Specimen slide stirring device

The specimen slide agitation device addresses the challenge of maintaining temperature performance and preventing sliding of the heat transfer surface by using a lifting stage to separate and reposition the heat transfer unit relative to the vibration unit, ensuring effective and wear-free agitation.

WO2025105039A1PCT designated stage expired Publication Date: 2025-05-22HITACHI HIGH TECH CORP
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Patent Information

Application Number
PCT/JP2024/033466
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-11-15
Filing Date
2024-09-19
Publication Date
2025-05-22

AI Technical Summary

Technical Problem

Existing specimen slide agitation devices face challenges in maintaining the temperature performance of reagents on slides without causing sliding of the heat transfer surface due to vibration, which can lead to deterioration of heat transfer performance and wear.

Method used

The specimen slide agitation device incorporates a slide stage, a temperature control unit, a heat transfer unit, and a lifting stage that separates and repositions the heat transfer unit relative to the vibration unit to prevent sliding, ensuring consistent temperature control during agitation.

Benefits of technology

This configuration ensures the temperature performance of the reagent on the slide is maintained without causing sliding of the heat transfer surface, thereby preventing deterioration of heat transfer performance and wear.

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Abstract

In order to ensure temperature performance of a reagent on a slide without causing a heat transfer surface sliding due to vibration, a specimen slide stirring device according to the present invention stirs and mixes, through vibration, a buffer liquid on a specimen slide on which a specimen is held on the surface, and a stain reaction reagent required for staining the specimen. The specimen slide stirring device is characterized by comprising: a slide stage that holds the specimen slide; a temperature adjustment unit that performs temperature adjustment of the specimen slide; and a heat transfer unit that transfers heat to the specimen slide so that the temperature of the temperature adjustment unit and the specimen slide is substantially constant; and a lifting / lowering stage for lifting and lowering a slide holding unit. The specimen slide stirring device is characterized in that: when stirring the buffer liquid and the stain reaction reagent, the lifting / lowering stage is lowered to separate the heat transfer unit and a vibration unit for vibrating the buffer liquid and the stain reaction reagent, before vibrating the buffer liquid and the stain reaction reagent; and, when transferring heat to the specimen slide via the heat transfer unit, the lifting / lowering stage is lifted to bring the heat transfer unit into contact with the vibration unit.
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Description

Specimen slide agitator

[0001] The present invention relates to a specimen slide agitator, and more particularly to a specimen slide agitator suitable for agitating and mixing a buffer solution on a specimen slide having a specimen held on its surface and a staining reaction reagent required for staining the specimen by vibration.

[0002] In recent years, in the field of pathology, there has been progress in the development of automated staining devices that mechanize the staining process in immunostaining, which detects antigens, a type of protein, in tissue specimens.

[0003] In the staining process, a buffer solution and various reagents for the staining reaction are dropped onto the sample solution on the slide glass at each step. To properly stain the sample, the buffer solution and staining reagents must be stirred with a stirrer, and the thoroughly mixed reagents must be allowed to react with the sample.

[0004] As a method for mixing a reagent on a slide glass, a stirring device is known that mixes the reagent by vibrating the slide glass onto which the reagent has been dropped.

[0005] Prior art documents relating to this stirring device include, for example, Patent Documents 1 and 2.

[0006] Patent Document 1 describes a slide glass transport device that includes a slide holder transport device, a slide glass specimen transport device for macro-imaging, and a slide glass specimen transport device for micro-imaging, in order to efficiently transport multiple slide holders from a preparation position to an imaging position, capture overall and micro images of all slide glass specimens in the slide holders, and transport them to the preparation position while minimizing the installation space.The slide holder transport device includes a multi-joint arm that is arranged downward from the top of the slide holder transport device and can move in three dimensions, and a slide holder gripping section that is arranged at the tip of the multi-joint arm and grips and releases the slide holder from above.

[0007] On the other hand, Patent Document 2 describes a slide glass transport device that, in order to achieve a simpler structure for removing a slide glass from a slide glass cassette and reliably transporting it to a predetermined position, includes at least a drawer hand with a protrusion at its tip for hooking the slide glass, a drive mechanism, and a positioning guide with a tapered introduction section at a position where the removed slide glass will enter. The drive mechanism performs a series of movements of advancing, raising, and retracting the drawer hand, and through this series of movements, the slide glass to be removed is placed one by one on the drawer hand. At this time, the slide glass placed on the drawer hand is pulled out with the protrusion of the drawer hand abutting its side, and as the drawer hand retracts, the drawer end located at the tip of the slide glass is pushed into the tapered introduction section of the positioning guide. As a result, both sides of the removed slide glass are smoothly guided by the guide rails of the positioning guide.

[0008] JP 2012-177804 A Japanese Patent No. 4871263 A

[0009] In an automatic staining apparatus using an agitator, in order to maintain a constant temperature of the reagent on the slide (15°C to 95°C), it is necessary to ensure the temperature performance of the reagent on the slide without causing sliding on the heat transfer surface due to vibration, and there has been a demand for the development of an agitator that can achieve this.

[0010] However, the above-mentioned Patent Documents 1 and 2 do not disclose any solutions to solve the above-mentioned problems.

[0011] The present invention has been made in consideration of the above points, and its purpose is to provide a specimen slide agitator that can ensure the temperature performance of the reagent on the slide without causing sliding of the heat transfer surface due to vibration.

[0012] In order to achieve the above-mentioned object, the specimen slide stirring device of the present invention is a specimen slide stirring device that stirs and mixes a buffer solution on a specimen slide holding a specimen on its surface and a staining reaction reagent required for staining the specimen by vibration, and comprises: a slide stage that holds the specimen slide; a temperature control unit that controls the temperature of the specimen slide; a heat transfer unit that transfers heat to the specimen slide so that the temperatures of the temperature control unit and the specimen slide are approximately constant; and a lifting stage that raises and lowers the slide holding unit; and when mixing the buffer solution and the staining reaction reagent, the lifting stage is lowered to separate the heat transfer unit from the vibration unit that vibrates the buffer solution and the staining reaction reagent before vibrating the buffer solution and the staining reaction reagent; and when transferring heat to the specimen slide via the heat transfer unit, the lifting stage is raised to bring the heat transfer unit into contact with the vibration unit.

[0013] According to the present invention, it is possible to ensure the temperature performance of the reagent on the slide without causing sliding of the heat transfer surface due to vibration.

[0014] FIG. 5 is a conceptual diagram of the specimen slide agitator according to the first embodiment of the present invention, showing the lifting stage in a descending state. FIG. 6 is a conceptual diagram of the specimen slide agitator according to the first embodiment of the present invention, showing the lifting stage in a ascending state. FIG. 7 is a perspective view showing the arrangement of the slide transport unit, vibration unit holding stage, slide fixing unit, and slide stage employed in the specimen slide agitator according to the first embodiment of the present invention. FIG. 8 is a diagram showing details of the connection state of the specimen slide, slide fixing unit, and vibration fixing unit in the specimen slide agitator according to the first embodiment of the present invention. FIG. 9 is a front view showing the lifting structure of the lifting stage in the specimen slide agitator according to the first embodiment of the present invention. FIG. 10 is a side view of the lifting stage in FIG. 5 when it is descending. FIG. 11 is a side view of the lifting stage in FIG. 5 when it is ascending.

[0015] The specimen slide agitator of the present invention will be described below based on the illustrated embodiment, in which the same reference numerals are used for the same components in each drawing.

[0016] The specimen slide agitator of the present invention will be described with reference to FIGS.

[0017] Figure 1 shows Example 1 of the specimen slide agitation device of the present invention, with the lifting stage 11 in a descending state, Figure 2 shows the lifting stage 11 in a ascending state, Figure 3 shows the arrangement of the slide transport unit 7, vibration unit holding stage 6, slide fixing unit 4, and slide stage 3 used in Example 1 of the specimen slide agitation device of the present invention, Figure 4 shows details of the connection state of the specimen slide 1, slide fixing unit 4, and vibration fixing unit 17 in Example 1 of the specimen slide agitation device of the present invention, Figure 5 shows a front view of the lifting structure of the lifting stage 11 in Example 1 of the specimen slide agitation device of the present invention, Figure 6 shows a side view of the lifting stage 11 in Figure 5 in a ascending state, and Figure 7 shows a side view of the lifting stage 11 in Figure 5 in a descending state.

[0018] As shown in Figures 1 and 2, the specimen slide agitation device of this embodiment agitates and mixes a buffer solution 2 on a specimen slide 1 holding a specimen on its surface and a staining reaction reagent required for staining the specimen by vibrating a vibration unit 5 using a driving force from a vibration drive unit (e.g., a vibration motor) 14 (described later).

[0019] Specifically, the device is roughly configured to include a slide stage 3 that holds a specimen slide 1, a temperature control unit (e.g., a Peltier element) 8 that controls the temperature of the specimen slide 1, a heat transfer unit 9 that detects temperature changes in the temperature control unit 8 using a Peltier element and a thermocouple and transfers heat to the specimen slide 1 so that the temperatures of the temperature control unit 8 and the specimen slide 1 remain approximately constant, and a lifting stage 11 that is configured to include an upper lifting stage 11a and a lower lifting stage 11b that lift and lower a slide holding unit that is configured by the heat transfer unit 9, the temperature control unit 8, and an insulating unit (an insulating material, e.g., plastic) 10 provided below the temperature control unit 8 and supported by the lower lifting stage 11b.

[0020] When the buffer solution 2 and the staining reaction reagent are mixed, the heat transfer unit 9, which transfers heat to the specimen slide 1 by lowering the upper lifting stage 11a of the lifting stage 11, and the vibration unit 5, which vibrates the buffer solution 2 and the staining reaction reagent, are separated before vibrating the buffer solution 2 and the staining reaction reagent (the state in Figures 1 and 6). On the other hand, when heat is transferred to the specimen slide 1 via the heat transfer unit 9, the lower lifting stage 11b of the lifting stage 11 is raised to bring the heat transfer unit 9 into contact with the vibration unit 5 (the vibration-side heat transfer unit 9a shown in Figures 6 and 7 is in contact with the vibration unit 5) (the state in Figures 2 and 7), and the temperature control unit 8 controls the temperature so as to maintain the temperature of the staining reaction reagent on the specimen slide 1 at a predetermined temperature.

[0021] In addition, the vibration unit 5 is connected to the vibration drive unit 14 via the eccentric cam 15, the linear link unit 16, and the vibration fixing unit 17 as shown in Figure 4, and the driving force of the vibration drive unit 14 is transmitted via the eccentric cam 15, the linear link unit 16, and the vibration fixing unit 17 to vibrate.

[0022] Furthermore, when the specimen slide 1 held on the slide stage 3 via the vibration unit holding stage 6 on the disk-shaped slide transport unit 7 reaches an arbitrary position, it is connected to the vibration fixing unit 17 on the disk-shaped driving fixing unit 22 side as shown in Figure 4.

[0023] Furthermore, the upper and lower lifting stages 11a and 11b are arranged with their connection parts facing each other in the horizontal direction, and when the lower lifting stage 11b is lowered (as in Figures 1 and 6), the connection parts of the upper and lower lifting stages 11a and 11b are connected to each other, and when the lower lifting stage 11b is raised (as in Figures 2 and 7), the driving force of the lifting drive unit (e.g., a linear motor) 18 mounted on the lifting drive device fixing unit 21 is transmitted via the linear motion unit 19 and the linear motion stage 20, causing the upper lifting stage 11a to move horizontally (to the right in the figure), thereby releasing the connection with the lower lifting stage 11b, and the lower lifting stage 11b rises, bringing the heat transfer unit 9 and the vibration unit 5 into contact.

[0024] Specifically, when the lower lifting stage 11b descends, as shown in Figure 6, the lower lifting stage 11b and the lifting stage fixing part 12 are fixed, and when the lower lifting stage 11b and the upper lifting stage 11a come into contact, a force is applied to the lower lifting stage 11b, causing the lifting link part 13 to descend and the lower lifting stage 11b to descend.

[0025] On the other hand, when the lower lifting stage 11b rises, the opposite occurs to when the lower lifting stage 11b falls; as shown in Figure 7, the contact between the lower lifting stage 11b and the upper lifting stage 11a is released, causing the lifting link section 13 to rise and the lower lifting stage 11b to rise.

[0026] Between the slide transport section 7 and the heat insulating section 10, there is disposed an elevation support section made up of a spring that expands when the lower lift stage 11b is elevated and contracts when the lower lift stage 11b is elevated.

[0027] Furthermore, the connection between the upper lift stage 11a and the lower lift stage 11b is formed in a wedge shape, which allows for space saving.

[0028] With this configuration of the present embodiment, when the lower lift stage 11b descends (as shown in FIGS. 1 and 6), the heat transfer unit 9 connected to the lower lift stage 11b of the lift stage 11 descends and separates from the vibration unit 5 (separation of the heat transfer unit 9 from the vibration unit 5 is determined by detecting a temperature drop on the vibration side via a thermocouple installed on the vibration side). In this state, the vibration unit 5 can be vibrated. When the lower lift stage 11b of the lift stage 11 ascends (as shown in FIGS. 2 and 7), the heat transfer unit 9 connected to the lower lift stage 11b ascends and contacts the vibration unit 5. Furthermore, while the specimen slide 1 is held by the vibration unit 5 and the buffer solution 2 and staining reaction reagent are not vibrating, the temperature of the buffer solution 2 on the specimen slide 1 can be adjusted by the temperature control unit 8. Note that reference numeral 9b in FIGS. 6 and 7 denotes the lift-side heat transfer unit.

[0029] Therefore, according to the specimen slide agitation device of this embodiment, when the lower lifting stage 11b of the lifting stage 11 descends (the state shown in Figures 1 and 6), the heat transfer unit 9 connected to the lower lifting stage 11b also descends and separates from the vibration unit 5. By vibrating the vibration unit 5 in this state, agitation is possible without generating a sliding surface, and it is possible to prevent the slide stage 3 and the heat transfer unit 9 from sliding and wearing due to the vibration, which would result in deterioration of heat transfer performance.

[0030] Furthermore, when the lower lifting stage portion 11b of the lifting stage 11 rises (as shown in Figures 2 and 7), the heat transfer portion 9 connected to the lower lifting stage portion 11b rises, bringing the heat transfer portion 9 into contact with the vibration portion 5. Furthermore, the specimen slide 1 is held by the vibration portion 5, and during non-vibration periods when the buffer solution 2 and the staining reaction reagent are not vibrating, the temperature of the buffer solution 2 on the specimen slide 1 can be adjusted by the temperature control portion 8.

[0031] Therefore, the specimen slide agitator of this embodiment can ensure the temperature performance of the reagent on the slide without causing sliding of the heat transfer surface due to vibration.

[0032] The present invention is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those including all of the described configurations. Furthermore, it is possible to replace part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment with other configurations.

[0033] 1...Specimen slide, 2...Buffer liquid, 3...Slide stage, 4...Slide fixing section, 5...Vibration section, 6...Vibration section holding stage, 7...Slide transport section, 8...Temperature control section, 9...Heat transfer section, 9a...Vibration side heat transfer section, 9b...Lifting side heat transfer section, 10...Insulation section, 11...Lifting stage, 11a...Lifting stage upper section, 11b...Lifting stage lower section, 12...Lifting stage fixing section, 13...Lifting link section, 13A..., 13a..., 13b..., 13c..., 13d..., 14...Vibration drive section, 15...Replying cam, 16...Linear link section, 17...Vibration fixing section, 18...Lifting drive section, 19...Linear section, 20...Linear stage, 21...Lifting drive device fixing section, 22...Drive fixing section, 23...Lift holding section.

Claims

1. A specimen slide agitation device which uses vibration to agitate and mix a buffer liquid on a specimen slide holding a specimen on its surface and a staining reaction reagent required for staining the specimen, comprising: a slide stage which holds the specimen slide; a temperature control unit which controls the temperature of the specimen slide; a heat transfer unit which transfers heat to the specimen slide so that the temperatures of the temperature control unit and the specimen slide are approximately constant; and a lifting stage which raises and lowers the slide holding unit; when mixing the buffer liquid and the staining reaction reagent, the lifting stage is lowered to separate the heat transfer unit from the vibration unit which vibrates the buffer liquid and the staining reaction reagent before vibrating the buffer liquid and the staining reaction reagent; and when transferring heat to the specimen slide via the heat transfer unit, the lifting stage is raised to bring the heat transfer unit into contact with the vibration unit.

2. A specimen slide agitation device according to claim 1, characterized in that the temperature control unit controls the temperature of the staining reaction reagent on the specimen slide to maintain it at a predetermined temperature.

3. A specimen slide agitation device as described in claim 1, characterized in that the lifting stage consists of an upper lifting stage and a lower lifting stage, and the slide holding unit is configured such that the heat transfer unit, the temperature control unit, and an insulating unit provided below the temperature control unit are supported by the lower lifting stage.

4. A specimen slide agitation device as described in claim 1, characterized in that the vibration unit is connected to a vibration drive unit, an eccentric cam, a linear link unit, and a vibration fixed unit via a vibration fixing unit, and the driving force of the vibration drive unit is transmitted via the eccentric cam, the linear link unit, and the vibration fixed unit to vibrate.

5. A specimen slide agitation device as described in claim 3, wherein the upper and lower lifting stages are arranged with their connection parts facing each other in the horizontal direction, and when the lifting stage descends, the connection parts of the upper and lower lifting stages are connected to each other, and when the lifting stage ascends, the upper lifting stage moves horizontally due to the driving force of a lifting drive unit, thereby releasing the connection with the lower lifting stage.

6. A specimen slide agitation device as described in claim 5, characterized in that, when the lifting stage descends, the heat transfer section connected to the lifting stage descends and separates from the vibration section, and in this state, vibrates the vibration section.

7. A specimen slide agitation device as described in claim 5, characterized in that, when the lifting stage is raised, the heat transfer section connected to the lifting stage rises and the heat transfer section comes into contact with the vibration section, and the specimen slide is held by the vibration section, and when the buffer liquid and the staining reaction reagent are not vibrating, the temperature of the buffer liquid on the specimen slide is adjusted by the temperature control section.

8. The specimen slide agitation device according to claim 5, wherein the connection between the upper part of the lifting stage and the lower part of the lifting stage is formed in a wedge shape.

Citation Information

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