tissue sample, the carrier material including a cleaning reagent; controlling the reactor to a temperature at which a first cleaning reagent vapor is generated from the carrier material; Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is discharged to the outside of the reactor; and condensing the exhausted first cleaning reagent vapor into a liquid by a first condenser to remove the first cleaning reagent vapor; A method is provided that includes:

[0024] According to the embodiment, the method for tissue processing can effectively and efficiently remove cleaning reagents (such as isopropanol) within the carrier material, thereby avoiding the addition of isopropanol removal reagents and subsequent waste chemical reagent disposal, reducing processing costs and being environmentally friendly.

[0025] In one embodiment, the method of the present disclosure further comprises supplying carrier material from the carrier material container to the reactor to infiltrate the cleared tissue sample, and controlling the carrier material supplied from the carrier material container to the reactor by an on-off valve in a cycle each including an open time of 1 to 10 seconds, preferably 1.5 seconds, and a closed time of 0.2 to 5 seconds, preferably 1.0 second.

[0026] According to this embodiment, the supply speed of carrier material such as molten paraffin from the carrier material container 200 to the reactor 100 can be slowed down, and the isopropanol in the molten paraffin can be properly separated from the paraffin under the operating condition (i.e., high temperature and negative pressure), thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short period of time when the molten paraffin is filled into the reactor 100 under the operating condition, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0027] In another embodiment, Controlling the reactor to a temperature at which the first cleaning reagent vapor is generated from the carrier material further comprises controlling the reactor to operate at a temperature of The temperature is increased from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and maintained at 75-90°C, preferably 85°C, for 30-40 minutes.

[0028] According to this embodiment, the temperature of the reactor is gradually increased so that isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working conditions, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0029] In another embodiment, Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is exhausted outside the reactor further comprises controlling the reactor to be operated at a pressure of: First stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes, preferably 15 minutes; Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes.

[0030] According to this embodiment, the pressure in the reactor is gradually reduced so that isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, to prevent the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working conditions, and further to avoid the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0031] In another embodiment, the method of the present disclosure comprises: removing a cleaning reagent from the carrier material container by a second condenser prior to delivering the carrier material from the carrier material container to the reactor; removing the cleaning reagent from the carrier material container by a second condenser; and controlling the carrier material container to a temperature at which a second cleaning reagent vapor is generated from the carrier material; controlling the carrier material container to be operated under a pressure in a cycle in which the generated second cleaning reagent vapor is exhausted to the outside of the carrier material container; Each cycle is a pressure of -20 to -75 kPa, preferably -40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds; and Optionally, ambient pressure for 5 seconds to 15 seconds, preferably 6 seconds; and condensing the exhausted second cleaning reagent vapor into a liquid by a second condenser to remove the second cleaning reagent vapor; Optionally further comprising:

[0032] According to this embodiment, the isopropanol in the carrier material can be completely removed.

[0033] In another embodiment, the method of the present disclosure further comprises providing a carrier material protection reagent to the reactor to remove the cleared tissue sample and cleaning reagents in the reactor before providing the carrier material from the carrier material container to the reactor; Preferably, the carrier material protection reagent comprises a cleaning reagent substitute, a mixture of a cleaning reagent substitute and a cleaning reagent, and a mixture of a cleaning reagent substitute and a carrier material.

[0034] Both the foregoing general description and the following detailed description are intended to be illustrative and are not to be construed as limiting the present disclosure. [Brief description of the drawings]

[0035] These and / or other aspects and advantages of the embodiment(s) of the present disclosure will become apparent and will be more readily appreciated from the following description taken in conjunction with the drawings. [Figure 1] FIG. 1 is a schematic diagram of a tissue processing device 1 according to one embodiment of the present disclosure. [Diagram 2] FIG. 2 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Diagram 3] FIG. 3 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Figure 4] FIG. 4 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Diagram 5] FIG. 5 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Figure 6] FIG. 6 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Figure 7] FIG. 7 is another schematic diagram of the tissue processing device 1 according to one embodiment of the present disclosure. [Figure 8A] FIG. 8A is a schematic diagram of a tissue processor 2 according to one embodiment of the present disclosure. [Figure 8B] FIG. 8B is a schematic diagram of tissue processing device 2 according to one embodiment of the present disclosure. [Figure 9]FIG. 9 is a schematic process flow diagram of a tissue processing device according to some embodiments of the present disclosure. [Figure 10] FIG. 10 is a flowchart of a method S1 for tissue processing according to some embodiments of the present disclosure. [Figure 11] FIG. 11 is another flow chart of a method S1 for tissue processing according to an embodiment of the present disclosure. [Figure 12] FIG. 12 is a flow chart of step S900 of a method S1 for tissue processing in one embodiment of the present disclosure. [Figure 13] FIG. 13 is a flow chart of a method S2 for tissue processing according to some embodiments of the present disclosure. [Figure 14] FIG. 14 is a graph of the temperature procedure in a reactor of a processing apparatus for infiltration according to one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] The embodiments of the present disclosure are described in detail below, examples of which are shown in the drawings. The embodiments described in this application with reference to the drawings are for illustration purposes and are used to generally understand the present disclosure. The embodiments should not be construed as limiting the present disclosure. Identical or similar elements and elements having identical or similar functions are marked by similar reference signs throughout the specification.

[0037] It should be explained that the terms used in this disclosure are only for the purpose of indicating certain embodiments and should not be construed as limiting the disclosure. When used in the embodiments (plural) of this disclosure and in the appended claims, the singular forms "a", "an" and "the" are meant to include the plural forms as well, unless otherwise clearly indicated in the context. When used in this application, the term "and / or" is also understood to include any one and all possible combinations of one or more of the associated listed items.

[0038] In this disclosure, terms such as "first" and "second" are used herein for descriptive purposes and are not intended to indicate or suggest the relative importance or prominence or quantity of the technical features referred to. That is, a feature defined with "first" and "second" may include one or more of that feature. In the specification of this disclosure, "plurality" means two or more than two of that feature, unless otherwise specified.

[0039] In the specification of the present disclosure, unless otherwise specified or limited, the terms "arranged," "connected," and "coupled" and variations thereof are used broadly and should be understood to include mechanical or electrical arrangements, connections, and couplings, and may be internal arrangements, connections, and couplings of two components, and may further be direct and indirect arrangements, connections, and couplings, which can be understood by those having ordinary skill in the art of the present invention according to the detailed embodiments of the present disclosure.

[0040] The improved tissue processing device and methods for tissue processing performed by the improved tissue processing device provided in the embodiments of the present disclosure are described below with reference to the drawings.

[0041] The improved method for tissue processing or tissue processing apparatus is capable of supporting xylene-free processing and effectively removing xylene substitutes (isopropanol, IPA, etc.) without the addition of additional protective chemical reagents (such as PARALAST) to remove isopropanol, thus simplifying the tissue processing method and significantly saving costs.

[0042] Furthermore, the provided tissue processing device supports purification of isopropanol during tissue processing without additional paraffin purification steps. Specifically, isopropanol in paraffin can be separated from paraffin gently and uniformly by controlling the paraffin feed rate, temperature and pressure in the reactor, and IPA bubbles can be avoided from being generated in a short time and from being trapped in the air system. The tissue processing device supports paraffin purification not only during tissue processing but also in non-tissue processing stages, so that highly purified paraffin can be obtained for subsequent infiltration in an effective, low-cost and simple manner, thereby extending the life of paraffin and contributing to obtaining high quality tissue samples.

[0043] In a first aspect of the present disclosure, a tissue processing device 1 is provided in multiple embodiments, as shown in FIGS.

[0044] In one embodiment, as shown in FIG. 1, the tissue processing apparatus 1 includes a reactor 100, a carrier material container 200, a second heater 300, a first condenser 400, and a first liquid container 500.

[0045] Reactor 100 The reactor 100 is configured to accommodate a tissue sample to be processed, and has a first carrier material inlet 101, a first carrier material outlet 102, a processing reagent inlet 103, a processing reagent outlet 104 and a first gas outlet 105.

[0046] In one embodiment, the first carrier material inlet 101 and the first carrier material outlet 102 of the reactor 100 are disposed separately.

[0047] In this embodiment, a first carrier material inlet 101 of the reactor 100 is connected via a tube to a carrier material outlet of the carrier material container 200 to receive the carrier material from the carrier material container 200. A first carrier material outlet 102 of the reactor 100 is connected via a tube to a carrier material outlet or a different inlet of the carrier material container 200 to recycle the carrier material.

[0048] In another embodiment, the first carrier material inlet 101 and the first carrier material outlet 102 of the reactor are combined in the same arrangement. In this embodiment, the carrier material is fed into and / or discharged out of the reactor via tubes through the same hole.

[0049] In one embodiment, the processing apparatus further includes a carrier material receptacle, the carrier material receptacle connected to the first carrier material outlet 102 for receiving spillage of the carrier material from the reactor.

[0050] In one embodiment, the reactor 100 has separate treatment reagent inlets 103 and treatment reagent outlets 104. In another embodiment, the reactor 100 has separate treatment reagent inlets 103 and treatment reagent outlets 104. In this embodiment, treatment reagents are fed into and / or discharged out of the reactor via tubes through the same holes.

[0051] In practice, the reactor 100 is a retort. The number of reactors 100 in the processing device 1 is not limited as long as it is appropriate for tissue sample processing. For example, the processing device 1 can include 1, 2, 3, 4, 5 or 6 retorts. Tissue samples are provided in cassettes of the retort during processing. The retort can accommodate 10, 50, 100, 150, 200 or 250 cassettes as needed. The cassette can be a hollow plastic box that can effectively allow chemical reagents to flow in or out. The retort and the cassette are resistant to the chemical action of the chemical reagents. The retort 100 is tightly sealed in the working environment. The temperature and pressure of the retort 100 can be controlled as needed during processing.

[0052] Carrier material container 200 The carrier material container 200 is configured to accommodate a tissue sample and has a second carrier material outlet 201 and a second gas outlet 202 connected to the first carrier material inlet 101 of the reactor 100. In this embodiment, the second carrier material outlet 201 can also be used as a carrier material recovery inlet, i.e. the carrier material is supplied from the carrier material container 200 to the reactor 100 or returned from the reactor 100 to the carrier material container 200 through the second carrier material outlet 201 via a tube.

[0053] In another embodiment, the carrier material container 200 further comprises a second carrier material inlet 203, which is connected to the first carrier material outlet 102 of the reactor 100. In this embodiment, the second carrier material inlet 203 and the second carrier material outlet 201 of the carrier material container 200 are arranged separately. Furthermore, the carrier material from the reactor 100 can be collected separately without being returned to the carrier material container 200.

[0054] The carrier material container 200 is tightly sealed in the working environment. The temperature and pressure of the carrier material container 200 can be controlled as required. The carrier material can be paraffin or oil suitable for wetting the tissue sample.

[0055] Second Heater 300 The second heater 300 is configured to heat the carrier material in the carrier material container 200. The second heater 300 may be located inside the carrier material container 200 or outside the carrier material container.

[0056] In one embodiment, the second heater 300 is a heating element coupled to a sidewall of the carrier material container 200. In another embodiment, the second heater 300 is an oven and the carrier material container 200 is disposed within a chamber of the oven. The second heater 300 is configured to control the carrier material container 200 to a temperature at which the carrier material is in a molten state, thereby allowing the carrier material to be delivered through a tube into a retort 100 or other device. For example, the temperature of the carrier material container 200 is controlled to a range of 65° C. to 85° C. (including any value within the range) so that cleaning reagents, such as isopropanol, can be completely separated from the carrier material in the carrier material container 200.

[0057] Preferably, the tube has a heater component around it so that the carrier material remains molten while it is being fed or discharged from the retort 100. The tube and its surrounding heater component can be disposed separately or combined into the same arrangement, such as a heated tube.

[0058] First condenser 400 and first liquid container 500 The first condenser 400 has a first air inlet 401 and a first liquid outlet 402 connected to the first gas outlet 105 of the reactor 100 and is configured to condense at least a portion of the gas from the reactor 100 into a liquid. The first liquid container 500 is connected to the first liquid outlet 402 of the first condenser 400 and is configured to receive condensed liquid from the first condenser 400.

[0059] In one embodiment, the first condenser 400 further includes a cooling coil 403, and optionally includes a cooling fan 404 and a cooling channel 405 surrounding the cooling coil 403, thereby enhancing cooling performance. Specifically, the first condenser 400 is configured to condense isopropanol vapor from a carrier material, such as paraffin, during paraffin infiltration. For example, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the isopropanol vapor can be condensed into liquid by the first condenser 400. The volume of the first liquid container can be 1 L, 5 L, 10 L, 15 L, 20 L, 25 L, or 30 L, but is not limited as long as it can sufficiently receive the condensed liquid from the first condenser 400. Surprisingly, it has been found that the addition of a condenser system in the processing equipment can effectively and efficiently remove isopropanol within the carrier material under appropriate temperature and pressure, thereby avoiding the need for additional isopropanol removal reagents and subsequent waste chemical reagent processing, thus reducing processing costs and making it more environmentally friendly.

[0060] On-Off Valve 600 As shown in FIG. 2, in another embodiment, the tissue processor 1 further comprises an on-off valve 600 .

[0061] An on-off valve 600 is disposed in a pipe connecting the first carrier material inlet 101 of the reactor and the second carrier material outlet 201 of the carrier material container 200 .

[0062] In this embodiment, the on-off valve 600 is configured to operate in cycles each including an open time of 1 second to 10 seconds, preferably 1.5 seconds, and a close time of 0.2 seconds to 5 seconds, preferably 1.0 seconds. The open time of the on-off valve 600 can be set to 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10 seconds, and the close time of the on-off valve can be set to 0.2, 0.5, 0.8, 1.0, 1.2, 1.5, 1.8, 2.0, 2.2, 2.5, 2.8, 3.0, 3.2, 3.5, 3.8, 4.0, 4.2, 4.5, 4.8, or 5 seconds. The on-off valve 600 is configured to be operated in a specific cycle, so as to slow down the supply speed of carrier material such as molten paraffin from the carrier material container 200 to the reactor 100, and properly separate the isopropanol in the molten paraffin from the paraffin under working conditions (i.e., high temperature and negative pressure), thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when filling the molten paraffin into the reactor 100 under working conditions, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0063] First Pressure Control Device 700 As shown in FIG. 3, in one embodiment, the tissue processing apparatus 1 further includes a first pressure control device 700 .

[0064] The first pressure control device 700 includes a pump 701, a pressure sensor 702, a hydraulic damper 703, an air valve 704, a relief valve 705, an air manifold 706, and tubing for pressure delivery. The first pressure control device 700 is fluidly connected to the retort 100 via tubing and provides positive or negative pressure to the retort 100. In one embodiment, during tissue processing, the reactor pressure is controlled by the first pressure control device 700 to a range of 20 kPa to -80 kPa. In this embodiment, during infiltration with a carrier material, the reactor pressure is controlled by the first pressure control device 700 to -15 kPa to -75 kPa.

[0065] Specifically, as shown in Fig. 14, the first pressure control device 700 is configured to control the reactor to be operated under the following pressures during infiltration: first stage: maintain pressure of -15 kPa to -50 kPa, preferably -40 kPa for 20 to 40 minutes, preferably 30 minutes, second stage: reduce pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes, preferably 15 minutes, third stage: maintain pressure of -60 kPa to -75 kPa, preferably -70 kPa for 10 to 25 minutes, preferably 15 minutes. More specifically, in the first stage, the reactor is controlled at a relatively higher pressure, such as -40 kPa, for about 30 minutes, thereby allowing a large amount of isopropanol to be slowly and uniformly produced from the carrier material to avoid the generation of IPA bubbles, in the second stage, the pressure of the reactor is further reduced to a desired pressure at a (certain) ramp rate over about 15 minutes for infiltration, thereby allowing the remaining isopropanol to be completely produced from the carrier material, and in the third stage, the reactor is controlled at about -70 kPa to perform infiltration of the tissue sample, so that the obtained tissue sample is of high quality.

[0066] According to this embodiment, the pressure in the reactor is gradually reduced, and isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, which prevents the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working condition, and further avoids the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0067] In another embodiment, the first pressure control device 700 is further connected to the carrier material container 200 and provides a positive or negative pressure to the carrier material container 200 .

[0068] First heater 800 As shown in FIG. 4, in one embodiment, the tissue processing apparatus 1 further comprises a first heater 800 .

[0069] The first heater 800 is configured to heat the processing reagents and / or carrier material in the reactor. In one embodiment, the first heater 800 is a heated lid. Specifically, the first heater 800 is configured to control the reactor 100 to operate at the following temperatures during infiltration: ramp from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and maintain at 75-90°C, preferably 85°C, for 30-40 minutes. More specifically, the best temperature for infiltration is chosen to be 85°C, because the boiling point of isopropanol is 82°C. That is, almost all of the isopropanol can be removed during infiltration. The temperature of the reactor 100 is gradually increased from 65°C-85°C, thus avoiding the generation of IPA bubbles in a short time due to a rapid temperature increase.

[0070] According to this embodiment, the temperature of the reactor is gradually increased, and isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, which prevents the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working conditions, and further avoids the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0071] Second capacitor 900 and second liquid container 1000 As shown in FIG. 5, in one embodiment, the tissue processor 1 further comprises a second capacitor 900 and a second liquid container 1000 .

[0072] The second condenser 900 has a second air inlet 901 and a second liquid outlet 902 connected to the second gas outlet 202 of the carrier material container 200 and is configured to condense at least a portion of the gas from the carrier material container 200 into liquid. In one embodiment, the second condenser 900 further includes a cooling coil 403, and optionally a cooling fan 404 and a cooling channel 405 surrounding the cooling coil 403. The second liquid container 1000 is connected to the second liquid outlet 902 of the second condenser 900 and is configured to receive condensed liquid from the second condenser 900. The configurations of the second condenser 900 and the second liquid container 1000 are similar to the first condenser 400 and the first liquid container 500, respectively, and will not be described in detail.

[0073] Specifically, the second condenser 900 is configured to condense isopropanol vapor from the carrier material, such as paraffin, before feeding the carrier material from the carrier material container 200 to the reactor 100. For example, 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 95% or 99% isopropanol vapor can be condensed into liquid by the second condenser 900. Surprisingly, it has been found that the addition of a condenser system in the processing equipment can effectively and efficiently remove isopropanol in the carrier material under suitable temperature and pressure, thereby avoiding further isopropanol removal reagents and subsequent waste chemical reagent processing, thus reducing production costs and being environmentally friendly.

[0074] In one embodiment, the first condenser 400 and the second condenser 900 are arranged separately, and the first liquid container 500 and the second liquid container 1000 are arranged separately. That is, the processing device 1 includes two sets of condensers to remove isopropanol. That is, the isopropanol in the reactor 100 is condensed by the first condenser 400, and the isopropanol in the carrier material container 200 is condensed by the second condenser 900. In another embodiment, the first condenser 400 and the second condenser 900 are the same arrangement, and the first liquid container 500 and the second liquid container 1000 are the same arrangement. That is, the processing device 1 includes one set of condensers to remove isopropanol. That is, the isopropanol in the reactor 100 and the isopropanol in the carrier material container 200 can be condensed by the same condenser.

[0075] In one embodiment, tissue processing is performed (i.e. working state), where isopropanol such as paraffin in the carrier material in the carrier material container 200 is removed by the second condenser 900 before delivering the carrier material from the carrier material container 200 to the reactor 100, and remaining isopropanol in the carrier material in the reactor 100 is further removed by the first condenser 400 during infiltration. In another embodiment, tissue processing is not performed (i.e. resting state), however isopropanol such as paraffin in the carrier material in the carrier material container 200 is removed by the second condenser 900.

[0076] According to this embodiment, the tissue processing device supports paraffin purification not only during tissue processing periods but also during non-tissue processing stages, i.e. it is possible to obtain highly purified paraffin for subsequent infiltration in an effective, low-cost and simple manner, thereby extending the paraffin's life span and contributing to obtaining high quality tissue samples.

[0077] Second Pressure Control Device 1100 As shown in FIG. 6, in one embodiment, the tissue processing apparatus 1 further includes a second pressure control device 1100 .

[0078] In one embodiment, the configuration of the second pressure control device 1100 is similar to the first pressure control device 700 and will not be described again.

[0079] Specifically, the second pressure control device 1100 is configured to control the carrier material container 200 to be operated under a pressure of cycles each including a pressure of −10 to −75 kPa, preferably −40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds, and an optional atmospheric pressure for 5 seconds to 15 seconds, preferably 6 seconds, so that the isopropanol can be completely separated from the carrier material, thereby obtaining a highly purified carrier material.

[0080] In one embodiment, the first pressure control device 700 and the second pressure control device 1100 are disposed separately. That is, the processing apparatus 1 includes two sets of pressure control devices. That is, the isopropanol in the reactor 100 can be discharged by the first pressure control device 700, and the isopropanol in the carrier material container 200 can be discharged by the second pressure control device 1100. In another embodiment, the first pressure control device 700 and the second pressure control device 1100 are the same arrangement. That is, the isopropanol in the reactor 100 and the isopropanol in the carrier material container 200 can be discharged by the same pressure control device.

[0081] Treatment Reagent Container 1200 As shown in FIG. 7, in one embodiment, the tissue processing device 1 further includes a processing reagent container 1200 .

[0082] The processing reagent container 1200 has an outlet 1202 and a recovery inlet 1201 , where the outlet 1202 is connected to the processing reagent inlet 103 of the reactor 100 and the recovery inlet 1201 is connected to the processing reagent outlet 104 of the reactor 100 .

[0083] In one embodiment, the outlet 1202 and the recovery inlet 1201 are arranged separately. In another embodiment, the outlet 1202 and the recovery inlet 1201 are combined in the same arrangement. That is, the process reagent is supplied from the process reagent container 1200 to the reactor 100 or discharged from the reactor 100 to the process reagent container 1200 via a tube through the same hole. In this embodiment, the process reagent container 1200 includes a fixing reagent container, a dehydration reagent container, a cleaning reagent container and optionally a carrier material protection reagent container. Furthermore, the first liquid container 500 and the second liquid container 1000 can be accommodated in the chamber of the process reagent container 1200. In this embodiment, the process reagent container 1200 can accommodate 1 to 100 sub-containers (including any value in the range). The sub-container may be a fixing reagent container, a dehydration reagent container, a cleaning reagent container, a carrier material protection reagent container or a condensate container, e.g., a bottle, of a volume suitable for holding chemical reagents such as formaldehyde solution, one-series concentrations of ethanol, isopropanol, paraffin and the like.

[0084] The multiple reagents in each reagent container are sequentially delivered into the reactor 100 or returned to the corresponding reagent container by the rotary valve 707. The rotary valve 707 can control which reagent is delivered into the reactor 100 through the corresponding tube and can cause the reagent to return to the corresponding reagent container. The process reagents are delivered into the reactor 100 by the action of the pressure control device 700 as described above. In one embodiment, the process reagent container 1200 contains 18 reagent bottles. The rotary valve 707 has 18 positions and controls the filling and / or withdrawing of the reagents in the 18 reagent bottles.

[0085] According to a first aspect, the tissue processing device supports paraffin purification not only during tissue processing but also during non-tissue processing stages, so that it is possible to obtain highly purified paraffin for subsequent infiltration in a low-cost and simple manner, thereby extending the life of paraffin and contributing to obtaining high-quality tissue samples.

[0086] In a second aspect of the present disclosure, as shown in FIGS. 10-14, there is provided in one or more embodiments a method S1 for tissue processing performed by the tissue processing apparatus 1 described in the first aspect.

[0087] As shown in FIG. 10, a method S1 for tissue processing performed by the tissue processing device 1 described in the first aspect includes the following steps. S100: Providing a tissue sample to be processed in a reactor; S200: Fixing the tissue sample with a fixative; S300: Dehydrating the fixed tissue sample with a dehydration reagent; S400: Cleaning the dehydrated tissue sample and reactor with a cleaning reagent to remove the dehydration reagent; S500: providing a carrier material from a carrier material container to a reactor so as to be infiltrated with the cleared tissue sample, where the carrier material includes a cleaning reagent; S600: Controlling the reactor to a temperature at which a first cleaning reagent vapor is generated from the carrier material; S700: Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is discharged to the outside of the reactor; and S800: The first cleaning reagent vapor discharged by a first condenser is condensed into a liquid to remove the first cleaning reagent vapor.

[0088] Regarding S100-S400, they are similar to those generally applied in the current tissue processing methods. The difference between the processing method of the present invention and the current processing methods mainly lies in S500-S800, which will be described in detail below.

[0089] In one embodiment, S500: supplying the carrier material from the carrier material container to the reactor to infiltrate the cleared tissue sample further includes controlling the carrier material supplied from the carrier material container to the reactor by an on-off valve in a cycle including an open time of 1-10 seconds, preferably 1.5 seconds, and a close time of 0.2-5 seconds, preferably 1.0 seconds, respectively. That is, the supply speed of the carrier material such as molten paraffin from the carrier material container to the reactor can be slowed down, and the isopropanol in the molten paraffin can be properly separated from the paraffin under the working condition (i.e., high temperature and negative pressure), thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under the working condition, and further avoiding the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0090] In one embodiment, S600: controlling the reactor to a temperature at which the first cleaning reagent vapor is generated from the carrier material further includes controlling the reactor to operate at a temperature of: increasing from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and maintaining at 75-90°C, preferably 85°C, for 30-40 minutes. According to this embodiment, the temperature of the reactor is gradually increased, so that the isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, which prevents the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working conditions, and further avoids the IPA bubbles entering the air system and blocking the air system by the paraffin.

[0091] In one embodiment, S700: controlling the reactor to a pressure at which the generated first cleaning reagent vapor is exhausted outside the reactor further comprises controlling the reactor to operate at the following pressures: First stage: Maintain a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes. Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min, for 5 to 25 minutes, preferably 15 minutes. Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes. According to this embodiment, the pressure in the reactor is gradually reduced, so that isopropanol vapor is generated slowly and uniformly from the carrier material in the reactor, which prevents the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is filled into the reactor under working conditions, and further avoids the IPA bubbles from entering the air system and blocking the air system by the paraffin.

[0092] In one embodiment, as shown in FIG. 11, the method S1 for tissue processing further comprises removing S900 a cleaning reagent from the carrier material container by a second condenser prior to S500.

[0093] As shown in FIG. 12, in this embodiment, S900: S901: controlling a carrier material container to a temperature at which a second cleaning reagent vapor is generated from the carrier material; S902: controlling the carrier material container to be operated under pressure in cycles in which the generated second cleaning reagent vapor is discharged outside the carrier material container, where each cycle includes a pressure of -20 to -75 kPa, preferably -40 kPa for 25 seconds to 45 seconds, preferably 34 seconds, and an optional atmospheric pressure for 5 seconds to 15 seconds, preferably 6 seconds; S903: The method further includes condensing the exhausted second cleaning reagent vapor into a liquid by a second condenser to remove the second cleaning reagent vapor.

[0094] According to this embodiment, a cleaning reagent such as isopropanol in a carrier material such as paraffin is partially removed in the carrier material container, for example 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% of the isopropanol is removed in the carrier material container. Residual cleaning reagents such as isopropanol in the carrier material are further removed in the reactor, for example 99%, 98%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2% or 1% of isopropanol are removed in the reactor, i.e., cleaning reagents such as isopropanol in the carrier material are completely removed without the addition of further protective chemical reagents, thereby simplifying the tissue processing method and significantly reducing costs.

[0095] According to a second aspect, the method for tissue processing is capable of effectively and efficiently removing cleaning reagents (such as isopropanol) within the carrier material, thereby reducing production costs and being environmentally friendly, as the addition of isopropanol removal reagents and subsequent waste chemical reagent disposal is avoided.

[0096] In a third aspect of the present disclosure, as shown in Figures 8A and 8B, a tissue processor 2 is provided in one or more embodiments. The tissue processor 2 includes a reactor 100, a carrier material container 200, a second heater 300, a second condenser 900, and a second liquid container 1000.

[0097] In another embodiment, the tissue processing device 2 further includes the on-off valve 600 described in the first aspect. In another embodiment, the tissue processing device 2 further includes the second pressure control device 1100 described in the first aspect. In another embodiment, the tissue processing device 2 further includes the first capacitor 400 and the first liquid container 500 described in the first aspect. In another embodiment, the tissue processing device 2 further includes the first pressure control device 700 described in the first aspect. In another embodiment, the tissue processing device 2 further includes the first heater 800 described in the first aspect. In another embodiment, the tissue processing device 2 further includes the processing reagent container 1200 described in the first aspect. The configurations and functions of the reactor 100, carrier material container 200, second heater 300, first condenser 400, first liquid container 500, on-off valve 600, first pressure control device 700, first heater 800, second condenser 900, second liquid container 1000, second pressure control device 1100 and processing reagent container 1200 are similar to those described in the first aspect, respectively, but will not be described again due to space constraints.

[0098] According to a third aspect, the tissue processing device supports paraffin purification not only during tissue processing but also during non-tissue processing stages, so that it is possible to obtain highly purified paraffin for subsequent infiltration in an effective, low-cost and simple manner, thereby extending the life of the paraffin and contributing to obtaining high quality tissue samples.

[0099] In a fourth aspect of the present disclosure, as shown in FIG. 13, in multiple embodiments, a method S2 for tissue processing performed by the tissue processing device 2 described in the third aspect is provided, the method including the following steps: S100: Providing a tissue sample to be processed in a reactor; S200: Fixing the tissue sample with a fixative; S300: Dehydrating the fixed tissue sample with a dehydration reagent; S400: Cleaning the dehydrated tissue sample and reactor with a cleaning reagent to remove the dehydration reagent; S500: Supplying carrier material from a carrier material container to a reactor so that the cleared tissue sample is infiltrated. Wherein, the method further comprises, before S500, S900: removing the cleaning reagent from the carrier material container by a second condenser.

[0100] In this embodiment, S900: removing the cleaning reagent from the carrier material container by the second condenser includes: S901: controlling a carrier material container to a temperature at which a second cleaning reagent vapor is generated from the carrier material; S902: Controlling the carrier material container so that the generated second cleaning reagent vapor is operated under a pressure of cycles to be discharged to the outside of the carrier material container, wherein each cycle includes a pressure of -20 to -75 kPa, preferably -40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds, and Optionally, atmospheric pressure for 5 seconds to 15 seconds, preferably 6 seconds. S903: The method further includes condensing the exhausted second cleaning reagent vapor into a liquid by a second condenser to remove the second cleaning reagent vapor.

[0101] In another embodiment, the method of the present invention further comprises the following steps after S500: S600: controlling a reactor to a temperature at which a first cleaning reagent vapor is generated from a carrier material; S700: Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is discharged to the outside of the reactor; and S800: Condensing the exhausted first cleaning reagent vapor into a liquid by a first condenser to remove the first cleaning reagent vapor.

[0102] The main difference between the method S1 for tissue processing and the method S2 for tissue processing is that in S1, the cleaning reagent in the carrier material is substantially removed in the reactor by the first capacitor, and optionally the cleaning reagent in the carrier material is removed in the carrier material container by the second capacitor before providing the carrier material from the carrier material container to the reactor (S500), while in S2, the cleaning reagent in the carrier material is substantially removed in the carrier material container by the second capacitor, and optionally the remaining cleaning reagent in the carrier material is further removed in the reactor by the first capacitor before providing the carrier material from the carrier material container to the reactor (S500). That is, in S1, the carrier material substantially contains the cleaning reagent before being provided from the carrier material container to the reactor, while in S2, the carrier material contains almost no cleaning reagent before being provided from the carrier material container to the reactor.

[0103] Details of S100, S200, S300, S400, S500, S600, S700, S800 and S900 in the embodiments of the fourth aspect are similar to those of the third aspect respectively and will not be described again due to space constraints. In S2, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% of the cleaning reagent in the carrier material has been removed by the second condenser before the carrier material is provided from the carrier material container to the reactor.

[0104] According to a fourth aspect, the method for tissue processing is capable of effectively and efficiently removing cleaning reagents (such as isopropanol) within the carrier material, thereby reducing processing costs and being environmentally friendly, as the addition of isopropanol removal reagents and subsequent waste chemical reagent disposal are avoided.

[0105] Working Example The present disclosure will now be described in more detail with the aid of examples, which should not be construed as limiting the present invention.

[0106] Example 1 Tissue samples were processed using the tissue processing device 1. In this example, only a pair of condenser systems (i.e., a first condenser 400 and a first liquid container 500) are provided. In this example, the cleaning reagent is isopropanol and the carrier material is paraffin. The paraffin used for tissue processing contains a large amount of isopropanol. The reactor is a retort and the carrier material container is an oven. The isopropanol in the paraffin was not removed in the oven before filling the paraffin in the retort. That is, the isopropanol was substantially removed in the retort during tissue processing.

[0107] In this example, the on-off valve operating cycle was investigated to evaluate the IPA removal efficiency. The on-off valve was operated in a series of cycles as follows: The retort temperature procedure was set to increase from 65° C. to 85° C. in 25 minutes and maintain at 85° C. for 35 minutes during infiltration. The retort pressure procedure was set to maintain at −40 kPa for 30 minutes, decrease from −40 kPa to −70 kPa in 15 minutes and maintain at −70 kPa for 15 minutes during infiltration. IPA removal efficiency, IPA foam production and tissue sample quality were measured and the results are shown in Table 1. Table 1. IPA removal effect under different operating cycles of on-off valve TIFF0007623471000001.tif28170

[0108] Example 2 The tissue processing method was similar to Example 1, except that different temperature settings were set in the retort as follows: Specifically, the on-off valve was operated in a cycle with an open time of 1.5 seconds and a closed time of 1.0 seconds each. The pressure profile of the retort was set to maintain at -40 kPa for 30 minutes, decrease from -40 kPa to -70 kPa within 15 minutes, and then maintain at -70 kPa for 15 minutes during infiltration. IPA removal efficiency, IPA foam production, and tissue sample quality were measured, and the results are shown in Table 2. Table 2. IPA removal effect under different temperature transitions carried out in the retort TIFF0007623471000002.tif47170

[0109] Example 3 The tissue processing method was similar to Example 1, except that different pressure profiles were set in the retort as follows: Specifically, the on-off valves were operated in cycles each containing 1.5 seconds of open time and 1.0 seconds of closed time. The temperature profile of the retort was set to increase from 65° C. to 85° C. in 25 minutes and to remain at 85° C. for 35 minutes during infiltration. IPA removal efficiency, IPA foam production, and tissue sample quality were measured, and the results are shown in Table 3. Table 3. IPA removal effect under different pressure transitions implemented in the retort TIFF0007623471000003.tif49170

[0110] Example 4 The tissue processing method is similar to Example 1, except that two sets of condenser systems are provided. The isopropanol in the paraffin was partially removed in the oven before filling the paraffin into the retort. That is, the isopropanol was partially removed in the oven and partially removed in the retort. Specifically, the on-off valve was operated in a cycle with an open time of 1.5 seconds and a closed time of 1.0 seconds, respectively. The temperature profile of the retort was set to increase from 65°C to 85°C in 25 minutes and to maintain at 85°C for 35 minutes during infiltration. The pressure profile of the retort was set to maintain at -40 kPa for 30 minutes, decrease from -40 kPa to -70 kPa in 15 minutes, and maintain at -70 kPa for 15 minutes during infiltration. The IPA removal efficiency, IPA foam generation, and tissue sample quality were measured, and the results are shown in Table 2.

[0111] It was shown that no IPA foam was produced during infiltration, 99% of the IPA was removed from the paraffin, and the tissue samples obtained were of high quality.

[0112] Example 5 The tissue processing method is similar to Example 1, except that a tissue processing device 2 having only a second capacitor 900 and a second liquid container 1000 was used to process the tissue samples. The isopropanol in the paraffin was substantially removed in an oven prior to filling the paraffin into the retort. Different temperatures and pressures in the oven were investigated and the results are shown in Table 4. Table 4. IPA removal efficiency under different conditions in a carrier container TIFF0007623471000004.tif46170

[0113] Example 6 In this example, a total of about 1120 mL of IPA was drained from the paraffin in the retort during the paraffin infiltration step (about 60 minutes). IPA amount (mass): 0.7683 x 1120 ≒ 860.5 g ≒ 13 mol Amount of heat required to drain 1120 mL of IPA from the paraffin in the retort: Calorific value=40.06KJ / mol×13mol=520.78KJ

[0114] If more than 80% of the IPA vapor is cooled in the cooling section(s) and the trap bottle, the cooling capacity of the cooling section and the trap bottle should be >520.78×80%≈417KJ. Therefore, a heat exchange capacity of 417KJ should be provided in the cooling section and the trap bottle to cool the IPA vapor.

[0115] Throughout this specification, the terms "one embodiment," "some embodiments," "one example," "particular example," or "some examples" mean that the particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the disclosure. In other words, the appearance of the phrase in various places throughout this specification does not necessarily refer to the same embodiment or example of the disclosure. Furthermore, particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples. Furthermore, different embodiments or examples described in the specification, as well as features of the embodiments or examples, may be combined without conflict by a person of ordinary skill in the art of the present invention.

[0116] Although illustrative embodiments have been shown and described, those having ordinary skill in the art of the present invention will recognize that the above-described embodiments should not be construed as limiting the present disclosure, and that changes, substitutions, and alterations can be made in the embodiments without departing from the spirit, principle, and scope of the present disclosure. The present invention can also be developed as a preferred embodiment as follows. (Form 1) a reactor configured to receive a tissue sample so that the tissue sample can be processed, the reactor having a first carrier material inlet, a first carrier material outlet, a processing reagent inlet, a processing reagent outlet and a first gas outlet; a carrier material container configured to contain a carrier material and having a second carrier material outlet connected to the first carrier material inlet of the reactor and a second gas outlet; a second heater configured to heat the carrier material in the carrier material container; a first condenser having a first air inlet and a first liquid outlet connected to the first gas outlet of the reactor and configured to condense at least a portion of the gas from the reactor into a liquid; a first liquid container connected to the first liquid outlet of the first condenser and configured to receive condensate from the first condenser; 1. A tissue processing device comprising: (Form 2) an on-off valve disposed in a pipe connecting the first carrier material inlet of the reactor and the second carrier material outlet of the carrier material container; Preferably, the on-off valve is configured to operate in a cycle that includes an open time of 1 to 10 seconds, preferably 1.5 seconds, and a close time of 0.2 to 5 seconds, preferably 1.0 seconds, 2. The tissue processing device according to embodiment 1. (Form 3) 3. The tissue processing apparatus according to claim 1 or 2, further comprising a first pressure control device configured to control the reactor to be operated under a pressure as follows: First stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes, preferably 15 minutes; Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes. (Form 4) a first heater configured to heat processing reagents and / or carrier materials in the reactor, preferably the first heater being a heated lid; Optionally, the first heater is configured to control the reactor to operate at a temperature of The tissue processing device according to any one of aspects 1 to 3, The temperature is increased from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and then maintained at 75-90°C, preferably 85°C, for 30-40 minutes. (Form 5) a second condenser having a second air inlet and a second liquid outlet connected to the second gas outlet of the carrier material container and configured to condense at least a portion of the gas from the carrier material container into a liquid; a second liquid container connected to the second liquid outlet of the second condenser and configured to receive condensate from the second condenser; 5. The tissue processing device according to any one of embodiments 1 to 4, further comprising: (Form 6) The tissue processing device of any one of claims 1 to 5, wherein the first condenser and the second condenser each include a cooling coil, and optionally further include a cooling fan and a cooling channel surrounding the cooling coil. (Form 7) a pressure of -20 to -75 kPa, preferably -40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds; Optionally, atmospheric pressure for 5 seconds to 15 seconds, preferably 6 seconds; The tissue processing apparatus of any one of the preceding embodiments, further comprising a second pressure control device configured to control the carrier material containers to be operated in cycles each including: (Form 8) a processing reagent container having an outlet and a recovery inlet; The outlet is connected to a treatment reagent inlet of the reactor, and the recovery inlet is connected to a treatment reagent outlet of the reactor; Preferably, the outlet and the recovery inlet are provided separately or combined into the same arrangement; Preferably, the processing reagent containers include a fixing reagent container, a dehydration reagent container, a cleaning reagent container and optionally a carrier material protection reagent container; The tissue processing device according to any one of aspects 1 to 7. (Form 9) The first carrier material inlet and the first carrier material outlet of the reactor are arranged separately or combined into the same arrangement; Optionally, the second carrier material inlet and the second carrier material outlet of the carrier material container are arranged separately or combined into the same arrangement, 9. The tissue processing device according to any one of aspects 1 to 8, optionally wherein the processing reagent inlet and the processing reagent outlet of the reactor are disposed separately or combined into the same arrangement. (Form 10) A method for tissue processing performed by the tissue processing device according to any one of aspects 1 to 9, Providing a tissue sample to be processed into a reactor; Fixing the tissue sample with a fixative; dehydrating the fixed tissue sample with a dehydration reagent; cleaning the dehydrated tissue sample and the reactor with a cleaning reagent to remove the dehydration reagent; providing a carrier material from a carrier material container to the reactor to infiltrate the cleared tissue sample, where the carrier material includes a cleaning reagent; controlling the reactor to a temperature at which a first cleaning reagent vapor is generated from the carrier material; Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is discharged to the outside of the reactor; and condensing the exhausted first cleaning reagent vapor into a liquid by a first condenser to remove the first cleaning reagent vapor; The method includes: (Form 11) The method of claim 10, wherein supplying the carrier material from the carrier material container to the reactor to infiltrate the cleared tissue sample further comprises controlling the carrier material supplied from the carrier material container to the reactor by an on-off valve in a cycle each including an open time of 1 to 10 seconds, preferably 1.5 seconds, and a closed time of 0.2 to 5 seconds, preferably 1.0 second. (Form 12) 12. The method of claim 10 or 11, wherein controlling the reactor to a temperature at which the first cleaning reagent vapor is generated from the carrier material further comprises controlling the reactor to operate at a temperature The temperature is increased from 50-70°C, preferably 65°C, to 75-90°C, preferably 85°C, at a rate of 0.5-2°C / min, preferably 1.5°C / min, and maintained at 75-90°C, preferably 85°C, for 30-40 minutes. (Form 13) 13. The method of any one of aspects 10 to 12, wherein controlling the reactor to a pressure at which the generated first cleaning reagent vapor is exhausted outside the reactor further comprises controlling the reactor to be operated at a pressure of: First stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes, preferably 15 minutes; Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes. (Form 14) removing a cleaning reagent from the carrier material container by a second condenser prior to delivering the carrier material from the carrier material container to the reactor; removing the cleaning reagent from the carrier material container by a second condenser; and controlling the carrier material container to a temperature at which a second cleaning reagent vapor is generated from the carrier material; controlling the carrier material container to be operated under a pressure in a cycle in which the generated second cleaning reagent vapor is exhausted to the outside of the carrier material container; Each cycle is a pressure of -20 to -75 kPa, preferably -40 kPa, for 25 seconds to 45 seconds, preferably 34 seconds; and Optionally, ambient pressure for 5 seconds to 15 seconds, preferably 6 seconds; and condensing the exhausted second cleaning reagent vapor into a liquid by a second condenser to remove the second cleaning reagent vapor; 14. The method of any one of aspects 10 to 13, optionally further comprising: (Form 15) providing a carrier material protection reagent to the reactor to remove the cleared tissue sample and cleaning reagents in the reactor prior to providing the carrier material from the carrier material container to the reactor; Preferably, the carrier material protection reagent comprises a cleaning reagent substitute, a mixture of a cleaning reagent substitute and a cleaning reagent, and a mixture of a cleaning reagent substitute and a carrier material; 15. The method according to any one of aspects 10 to 14. [Explanation of symbols]

[0117] 100: Reactor 101: First carrier material inlet 102: First carrier material outlet 103: Processing reagent inlet 104: Processing reagent outlet 105: First gas outlet 200: Carrier material container 201: second carrier material outlet 202: Second gas outlet 203: second carrier material inlet 300: Second heater 400: First capacitor 401: First air inlet 402: First liquid outlet 403: Cooling coil 404: Cooling fan 405: Cooling channel 500: First liquid container 600: On-off valve 700: First pressure control device 701: Pump 702: Pressure sensor 703: Water and hydraulic dampers 704: Air valve 705: Relief valve 706: Air manifold 707: Rotary valve 800: 1st heater 900: Second capacitor 901: Second air inlet 902: Second liquid outlet 1000: Second liquid container 1100: second pressure control device 1200: Processing reagent container 1201: Collection entrance 1202: Outlet

Claims

1. Providing a tissue sample to be processed into a reactor; Fixing the tissue sample with a fixative; dehydrating the fixed tissue sample with a dehydration reagent; cleaning the dehydrated tissue sample and the reactor with a cleaning reagent to remove the dehydration reagent; providing a carrier material from a carrier material container to the reactor to infiltrate the cleared tissue sample, where the carrier material includes a cleaning reagent; controlling the reactor to a temperature at which a first cleaning reagent vapor is generated from the carrier material; Controlling the reactor to a pressure at which the generated first cleaning reagent vapor is exhausted to the outside of the reactor; and condensing the exhausted first cleaning reagent vapor into a liquid by a first condenser to remove the first cleaning reagent vapor; 23. A method for tissue processing comprising:

2. 2. The method of claim 1, wherein supplying the carrier material from the carrier material container to the reactor to infiltrate the cleared tissue sample further comprises controlling the carrier material supplied from the carrier material container to the reactor by an on-off valve in cycles each including an open time of 1 to 10 seconds and a closed time of 0.2 to 5 seconds.

3. 3. The method of claim 1 or 2, wherein controlling the reactor to a temperature at which the first cleaning reagent vapor is generated from the carrier material further comprises controlling the reactor to operate at a temperature of: The temperature is increased from 50-70° C. to 75-90° C. at a rate of 0.5-2° C. / min, and maintained at 75-90° C. for 30-40 minutes.

4. 4. The method according to any one of claims 1 to 3, wherein controlling the reactor to a pressure at which the generated first cleaning reagent vapor is exhausted outside the reactor further comprises controlling the reactor to be operated at a pressure of: First stage: maintain pressure between -15kPa and -50kPa for 20-40 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes; Third stage: Maintain pressure between -60 kPa and -75 kPa for 10 to 25 minutes.

5. removing a cleaning reagent from the carrier material container by a second condenser prior to delivering the carrier material from the carrier material container to the reactor; removing the cleaning reagent from the carrier material container by a second capacitor; controlling the carrier material container to a temperature at which the second cleaning reagent vapor is generated from the carrier material; controlling the carrier material container to be operated under a pressure in a cycle in which the generated second cleaning reagent vapor is exhausted to the outside of the carrier material container; Each cycle is A pressure of -20 to -75 kPa for 25 to 45 seconds, and Atmospheric pressure for 5 seconds to 15 seconds; and condensing the exhausted second cleaning reagent vapor into a liquid by a second condenser to remove the second cleaning reagent vapor; The method of any one of claims 1 to 4, further comprising:

6. A method for producing a method for a method according to any one of claims 1 to 5, a reactor (100) configured to accommodate a tissue sample so that the tissue sample can be processed, the reactor having a first carrier material inlet (101), a first carrier material outlet (102), a processing reagent inlet (103), a processing reagent outlet (104) and a first gas outlet (105); a carrier material container (200) configured to accommodate a carrier material and having a second carrier material outlet (201) connected to the first carrier material inlet (101) of the reactor (100) and a second gas outlet (202); a second heater (300) configured to heat the carrier material in the carrier material container (200); a first condenser (400) having a first air inlet (401) and a first liquid outlet (402) connected to the first gas outlet (105) of the reactor (100) and configured to condense at least a portion of the gas from the reactor (100) into a liquid; a first liquid container (500) connected to the first liquid outlet (402) of the first condenser (400) and configured to receive condensate from the first condenser (400); A tissue processing device (1).

7. The reactor (100) further includes an on-off valve (600) disposed in a pipe connecting a first carrier material inlet (101) of the reactor (100) and a second carrier material outlet (201) of the carrier material container (200); The on-off valve (600) is configured to be operated in cycles each including an open time of 1 to 10 seconds and a close time of 0.2 to 5 seconds; The tissue processing device (1) according to claim 6.

8. The tissue processing apparatus (1) of claim 6 or 7, further comprising a first pressure control device (700) configured to control the reactor (100) to be operated under a pressure as follows: First stage: maintain pressure between -15 kPa and -50 kPa for 20-40 minutes; Second stage: reduce the pressure at a rate of 0.5-4 kPa / min for 5-25 minutes; Third stage: Maintain pressure between -60 kPa and -75 kPa for 10 to 25 minutes.

9. The reactor further includes a first heater (800) configured to heat processing reagents and / or carrier materials in the reactor (100), the first heater (800) being a heated lid; The first heater (800) is configured to control the reactor (100) to operate at a temperature of: A tissue processing device (1) according to any one of claims 6 to 8, The temperature is increased from 50-70° C. to 75-90° C. at a rate of 0.5-2° C. / min, and maintained at 75-90° C. for 30-40 minutes.

10. A second condenser (900) having a second air inlet (901) and a second liquid outlet (902) connected to the second gas outlet (202) of the carrier material container (200) and configured to condense at least a portion of the gas from the carrier material container (200) into a liquid; a second liquid container (1000) connected to the second liquid outlet (902) of the second condenser (900) and configured to receive condensate from the second condenser (900); The tissue processing device (1) according to any one of claims 6 to 9, further comprising:

11. A tissue processing device (1) as described in claim 6 or 10, wherein the first condenser (400) and the second condenser (900) each include a cooling coil (403) and further include a cooling fan (404) and a cooling channel (405) surrounding the cooling coil (403).

12. A pressure of -20 to -75 kPa for 25 seconds to 45 seconds; Ambient pressure for 5 seconds to 15 seconds; The tissue processing apparatus (1) according to any one of claims 6 to 11, further comprising a second pressure control device (1100) configured to control the carrier material containers (200) to be operated in cycles each comprising:

13. The method further includes a treatment reagent container (1200) having an outlet (1201) and a recovery inlet (1202), The outlet (1201) is connected to the treatment reagent inlet (103) of the reactor (100), and the recovery inlet (1202) is connected to the treatment reagent outlet (104) of the reactor (100); The discharge port (1201) and the recovery inlet (1202) are arranged separately or combined into the same arrangement; The processing reagent containers (1200) include a fixing reagent container, a dehydration reagent container, a cleaning reagent container, and a carrier material protection reagent container; A tissue processing device (1) according to any one of claims 6 to 12.

14. The first carrier material inlet (101) and the first carrier material outlet (102) of the reactor (100) are arranged separately or combined into the same arrangement; The second carrier material inlet and the second carrier material outlet of the carrier material container (200) are arranged separately or combined into the same arrangement; The tissue processing device (1) according to any one of claims 6 to 13, wherein the processing reagent inlet (103) and the processing reagent outlet (104) of the reactor (100) are arranged separately or combined into the same arrangement.

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