Xylene-free tissue processor and method of tissue processing
By designing a tissue processor that uses temperature and pressure control to gradually remove isopropanol, the high cost and air system blockage problems of existing technologies are solved, achieving simplified and efficient tissue sample processing.
Patent Information
- Application Number
- CN202080106052.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2020-08-10
- Publication Date
- 2026-01-23
- Estimated Expiration
- 2040-08-10
AI Technical Summary
Existing tissue processing methods that use xylene alternatives such as isopropanol require additional chemical protective agents, leading to high costs and air system blockage problems, and existing equipment is complex.
Design an organization processor comprising a reactor, a carrier material container, a heater, a condenser, and a pressure control device to gradually remove isopropanol by controlling temperature and pressure, avoiding the generation of large amounts of foam, and simplifying the processing.
It effectively removes isopropanol, simplifies the processing procedure, reduces costs, extends equipment life, avoids air system blockage, and yields high-quality tissue samples.
Smart Images

Figure CN116670491B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of tissue processing, and more particularly to a tissue processor and a method for processing tissue using the tissue processor. Background Technology
[0002] Biological tissue samples are crucial for biological research, medical pathology testing, and other related fields. Tissue processing methods typically include fixing the tissue sample, dehydrating the fixed tissue sample with a dehydrating agent, cleaning the dehydrated tissue sample with a cleaning agent to remove the dehydrating agent, and impregnating the cleaned tissue sample with a carrier material. Xylene, a colorless and transparent liquid, is a highly irritating and carcinogenic substance harmful to humans. In tissue processing methods, it is commonly used to remove dehydrating agents, such as ethanol, from tissue samples. It is necessary to remove xylene to ensure a safe working environment.
[0003] Alternatives to xylene, such as isopropanol (IPA), have been proposed for use in tissue processing methods. CN101929927B discloses a xylene-free tissue sample processing method, which includes adding a carrier material protective agent, such as PARALAST, to remove isopropanol from the tissue sample and the reactor after cleaning the dehydrated tissue sample with isopropanol, thereby reducing the amount of isopropanol mixed into the carrier material, such as paraffin.
[0004] However, this xylene-free method requires the use of additional reagents (such as parasitoids), resulting in high costs and complex processes, partly due to the disposal of waste chemicals such as parasitoids. Furthermore, other existing tissue processing methods or equipment that support xylene-free treatments often result in carrier material entering the air system, clogging it, increasing maintenance costs, and reducing equipment lifespan.
[0005] Therefore, there is an urgent need for an improved xylene-free processor and a tissue treatment method using the processor, particularly one that can remove isopropanol in an efficient, low-cost and simple manner. Summary of the Invention
[0006] This application attempts to address at least one problem existing in the related art, at least to some extent. Therefore, an organization processor and a method for organization processing performed by said organization processor are provided.
[0007] An embodiment of the first aspect provides an organization processor (1), comprising:
[0008] Reactor (100),
[0009] Configured to accommodate tissue samples and allow processing of said tissue samples, and
[0010] It is provided with 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);
[0011] Carrier material container (200),
[0012] It is configured to contain carrier material and is provided with a second carrier material outlet (201) and a second gas outlet (202) connected to the first carrier material inlet (101) of the reactor (100);
[0013] A second heater (300) is configured to heat the carrier material in the carrier material container (200);
[0014] First condenser (400),
[0015] The reactor (100) is provided with a first gas inlet (401) and a first liquid outlet (402) connected to the first gas outlet (105) of the reactor (100), and
[0016] Configured to condense at least a portion of the gas from the reactor (100) into a liquid; and
[0017] A first liquid container (500) is connected to the first liquid outlet (402) of the first condenser (400) and configured to receive condensed liquid from the first condenser (400).
[0018] According to the embodiments of this application, the provided tissue processor can support xylene-free processing and can effectively remove xylene substitutes (such as isopropanol, IPA) during processing without adding additional chemical protective agents (such as PARALAST) to remove isopropanol, thus simplifying the tissue processing method and significantly saving costs.
[0019] In one embodiment, the tissue processor (1) further includes 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).
[0020] Preferably, the switching valve (600) is configured to operate periodically, with each cycle including an opening time of 1-10 seconds, preferably 1.5 seconds, and a closing time of 0.2-5 seconds, preferably 1.0 second.
[0021] According to the embodiments of this application, the rate at which carrier material, such as molten paraffin, is supplied from carrier material container 200 to reactor 100 can be slowed down, and under operating conditions (i.e., high temperature and negative pressure), isopropanol in the molten paraffin can be properly separated from the paraffin, thereby avoiding the generation of a large amount of foam in the paraffin in a short time when the molten paraffin is filled into reactor 100 under operating conditions, and further preventing isopropanol foam from entering the air system and being blocked by the paraffin.
[0022] In another embodiment, the tissue processor (1) further includes a first pressure control device (700) configured to control the reactor (100) to operate at pressures such that:
[0023] First stage: Maintain a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes.
[0024] Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes, preferably 15 minutes.
[0025] Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes.
[0026] According to the embodiments of this application, the pressure in the reactor is gradually reduced, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the generation of a large amount of foam in the isopropanol in the paraffin when the molten paraffin is charged into the reactor under working conditions, and further preventing the isopropanol foam from entering the air system and being blocked by the paraffin.
[0027] In another embodiment, the tissue processor (1) further includes a first heater (800) configured to heat the treatment reagents and / or the carrier material in the reactor (100), preferably, the first heater (800) is a heating cap.
[0028] Optionally, the first heater (800) is configured to control the reactor (100) to operate at the following temperature:
[0029] The temperature is increased from 50 to 70°C, preferably 65°C, to 75 to 90°C, preferably 85°C, at a rate of 0.5 to 2°C / min, preferably 1.5°C / min, and then maintained at 75 to 90°C, preferably 85°C, for 30 to 40 minutes.
[0030] According to the embodiments of this application, the temperature of the reactor is gradually increased, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the generation of a large amount of foam in the isopropanol in the paraffin when the molten paraffin is charged into the reactor under working conditions, and further preventing the isopropanol foam from entering the air system and being blocked by the paraffin.
[0031] In another embodiment, the tissue processor (1) further includes: a second condenser (900) having a second gas 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; and
[0032] A second liquid container (1000) is connected to the second liquid outlet (902) of the second condenser (900) and configured to receive condensed liquid from the second condenser (900).
[0033] In this embodiment, the first condenser (400) and the second condenser (900) each include a cooling coil (403), and optionally also include a cooling fan (404) and a cooling channel (405) surrounding the cooling coil (403).
[0034] According to the embodiments of this application, isopropanol in the carrier material can be completely removed.
[0035] In another embodiment, the tissue processor (1) further includes a second pressure control device (1100) configured to control the carrier material container (200) to operate periodically under pressure, each cycle including
[0036] A pressure of -20 to -75 kPa, preferably -40 kPa, is sustained for 25 to 45 seconds, preferably 34 seconds.
[0037] The environmental pressure can be selected for 5 to 15 seconds, preferably 6 seconds.
[0038] According to the embodiments of this application, isopropanol in the carrier material can be completely removed.
[0039] In another embodiment, the tissue processor (1) further includes a treatment reagent container (1200) provided with a discharge port (1201) and a reflux inlet (1202), wherein the discharge port (1201) is connected to the treatment reagent inlet (103) of the reactor (100), and the reflux inlet (1202) is connected to the treatment reagent outlet (104) of the reactor (100).
[0040] Preferably, the discharge port (1201) and the return inlet (1202) are arranged separately or combined into the same arrangement.
[0041] Preferably, the treatment reagent container (1200) includes a fixed reagent container, a dehydration reagent container, a cleaning reagent container, and an optional carrier material to protect the reagent container.
[0042] 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.
[0043] 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.
[0044] Optionally, the treatment reagent inlet (103) and the treatment reagent outlet (104) of the reactor (100) are arranged separately or combined into the same arrangement.
[0045] A second aspect embodiment provides a tissue processing method, executed by a tissue processor (1) described in a first aspect embodiment, wherein the method includes:
[0046] The tissue sample to be processed is provided to the reactor.
[0047] The tissue sample was fixed with a fixation reagent.
[0048] The fixed tissue samples were dehydrated using a dehydrating agent.
[0049] The dehydrated tissue sample and the reactor are cleaned with a cleaning agent to remove the dehydrating agent.
[0050] A carrier material container is supplied to the reactor to impregnate a cleaned tissue sample, wherein the carrier material contains the cleaning agent.
[0051] The reactor is controlled at a temperature that generates the first cleaning agent vapor from the carrier material.
[0052] The reactor is controlled at a pressure such that the generated cleaning agent vapor is discharged from the reactor.
[0053] The first cleaning agent vapor is condensed into a liquid by the first condenser to remove the first cleaning agent vapor.
[0054] According to the embodiments of this application, the tissue treatment method can effectively and efficiently remove cleaning agents (such as isopropanol) from the carrier material, thereby avoiding the need for additional isopropanol removal agents and subsequent disposal of waste chemical reagents, thus saving production costs and being environmentally friendly.
[0055] In one embodiment, the provision of carrier material from the carrier material container to the reactor for impregnating the cleaned tissue sample further includes:
[0056] The carrier material is periodically supplied to the reactor from the carrier material container by means of a switching valve, each cycle including an opening time of 1 to 10 seconds, preferably 1.5 seconds, and a closing time of 0.2 to 5 seconds, preferably 1.0 second.
[0057] According to the embodiments of this application, the rate at which carrier material, such as molten paraffin, is supplied from carrier material container 200 to reactor 100 can be slowed down, and under operating conditions (i.e., high temperature and negative pressure), isopropanol in the molten paraffin can be properly separated from the paraffin, thereby avoiding the generation of a large amount of foam in the paraffin in a short time when the molten paraffin is filled into reactor 100 under operating conditions, and further preventing isopropanol foam from entering the air system and being blocked by the paraffin.
[0058] In another embodiment, controlling the reactor at a temperature that generates the first cleaning agent vapor from the carrier material further includes: controlling the reactor to operate at the following temperature:
[0059] The temperature is increased from 50 to 70°C, preferably 65°C, to 75 to 90°C, preferably 85°C, at a rate of 0.5 to 2°C / min, preferably 1.5°C / min, and then maintained at 75 to 90°C, preferably 85°C, for 30 to 40 minutes.
[0060] According to the embodiments of this application, the temperature of the reactor is gradually increased, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the generation of a large amount of foam in the isopropanol in the paraffin when the molten paraffin is charged into the reactor under working conditions, and further preventing the isopropanol foam from entering the air system and being blocked by the paraffin.
[0061] In another embodiment, controlling the reactor at a pressure such that the generated cleaning agent vapor is discharged from the reactor further comprises: controlling the reactor to operate at the following pressure:
[0062] First stage: Maintain a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes.
[0063] Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes, preferably 15 minutes.
[0064] Third stage: Maintain a pressure of -60 kPa to -75 kPa, preferably -70 kPa, for 10 to 25 minutes, preferably 15 minutes.
[0065] According to the embodiments of this application, the pressure in the reactor is gradually reduced, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the generation of a large amount of foam in the isopropanol in the paraffin when the molten paraffin is charged into the reactor under working conditions, and further preventing the isopropanol foam from entering the air system and being blocked by the paraffin.
[0066] In another embodiment, the method further includes removing the cleaning agent from the carrier material container via a second condenser before supplying the carrier material to the reactor.
[0067] Optionally, removing the cleaning agent from the carrier material container via a second condenser further includes:
[0068] The carrier material container is controlled to operate at a temperature that generates the second cleaning agent vapor from the carrier material.
[0069] The carrier material container is controlled to operate periodically at a pressure that causes the generated second cleaning agent vapor to be discharged from the carrier material container, each cycle including:
[0070] A pressure of -20 to -75 kPa, preferably -40 kPa, is sustained for 25 to 45 seconds, preferably 34 seconds.
[0071] The optional environmental pressure lasts for 5 to 15 seconds, preferably 6 seconds, and
[0072] The second cleaning agent vapor is condensed into a liquid by the second condenser to remove the second cleaning agent vapor.
[0073] According to the embodiments of this application, isopropanol in the carrier material can be completely removed.
[0074] In another embodiment, before providing the carrier material from the carrier material container to the reactor, the method further includes: providing a carrier material protective agent to the reactor to remove cleaning agents from the cleaned tissue sample and from the reactor.
[0075] Preferably, the carrier material protective agent includes a cleaning agent substitute, a mixture of cleaning agent substitutes and cleaning agents, and a mixture of cleaning agent substitutes and carrier material.
[0076] It should be understood that the foregoing general description and the following detailed description are explanatory and should not be construed as limiting this application. Attached Figure Description
[0077] These and / or other aspects and advantages of the embodiments of this application will become apparent and more readily understood from the following description with reference to the accompanying drawings, wherein:
[0078] Figure 1 This is a schematic diagram of an organization processor 1 according to one embodiment of this application;
[0079] Figure 2 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0080] Figure 3 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0081] Figure 4 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0082] Figure 5 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0083] Figure 6 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0084] Figure 7 This is another schematic diagram of an organization processor 1 according to one embodiment of the present application;
[0085] Figure 8A This is a schematic diagram of an organization processor 2 according to one embodiment of this application;
[0086] Figure 8B This is a schematic diagram of an organization processor 2 according to one embodiment of this application;
[0087] Figure 9 This is a schematic process flow diagram of an organization processor according to some embodiments of this application;
[0088] Figure 10 This is a flowchart of an organization processing method S1 according to some embodiments of this application;
[0089] Figure 11 This is another flowchart of the organization processing method S1 according to one embodiment of this application;
[0090] Figure 12This is a flowchart of step S900 of the tissue processing method S1 according to one embodiment of this application;
[0091] Figure 13 This is a flowchart of the organization and processing method S2 according to some embodiments of this application; and
[0092] Figure 14 This is a temperature program diagram of the processor immersed in the reactor according to one embodiment of this application.
[0093] Figure label:
[0094] Reactor 100
[0095] First carrier material inlet 101
[0096] First carrier material outlet 102
[0097] Reagent processing inlet 103
[0098] Processing reagent outlet 104
[0099] First gas outlet 105
[0100] Carrier material container 200
[0101] Second carrier material export 201
[0102] Second gas outlet 202
[0103] Second carrier material inlet 203
[0104] Second heater 300
[0105] First condenser 400
[0106] First gas inlet 401
[0107] First liquid outlet 402
[0108] Cooling coil 403
[0109] Cooling fan 404
[0110] Cooling channel 405
[0111] First liquid container 500
[0112] Switch valve 600
[0113] First pressure control device 700
[0114] Pump 701
[0115] Pressure sensor 702
[0116] Hydraulic damper 703
[0117] Air valve 704
[0118] Safety valve 705
[0119] Air Manifold 706
[0120] Rotary valve 707
[0121] First heater 800
[0122] Second condenser 900
[0123] Second gas inlet 901
[0124] Second liquid outlet 902
[0125] Second liquid container 1000
[0126] Second pressure control device 1100
[0127] 1200 reagent containers
[0128] Reflux entry point 1201
[0129] Discharge port 1202 Detailed Implementation
[0130] The embodiments of this application are described in detail below, with examples shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are illustrative and intended to provide a general understanding of the invention. These embodiments should not be construed as limiting the scope of this application. Throughout the specification, identical or similar components and components having identical or similar functions are indicated by similar numerical designations.
[0131] It should be noted that the terminology used in this application is for the purpose of describing specific embodiments only and should not be construed as limiting the scope of this application. As used in the embodiments of this application and the appended claims, the singular forms “a,” “an,” and “the” mean to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that, as used in this application, the term “and / or” represents and includes any one and all possible combinations of one or more of the associated listed items.
[0132] In this application, terms such as “first” and “second” are used in description and do not imply relative importance or significance, or imply the number of technical features referred to. Therefore, a feature defined by “first” and “second” may include one or more such features. In this specification, “multiple” means two or more of these features, unless otherwise specified.
[0133] In this application specification, it should be understood that, unless otherwise specified or limited, the terms “arrangement,” “connection,” and “linkage,” and their variations, are used extensively to include, for example, mechanical or electrical arrangement, connection, and linking, as well as the internal arrangement, connection, and linking of two components, and further, direct and indirect arrangements, connections, and links. Those skilled in the art will understand these contents based on the detailed embodiments of this application.
[0134] An improved tissue processor and a tissue processing method executed by the improved tissue processor are described below with reference to the accompanying drawings.
[0135] This improved tissue processing method or tissue processor supports xylene-free processing and can effectively remove xylene substitutes (such as isopropanol, IPA) without the need for additional chemical protective agents (such as PARALAST) to remove isopropanol, thus simplifying the tissue processing method and significantly saving costs.
[0136] Furthermore, the provided tissue processor supports the purification of isopropanol during tissue processing without the need for additional paraffin purification steps. Specifically, by controlling the paraffin feed rate, reactor temperature, and pressure, isopropanol can be uniformly and gently separated from paraffin, avoiding the generation of isopropanol foam in a short time and preventing isopropanol foam from entering the air system. This tissue processor supports paraffin purification not only during tissue processing but also during non-tissue processing stages, thus enabling the efficient, low-cost, and simple acquisition of highly purified paraffin for subsequent infiltration, thereby extending the lifespan of paraffin and contributing to the acquisition of high-quality tissue samples.
[0137] as follows Figures 1 to 9 As shown, an organization processor 1 is provided in an embodiment of the first aspect of this application.
[0138] In one implementation, such as Figure 1 As shown, the tissue processor 1 includes a reactor 100, a carrier material container 200, a second heater 300, a first condenser 400, and a first liquid container 500.
[0139] Reactor 100
[0140] The reactor 100 is configured to contain and process tissue samples, and is provided with 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.
[0141] In one embodiment, the first carrier material inlet 101 and the first carrier material outlet 102 of the reactor 100 are arranged separately.
[0142] In this embodiment, the first carrier material inlet 101 of the reactor 100 is connected via a pipeline to the carrier material outlet of the carrier material container 200 to receive carrier material from the carrier material container 200. The first carrier material outlet 102 of the reactor 100 is connected via a pipeline to the carrier material outlet of the carrier material container 200 or a different inlet to circulate the carrier material.
[0143] In another embodiment, the first carrier material inlet 101 and the first carrier material outlet 102 of the reactor are combined into the same arrangement. In this embodiment, the carrier material is supplied to and / or discharged from the reactor through a pipe from the same orifice.
[0144] In one embodiment, the processor further includes a carrier material receiver connected to the first carrier material outlet 102 for receiving carrier material overflowing from the reactor.
[0145] In one embodiment, the reagent inlet 103 and reagent outlet 104 of reactor 100 are arranged separately. In another embodiment, the reagent inlet 103 and reagent outlet 104 of reactor 100 are combined into a single arrangement. In this embodiment, the reagent is supplied to and / or discharged from the reactor through a pipe from the same orifice.
[0146] In practice, reactor 100 is a cassette. The number of reactors 100 in processor 1 is unlimited, provided it is suitable for processing tissue samples. For example, reactor 1 may include one, two, three, four, five, or six cassettes. During processing, tissue samples are fed into cassettes within the cassette. The cassette can hold 10, 50, 100, 150, 200, or 250 cassettes as needed. The cassettes can be hollow plastic boxes that allow for efficient flow and discharge of chemical reagents. The cassette and cassettes are resistant to the chemical action of the reagents. The cassette 100 is tightly sealed in the working environment. During processing, the temperature and pressure of the cassette 100 can be controlled as needed.
[0147] Carrier material container 200
[0148] The carrier material container 200 is configured to contain carrier material and is provided with a second carrier material outlet 201 and a second gas outlet 202 connected to a 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 return inlet. That is, 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 via a pipeline through the second carrier material outlet 201.
[0149] In another embodiment, the carrier material container 200 is further provided with a second carrier material inlet 203 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 flowing back to the carrier material container 200.
[0150] 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 needed. The carrier material can be paraffin or an oil suitable for wetting tissue samples.
[0151] Second heater 300
[0152] The second heater 300 is configured to heat the carrier material in the carrier material container 200. The second heater 300 can be placed inside the carrier material container 200 or outside the carrier material container 200.
[0153] In one embodiment, the second heater 300 is a heating element connected to the side wall of the carrier material container 200. In another embodiment, the second heater 300 is an oven, and the carrier material container 200 is arranged in the cavity of the oven. The second heater 300 is configured to control the carrier material container 200 at a temperature where the carrier material is in a molten state, thereby allowing the carrier material to be supplied via piping to the retort 100 or other device. For example, controlling the temperature in the carrier material container 200 within the range of 65°C to 85°C (inclusive), thus enabling complete separation of cleaning agents such as isopropanol from the carrier material in the carrier material container 200.
[0154] Preferably, the conduit is provided with a heating element surrounding it, thereby keeping the carrier material in a molten state during the supplying or discharging of the carrier material to or from the retort 100. The conduit and the heating element surrounding it may be arranged separately or in the same arrangement, such as a heating tube.
[0155] First condenser 400 and first liquid container 500
[0156] The first condenser 400 is provided with a first gas 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.
[0157] In one embodiment, the first condenser 400 further includes a cooling coil 403, and optionally a cooling fan 404 and cooling channels 405 surrounding the cooling coil 403, thereby enhancing cooling performance. Specifically, the first condenser 400 is primarily configured to condense isopropanol vapor from a carrier material such as paraffin during paraffin impregnation. For example, the first condenser 400 can condense 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% isopropanol vapor into liquid. The volume of the first liquid container can be 1L, 5L, 10L, 15L, 20L, 25L, or 30L, and is not limited thereto, as long as it can adequately receive the condensate from the first condenser 400. Surprisingly, adding a condenser system to the processor enables the effective and efficient removal of isopropanol from the carrier material at the appropriate temperature and pressure, thereby avoiding the need for additional isopropanol removal reagents and subsequent disposal of waste chemical reagents. This saves production costs and is environmentally friendly.
[0158] Switch valve 600
[0159] like Figure 2 As shown, in another embodiment, the tissue processor 1 also includes a switching valve 600.
[0160] The switching valve 600 is arranged in the pipeline connecting the first carrier material inlet 101 of the reactor and the second carrier material outlet 201 of the carrier material container 200.
[0161] In this embodiment, the switching valve 600 is configured to operate periodically, each cycle including an opening time of 1 to 10 seconds, preferably 1.5 seconds, and a closing time of 0.2 to 5 seconds, preferably 1.0 second. The opening time of the switching 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. The closing time of the switching 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 switching valve 600 is configured to operate at a specific cycle, thereby slowing down the rate at which carrier material, such as molten paraffin, is supplied from the carrier material container 200 to the reactor 100. Under operating conditions (i.e., high temperature and negative pressure), isopropanol in the molten paraffin can be properly separated from the paraffin, thus preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is charged into the reactor 100 under operating conditions. Furthermore, it prevents isopropanol foam from entering the air system and being blocked by the paraffin.
[0162] First pressure control device 700
[0163] like Figure 3 As shown, in one embodiment, the tissue processor 1 further includes a first pressure control device 700.
[0164] The first pressure control device 700 includes a pump 701, a pressure sensor 702, a hydraulic damper 703, an air valve 704, a safety valve 705, an air manifold 706, and a pressure delivery pipeline. The first pressure control device 700 is fluidly connected to the necked still 100 via pipeline to provide positive or negative pressure to the necked still 100. In one embodiment, during tissue processing, the first pressure control device 700 controls the reactor temperature within the range of 20 kPa to -80 kPa. In this embodiment, during the impregnation of the carrier material, the first pressure control device 700 controls the reactor pressure within the range of -15 kPa to -75 kPa.
[0165] Specifically, such as Figure 14 As shown, the first pressure control device 700 is configured to control the reactor to operate at the following pressures during immersion: a first stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; a second stage: reducing the pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes, preferably 15 minutes; and a third stage: maintaining a 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 high pressure, such as -40 kPa, for 30 minutes, thereby allowing a large amount of isopropanol to be generated uniformly and gently from the carrier material, and avoiding the formation of isopropanol foam; in the second stage, the pressure of the reactor is further reduced at a slow rate for about 15 minutes to reach the desired immersion pressure, thereby allowing the complete generation of the remaining isopropanol from the carrier material; and in the third stage, the reactor is controlled at about -70 kPa for immersion of the tissue sample. Thus, the resulting tissue sample is of high quality.
[0166] According to this implementation, the pressure in the reactor is gradually reduced, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently. This avoids the large amount of foam generated by isopropanol in the paraffin when it is filled into the reactor under working conditions, and further prevents isopropanol foam from entering the air system and being blocked by the paraffin.
[0167] In another embodiment, the first pressure control device 700 is further connected to the carrier material container 200 to provide positive or negative pressure to the carrier material container 200.
[0168] First heater 800
[0169] like Figure 4 As shown, in one embodiment, the tissue processor 1 further includes a first heater 800.
[0170] The first heater 800 is configured to heat the treatment reagent and / or carrier material in the reactor. In this embodiment, the first heater 800 is a heating cap. Specifically, the first heater 800 is configured to control the reactor 100 to operate at the following temperature during immersion: increasing from 50 to 70°C, preferably 65°C, to 75 to 90°C, preferably 85°C, at a rate of 0.5 to 2°C / min, preferably 1.5°C / min, and then maintaining at 75 to 90°C, preferably 85°C, for 30 to 40 minutes. More specifically, since the boiling point of isopropanol is 82°C, the optimal immersion temperature is chosen to be 85°C, thereby allowing almost all of the isopropanol to be removed during immersion. The temperature of the reactor 100 is gradually increased from 65°C to 85°C, thus avoiding the formation of isopropanol foam in a short time due to a rapid increase in temperature.
[0171] According to this implementation, the temperature of the reactor is gradually increased, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently. This avoids the large amount of foam generated by isopropanol in the paraffin when it is filled into the reactor under working conditions, and further prevents isopropanol foam from entering the air system and being blocked by the paraffin.
[0172] Second condenser 900 and second liquid container 1000
[0173] like Figure 5 As shown, in one embodiment, the tissue processor 1 further includes a second condenser 900 and a second liquid container 1000.
[0174] The second condenser 900 is provided with a second gas 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 includes 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 those of the first condenser 400 and the first liquid container 500, respectively, and will not be described in detail further.
[0175] Specifically, the second condenser 900 is primarily configured to condense isopropanol vapor from a carrier material, such as paraffin, before the carrier material is supplied from the carrier material container 200 to the reactor 100. For example, the second condenser 900 is capable of condensing isopropanol vapor into liquid at concentrations of 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 95%, or 99%. Surprisingly, adding a condenser system to the processor enables effective and efficient removal of isopropanol from the carrier material at suitable temperatures and pressures, thereby avoiding the need for additional isopropanol removal reagents and subsequent waste chemical treatment, thus saving production costs and being environmentally friendly.
[0176] In one embodiment, the first condenser 400 and the second condenser 900 are arranged separately, as are the first liquid container 500 and the second liquid container 1000. Therefore, the processor 1 includes two sets of condensers for removing isopropanol. That is, the first condenser 400 condenses the isopropanol in the reactor 100, and the second condenser 900 condenses the isopropanol in the carrier material container 200. In another embodiment, the first condenser 400 and the second condenser 900 are arranged in the same configuration, and the first liquid container 500 and the second liquid container 1000 are also arranged in the same configuration. Therefore, the processor 1 includes one set of condensers for removing isopropanol. That is, both the isopropanol in the reactor 100 and the isopropanol in the carrier material container 200 can be condensed using the same condenser.
[0177] In one embodiment, a tissue treatment (i.e., an operating state) is performed, wherein isopropanol in the carrier material, such as paraffin, in the carrier material container 200 is removed by a second condenser 900 before the carrier material is supplied from the carrier material container 200 to the reactor 100, and during impregnation, residual isopropanol in the carrier material in the reactor 100 is further removed by a first condenser 400. In another embodiment, no tissue treatment is performed (i.e., a resting state); however, isopropanol in the carrier material, such as paraffin, in the carrier material container 200 is removed by a second condenser 900.
[0178] According to this implementation, the tissue processor supports paraffin purification not only during the tissue processing stage but also during the non-tissue processing stage. Therefore, it can obtain highly purified paraffin for subsequent infiltration in an efficient, low-cost, and simple manner, thereby extending the lifespan of paraffin and contributing to the acquisition of high-quality tissue samples.
[0179] Second pressure control device 1100
[0180] like Figure 6As shown, in one embodiment, the tissue processor 1 further includes a second pressure control device 1100.
[0181] In one embodiment, the configuration of the second pressure control device 1100 is similar to that of the first pressure control device 700, and will not be described in detail here.
[0182] Specifically, the second pressure control device 1100 is configured to control the carrier material container 200 to operate periodically under pressure, each cycle including: a pressure from -10 to -75 kPa, preferably -40 kPa, for 25 to 45 seconds, preferably 34 seconds, and optionally an ambient pressure for 5 to 15 seconds, preferably 6 seconds. Therefore, isopropanol can be completely separated from the carrier material, resulting in a highly purified carrier material.
[0183] In one embodiment, the first pressure control device 700 and the second pressure control device 1100 are arranged separately, thus the processor 1 includes two sets of pressure control devices. That is, the first pressure control device 700 can discharge isopropanol from the reactor 100, and the second pressure control device 1100 can discharge isopropanol from the carrier material container 200. In another embodiment, the first pressure control device 700 and the second pressure control device 1100 are arranged in the same manner. That is, isopropanol in both the reactor 100 and the carrier material container 200 can be discharged through the same pressure control device.
[0184] 1200 reagent containers
[0185] like Figure 7 As shown, in one embodiment, the tissue processor 1 further includes a processing reagent container 1200.
[0186] The reagent container 1200 is provided with a discharge port 1202 and a reflux inlet 1201. The discharge port 1202 is connected to the reagent inlet 103 of the reactor 100, and the reflux inlet 1201 is connected to the reagent outlet 104 of the reactor 100.
[0187] In one embodiment, the outlet 1202 and the reflux inlet 1201 are arranged separately. In another embodiment, the outlet 1202 and the reflux inlet 1201 are arranged in the same way. That is, the treatment reagent is supplied from the treatment reagent container 1200 to the reactor 100 or drawn from the reactor 100 to the treatment reagent container 1200 through a pipe from the same orifice. In this embodiment, the treatment reagent container 1200 includes a fixed reagent container, a dehydration reagent container, a cleaning reagent container, and optionally a carrier material protection reagent container. Further, the chamber of the treatment reagent container 1200 is capable of accommodating a first liquid container 500 and a second liquid container 1000. In this embodiment, the treatment reagent container 1200 is capable of accommodating 1-100 sub-containers, and any value falling within this range. The sub-containers can be fixed reagent containers, dehydration reagent containers, cleaning reagent containers, carrier material protection reagent containers, or condensate containers, for example, bottles of any volume suitable for accommodating chemical reagents, such as formaldehyde solution, ethanol, isopropanol, paraffin, etc., at various concentrations.
[0188] Multiple reagents in their respective reagent containers are supplied to reactor 100 and / or sequentially returned to their respective reagent containers via rotary valve 707. Rotary valve 707 can control which reagent is supplied to reactor 100 via corresponding piping and can allow the reagent to return to its respective reagent container. Processing reagents are supplied to reactor 100 by the pressure control device 700 as described above. In one exemplary embodiment, processing reagent container 1200 contains 18 reagent bottles. Rotary valve 707 has 18 positions to control the filling and / or discharging of the 18 reagent bottles.
[0189] According to the first aspect, the tissue processor supports paraffin purification not only during the tissue processing stage but also during the non-tissue processing stage. Therefore, it can obtain highly purified paraffin in an efficient, low-cost, and simple manner for subsequent infiltration, thereby extending the lifespan of paraffin and contributing to the acquisition of high-quality tissue samples.
[0190] like Figure 10-14 As shown, a second aspect of this application provides an organization processing method S1 executed by the organization processor 1 described in the first aspect above.
[0191] like Figure 10 As shown, the tissue processing method S1 executed by the tissue processor 1 as described in the first aspect above includes the steps of:
[0192] S100: Provide the tissue sample to be processed to the reactor.
[0193] S200: Fix tissue samples with fixatives.
[0194] S300: Dehydrate fixed tissue samples using a dehydration reagent.
[0195] S400: Clean the dehydrated tissue samples and reactor with a cleaning agent to remove the dehydrating agent.
[0196] S500: A carrier material is supplied from a carrier material container to the reactor to impregnate a cleaned tissue sample, wherein the carrier material contains a cleaning agent.
[0197] S600: The reactor is controlled at a temperature that allows the first cleaning agent vapor to be generated from the carrier material.
[0198] S700: The reactor is controlled at a pressure such that the generated first cleaning agent vapor is discharged from the reactor, and
[0199] S800: The first cleaning reagent vapor that is drawn in is condensed into a liquid by the first condenser to remove the first cleaning reagent vapor.
[0200] For steps S100 to S400, they are similar to methods commonly used in existing tissue processing methods. The main difference between the processing method of this application and existing processing methods lies in steps S500-S800, which are described in detail below:
[0201] In one embodiment, S500: supplying carrier material from the carrier material container to the reactor to impregnate the cleaned tissue sample, further comprising: controlling the periodic supply of carrier material from the carrier material container to the reactor via an on / off valve, each cycle comprising an on time of 1 to 10 seconds, preferably 1.5 seconds, and an off time of 0.2 to 5 seconds, preferably 1.0 second. Therefore, the rate at which carrier material, such as molten paraffin, is supplied from the carrier material container to the reactor can be slowed down, and under operating conditions (i.e., high temperature and negative pressure), isopropanol in the molten paraffin can be properly separated from the paraffin, thereby preventing the isopropanol in the paraffin from generating a large amount of foam in a short time when the molten paraffin is introduced into the reactor under operating conditions, and further preventing isopropanol foam from entering the air system and clogging the air system by the paraffin.
[0202] In one embodiment, S600: controlling the reactor at a temperature that generates the first cleaning agent vapor from the carrier material further includes: controlling the reactor to operate at a temperature that increases from 50 to 70°C, preferably 65°C, to 75 to 90°C, preferably 85°C at a rate of 0.5 to 2°C / min, preferably 1.5°C / min, and then maintaining at 75 to 90°C, preferably 85°C, for 30 to 40 minutes. According to this embodiment, the reactor temperature gradually increases, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the rapid generation of large amounts of foam from isopropanol in the paraffin when molten paraffin is introduced into the reactor under operating conditions, and further preventing isopropanol foam from entering the air system and clogging it with paraffin.
[0203] In one embodiment, S700: controlling the reactor at a pressure such that the generated cleaning agent vapor is discharged from the reactor, further comprising: controlling the reactor to operate at the following pressures: a first stage: maintaining a pressure of -15 kPa to -50 kPa, preferably -40 kPa, for 20 to 40 minutes, preferably 30 minutes; a second stage: reducing the pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes, preferably 15 minutes; a third stage: maintaining 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, thereby allowing the carrier material in the reactor to generate isopropanol vapor uniformly and gently, avoiding the rapid generation of large amounts of foam from isopropanol in the paraffin when molten paraffin is charged into the reactor under operating conditions, and further preventing isopropanol foam from entering the air system and clogging it with paraffin.
[0204] In one implementation, such as Figure 11 As shown, prior to S500, the tissue treatment method S1 further includes: S900: removing cleaning reagent from the carrier material container through a second condenser.
[0205] like Figure 12 As shown, in this embodiment, S900 further includes:
[0206] S901: Control the carrier material container to operate at a temperature that causes the second cleaning reagent vapor to be generated from the carrier material;
[0207] S902: The carrier material container is controlled to operate periodically at a pressure that causes the generated second cleaning agent vapor to be discharged from the reactor, wherein each cycle includes: a pressure from -20 to -75 kPa, preferably -40 kPa, for 25 to 45 seconds, preferably 34 seconds, and optionally an ambient pressure for 5 to 15 seconds, preferably 6 seconds; and
[0208] S903: The second cleaning agent vapor that is drawn in is condensed into a liquid by the second condenser to remove the second cleaning agent vapor.
[0209] According to this embodiment, in the carrier material container, a portion of the cleaning agent, such as isopropanol, is removed from the carrier material. 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 from the carrier material container. The remaining cleaning agent, such as isopropanol, in the carrier material is further removed in a 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 the isopropanol is removed in the reactor. Therefore, cleaning agents such as isopropanol in the carrier material are completely removed without the need for additional chemical protective agents, thus simplifying tissue processing methods and significantly saving costs.
[0210] According to the second aspect, the tissue treatment method can effectively and efficiently remove cleaning agents (such as isopropanol) from the carrier material, thereby avoiding the need for additional isopropanol removal agents and subsequent disposal of waste chemical reagents, thus saving production costs and being environmentally friendly.
[0211] like Figure 8A and 8B As shown, an embodiment of the third aspect of this application provides a tissue processor 2. 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.
[0212] In another embodiment, the tissue processor 2 further includes the switching valve 600 as described in the first aspect above. In another embodiment, the tissue processor further includes the second pressure control device 1100 as described in the first aspect above. In another embodiment, the tissue processor 2 further includes the first condenser 400 and the first liquid container 500 as described in the first aspect above. In another embodiment, the tissue processor 2 further includes the first pressure control device 700 as described in the first aspect above. In another embodiment, the tissue processor 2 further includes the first heater 800 as described in the first aspect above. In another embodiment, the tissue processor 2 further includes the processing reagent container 1200 as described in the first aspect above. The configuration and function of the reactor 100, carrier material container 200, second heater 300, first condenser 400, first liquid container 500, switching 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 above, and will not be repeated due to space limitations.
[0213] According to the third aspect, the tissue processor supports paraffin purification not only during the tissue processing stage but also during the non-tissue processing stage. Therefore, it can obtain highly purified paraffin in an efficient, low-cost, and simple manner for subsequent infiltration, thereby extending the lifespan of paraffin and helping to obtain high-quality tissue samples.
[0214] like Figure 13 As shown, an embodiment of the fourth aspect of this application provides a tissue processing method S2 executed by the tissue processor 2 as described in the third aspect above, comprising the steps of:
[0215] S100: Provide the tissue sample to be processed to the reactor.
[0216] S200: Fix tissue samples with fixatives.
[0217] S300: Dehydrate fixed tissue samples using a dehydration reagent.
[0218] S400: Clean the dehydrated tissue samples and reactor with a cleaning agent to remove the dehydrating agent.
[0219] S500: Supply carrier material from the carrier material container to the reactor to impregnate the cleaned tissue sample.
[0220] Prior to S500, the method also includes S900: removing the cleaning agent from the carrier material container via a second condenser.
[0221] In this embodiment, S900: removing the cleaning agent from the carrier material container via a second condenser, further comprising:
[0222] S901: Controls the carrier material container to operate at a temperature that allows the second cleaning reagent vapor to be generated from the carrier material.
[0223] S902: The carrier material container is controlled to operate periodically at a pressure that causes the generated second cleaning agent vapor to be discharged from the reactor, each cycle comprising: a pressure from -20 to -75 kPa, preferably -40 kPa, for 25 to 45 seconds, preferably 34 seconds, and optionally an ambient pressure for 5 to 15 seconds, preferably 6 seconds, and
[0224] S903: The second cleaning agent vapor that is drawn in is condensed into a liquid by the second condenser to remove the second cleaning agent vapor.
[0225] In another embodiment, the method further includes the following steps after S500:
[0226] S600: The reactor is controlled at a temperature that allows the first cleaning agent vapor to be generated from the carrier material.
[0227] S700: The reactor is controlled at a pressure that allows the generated cleaning agent vapors to be discharged from the reactor.
[0228] S800: The first cleaning reagent vapor that is drawn in is condensed into a liquid by the first condenser to remove the first cleaning reagent vapor.
[0229] The main difference between tissue processing method S1 and tissue processing method S2 is as follows: In S1, the cleaning agent in the carrier material is substantially removed in the reactor by a first condenser, and optionally, in S500: before the carrier material is supplied from the carrier material container to the reactor for impregnation of the cleaned tissue sample, the cleaning agent in the carrier material container is removed by a second condenser; while in S2, before S500: before the carrier material is supplied from the carrier material container to the reactor for impregnation of the cleaned tissue sample, the cleaning agent in the carrier material container is substantially removed by a second condenser, and optionally, any remaining cleaning agent in the carrier material is further removed in the reactor by a first condenser. Therefore, in S1, the carrier material contains substantial cleaning agent before being supplied from the carrier material container to the reactor, while in S2, the carrier material contains almost no cleaning agent before being supplied from the carrier material container to the reactor.
[0230] In the implementation of the fourth aspect, the details of S100, S200, S300, S400, S500, S600, S700, S800, and S900 are similar to those in the third aspect, and will not be described further due to space limitations. In S2, before the carrier material is supplied from the carrier material container to the reactor, the second condenser has removed 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and 99% of the cleaning agent from the carrier material.
[0231] According to the fourth aspect, the tissue treatment method can effectively and efficiently remove cleaning agents (such as isopropanol) from the carrier material, thereby avoiding the need for additional isopropanol removal agents and subsequent disposal of waste chemical reagents, thus saving production costs and being environmentally friendly.
[0232] Example
[0233] This application will be described in more detail with reference to embodiments. It should be understood that this application is not limited to the following embodiments.
[0234] Example 1
[0235] Tissue samples are processed using tissue processor 1. In this embodiment, only one condensation system is provided (i.e., a first condenser 400 and a first liquid container 500). In this embodiment, the cleaning agent is isopropanol, and the carrier material is paraffin. The paraffin used for tissue processing contains a large amount of isopropanol. The reactor is a swivel still, and the carrier material container is an oven. The isopropanol in the paraffin is not removed in the oven before it is filled into the swivel still; therefore, isopropanol is substantially removed in the swivel still during tissue processing.
[0236] In this embodiment, the operating cycle of the switching valve was studied to evaluate the isopropanol removal efficiency. The switching valve was operated in a series of cycles as shown below. The temperature program of the retort was set to increase from 65°C to 85°C within 25 minutes, and then maintain at 85°C for 35 minutes during immersion. The pressure program 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 immersion. Isopropanol removal efficiency, isopropanol foam formation, and tissue sample quality were measured, and the results are shown in Table 1.
[0237] Table 1. Isopropanol removal efficiency under different operating cycles of the switching valve.
[0238]
[0239]
[0240] Example 2
[0241] Except for the temperature program set in the breech-mounted steamer as shown below, the tissue processing method was similar to that in Example 1. Specifically, the switching valve was operated periodically, with each cycle including a 1.5s opening time and a 1.0s closing time. The pressure program of the breech-mounted steamer 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 the immersion period. Isopropanol removal efficiency, isopropanol foam formation, and tissue sample quality were measured, and the results are shown in Table 2.
[0242] Table 2 shows the removal efficiency of isopropanol under different temperature programs performed in the retort.
[0243]
[0244] Example 3
[0245] Except for the pressure program set in the breech-mounted steamer as shown below, the tissue processing method was similar to that in Example 1. Specifically, the switching valve was operated periodically, with each cycle including a 1.5s opening time and a 1.0s closing time. The temperature program of the breech-mounted steamer was set to increase from 65°C to 85°C within 25 minutes, and then maintain at 85°C for 35 minutes during the immersion period. Isopropanol removal efficiency, isopropanol foam formation, and tissue sample quality were measured, and the results are shown in Table 2.
[0246] Table 3. Isopropanol removal efficiency under different pressure programs performed in the swivel still.
[0247]
[0248] Example 4
[0249] Except for the two condensation systems, the tissue processing method was similar to that in Example 1. Before filling the swirl still with paraffin, some isopropanol was removed from the paraffin in an oven; thus, some isopropanol was removed in the oven, and some was removed in the swirl still. Specifically, the switching valve was operated periodically, with each cycle consisting of a 1.5s opening time and a 1.0s closing time. The temperature program for the swirl still was set to increase from 65°C to 85°C over 25 minutes, and then maintain at 85°C for 35 minutes during immersion. The pressure program for the swirl still was set to maintain at -40 kPa for 30 minutes, decrease from -40 kPa to -70 kPa over 15 minutes, and then maintain at -70 kPa for 15 minutes during immersion. The isopropanol removal efficiency, isopropanol foam formation, and tissue sample quality were measured, and the results are shown in Table 2. The results indicate that no isopropanol foam was generated during immersion, 99% of the isopropanol was removed from the paraffin, and the resulting tissue samples were of high quality.
[0250] Example 5
[0251] Except for using tissue processor 2, which is equipped with only a second condenser 900 and a second liquid container 1000, to process tissue samples, the tissue processing method was similar to that in Example 1. Isopropanol in the paraffin was substantially removed in an oven before the paraffin was filled into the retort. Different temperatures and pressures in the oven were investigated, and the results are shown in Table 5.
[0252] Table 4. Isopropanol removal efficiency in carrier material containers under different conditions
[0253]
[0254]
[0255] Example 6
[0256] In this embodiment, during the paraffin impregnation step (approximately 60 minutes), a total of approximately 1120 mL of isopropanol was removed from the paraffin in the curved-neck still.
[0257] Mass of isopropanol: 0.7683 × 1120 ≈ 860.5 g ≈ 13 mol
[0258] The heat released from the paraffin in the retort: 1120 mL of isopropanol
[0259] Heat = 40.06 kJ / mol × 13 mol = 520.78 kJ
[0260] If 80% or more of the isopropanol vapor is to be cooled in the cooling components and separator (Trap bottle), the cooling capacity of the cooling components and separator should be >520.78 × 80% ≈ 417 kJ. Therefore, in order to cool the isopropanol vapor, the cooling components and separator should be provided with a heat exchange capacity of 417 kJ.
[0261] In this specification, the terms "one embodiment," "some embodiments," "an example," "a specific example," or "or some examples" refer to specific features, structures, materials, or characteristics associated with at least one embodiment or example of this application. Therefore, the aforementioned phrases appearing throughout this specification do not necessarily refer to the same embodiment or example of this application. Furthermore, specific features, structures, materials, or characteristics can be combined in any suitable manner in one or more embodiments or examples. Moreover, the different embodiments or examples described in this specification, as well as the features of those embodiments or examples, can be combined by those skilled in the art without conflict.
[0262] Although illustrative embodiments have been shown and described, those skilled in the art will understand that the above embodiments should not be construed as limiting this application, and that changes, substitutions and modifications can be made to the embodiments without departing from the spirit, principles and scope of this application.
Claims
1. An tissue processor (1), comprising: Reactor (100), Configured to accommodate tissue samples and allow processing of said tissue samples, and It is provided with 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); Carrier material container (200), It is configured to contain carrier material and is provided with a second carrier material outlet (201) and a second gas outlet (202) connected to the first carrier material inlet (101) of the reactor (100); A second heater (300) is configured to heat the carrier material in the carrier material container (200); First condenser (400), The reactor (100) is provided with a first gas 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; and A first liquid container (500) is connected to the first liquid outlet (402) of the first condenser (400) and configured to receive condensed liquid from the first condenser (400). The tissue processor (1) further includes a first pressure control device (700) configured to control the reactor (100) to operate at the following pressures: Phase 1: Maintain a pressure of -15 kPa to -50 kPa for 20 to 40 minutes. Second stage: The pressure is reduced at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes. The third stage: maintain a pressure of -60 kPa to -75 kPa for 10 to 25 minutes, and The tissue processor (1) further includes a switching valve (600) configured to operate periodically, arranged 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).
2. The tissue processor (1) according to claim 1, wherein the switching valve (600) is configured to operate periodically, each cycle including an opening time of 1 to 10 seconds and a closing time of 0.2 to 5 seconds.
3. The tissue processor (1) according to claim 1, wherein The first pressure control device (700) is configured to control the reactor (100) to operate at the following pressures: Phase 1: Maintain a pressure of -40 kPa for 30 minutes. Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min for 15 minutes. Phase 3: Maintain a pressure of -70 kPa for 15 minutes; and The switching valve (600) is configured to operate periodically, with each cycle consisting of an opening time of 1.5 seconds and a closing time of 1.0 second.
4. The tissue processor (1) according to claim 1, further comprising a first heater (800) configured to heat the processing reagent and / or the carrier material in the reactor (100).
5. The tissue processor (1) according to claim 4, wherein the first heater (800) is configured to control the reactor (100) to operate at the following temperature: Increase the temperature from 50 to 70°C to 75 to 90°C at a rate of 0.5 to 2°C / min, and then maintain the temperature at 75 to 90°C for 30 to 40 minutes.
6. The tissue processor (1) according to claim 4, wherein the first heater (800) is configured to control the reactor (100) to operate at the following temperature: The temperature was increased from 65°C to 85°C at a rate of 1.5°C / min, and then held at 85°C for 30 to 40 minutes.
7. The tissue processor (1) according to claim 1, further comprising: Second condenser (900), A second gas inlet (901) and a second liquid outlet (902) are provided, which are 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; and A second liquid container (1000) is connected to the second liquid outlet (902) of the second condenser (900) and configured to receive condensed liquid from the second condenser (900).
8. The tissue processor (1) according to claim 7, wherein the first condenser (400) and the second condenser (900) each include a cooling coil (403).
9. The tissue processor (1) according to any one of claims 1 to 8, further comprising a second pressure control device (1100) configured to control the carrier material container (200) to operate periodically under pressure, each cycle including The pressure of -20 to -75 kPa is maintained for 25 to 45 seconds.
10. The tissue processor (1) according to claim 9, wherein each cycle comprises The pressure of -40 kPa was maintained for 34 seconds.
11. The tissue processor (1) according to claim 9, wherein each cycle further comprises: The environmental pressure lasts for 5 to 15 seconds.
12. The tissue processor (1) according to claim 1 further includes a treatment reagent container (1200) provided with an outlet (1201) and a reflux inlet (1202), wherein the outlet (1201) is connected to the treatment reagent inlet (103) of the reactor (100), and the reflux inlet (1202) is connected to the treatment reagent outlet (104) of the reactor (100).
13. The tissue processor (1) according to claim 12, wherein the processing reagent container (1200) comprises a fixation reagent container, a dehydration reagent container, and a cleaning reagent container.
14. The tissue processor (1) according to claim 1, wherein 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 (201) of the carrier material container (200) are arranged separately or combined into the same arrangement, and / or The reagent inlet (103) and reagent outlet (104) of the reactor (100) are arranged separately or combined into the same arrangement.
15. A tissue processing method, performed by a tissue processor (1) according to any one of claims 1 to 14, wherein the method comprises: The tissue sample to be processed is provided to the reactor. The tissue sample was fixed with a fixative. The fixed tissue samples were dehydrated using a dehydrating agent. The dehydrated tissue sample and the reactor are cleaned with a cleaning agent to remove the dehydrating agent. A carrier material container is supplied to the reactor to impregnate a cleaned tissue sample, wherein the carrier material contains the cleaning agent. The reactor is controlled at a temperature that generates the first cleaning agent vapor from the carrier material. The reactor is controlled at a pressure such that the generated first cleaning agent vapor is discharged from the reactor. The first cleaning agent vapor, drawn in, is condensed into a liquid by a first condenser to remove the first cleaning agent vapor. Controlling the reactor to a pressure such that the generated first cleaning agent vapor is discharged from the reactor further includes: controlling the reactor to operate at the following pressure: Phase 1: Maintain a pressure of -15 kPa to -50 kPa for 20 to 40 minutes. Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min for 5 to 25 minutes. The third stage: maintain a pressure of -60 kPa to -75 kPa for 10 to 25 minutes; and The provision of carrier material from the carrier material container to the reactor for impregnating the cleaned tissue sample further includes: The carrier material is periodically supplied to the reactor from the carrier material container by means of an on / off valve, each cycle including an on time of 1 to 10 seconds and an off time of 0.2 to 5 seconds.
16. The method of claim 15, wherein The reactor is controlled to operate at the following pressures: Phase 1: Maintain a pressure of -40 kPa for 30 minutes. Second stage: Reduce the pressure at a rate of 0.5 to 4 kPa / min for 15 minutes. Phase 3: Maintain a pressure of -70 kPa for 15 minutes; and Each cycle of controlling the switching valve includes a 1.5-second opening time and a 1.0-second closing time.
17. The method of claim 15, wherein controlling the reactor at a temperature such that the first cleaning agent vapor is generated from the carrier material further comprises: The reactor is operated at the following temperatures: Increase the temperature from 50 to 70°C to 75 to 90°C at a rate of 0.5 to 2°C / min, and then maintain the temperature at 75 to 90°C for 30 to 40 minutes.
18. The method of claim 17, wherein the reactor is controlled to operate at the following temperature: The temperature was increased from 65°C to 85°C at a rate of 1.5°C / min, and then held at 85°C for 30 to 40 minutes.
19. The method of claim 15, further comprising, before supplying the carrier material from the carrier material container to the reactor: The cleaning agent is removed from the carrier material container via a second condenser.
20. The method of claim 19, wherein removing the cleaning agent from the carrier material container via a second condenser further comprises: The carrier material container is controlled to operate at a temperature that generates the second cleaning agent vapor from the carrier material. The carrier material container is controlled to operate periodically at a pressure that causes the generated second cleaning agent vapor to be discharged from the carrier material container, each cycle including: The pressure of -20 to -75 kPa was maintained for 25 to 45 seconds, and The second cleaning agent vapor is condensed into a liquid by the second condenser to remove the second cleaning agent vapor.
21. The method of claim 20, wherein each cycle comprises: The pressure of -40 kPa was maintained for 34 seconds.
22. The method of claim 20, wherein each cycle further comprises: The environmental pressure lasts for 5 to 15 seconds.
23. The method according to any one of claims 15 to 22, further comprising, before supplying the carrier material from the carrier material container to the reactor: A carrier material protective agent is provided to the reactor to remove the cleaning agent from the cleaned tissue sample and from the reactor.
24. The method of claim 23, wherein the carrier material protective agent comprises: Cleaning reagent substitutes, mixtures of the cleaning reagent substitutes and the cleaning reagents, and mixtures of the cleaning reagent substitutes and the carrier material.
Citation Information
Patent Citations
Methods for Automated Processing of Tissue Samples in Tissue Processors
CN101929927B
Method of automatically processing tissue samples in a tissue processor
CN101929927A
Closed tissue dehydration system, and controlling method thereof
CN104964858A