Intelligent immunohistochemical staining instrument
By introducing a heating array and sensing module into the immunohistochemical staining instrument, monitoring the temperature and adjusting the heater power, and optimizing parameters with a transmittance sensor, the problems of throughput and consistency were solved, achieving efficient and low-cost staining.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-31
- Publication Date
- 2026-04-03
AI Technical Summary
Existing immunohistochemical staining instruments have low throughput and struggle to ensure consistency in sample processing during high-throughput processing, leading to deviations in staining results.
A heating array and sensing module are used. The temperature of the repair module is monitored by a temperature sensor and the heater power is adjusted. Combined with a transmittance sensor to monitor the staining effect, the parameters are dynamically adjusted to ensure consistency and throughput requirements.
It achieves increased throughput without increasing instrument size, while ensuring consistency in sample processing and staining effects, and reducing equipment costs.
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Figure CN121783658A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of immunohistochemical staining instrument technology, specifically relating to an intelligent immunohistochemical staining instrument. Background Technology
[0002] Immunohistochemical staining instruments are automated devices used in pathological, biological, and medical research. Their core function is to add various reagents to tissue samples on glass slides through program control, and then incubate and wash them at specific temperatures, ultimately making specific target protein antigens visible and localized on the tissue sections.
[0003] Currently available immunohistochemical staining instruments generally have low throughput, failing to meet the actual needs of domestic users. Furthermore, their common operating mode involves fixing slides inside the machine to complete the entire immunohistochemical staining process. This approach does not fully utilize the internal space of the instrument. Increasing throughput requires increasing the number of slide placement positions, resulting in a very large instrument size. However, practical usage conditions often do not allow for such a large instrument. Therefore, Chinese patent CN118090379B discloses an immunohistochemical staining instrument, including: a material tank module, a repair module, a visual recognition module, and a circling module. The system comprises a module, a small reagent tray module, an incubation module, a cleaning module, and a robotic arm. A material tank module is used to load slides. The robotic arm grips at least a portion of the slide and transfers it from the material tank module to the repair module, where reagents are added. The repaired slide is then transferred to a visual recognition module, which identifies the position and outline of the tissue sample on the slide. A circling module is used to draw a circle around the tissue sample on the slide. The slide is then transferred from the circling module to the small reagent tray module, where reagents are added. After reagent addition, the slide is placed in the incubation module for reaction, and then transferred to the cleaning module for cleaning. This application adopts a streamlined design concept, allowing slides to circulate via a carrier, significantly increasing throughput without increasing the instrument's size.
[0004] However, during high-throughput parallel processing, slight differences in environmental parameters such as temperature, humidity, mechanical motion error, and reagent dosage make it difficult to maintain consistent processing conditions between different samples, leading to deviations in staining results. For example, in the repair module, uneven heating temperatures in each repair tank affect the repair effect, resulting in inconsistent output. Therefore, a highly consistent intelligent immunohistochemical staining instrument is needed. Summary of the Invention
[0005] To address the aforementioned problems in the existing technology, this invention provides an intelligent immunohistochemical staining instrument with high output consistency.
[0006] The objective of this invention can be achieved through the following technical solutions: An intelligent immunohistochemical staining instrument includes a control module and a heating array and a sensing module electrically connected to the control module. The heating array includes a plurality of heaters electrically connected to the control module. The plurality of heaters are disposed in a repair module. The repair module is provided with a plurality of working areas corresponding to the plurality of heaters. The sensing module includes a plurality of temperature sensors, which are provided in a corresponding manner to the plurality of heaters. The temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range, and if it exceeds the threshold range, instruct the heater of the corresponding work area to reduce the power, and if it is below the threshold range, instruct the heater of the corresponding work area to increase the power.
[0007] As a preferred embodiment of the present invention, the plurality of temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data Tn to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range and instruct the heater power of the corresponding work area to increase by A1 times, where A1=1+(T0-Tn) / T0×c, T0 is the middle value of the temperature threshold range, P0 is the pre-input power reference value, and c is the pre-input constant.
[0008] As a preferred embodiment of the present invention, the control module is used to calculate the temperature consistency of the repair module based on the variance of several temperature data. The control module determines whether the temperature consistency exceeds the variance threshold and issues an alarm when the threshold is exceeded.
[0009] As a preferred embodiment of the present invention, the control module is used to count the flux, and the control module is used to determine whether the flux exceeds a threshold, and to increase the value of the variance threshold when the determination result is yes.
[0010] As a preferred embodiment of the present invention, the control module is used to calculate the flux L, and the control module is used to adjust the variance threshold to A1 times the original value, where A2 = L / L0 × d, d is a pre-input correction coefficient, and L0 is a pre-input flux reference value.
[0011] As a preferred embodiment of the present invention, the control module is electrically connected to a transmittance sensor, which is disposed in a material tank for storing glass slides. The transmittance sensor is used to monitor the transmittance of the stained glass slides in the material tank and upload the transmittance data to the control module.
[0012] As a preferred embodiment of the present invention, the transmittance sensor is used to monitor the transmittance of the stained glass slides at various locations in the material tank and upload several transmittance data to the control module. The control module is used to determine the consistency of the transmittance data and reduce the value of the variance threshold when the consistency is lower than the threshold.
[0013] The beneficial effects of this invention are as follows: (1) By setting several independent temperature sensors and heating elements in the repair tank, several parts of the repair tank are heated independently, so that the system can independently monitor the temperature of each area and adjust the heating power of each area independently according to the detection results, thereby achieving precise and uniform control of the temperature field in the repair tank and ensuring the consistency of the output samples. (2) By adjusting the variance threshold according to the throughput, the variance threshold is lowered when the throughput is high and the processing cycle needs to be shortened, thereby relaxing the consistency requirements. When the throughput is low and the processing accuracy can be taken into account, the variance threshold is increased, thereby narrowing the consistency requirements. This achieves dynamic optimization of monitoring parameters. (3) By integrating a transmittance sensor at the bottom of each slide holder slot in the material tank module to measure transmittance, the staining effect of the stained samples in the material tank module can be easily evaluated while controlling the overall equipment cost. (4) By further adjusting the variance threshold based on the monitoring results of several transmittance sensors, the variance threshold is dynamically narrowed when the transmittance consistency is poor, that is, when the staining finished products of several slides are significantly different, thus further realizing the dynamic adjustment of the optimized monitoring parameters. Attached Figure Description
[0014] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to the accompanying drawings.
[0015] Figure 1 This is a block diagram of the control loop of the present invention. Detailed Implementation
[0016] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided.
[0017] Please see Figure 1 A smart immunohistochemical staining instrument includes a control module and a heating array and a sensing module electrically connected to the control module. The heating array includes a plurality of heaters electrically connected to the control module. The plurality of heaters are disposed in a repair module. The repair module is provided with a plurality of working areas corresponding to the plurality of heaters. The sensing module includes a plurality of temperature sensors, which are provided in a corresponding manner to the plurality of heaters. Several temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range, and when it exceeds the threshold range, it instructs the heater of the corresponding work area to reduce the power, and when it is below the threshold range, it instructs the heater of the corresponding work area to increase the power. Specifically, the intelligent immunohistochemical staining instrument includes at least a shell, which contains a material tank, a repair module, an incubation module, a cleaning module, and a robotic arm. The operator places the slide to be processed in the material tank, and the robotic arm sequentially transfers the slide to the repair module, the incubation module, and the cleaning module to complete the immunohistochemical staining process. Afterward, the robotic arm transfers the stained slide back to the material tank. The repair module includes several points for placing the slides to be processed. These points are divided into several working areas. Each working area is equipped with a heater, and each heater is electrically connected to the control module. Additionally, a temperature sensor is installed above each working area. The control module assigns a number to each work area, temperature sensor, and heater. Temperature sensors and heaters located in the same work area have the same number. In this case, the control module can identify the temperature sensor and heater in the same work area by judging the number. When the temperature sensor corresponding to a certain heater reports a temperature higher than the set threshold, the control module instructs the power supply of the heater with the same number to achieve temperature control. Specifically, during the control process, several temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data Tn to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range and instructs the heater power of the corresponding work area to increase by A1 times, where A1=1+(T0-Tn) / T0×c, T0 is the middle value of the temperature threshold range, c is a pre-input constant, and n is the work area number. When the temperature data Tn of area numbered n is uploaded to the control module; When Tn is large and exceeds the threshold range, the control module calculates that the multiple A1 is less than 1, and then instructs the heater with number n to reduce its power, so that the temperature of the working area approaches the center value T0 of the set range. When Tn is small and below the threshold range, the control module calculates that the multiple A1 is greater than 1, and then instructs the heater numbered n to increase its power, so that the temperature of the working area approaches the center value T0 of the set range. By setting several independent temperature sensors and heating elements in the repair tank, the system can independently heat several parts of the repair tank, enabling it to independently monitor the temperature of each area and independently adjust the heating power of each area based on the detection results. This achieves precise and uniform control of the temperature field in the repair tank, ensuring the consistency of the output samples.
[0018] In some cases, when the heating rate is inconsistent in several work areas due to random differences in equipment operation, the processing speed of the glass slides to be processed in different areas will be inconsistent, making it difficult to predict the processing completion time, affecting the processing cycle of subsequent processes, and at the same time, there is a probability that the processing time will be too short or too long. To this end, the control module is used to calculate the temperature consistency of the repair module based on the variance of several temperature data. The control module determines whether the temperature consistency exceeds the variance threshold and issues an alarm when it exceeds the threshold.
[0019] Under different throughput conditions, the processing cycle needs to be shortened appropriately. Therefore, the temperature consistency requirement can be relaxed appropriately, that is, the set value of the variance threshold can be reduced, and the frequency of triggering alarms can be reduced to meet the needs of high throughput operation. Therefore, the control module is used to count the flux, and the control module is used to determine whether the flux exceeds the threshold, and increases the value of the variance threshold when the determination result is yes.
[0020] Specifically, since the control module is used to control the robotic arm that moves the glass slide, the control module can count the throughput by the frequency of the robotic arm's movements. When the robotic arm performs 10 operations per unit time, the throughput is determined to be 10 units. The control module calculates the flux L. The control module is used to adjust the variance threshold to A2 times the original value, where A2 = L / L0 × d, d is a pre-input correction coefficient, and L0 is a pre-input flux reference value. When L is high, A2 is greater than 1, the variance threshold is increased accordingly, allowing a larger temperature fluctuation range, thereby reducing the probability of alarm triggering and adapting to the needs of high-throughput operation; when L is low, A2 is less than 1, the variance threshold is reduced, the system has stricter requirements for temperature consistency, and ensures the stability of processing quality under low load. By adjusting the variance threshold based on throughput, the system can relax consistency requirements by lowering the variance threshold when throughput is high and processing cycles need to be shortened, and tighten the variance threshold when throughput is low and processing accuracy can be maintained, thereby narrowing consistency requirements. This enables dynamic optimization of monitoring parameters.
[0021] The control module is electrically connected to a transmittance sensor, which is installed in a material tank for storing glass slides. The transmittance sensor is used to monitor the transmittance of the stained glass slides in the material tank and upload the transmittance data to the control module. The transmittance sensor is used to monitor the transmittance of the stained glass slides at various points in the material tank and upload several transmittance data to the control module. The control module is used to determine the consistency of the transmittance data and reduce the value of the variance threshold when the consistency is lower than the threshold. In this embodiment, the material tank includes at least a plurality of plate-shaped structures. The main body of each plate-shaped structure is a plate made of transparent material parallel to the ground. Several grooves are provided on the upper surface of the plate. The shape of the grooves is set to match the glass slides. Each groove is used to place the glass slides. The material tank is divided into a to-be-treated area and a treated area. In use, the operator places the glass slide to be treated on the to-be-treated area in the material tank. The robotic arm picks up the glass slide from the to-be-treated area for staining treatment and places the stained glass slide into the treated area of the material tank. The transmittance sensor is used to monitor the transmittance of the stained glass slides at various points in the material tank and upload several transmittance data to the control module. The control module is used to determine the consistency of the transmittance data and reduce the value of the variance threshold when the consistency is lower than the threshold. Specifically, the transmittance sensor is placed below the treated area of the material tank, and an illumination lamp is set above the treated area. The illumination lamp and the transmittance sensor are switched on and off synchronously. The illumination lamp or the transmittance sensor is manually turned on by the control module or the operator when needed. The light from the illumination lamp passes through the material tank and the dyed glass slide. At this time, the transmittance sensor can read the transmittance of the light it receives and then determine the transmittance of the dyed glass slide above it, and thus roughly determine the dyeing result and dyeing consistency. When the transmittance consistency is poor, that is, when the staining effect of multiple slides is significantly different, it indicates that there may be undetected environmental inconsistencies in the previous steps. It is necessary to further tighten the judgment criteria to improve the sensitivity to whether the environmental consistency meets the standard. At this time, the control module will automatically increase the sensitivity of the transmittance variance judgment threshold to improve the sensitivity to whether the environmental consistency meets the standard. By further adjusting the variance threshold based on the monitoring results of several transmittance sensors, the variance threshold is dynamically narrowed when the transmittance consistency is poor, i.e., when the staining results of several slides differ greatly, thus further realizing the dynamic adjustment of the optimized monitoring parameters.
[0022] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.
Claims
1. An intelligent immunohistochemical staining instrument, characterized in that: The system includes a control module and a heating array and a sensing module electrically connected to the control module. The heating array includes several heaters electrically connected to the control module. The heaters are disposed in the repair module. The repair module has several working areas corresponding to the heaters. The sensing module includes several temperature sensors, and the temperature sensors are disposed in a one-to-one correspondence with the heaters. Several temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range, and if it exceeds the threshold range, instruct the heater of the corresponding work area to reduce the power, and if it is below the threshold range, instruct the heater of the corresponding work area to increase the power.
2. The intelligent immunohistochemical staining instrument according to claim 1, characterized in that: The temperature sensors are used to monitor the temperature of the corresponding work area and upload the temperature data Tn to the control module. The control module is used to determine whether the temperature of the corresponding work area exceeds the temperature threshold range and instruct the heater power of the corresponding work area to increase by A1 times, where A1=1+(T0-Tn) / T0×c, T0 is the middle value of the temperature threshold range, and c is a pre-input constant.
3. The intelligent immunohistochemical staining instrument according to claim 2, characterized in that: The control module is used to calculate the temperature consistency of the repair module based on the variance of several temperature data. The control module determines whether the temperature consistency exceeds the variance threshold and issues an alarm when it exceeds the threshold.
4. The intelligent immunohistochemical staining instrument according to claim 3, characterized in that: The control module is used to count the flux and to determine whether the flux exceeds a threshold. If the determination result is yes, the value of the variance threshold is increased.
5. The intelligent immunohistochemical staining instrument according to claim 4, characterized in that: The control module is used to calculate the flux L and adjust the variance threshold to A2 times the original value, where A2 = L / L0 × d, d is a pre-input correction coefficient, and L0 is a pre-input flux reference value.
6. The intelligent immunohistochemical staining instrument according to claim 5, characterized in that: The control module is electrically connected to a transmittance sensor, which is installed in a material tank for storing glass slides. The transmittance sensor is used to monitor the transmittance of the stained glass slides in the material tank and upload the transmittance data to the control module.
7. The intelligent immunohistochemical staining instrument according to claim 6, characterized in that: The transmittance sensor is used to monitor the transmittance of the stained glass slides at various points in the trough and upload several transmittance data to the control module. The control module is used to determine the consistency of the transmittance data and reduce the variance threshold value when the consistency is lower than the threshold.
Citation Information
Patent Citations
An immunohistochemical staining instrument
CN118090379B