JP2004028910A - Apparatus and method for preparing sliced sample - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus for preparing sliced samples for reducing burden on worker and preventing the occurrence of human error. <P>SOLUTION: The sliced sample preparing apparatus 10 comprises a knife 28 for cutting a sample block 20 into slices of specific thickness, and a cut slice 31 is made to adhere to a carrier tape 11 by static electricity. The slice 31 is transcribed onto a glass slide 40 via an adhesive liquid 41 applied to the glass slide 40. The sliced sample preparing apparatus 10 is provided with a transfer robot 70 for transferring the glass slide 40 to which the slice 31 is adhering and developing devices 51 and 52 for vaporizing the adhesive liquid 41 by heating the glass slide 40 to which the slide is adhering. In the first developing device 51, the glass slide 40 to which the slice is adhering is heated at relatively high temperatures in a short time. In the second developing device 52, the glass slide 40 to which the slice is adhering is heated at relatively low temperatures in a long time. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an apparatus and a method for preparing a thin section sample used for analysis of physicochemical samples, microscopic observation of biological samples, and the like.
[0002]
[Prior art]
2. Description of the Related Art A microtome for producing a thin section sample used for microscopic observation of a physicochemical sample analysis, a biological sample, or the like is known. A microtome is an apparatus for preparing a thin section by slicing a specimen embedded in paraffin or the like with a knife.
[0003]
The thin section is attached to a thin-section assisting member such as a carrier tape by, for example, static electricity, and then the thin section attached to the thin-section assisting member is transferred to a slide glass coated with an adhesive liquid (for example, water). . The slide glass to which the slices are attached is housed in, for example, an extension device provided with a drying chamber and heated to evaporate the adhesive liquid, whereby wrinkles or curls generated during the slice are stretched, and the slide glass is applied to the slide glass. The thin section is fixed tightly. Thus, a thin section sample for tissue observation is obtained.
[0004]
The stretching device heats the thin section sample using a heating means such as a heater in order to dry the adhesive liquid and stretch the thin section. Here, as for the extension time (heating time), the worker removes the thin section sample from the extension device when a predetermined time has elapsed.
[0005]
[Problems to be solved by the invention]
However, the extension time varies depending on the thin section sample, and when the extension time is several seconds to several tens of seconds, it is necessary to put it in the extension device and immediately take it out of the extension device, and the operator must constantly monitor. For this reason, when the number of thin section samples is large, providing an appropriate extension time was a serious task.
[0006]
For example, when continuously processing thin section samples having different extension times, it is indispensable for the operator to grasp the extension time data of all the thin section samples, and when the number of processed thin section samples increases, There is a concern that a high quality thin section sample cannot be obtained due to occurrence of human error.
[0007]
If the strength of fixing the thin section to the slide glass is insufficient, the thin section may fall off the slide glass in a subsequent staining step or the like. Conversely, if it extends too much, there is a problem that the thin section is unnecessarily widened.
[0008]
Accordingly, an object of the present invention is to reduce the burden on an operator who prepares a thin-section sample, prevent the occurrence of human error, and stably prepare a good-section sample. An object is to provide an apparatus and a manufacturing method.
[0009]
[Means for Solving the Problems]
The thin-slice sample preparation apparatus of the present invention includes cutting means for cutting the sample block to a predetermined thin-section thickness by the knife by relatively moving the sample block and the knife, and applying static electricity to the cut thin-section. A thin-strip conveying means for adsorbing and sending the carrier to a carrier tape, and supplying an adhesive liquid to the surface of the slide glass, and transferring the thin slice adsorbed to the carrier tape onto the slide glass via the adhesive liquid. Transfer means, a stretching device that evaporates the adhesive liquid by heating the slide glass with the thin section to which the thin section is attached to a predetermined temperature, a transport robot that transports the slide glass with the thin section, and the stretching apparatus After the slide glass with the thin section is heated for a predetermined time, before the slide glass with the thin section is taken out from the stretching device, And a control means for controlling the conveying robot.
[0010]
One example of the extension device includes a contact-type heating unit such as a hot plate or a heater block for heating a floor surface on which the slide glass with thin sections is placed. Alternatively, another example of the stretching device includes a drying chamber for accommodating the slide glass with thin sections, and a non-contact heating means such as an infrared lamp, a heater, or microwave heating provided in the drying chamber.
[0011]
In a preferred embodiment of the present invention, the transfer robot is an XYZ three-axis orthogonal type robot.
In a preferred embodiment of the present invention, the apparatus further includes a plurality of the stretching devices capable of individually setting a heating temperature, and the control unit selects one of the plurality of stretching devices according to the slide glass with the thin section. Controlling the transfer robot so as to carry the slide glass with the thin section into it, and after the slide glass with the thin section is heated for a predetermined time, removes the slide glass with the thin section from the extension device. Control. In addition, the control unit can arbitrarily set the temperature of each of the stretching devices and the heating time of the slide glass with thin sections by the stretching devices, and the transfer robot transfers the slide glass with thin sections to the plurality of slide glasses. It can be sent to the extension device in any order.
[0012]
The thin section sample preparation method of the present invention includes a cutting step of cutting the sample block to a predetermined thin section thickness by the knife by relatively moving the sample block and the knife, and applying a static electricity to the cut thin section. A thin-slice conveying step of adsorbing and sending the carrier to a carrier tape, supplying an adhesive liquid to the surface of the slide glass, and transferring the thin slice adsorbed to the carrier tape onto the slide glass via the adhesive liquid. A transferring step, a carrying-in step of carrying the slide glass with the thin section to which the thin section is attached, into a stretching apparatus heated to a predetermined temperature by a transfer robot, and a sliding glass with the thin section carried into the stretching apparatus. The elongating step of evaporating the adhesive liquid, and transporting the slide glass with the thin slices for a predetermined time by the extending device. It has and a carry-out step of taking out from the stretching device the thin sections with a slide glass by bots.
[0013]
In a preferred embodiment of the present invention, after the slide glass with thin sections is heated by the extension device at a first temperature and a first time, the slide glass is heated at a second temperature lower than the first temperature and for a first time. The slide glass with the thin section is heated for a longer second time. For example, the first temperature is 40C to 60C, the first time is 10 seconds to 5 minutes, the second temperature is 25C to 40C, and the second time is 10 minutes to 24 hours. is there.
[0014]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, a first embodiment of the present invention will be described with reference to FIGS. The thin-section sample preparing apparatus 10 shown in FIG. 1 includes a supply reel 12 for feeding out a carrier tape 11 functioning as a thin-section assisting member, and a take-up reel 13 for winding the carrier tape 11. By rotating the take-up reel 13 by the tape drive mechanism 14, the carrier tape 11 moves in the direction indicated by the arrow R.
[0015]
A sample transport mechanism 21 for moving a sample block 20 to be sliced in a direction indicated by an arrow F1 along a movement path of the carrier tape 11 is provided. One example of the sample block 20 is one in which a subject such as a biological sample is embedded in an embedding material (for example, paraffin).
[0016]
A first charging device 25, a cooler 26, a second charging device 27, and a knife 28 are provided at positions corresponding to the stages ST1 to ST4 along the moving path of the carrier tape 11 from the upstream side to the downstream side. A slicing device 29 and the like are arranged. The first charging device 25 gives a positive charge to the sample block 20. The second charging device 27 gives a negative charge to the carrier tape 11.
[0017]
The knife 28 can be moved to a predetermined position by a knife drive mechanism 32 so that the surface of the sample block 20 can be sliced by an amount corresponding to the thickness of a predetermined slice 31. Note that the knife 28 may be fixed and the sample block 20 may be moved by an amount corresponding to a predetermined thickness of the thin section 31.
[0018]
The slicer 29 provided with the knife 28 and the sample transport mechanism 21 constitute a cutting means according to the present invention. The cutting means only needs to be able to cut the sample block 20 to a predetermined thin section thickness with the knife 28, and thus the knife 28 may be moved relatively to the sample block 20.
[0019]
The carrier tape 11, the tape driving mechanism 14, the guide roll 35, and the like are an example of a thin-section conveying unit for sending out the thin-section 31 adsorbed to the carrier tape 11 by static electricity in a direction indicated by an arrow F2.
[0020]
As shown in FIG. 2, an adhesive liquid supply mechanism 42 for dropping water as an example of the adhesive liquid 41 is provided on the upper surface of the slide glass 40. As the bonding liquid 41, for example, water containing ethyl alcohol may be used.
[0021]
A transfer stage ST5 is provided in the middle of the transport path of the carrier tape 11. In this transfer stage ST5, the thin section 31 attached to the carrier tape 11 carried between the guide rolls 45 and 46 is transferred onto the slide glass 40 via the adhesive liquid 41 as shown in FIG. It has become so. The transfer stage ST5, the adhesive liquid supply mechanism 42, and the like are examples of a transfer unit according to the present invention. In this specification, the slide glass 40 to which the thin section 31 is transferred is referred to as a slide glass 40 with a thin section.
[0022]
As shown in FIG. 5, a first extension device 51, a second extension device 52, and a thin section sample storage unit 53 are provided. Hot plates 55 and 56 are provided on the floors of the extension devices 51 and 52, respectively, as an example of a contact-type heating unit.
[0023]
These hot plates 55 and 56 have a heater 61 arranged on the back surface of a metal plate 60 constituting the floor surface of the extension devices 51 and 52, as shown in FIG. With 62, the heating temperature of each of the extension devices 51 and 52 can be set individually.
[0024]
For example, the hot plate 55 of the first extension device 51 heats the slide glass 40 with thin sections at a first temperature (for example, around 50 ° C.), and the hot plate 56 of the second extension device 52 The heater power supply 63 is controlled by the controller 62 so as to heat the slide glass with thin sections 40 at a second temperature lower than the temperature (for example, around 30 ° C.).
[0025]
The thin section sample preparation apparatus 10 includes an XYZ three-axis orthogonal type transfer robot 70 as an example of transfer means. As shown in FIG. 4 and the like, the transfer robot 70 includes a robot hand 73 having finger portions 71 and 72 capable of holding the slide glass 40, a robot driving mechanism 74 for driving the robot hand 73, and the like.
[0026]
As shown in FIGS. 5 and 6, the transfer robot 70 includes an X-axis linear system 80 extending in the length direction of the slide glass 40, a Y-axis linear system 81 extending in the width direction of the slide glass 40, and a thickness of the slide glass 40. The robot can be moved in a desired direction by a desired amount by a robot driving mechanism 74 including a Z-axis linear system 82 that can move up and down in the direction. Each of the linear systems 80, 81, and 82 includes a linear guide rail, a ball screw, a servomotor (not shown) for rotating the ball screw, and the like.
[0027]
The controller 62 shown in FIG. 4 functions as control means for controlling the operation of the robot driving mechanism 74. The controller 62 controls the operation of the transfer robot 70 according to the slide glass 40 with a thin section so that the slide glass 40 with a thin section can be heated at an optimal temperature and time.
[0028]
That is, one of the plurality of stretching devices 51 and 52 having different temperatures is selected according to the type of the slice 31 and the state of the slice, and the slide glass 40 with the slice is moved to the stretching device 51 (or 52). Carry in. After the slide glass with thin sections 40 is heated for a predetermined time, the transfer robot 70 is controlled so that the slide glass with thin sections 40 is taken out from the extension device 51 (or 52).
[0029]
Next, a method for preparing a thin section sample using the thin section sample preparation apparatus 10 will be described.
While moving the sample block 20 in the direction of arrow F1 (shown in FIG. 1) by the sample transport mechanism 21, positive charges are applied to the sample block 20 by the first charging device 25 on the stage ST1. After being cooled by the cooler 26 in the stage ST2, a negative charge is given to the carrier tape 11 by the second charging device 27 in the stage ST3.
[0030]
In the cutting step, the vicinity of the surface of the sample block 20 is cut by the knife 28 to a predetermined thickness of the thin section 31 at the stage ST4. The thin section 31 is attracted to the carrier tape 11 by static electricity.
[0031]
The thin section 31 thus adhered to the carrier tape 11 moves in the arrow F2 direction in the thin section transport step, and is transported together with the carrier tape 11 to the transfer stage ST5. The slide glass 40 to which the adhesive liquid 41 has been applied in advance is carried into the transfer stage ST5 by the transfer robot 70.
[0032]
In the transfer step, the thin section 31 attached to the carrier tape 11 is pressed against the adhesive liquid 41 on the slide glass 40 at the transfer stage ST5, and then only the carrier tape 11 is separated from the slide glass 40. Thus, the thin section 31 adheres to the adhesive liquid 41 on the slide glass 40, and the thin section 31 is transferred onto the slide glass 40.
[0033]
The slide glass 40 with the thin section to which the thin section 31 has adhered is carried into the extension device 51 (or 52) by the transfer robot 70 in the carrying-in step. For example, the slide glass with thin sections 40 is placed on the floor of the first extension device 51. The floor surfaces of the extension devices 51 and 52 are set to a predetermined temperature in advance. For example, the hot plate 55 of the first extension device 51 is heated to around 50 ° C., and the hot plate 56 of the second extension device 52 is heated to around 30 ° C.
[0034]
In the extension process, the adhesive liquid 41 on the slide glass with thin sections 40 evaporates inside the extension device 51 (or 52). The wrinkles and curls generated in the thin section 31 at the time of the thin section are extended by increasing the temperature, and adhere to the slide glass 40 by evaporating the adhesive liquid 41.
[0035]
After the extension time individually set in advance by the controller 62 elapses, the slide glass 40 with the thin section heated in the first extension device 51 is moved by the first extension device 51 by the transport robot 70 in the unloading process. It is carried out from. After that, it is carried into the second extension device 52 as needed.
[0036]
For example, after the slide glass 40 with a thin section is heated at 50 ° C. for 2 minutes in the first extension device 51, the slide glass 40 with the thin section is placed on the hot plate 56 of the second extension device 52 by the transfer robot 70. Placed on
[0037]
In the second extension device 52, the slide glass with thin sections 40 is heated at a temperature lower than that of the first extension device 51 for a longer time than that of the first extension device 51. As an example, the slide glass with thin sections 40 is heated for 30 minutes in the second extension device 56.
[0038]
After the elapse of a predetermined extension time, the slide glass 40 with a thin section is taken out of the second extension device 52 by the transfer robot 70 and automatically transferred to an empty space in the thin section sample storage unit 53.
[0039]
By performing each of the steps described above, the slide glass with thin sections 40 is heated at 50 ° C. for 2 minutes and then heated at 30 ° C. for 30 minutes.
Heating at a high temperature increases the heating efficiency of the slide glass 40 with thin sections, but wrinkles may occur on the thin sections 31. At low temperatures, no wrinkles occur, but the drying time becomes longer.
[0040]
In the thin-section sample preparing apparatus 10 of this embodiment, most of the water is evaporated by first heating the first stretching apparatus 51 at a relatively high temperature for a short time (10 seconds to 5 minutes), and thereafter, By heating the second section 52 at a relatively low temperature for a long time (10 minutes to 24 hours), it is possible to suppress wrinkles from occurring in the thin section 31 and shorten the drying time. The heating temperature and the heating time are changed according to the type of the slice 31 and the state of the slice, and the like, and the optimal heating temperature and the heating time are set in the controller 62.
[0041]
In this embodiment, the XYZ three-axis orthogonal transfer robot 70 is used because it is not necessary to change the direction of the slide glass 40 when transferring the slide glass 40 with thin sections. The transfer robot 70 transfers the slide glass 40 with the robot hand 73 sandwiching the slide glass 40 from both sides.
[0042]
Such a three-axis orthogonal transfer robot 70 can be manufactured at a relatively low cost and is compact by employing the linear systems 80, 81, 82 extending in three directions of XYZ.
[0043]
FIG. 7 shows extension devices 51 and 52 according to the second embodiment of the present invention. In this embodiment, the first extension device 51 and the second extension device 52 include drying chambers 91 and 92, respectively. By providing an infrared lamp 93 as an example of a non-contact type heating means inside the drying chambers 91 and 92, the slide glass 40 with thin sections is heated from above by radiant heat.
[0044]
Shutters 95 and 96 are provided above the drying chambers 91 and 92, and the shutters 95 and 96 are opened when the transfer robot 70 enters the drying chambers 91 and 92. Regarding other configurations and operations, the second embodiment is the same as the above-described first embodiment. Note that, other than the infrared lamp 93, non-contact heating means such as heating by a heater or heating by a microwave may be used.
[0045]
Either of the extension devices 51 and 52 may be used depending on the type of the slice 31 and the state of the slice. The robot hand 73 may be a vacuum-type suction cup that sucks the slide glass 40 by negative pressure, instead of using the finger portions 71 and 72 that hold the slide glass 40 from both sides.
[0046]
In each of the embodiments described above, the case where two extension devices 51 and 52 are provided has been described, but the number of extension devices may be one. In the case of one stretching device, the temperature of the stretching device is adjusted to first hold the slide glass 40 with thin sections at a high temperature for a short period of time, then lower the set temperature, and slide the slide glass 40 with thin sections at a low temperature. After heating for a long time, by taking it out of the stretching device, a high-quality thin-section sample can be manufactured in the same manner as in the above embodiment.
[0047]
A case where a robot 100 (shown by a two-dot line in FIG. 7) capable of taking out a processed thin section sample (slide glass 40 with a thin section) from the thin section sample storage unit 53 is provided separately from the transfer robot 70. , The thin section sample can be processed automatically for a longer time.
[0048]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, the burden of the operator who manufactures a thin section sample is reduced, the human error by an operator can be eliminated, and a good thin section sample can be manufactured stably.
[0049]
In the present invention, when heating at a relatively high first temperature for a short time and then heating at a second temperature lower than the first temperature for a long time, a more favorable thin section sample is produced. can do.
[Brief description of the drawings]
FIG. 1 is a front view of a part of a thin section sample preparation apparatus according to a first embodiment of the present invention.
FIG. 2 is a front view of a part of an adhesive liquid supply mechanism for supplying an adhesive liquid to a slide glass.
FIG. 3 is a cross-sectional view showing a state in which the adhesive liquid and the thin section are supplied onto a slide glass by the thin section sample preparation apparatus shown in FIG.
FIG. 4 is a front view showing a part of a transfer robot used in the thin section sample preparing apparatus shown in FIG. 1;
FIG. 5 is a plan view showing a transfer robot and an extension device of the thin section sample preparation device shown in FIG. 1;
FIG. 6 is a sectional view showing the transfer robot and the extension device shown in FIG. 5;
FIG. 7 is a cross-sectional view illustrating a transfer robot and an extension device of the thin-section sample preparation device according to the second embodiment of the present invention.
[Explanation of symbols]
Reference Signs List 10: Thin section sample preparation apparatus 11: Carrier tape 14: Tape drive mechanism (thin section transport means)
20 sample block 28 knife 29 slicer (cutting means)
31 Thin section 40 Slide glass 41 Adhesive liquids 51 and 52 Extension devices 55 and 56 Hot plates (contact heating means)
62 ... Controller (control means)
70 ... transfer robot (XYZ 3-axis orthogonal type robot)
93 ... Infrared lamp (non-contact heating means)

Claims (8)

Cutting means for cutting the sample block to a predetermined thin section thickness by the knife by relatively moving the sample block and the knife;
Thin-section conveying means for adsorbing the cut thin-section to a carrier tape by static electricity and sending it out,
A transfer means for supplying an adhesive liquid to the surface of the slide glass, and transferring the thin section adsorbed to the carrier tape onto the slide glass via the adhesive liquid.
A stretching device that evaporates the adhesive liquid by heating the slide glass with the thin section to which the thin section is attached to a predetermined temperature,
A transfer robot for transferring the slide glass with the thin section,
Control means for controlling the transport robot to take out the slide glass with a thin section from the stretching apparatus after the slide glass with the thin section is heated for a predetermined time by the stretching apparatus,
A thin section sample preparation apparatus comprising: The thin section sample preparing apparatus according to claim 1, wherein the extension apparatus includes a contact-type heating unit using a hot plate that heats a floor surface on which the slide glass with the thin section is placed. . The stretching device includes a drying chamber that accommodates the slide glass with thin sections, and a non-contact heating unit that heats the slide glass with thin sections by any of an infrared lamp, a heater, and microwave heating provided in the drying chamber. The thin-section sample preparing apparatus according to claim 1, further comprising: The thin section sample preparation apparatus according to claim 1, wherein the transfer robot is an XYZ three-axis orthogonal type robot. The apparatus further includes a plurality of the stretching devices capable of individually setting a heating temperature, wherein the control unit controls the stretching glass selected from the plurality of stretching devices according to the slide glass with a thin slice to the stretching glass selected from the plurality of stretching devices. Controlling the transfer robot so that the slide glass is carried in, and after the slide glass with the thin section is heated for a predetermined time, the transfer robot is controlled so as to take out the slide glass with the thin section from the extension device. It is possible to arbitrarily set the temperature of each of the stretching devices and the heating time of the slide glass with thin sections by the stretching devices, and to transfer the slide glass with thin sections to the plurality of stretching devices by the transfer robot. The thin-section sample preparing apparatus according to any one of claims 1 to 4, wherein the sample can be fed in order. A cutting step of cutting the sample block to a predetermined thin section thickness by the knife by relatively moving the sample block and the knife;
A thin section transporting step in which the cut thin section is attracted to a carrier tape by static electricity and sent out,
Supplying an adhesive liquid to the surface of the slide glass, a transfer step of transferring the thin slices adsorbed to the carrier tape onto the slide glass via the adhesive liquid,
A carrying step of carrying the slide glass with the thin section to which the thin section is attached, by a transfer robot, to a stretching device that is heated to a predetermined temperature,
A stretching step of evaporating the adhesive liquid of the slide glass with the thin section carried into the stretching device,
After the slide glass with thin sections is heated for a predetermined time by the stretching device, the carrying robot takes out the slide glass with thin sections from the stretching device by the transfer robot,
A method for preparing a thin section sample, comprising: After the slide glass with thin sections is heated by the stretching device at a first temperature and a first time, a second time lower than the first temperature and a second time longer than the first time The method for preparing a thin section sample according to claim 6, wherein the slide glass with the thin section is heated by the method. The first temperature is 40 ° C to 60 ° C, the first time is 10 seconds to 5 minutes, the second temperature is 25 ° C to 40 ° C, and the second time is 10 minutes to 24 hours. The method for preparing a thin section sample according to claim 7, wherein:

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