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WO2025086267A1 - Systèmes de coloration d'immunohistochimie (ihc) à commande dynamique et procédé à angle réglable - Google Patents

Systèmes de coloration d'immunohistochimie (ihc) à commande dynamique et procédé à angle réglable Download PDF

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Publication number
WO2025086267A1
WO2025086267A1 PCT/CN2023/127243 CN2023127243W WO2025086267A1 WO 2025086267 A1 WO2025086267 A1 WO 2025086267A1 CN 2023127243 W CN2023127243 W CN 2023127243W WO 2025086267 A1 WO2025086267 A1 WO 2025086267A1
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WIPO (PCT)
Prior art keywords
staining
heating chamber
hier
ihc
stainer
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PCT/CN2023/127243
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English (en)
Inventor
Jee Jong Shum
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Shenzhen Prs Ltd
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Shenzhen Prs Ltd
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Publication date
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Priority to PCT/CN2023/127243 priority Critical patent/WO2025086267A1/fr
Publication of WO2025086267A1 publication Critical patent/WO2025086267A1/fr
Pending legal-status Critical Current
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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)

Definitions

  • This description relates to immunohistochemistry (IHC) staining and associated systems, devices, methods, and apparatuses including a system of an adjustable angle rocking action mechanism that improves the performance and efficiency of automated staining processes by achieving optimal mixing of buffers and reagents.
  • IHC immunohistochemistry
  • Stationary automated stainers do not perform well in distributing a staining solution throughout a tissue sample, and at times result in non-uniform staining, and non-uniform staining contributes to false indications in tissue analysis, for example, overly concentrated stain or faint stain indicating cancerous tissue.
  • the present disclosure relates to an adjustable angle rocking action which uses gravity to perform a smooth and gentle mixing of the buffer or reagent by turning the chamber + and -8° slowly multiple times which is able to refresh the heat induced epitope retrieval (HIER) buffer inside the capillary gap, and also washes off the excess formalin so as to expose the maximum number of antigen sites.
  • HIER heat induced epitope retrieval
  • a Legend 6G Stainer includes a dynamically controlled external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air.
  • the Legend 6G Stainer further includes an adjustable air pressure control mechanism that regulates the pressurization of the heating chamber.
  • the Legend 6G Stainer further includes a capillary gap cover that protects a tissue during the HIER IHC staining process to ensure even heat distribution within a buffer pool.
  • the Legend 6G Stainer further includes a submersion system that submerges a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling, the heating chamber and associated components allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements.
  • the Legend 6G Stainer further includes that heating chamber and the associated components are capable of being rotated so as to uniformly mix a reagent and a buffer.
  • a staining system includes a dynamically controlled external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air.
  • the staining system further includes an adjustable air pressure control mechanism configured to regulate the pressurization of the heating chamber.
  • the staining system further includes a capillary gap cover that protects a tissue during the HIER IHC staining process to ensure even heat distribution within a buffer pool.
  • the staining system further includes a submersion system that submerges a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling, the heating chamber and associated components allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements.
  • the Legend 6G Stainer further includes that heating chamber and the associated components are capable of being rotated so as to uniformly mix a reagent and a buffer.
  • a staining method comprising dynamically controlling an external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air, regulating the pressurization of the heating chamber using an adjustable air pressure control mechanism, ensuring even heat distribution within a buffer pool using a capillary gap cover that protects a tissue during the HIER IHC staining process, submerging a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling using a submersion system, allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements using the heating chamber and associated components, and rotating the heating chamber and the associated components so as to uniformly mix a reagent and a buffer.
  • HIER Heat Induced Epitope Retrieval
  • IHC immuno
  • FIG. 1 is a schematic diagram of a stainer system, in accordance with some embodiments.
  • FIG. 2 is a block diagram of system architecture in accordance with some embodiments.
  • Figure 3 is a sequence diagram of a method of rotating the stainer system in accordance with some embodiments.
  • Figure 4 is a cross section view of the rotating stainer system in accordance with some embodiments.
  • first and second features are formed in direct contact
  • additional features may be formed between the first and second features, such that the first and second features may not be in direct contact
  • present disclosure may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed.
  • the other systems uneven heating causes bubble formation and cell cluster detachment, while in other systems an air knife displaces reagents and results in the loss of cell features.
  • the capillary gap, resembling a clam, also contributes to material loss from sectioned cells.
  • the Leica system uses a pump to suck liquid back and forth for mixing, the pump being too aggressive, resulting occasionally in folding of a tissue on the top and bottom.
  • the Ventana system uses an air knife to displace reagents and mixing. This aggressive mixing and washing scavenges unknown amounts of materials out of sectioned cells, which leads to loss of the cell’s cytoplasm and nucleus features.
  • the Dako capillary gap acts like a clam by opening and closing to move reagents about the tissue, however, the opening (pull force) is very hard on tissues because this pulling force sucks materials out of the sectioned cells.
  • FIG 1 is a schematic diagram of a stainer system 100 (hereinafter referred to as “stainer system 100” ) , in accordance with some embodiments.
  • Figure 1 is simplified for the purpose of illustration.
  • the stainer system 100 is capable of carrying out, or being used for, one or more staining processes or procedures. See the below features also in the cross-section view of Figure 4.
  • the stainer system 100 includes a cover 102.
  • the cover 102 comprises a material suitable for forming an air-tight enclosure.
  • the cover 102 comprises a hard plastic or metallic material.
  • the cover 102 comprises a plexi-glass material.
  • the cover 102 comprises a polypropylene material.
  • the cover 102 comprises a polypropylene and polyethylene blend material.
  • the cover 102 comprises an acrylic material.
  • the cover 102 comprises another material.
  • the stainer system 100 includes a container 104.
  • the container 104 comprises a material suitable for forming an air-tight enclosure.
  • the container 104 comprises a high temperature hard plastic material.
  • the container 104 comprises a plexi-glass metallic material.
  • the container 104 comprises a Teflon coating material.
  • the container 104 comprises a polypropylene material.
  • the container 104 comprises a polypropylene and polyethylene blend material.
  • the container 104 comprises an acrylic material.
  • the container 104 comprises another material.
  • the cover 102 and the container 104 are comprised of the same material. In some embodiments, the cover 102 and the container 104 are comprised of different materials.
  • the stainer system 100 includes a hinge 106 attached to the cover 102 and the container 104.
  • the hinge 106 allows for opening and closing of the cover 102.
  • the cover 102 and the container 104 are attached by more than one hinge or a hinge alternative.
  • the hinge 106 comprises a metallic material.
  • the hinge 106 comprises a plastic material.
  • the hinge 106 comprises a material that is the same material as the cover 102 or the container 104. In some embodiments, a hinge is not used.
  • the container 104 forms a chamber area.
  • the chamber area is a heating chamber of low mass capable of being pressurized by external air or air from sources external to the chamber area, such as an air tank compressor, etc.
  • the chamber area includes an air-circulating section or portion for circulating air.
  • the air is heated.
  • the chamber area is an air-heating area or portion.
  • the heating chamber area and associated components allow users to adjust a pressure within a psi range, such as a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements.
  • the cover 102 and the container 104 form an air-tight enclosure.
  • the cover 102 and the container 104 are capable of forming an air-tight seal.
  • the stainer system 100 includes a fan 108.
  • the fan is suitable for circulating air within a chamber area, causing the temperature of the air to equilibrate or become more consistent.
  • the fan 108 comprises an electrical fan.
  • the fan 108 is enclosed, shielded, or substantially enclosed or shielded.
  • the fan 108 is in communication with one or more processors, controllers, microcontrollers, or circuits.
  • the fan 108 speed is capable of being controlled by the one or more processors, controllers, microcontrollers, or circuits.
  • the fan 108 speed is adjusted based on a temperature of a chamber area.
  • the fan 108 speed is adjusted based on a temperature of dewax process.
  • a buffer liquid as described herein.
  • the stainer system 100 includes a heater element 110.
  • the heater element is suitable for heating or increasing the temperature of the air HIER buffer in a chamber area.
  • the heater element 110 comprises an electrical heater.
  • the heater element 110 is enclosed, shielded, or substantially enclosed or shielded.
  • the heater element 110 is in communication with one or more processors, controllers, microcontrollers, or circuits.
  • the heater element 110 temperature is capable of being controlled by the one or more processors, controllers, microcontrollers, or circuits.
  • the heater element 110 temperature is adjusted based on a temperature of a 114 chamber area.
  • the heater element 110 temperature is adjusted based on a temperature of a buffer liquid, as described herein.
  • the stainer system 100 includes an air inlet/outlet 112.
  • the air inlet/outlet 112 forms an air-tight passage into a chamber area.
  • the air inlet/outlet 112 is capable of adding or removing air from a chamber area.
  • the air inlet/outlet 112 is connected to an air pump or similar device.
  • the air inlet/outlet 112 is in communication with one or more processors, controllers, microcontrollers, or circuits.
  • the air pressure in a chamber area is capable of being controlled by the one or more processors, controllers, microcontrollers, or circuits.
  • the air pressure is controlled by an adjustable air pressure control mechanism 130.
  • the air pressure in a chamber area is adjusted based on a temperature of a chamber area. In some embodiments, the air pressure in a chamber area is adjusted based on a temperature of a buffer area, as described herein.
  • the adjustable air pressure control mechanism 130 comprises an air pressure measurement gauge or measurement device connected to a valve. In some embodiments, the valve is opened or closed to allow for air pressure adjustment.
  • the stainer system 100 includes a seating area 114.
  • the seating area 114 is capable of, or suitable for, holding a slide 114a or IHC utensil for staining. In some embodiments, stack a slide over another in an angle, so the chamber is capable to hold more slides per each staining process.
  • the slide or IHC utensil for staining includes a capillary gap cover that protects a tissue during an HEIR IHC staining process to ensure even heat distribution within a buffer pool.
  • the seating area 114 is capable of, or suitable for, containing a liquid, such as a buffer liquid.
  • the seating area 114 is capable of, or suitable for, containing a buffer pool 114b.
  • the seating area 114 includes or comprises a submersion system 128 that submerges a slide within a buffer pool to eliminate formation of hot spots and micro nucleated boiling.
  • the seating area 114 comprises a material suitable for conducting heat.
  • the seating area 114 comprises a hard plastic metallic material prefer stainless steel.
  • the seating area 114 comprises a plexi-glass material.
  • the seating area 114 comprises a polypropylene material.
  • the seating area 114 comprises a polypropylene and polyethylene blend material.
  • the seating area 114 comprises an acrylic material.
  • the seating area 114 comprises another material. In some embodiments, the seating area 114 comprises a dark or colored material usable to block light. In some embodiments, a submersion system 128 comprises a dish, bowl, or other device capable of containing a liquid.
  • the slide 114a is in a flat orientation 120, hence the staining is limited to the top layer opposed to staining of sub-layers.
  • the turning of the container 104 is able to achieve the maximum antigen retrieval process.
  • the slide 114a experiences a dynamic movement that facilitates optimal antigen retrieval.
  • the controlled rocking motion ensures comprehensive mixing of the buffer throughout the capillary gap, allowing for consistent and efficient staining.
  • the adjustable angle rocking action is able to be further customized for different stages of the staining process to optimize results.
  • a higher angle such as an approximately 30° downward position 120, is able to expedite the removal of wax and xylene.
  • a lower angle of an approximately 15° downward position 124/126 provides sufficient time for thorough removal of xylene residues.
  • the slide 114a is in a horizontal position (0°) 120 to maintain ideal conditions for the staining process.
  • This innovative feature offers flexible settings, empowering users to experiment with different angles and timings to achieve the best staining results based on specific tissue types and staining requirements.
  • the embodiments of the present disclosure provide numerous advantages to the field of automated staining.
  • the embodiments in the present disclosure hold immense potential across various domains, including medical diagnostics, research, and pathology, where automated staining techniques play a crucial role in achieving accurate and reliable results.
  • the embodiments in the present disclosure have numerous advantages, including improved staining uniformity such that the controlled rocking motion ensures comprehensive mixing, resulting in more uniform staining outcomes; preservation of cellular features such that the gentle mixing process minimizes the extraction of cellular materials, preserving crucial cytoplasm and nucleus features; enhanced antigen retrieval such that optimal exposure of antigen sites is achieved, leading to improved staining efficiency; customizability such that the mechanism allows users to adjust the rocking angles for different stages of the staining process, enabling optimization and flexibility; and applicability such that embodiments are able to be integrated into various automated staining systems, catering to diverse domains such as medical diagnostics, research, and pathology.
  • the seating area 114 is removable attached to the container 204. In some embodiments, the seating area 114 is cup-shaped, rectangularly and cup-shaped, or U-shaped, and removably attached to the container 104. In some embodiments, the seating area 114 allows for suspension of an IHC slide, device, or utensil above a chamber area, allowing for heat conduction from the chamber area, through the seating area 114 or through a buffer liquid or pool.
  • the stainer system 100 includes a liquid drain 116 from the seating area 114.
  • the liquid drain 116 allows for removal of liquid, such as a liquid buffer, from the seating area 114.
  • the stainer system 100 includes a temperature sensor 118.
  • the temperature sensor 118 allows for determination of a temperature of a liquid such as a buffer liquid in which an IHC slide or device is immersed.
  • the temperature sensor 118 is in communication with one or more processors, controllers, microcontrollers, or circuits.
  • the temperature of a liquid, such as a buffer liquid is capable of being controlled by the one or more processors, controllers, microcontrollers, or circuits.
  • the temperature of a liquid, such as a buffer liquid is adjusted based on a temperature of a chamber area, or vice versa.
  • various systems, sub-systems, and components from the aforementioned are combined and in communication with the same controlling unit comprising one or more processors, controllers, microcontrollers, or circuits.
  • temperatures are continuously monitored by one or more temperature sensors. In some embodiments, temperatures are determined at predetermined intervals by one or more temperature sensors. For example, temperatures may be determined by one or more temperature sensors in a buffer liquid, chamber area, etc.
  • air pressures are continuously monitored by one or more pressure sensors. In some embodiments, air pressures are determined at predetermined intervals by one or more pressure sensors. For example, air pressures may be determined by one or more pressure sensors in a chamber area, etc.
  • the temperature and pressure readings and measurements from various sensors are delivered to a controlling unit, for example.
  • the controlling unit allows for synchronization, adjustment, and calibration of various system components based on various system environment measurements.
  • one or more signals may be delivered by the controlling unit to a heating element to increase or decrease the temperature so as to adjust the temperature of the buffer pool.
  • one or more signals may be delivered by the controlling unit to a compressor element or system to increase or decrease the air pressure by adding or removing air through an air inlet/outlet so as to adjust the air pressure of the chamber area.
  • physical chemistry relationships between temperature and pressure are used to adjust environment conditions in a chamber area or buffer pool. For example, pressure adjustments are used to modify boiling points and chamber temperatures and humidities for example, and vice versa.
  • the systems and methods herein are usable to dynamically control environment conditions, such as the conditions of a heating chamber or buffer pool, during a staining process.
  • environment conditions such as the conditions of a heating chamber or buffer pool
  • the systems and methods herein help to prevent tissue damage, bubble formation, and uneven mixing of reagent and buffer during staining.
  • FIG. 2 is a block diagram of system architecture 200 in accordance with some embodiments.
  • System architecture 200 includes a hardware processor 202 and a non-transitory, computer readable storage medium 204 encoded with, i.e., storing, the computer program code 206, i.e., a set of executable instructions.
  • Computer readable storage medium 204 is also encoded with instructions 207 for interfacing with external devices.
  • the processor 202 is electrically coupled to the computer readable storage medium 204 via a bus 208.
  • the processor 202 is also electrically coupled to an I/O interface 210 by bus 208.
  • a network interface 212 is also electrically connected to the processor 202 via bus 208.
  • Network interface 212 is connected to a network 214, so that processor 202 and computer readable storage medium 204 are capable of connecting to external elements via network 214.
  • the processor 202 is configured to execute the computer program code 206 encoded in the computer readable storage medium 204 in order to cause system architecture 200 to be usable for performing a portion or all of the operations as described herein.
  • the processor 202 is a central processing unit (CPU) , a multi-processor, a distributed processing system, an application specific integrated circuit (ASIC) , or a suitable processing unit.
  • CPU central processing unit
  • ASIC application specific integrated circuit
  • the computer readable storage medium 204 is an electronic, magnetic, optical, electromagnetic, infrared, or a semiconductor system (or apparatus or device) .
  • the computer readable storage medium 204 includes a semiconductor or solid-state memory, a magnetic tape, a removable computer diskette, a random access memory (RAM) , a read-only memory (ROM) , a rigid magnetic disk, or an optical disk.
  • the computer readable storage medium 304 includes a compact disk-read only memory (CD-ROM) , a compact disk-read/write (CD-R/W) , or a digital video disc (DVD) .
  • the storage medium 204 stores the computer program code 206 configured to cause system architecture 200 to perform a portion or all of the operations as described herein. In some embodiments, the storage medium 204 also stores information needed for performing a portion or all of the operations as described herein as well as information generated during performing a portion or all of the operations as described herein, such as a user interface parameter 316.
  • the storage medium 204 stores instructions 207 for interfacing with external devices.
  • the instructions 207 enable processor 202 to generate instructions readable by the external devices to effectively implement a portion or all of the operations as described herein.
  • System architecture 200 includes I/O interface 210.
  • I/O interface 210 is coupled to external circuitry.
  • I/O interface 210 includes a keyboard, keypad, mouse, trackball, trackpad, or cursor direction keys for communicating information and commands to processor 202.
  • System architecture 200 also includes network interface 212 coupled to the processor 202.
  • Network interface 212 allows computer architecture 200 to communicate with network 214, to which one or more other computer systems are connected.
  • Network interface 212 includes wireless network interfaces such as BLUETOOTH, WIFI, WIMAX, GPRS, or WCDMA; or wired network interface such as ETHERNET, USB, or IEEE-1394.
  • wireless network interfaces such as BLUETOOTH, WIFI, WIMAX, GPRS, or WCDMA
  • wired network interface such as ETHERNET, USB, or IEEE-1394.
  • the apparatus is another device capable of processing logical functions in order to perform the operations herein.
  • the controller and the storage unit need not be entirely separate devices, but share circuitry or one or more computer-readable mediums in some embodiments.
  • the storage unit includes a hard drive storing both the computer-executable instructions and the data accessed by the controller, and the controller includes a combination of a central processing unit (CPU) and RAM, in which the computer-executable instructions are able to be copied in whole or in part for execution by the CPU during performance of the operations herein.
  • CPU central processing unit
  • a program that is installed in the computer is capable of causing the computer to function as or perform operations associated with apparatuses of the embodiments described herein.
  • a program is executable by a processor to cause the computer to perform certain operations associated with some or all of the blocks of flowcharts and block diagrams described herein.
  • At least some embodiments are described with reference to flowcharts and block diagrams whose blocks represent (1) steps of processes in which operations are performed or (2) sections of a controller responsible for performing operations.
  • certain steps and sections are implemented by dedicated circuitry, programmable circuitry supplied with computer-readable instructions stored on computer-readable media, or processors supplied with computer-readable instructions stored on computer-readable media.
  • dedicated circuitry includes digital or analog hardware circuits and include integrated circuits (IC) or discrete circuits.
  • programmable circuitry includes reconfigurable hardware circuits including logical AND, OR, XOR, NAND, NOR, and other logical operations, flip-flops, registers, memory elements, etc., such as field-programmable gate arrays (FPGA) , programmable logic arrays (PLA) , etc.
  • FPGA field-programmable gate arrays
  • PLA programmable logic arrays
  • the computer readable storage medium includes a tangible device that is able to retain and store instructions for use by an instruction execution device.
  • the computer readable storage medium includes, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing.
  • a non- exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM) , a read-only memory (ROM) , an erasable programmable read-only memory (EPROM or Flash memory) , a static random access memory (SRAM) , a portable compact disc read-only memory (CD-ROM) , a digital versatile disk (DVD) , a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing.
  • RAM random access memory
  • ROM read-only memory
  • EPROM or Flash memory erasable programmable read-only memory
  • SRAM static random access memory
  • CD-ROM compact disc read-only memory
  • DVD digital versatile disk
  • memory stick a floppy disk
  • a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded there
  • a computer readable storage medium is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable) , or electrical signals transmitted through a wire.
  • computer readable program instructions described herein are downloadable to respective computing/processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network or a wireless network.
  • the network includes copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers or edge servers.
  • a network adapter card or network interface in each computing/processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing/processing device.
  • computer readable program instructions for carrying out operations described above are assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the C programming language or similar programming languages.
  • the computer readable program instructions are executed entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server.
  • the remote computer is connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN) , or the connection is made to an external computer (for example, through the Internet using an Internet Service Provider) .
  • electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA) , or programmable logic arrays (PLA) execute the computer readable program instructions by utilizing state information of the computer readable program instructions to individualize the electronic circuitry, in order to perform aspects of the subject disclosure.
  • Figure 3 is a sequence diagram of a method 300 of rotating the stainer system in accordance with some embodiments.
  • a staining method comprising dynamically controlling an external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process 302.
  • the heating chamber being of low mass is capable of 304 being pressurized by external air, regulating the pressurization of the heating chamber using an adjustable air pressure control mechanism, 306 ensuring even heat distribution within a buffer pool using a capillary gap cover that protects a tissue during the HIER IHC staining process, 308 submerging a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling using a submersion system, 310 allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements using the heating chamber and associated components, and 312/314 rotating the heating chamber and the associated components so as to uniformly mix a reagent and a buffer.
  • HIER Heat
  • a Legend 6G Stainer includes a heating chamber and associated components are capable of being rotated so as to uniformly mix a reagent and a buffer.
  • the heating chamber is dynamically controlled external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air.
  • the Legend 6G Stainer further includes an adjustable air pressure control mechanism that regulates the pressurization of the heating chamber.
  • the Legend 6G Stainer further includes a capillary gap cover that protects a tissue during the HIER IHC staining process to ensure even heat distribution within a buffer pool.
  • the Legend 6G Stainer further includes a submersion system that submerges a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling, the heating chamber and associated components allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements.
  • the Legend 6G Stainer of Supplemental Note 1 wherein the heating chamber maintains a temperature range and a boing point between 100 and 130°C, reducing the risk of tissue damage and enabling precise control during the HIER IHC staining process.
  • the Legend 6G Stainer of any of Supplemental Notes 1-2 further comprising a pressure control system that adjusts the air pressure in real-time to prevent the formation of bubbles, ensuring effective antigen retrieval and staining.
  • a staining system includes a dynamically controlled external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air.
  • the staining system further includes an adjustable air pressure control mechanism configured to regulate the pressurization of the heating chamber.
  • the staining system further includes a capillary gap cover that protects a tissue during the HIER IHC staining process to ensure even heat distribution within a buffer pool.
  • the staining system further includes a submersion system that submerges a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling, the heating chamber and associated components allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements.
  • the Legend 6G Stainer further includes that the heating chamber and the associated components are capable of being rotated so as to uniformly mix a reagent and a buffer.
  • the staining system of Supplemental Note 6 wherein the heating chamber maintains a temperature range and a boing point between 100 and 130°C, reducing the risk of tissue damage and enabling precise control during the HIER IHC staining process.
  • the staining system of any of Supplemental Notes 6-7 further comprising a pressure control system configured to adjust the air pressure in real-time to prevent the formation of bubbles, ensuring effective antigen retrieval and staining.
  • the staining system of any of Supplemental Notes 6-9 wherein the capillary gap cover protects the slide from uneven heating and other irregularities that lead to formation of bubbles, preventing staining issues, and breaking off of cell clusters.
  • a staining method comprising dynamically controlling an external air pressurized heating chamber designed for a Heat Induced Epitope Retrieval (HIER) immunohistochemistry (IHC) staining process, said heating chamber being of low mass and capable of being pressurized by external air, regulating the pressurization of the heating chamber using an adjustable air pressure control mechanism, ensuring even heat distribution within a buffer pool using a capillary gap cover that protects a tissue during the HIER IHC staining process, submerging a slide within the buffer pool to eliminate formation of hot spots and micro nucleated boiling using a submersion system, allowing users to adjust a pressure within a range of 8 to 12 psi, thereby providing control over a boiling point of the HIER IHC staining process for different tissue types and staining protocol requirements using the heating chamber and associated components, and rotating the heating chamber and the associated components so as to uniformly mix a reagent and a buffer.
  • HIER Heat Induced Epitope Retrieval
  • IHC immuno
  • the staining system of Supplemental Note 11 further comprising maintaining a temperature range and a boing point between 100 and 130°C, reducing the risk of tissue damage and enabling precise control during the HIER IHC staining process using the heating chamber.
  • the staining method of any of Supplemental Notes 11-12 further comprising adjusting the air pressure in real-time to prevent the formation of bubbles, ensuring effective antigen retrieval and staining using a pressure control system.
  • the staining method of any of Supplemental Notes 11-14 further comprising protecting the slide from uneven heating and other irregularities that lead to formation of bubbles, preventing staining issues, and breaking off of cell clusters using the capillary gap cover.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un système de coloration (100) comprenant une chambre de chauffage sous pression d'air externe à commande dynamique pour un processus de coloration d'immunohistochimie (IHC) de récupération d'épitopes induite par la chaleur (HIER), ladite chambre de chauffage étant de faible masse et pouvant être mise sous pression par de l'air externe. Le système de coloration (100) comprend un mécanisme de commande de pression d'air réglable (130). Le système de coloration (100) comprend en outre un couvercle à espace capillaire (102) qui protège un tissu pendant le processus de coloration IHC HIER pour assurer une distribution de chaleur uniforme à l'intérieur d'un groupe de tampons (114b). Le système de coloration (100) comprend en outre un système d'immersion (128) qui immerge une lame (114a) à l'intérieur du groupe de tampons (114b), la chambre de chauffage et les composants associés permettant aux utilisateurs d'ajuster une pression dans une plage de 8 à 12 psi. Le système de coloration (100) comprend en outre la chambre de chauffage et les composants associés peuvent être mis en rotation de façon à mélanger uniformément un réactif et un tampon.
PCT/CN2023/127243 2023-10-27 2023-10-27 Systèmes de coloration d'immunohistochimie (ihc) à commande dynamique et procédé à angle réglable Pending WO2025086267A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060153736A1 (en) * 2003-09-09 2006-07-13 Kalra Krishan L Sample processing system
US20100028978A1 (en) * 2005-05-24 2010-02-04 Angros Lee H In situ heat induced antigen recovery and staining apparatus and method
WO2015199976A1 (fr) * 2014-06-24 2015-12-30 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Microdissection activée par une cible
US9945763B1 (en) * 2011-02-18 2018-04-17 Biocare Medical, Llc Methods and systems for immunohistochemistry heat retrieval of biological samples
CN113785184A (zh) * 2019-05-14 2021-12-10 文塔纳医疗系统公司 包括生物学样品处理腔室的系统
CN115667874A (zh) * 2020-05-27 2023-01-31 安捷伦科技有限公司 用于处理生物样本的设备和方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060153736A1 (en) * 2003-09-09 2006-07-13 Kalra Krishan L Sample processing system
US20100028978A1 (en) * 2005-05-24 2010-02-04 Angros Lee H In situ heat induced antigen recovery and staining apparatus and method
US9945763B1 (en) * 2011-02-18 2018-04-17 Biocare Medical, Llc Methods and systems for immunohistochemistry heat retrieval of biological samples
WO2015199976A1 (fr) * 2014-06-24 2015-12-30 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Microdissection activée par une cible
CN113785184A (zh) * 2019-05-14 2021-12-10 文塔纳医疗系统公司 包括生物学样品处理腔室的系统
CN115667874A (zh) * 2020-05-27 2023-01-31 安捷伦科技有限公司 用于处理生物样本的设备和方法

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