WO2020116406A1 - Hollow sampling needle system for sampling biological microsection - Google Patents

Abstract

[Problem] To provide a hollow sampling needle system for sampling a biological microsection, said hollow sampling needle system enabling sampling and collection of the microsection without requiring detailed setup of descending limit position even in a case where a conventional punching method brings about an incomplete cutting state. [Solution] A hollow sampling needle system for sampling a biological microsection from a biological specimen, said hollow sampling needle system being configured from a hollow sampling needle 101 for cutting and sampling the microsection from the biological specimen, a placement part on which the biological specimen is placed, and a cushioning mechanism which alleviates a crash impact when the hollow sampling needle 101 collides with the placement part upon sampling of the microsection.

Description

Hollow collection needle system for biological microsection collection

The present invention relates to a hollow collection needle system for collecting biological microsections for performing protein, metabolites, genes, gene expression analysis and the like required in fields such as life science and medical care to collect microsections from biological tissue. is there.

In the fields of life science and medicine, in order to elucidate and utilize life activities, molecules such as genes (DNA), gene expression (mRNA), proteins and metabolites that are components of life are analyzed. Recently, the sensitivity and analysis capability of analyzers have improved dramatically. As a result, analysis on a one-cell level has become possible. In response to this, an international program (Human Cell Atlas) is starting to investigate what kind of cells are in the human body and where and how they exist. For this purpose, it is necessary to collect microsections from various parts of the living body, make one cell if necessary, and analyze them.

For this, it is necessary to collect many microsections from a living body in a short time, but the present inventors have already constructed a system that realizes this using a metal hollow collecting needle (Patent Document 1). ). This system can be installed in an inverted microscope. The position to be sampled is determined by looking at the microscopic image of the biological sample, and the positional information of the site to be sampled is acquired from the microscopic image of the biological sample. It is a system that drives the sampling actuator by using the position information, lowers the sampling needle unit to the lower limit, and punches and collects a microsection from the target position.

International publication WO2017/061387

In the sample collection system described in Patent Document 1, a biological sample to be collected is placed on a petri dish or a slide glass and placed at a predetermined position on the microscope. A film such as a silicon sheet or PDMS is laid under the biological specimen to prevent the hollow sampling needle from being damaged. The hollow collection needle penetrates the biological specimen, produces a microsection, and stops in the middle of the silicon film. Since the microsection is held inside the hollow collection needle, it is pushed out and collected using a solution or the like. For this purpose, it is necessary to finely adjust the lower limit position so that the tip of the hollow sampling needle penetrates the biological specimen, that is, stays inside the silicon sheet or PDMS membrane. If the tip of the hollow sampling needle goes too far, the petri dish or the slide glass collides with the tip of the hollow sampling needle, and the hollow sampling needle is damaged. On the other hand, if the tip of the needle does not penetrate the biological sample, it is not possible to collect a microsection from the biological sample.

When collecting microsections from multiple parts of the target biological sample, it is desirable that the hollow sampling needle always stops immediately after punching the biological sample, halfway through the silicon sheet. When punching out various parts, there are a case where the sampling needle unit moves in the XY direction on the surface of the biological sample and punches, and a case where the biological sample holder moves to move the sampling site directly below the hollow sampling needle and punches. is there. In either case, the biological specimen needs to be placed parallel to the moving plane. If they are not parallel, the lower limit position of the hollow sampling needle may be below the surface of the sample holding table holding the biological sample or may not reach the surface. In this case, there arises a problem that the tip of the hollow sampling needle is damaged or the biological sample cannot be punched out.

On the other hand, a biological sample may be placed directly on a quartz slide glass due to optical requirements such as measurement of fluorescence. In this case, the hollow sampling needle collides with the quartz surface, and the tip is easily damaged.

Also, the tip of the hollow sampling needle has an annular shape, and the end surface is usually formed flat. However, depending on the quality of the hollow collection needle, a part may be missing or the tip of the needle may not be flat. In such a case, a part of the hollow collection needle penetrates the biological specimen, but another part does not penetrate. In this case, since the micro section is partially connected to the biological sample, it is not punched out as a micro section and cannot be collected inside the hollow collection needle.

The biological specimen is held in a glass or quartz petri dish or slide glass, but if the tip of the hollow sampling needle hits the surface of the glass or quartz, the hollow sampling needle will be damaged. For this reason, it is necessary to strictly set the position of the lower limit of the descent, which is troublesome. On the other hand, if the blade at the tip of the hollow sampling needle is not flat, there is a part of the obtained microsection that is partially connected to the biological sample, and it becomes difficult to collect the microsection. Also, if the plane formed by the biological sample holder on which the biological sample is placed is not parallel to the operation plane of the sampling needle drive mechanism that moves the hollow sampling needle or the sample holder drive mechanism that moves the biological sample holder, depending on the sampling position. The distance between the lower limit position where the hollow sampling needle descends and the surface of the biological sample holder changes, and the cutting is also insufficient and the microsection cannot be collected and collected.

　In order to know the function of the living body, it is important to obtain gene expression and protein expression information at various parts of the biological specimen. For this purpose, it is necessary to collect microsections for analysis from various parts of the biological specimen. A sampling system that enables this requires a sampling needle unit that can repeatedly collect microsections. In order to punch and collect a biological sample, it is necessary that the hollow collection needle reaches the surface of the biological sample holding table on which the biological sample is placed. For punching and sampling various parts, the hollow sampling needle or the biological sample holder is moved along the XY plane. However, when the movement of the hollow sampling needle or the biological sample holder on the XY plane does not coincide with the plane of the biological sample holder, inconvenience occurs. That is, the hollow sampling needle does not punch through a part or the whole of the biological sample depending on the sampling site, or the hollow sampling needle violently collides with the surface of a petri dish or a slide glass on which the biological sample is placed and damages the hollow sampling needle. It may happen. The biological specimen may not be punched out hard, or the hollow sampling needle may be slightly overhanging, which may prevent punching.

　It was desired to develop new technology to solve these difficulties. In other words, it is not necessary to set the lowering limit of the tip of the hollow sampling needle in detail, and it is possible to prevent damage to the hollow sampling needle during punching and develop a method or system that punches through any biological sample. Was wanted.

The present invention has been made to overcome such difficulties. That is, it is an object of the present invention to disclose a means that does not require detailed setting of the lower limit position and that enables microsections to be collected and collected even when an incomplete cutting situation occurs due to punching by the conventional method.

In order to overcome the above problems, in the present invention, the collecting needle unit is composed of at least a hollow collecting needle, a collecting needle holder that holds the hollow collecting needle, and a collecting needle holder cover. The sampling needle unit is attached to a movable arm that moves up and down by a Z-axis actuator via a sampling needle holder cover. At the time of collection, the movable arm lowers to lower the hollow collection needle and punch out the biological specimen. A spring mechanism is attached so that the axis of the sampling needle holder and the axis of the spring are substantially the same, and when the sampling needle is subjected to excessive force, it moves vertically with respect to the sampling needle holder cover. In the system of the present invention, the hollow sampling needle is set so as to come below the upper surface position of the petri dish or slide glass on which the biological sample is placed. As a result, even if the lower position of the biological sample fluctuates up and down, the hollow sampling needle is not damaged and the biological sample can be completely punched out. Although the hollow collecting needle collides with a petri dish or a slide glass, a large damage of the hollow collecting needle can be avoided by the spring mechanism. Since the spring mechanism can be set so as to be punched out by the hollow collecting needle even when the lower position of the biological sample fluctuates by about 0.5 mm at maximum, it is not necessary to set the lower limit position of the hollow collecting needle in detail.

The spring is arranged coaxially with the collection needle holder and is installed between the stopper and the collection needle holder cover provided near the tip of the hollow collection needle mounting side of the collection needle holder. Alternatively, it may be provided on the opposite side or in the middle of the hollow needle collecting needle mounting side of the needle collecting holder. Further, it may be mounted in a movable arm that holds the sampling needle unit.

On the other hand, if the cutting edge surface of the hollow sampling needle is not flat or parallel to the biological specimen holder, the biological specimen cannot be cut completely. In the present invention, as a method for avoiding such a difficulty, a micromesh can be collected by providing a rotation mechanism to the collection needle holder and rotating the hollow collection needle. In general, an object can be cut with a weaker force when it is pressed in the cutting direction and simultaneously rubbed in the horizontal direction, rather than being simply pressed in the cutting direction. In this case, the force applied to the cutting edge may be small, and there is an advantage that even a hard biological sample is less likely to be collected.

In a hollow collection needle system for collecting biological microsections that has a rotation mechanism, it is important to rotate the hollow collection needle accurately about the center of the hollow collection needle. If the axis of rotation does not coincide with the central axis of the hollow sampling needle, the tip of the hollow sampling needle will precess and damage the biological specimen. For this reason, in the present invention, an eccentricity preventive body for holding the tip of the hollow collecting needle is provided to prevent the hollow collecting needle from shaking. Further, after the hollow sampling needle bites into the biological sample, the hollow sampling needle rotates to prevent unnecessary damage to the biological sample.

Since the collected micro-sections are pushed out by the solution flow, the piping for the passage of the solution flow also consists of a rotating part and a fixed part. During this period, the pipes are connected via an O-ring to prevent distortion in the pipes.

With this method, it is possible to punch and collect thick biological specimens using a hollow needle collection system for biological microsections equipped with a rotation mechanism. In this case, the adhesive force between the collected micro-section and the inside of the hollow collection needle is large, and it may not be possible to push out only by the pressure of the solution flow. In preparation for such a case, in addition to the solution flow, the hollow collection needle holder is equipped with a push rod capable of penetrating the tip of the hollow collection needle. At the time of collecting the microsection, the extrusion rod is pushed in, and the microsection is attached to the tip of the extrusion rod and ejected from the hollow sampling needle. Further, the micro-section at the tip is transported to the collection container by the solution flow. A tungsten wire thinner than the inner diameter of the hollow sampling needle is used as the push rod. As a guide, the outer diameter of the wire should be 70% or less of the inner diameter of the hollow sampling needle.

A hollow microcollection needle system for collecting biological microsections according to the present invention is a hollow microcollection needle system for collecting microscopic sections from a biological specimen, and a hollow collection needle for cutting and collecting the microsections from the biological specimen. A mounting mechanism for mounting the biological specimen, and a cushioning mechanism for mitigating an impact caused by the collision when the hollow collection needle and the mounting part collide with each other when the micro section is collected. Is characterized by.

A hollow collection needle system for collecting biological microscopic slices according to the present invention includes a collection needle holder that holds the hollow collection needle, and a collection needle holder cover that movably inserts the collection needle holder. Has an elastic body that is deformable in the moving direction of the sampling needle holder, and when an external force of a predetermined amount or more is applied to the hollow sampling needle at the time of collecting the microsection, the elastic body is deformed, and The collection needle holder may move within the collection needle holder cover.

In addition, the hollow collection needle system for collecting biological microsections of the present invention may include a rotation mechanism that rotates the collection needle holder, and the collection needle holder may be rotatable around the axis of the hollow collection needle. ..

Further, the hollow collection needle system for collecting a living body micro-section of the present invention is provided with a solution discharge mechanism, causes a solution to flow in the hollow collection needle, and the micro-section held in the hollow collection needle is externalized together with the solution. May be ejected.

Further, a hollow collection needle system for collecting a living body micro-section of the present invention comprises an extruding section and an extruding section drive mechanism for moving the extruding section, and extruding the micro-section held in the hollow collecting needle. Depending on the part, it may be pushed out.

Further, in the hollow collection needle system for collecting biological micro-sections of the present invention, the elastic body is a compression coil spring, and the collection needle holder is inserted into the compression coil spring, and the hollow collection needle and the collection needle holder. The sampling needle unit including the sampling needle holder cover and the compression coil spring may be attached to a movable arm that moves the sampling needle unit.

Further, in the hollow collection needle system for collecting biological microsections of the present invention, the collection needle holder includes a holding member for holding the hollow collection needle, and a positioning portion for positioning the hollow collection needle is formed in the holding member. There is a case.

Further, in the hollow collecting needle system for collecting biological microscopic slices of the present invention, the hollow collecting needle may be made of metal and the inner diameter may be 0.5 mm to 0.2 mm.

Further, in the hollow collection needle system for collecting biological microsections of the present invention, the hollow collection needle may be made of metal and the inner diameter may be 0.2 mm to 0.05 mm.

Further, in the hollow microcollection needle system for collecting biological microsections of the present invention, the buffering mechanism has an elastic member that holds the placement section, and at the time of collection of the microsection, a predetermined amount or more with respect to the placement section. When an external force is applied, the elastic member may be deformed and the placing part may move.

Further, a hollow collection needle system for collecting biological microsections of the present invention comprises a collection needle holder for holding the hollow collection needle, and a rotating mechanism for rotating the collection needle holder, wherein the collection needle holder is the hollow collection needle. It may be rotatable about the axis of the needle.

It is possible to prevent the hollow collecting needle from being damaged even if the hollow collecting needle comes into contact with a mounting container such as a petri dish or a slide glass on which the biological sample is mounted. The rotation mechanism cuts the target by rubbing the blade of the hollow sampling needle against the target to facilitate punching. As a result, even with a hard biological sample, or even if the hollow sampling needle is partially lacking, it is possible to punch out a microsection from the biological sample. The rotating mechanism enables cutting and punching without strongly pressing the blade of the hollow collecting needle against the biological sample, so that the hollow collecting needle can be prevented from being damaged and can last long. As a result, many microsections can be collected without replacing the hollow collection needle. This is effective for collecting many microsections fully automatically.

FIG. 3 is a conceptual diagram of a hollow microcollection needle system for collecting biological microsections equipped with the collection needle unit of the first embodiment. The same is a photograph showing an example of a hollow collection needle system for collecting biological microsections. 3 is a schematic view of a sampling needle unit including a spring mechanism, a rotation mechanism, and a push rod mechanism. FIG. 3 is a vertical cross-sectional view of the hollow collection needle and the collection needle holder cover showing the attachment structure of the hollow collection needle. 9 is a schematic view of a sampling needle unit including a rotation mechanism using a spring mechanism and a bearing according to the second embodiment. 9 is a schematic view of a hollow collection needle unit including a spring mechanism of Example 3. 10 is a schematic view of another hollow collection needle unit including the spring mechanism of the third embodiment. 9 is a schematic view of a hollow collection needle unit in which the spring mechanism of Example 4 is installed on a movable arm. FIG. 8 is a plan view showing a state where a biological sample is placed on a slide glass to which a sponge-like substance of Example 5 is attached. FIG. 3 is a side view showing a state where a biological sample is placed on a slide glass having a sponge-like substance attached thereto. FIG. 3 is a bottom view showing a state where a biological sample is placed on a slide glass having a sponge-like substance attached thereto. FIG. 3 is a plan view showing a state where a biological sample is placed on a petri dish to which the sponge-like substance is attached. FIG. 3 is a side view showing a state where a biological sample is placed on a petri dish to which the sponge-like substance is attached. FIG. 3 is a bottom view showing a state where a biological sample is placed on a petri dish to which the sponge-like substance is attached. FIG. 7 is a plan view showing a state in which the petri dish is attached to the biological sample holding base using the same spacer. FIG. 5 is a vertical cross-sectional view showing a state in which the petri dish is attached to the biological sample holding base using the same spacer. FIG. 3 is a vertical cross-sectional view of the hollow collection needle and the collection needle holder cover showing the attachment structure of the hollow collection needle.

In the present specification, the “living body sample” refers to a part or all of an individual living body such as an animal, a human, a plant, a microorganism. Specifically, it refers to tissue material derived from animals, humans or plants. Biological specimens include materials for biopsy taken from patients with the disease.

In the present specification, “sample”, “microsection sample” or “microsection” means collection of a part or all of the “biological specimen” for observation, analysis, analysis, diagnosis of disease, etc. Microscopic section.

In addition, the reaction cell in the present specification is a container for containing the collected samples, a container in which these are connected, and a container containing a “titer plate” or what is generally called a “microtiter plate”.

In the present specification, the term “microscope” refers to a device for acquiring and observing an image of a biological specimen, such as an optical microscope, a fluorescence microscope, a Raman microscope, or a laser microscope. The image information obtained by this device is loaded into a computer and the sampling position is determined. The image image coordinates are converted into the coordinates of the sampling system, and the amount of movement of the biological sample holder driving XY actuator is calculated. Here, the image image coordinates are a coordinate system in which one pixel of the light receiving element of the camera is used as a unit, and are unique to the observation equipment. The sampling system coordinates are a coordinate system in which one step of the actuator is a step size with reference to the moving direction of the actuator that drives the XY coordinates of the biological sample holder and the hollow sampling needle.

In the present specification, the sampling position is the XY coordinate position of the location where the hollow sampling needle descends to collect a microsection. The collection site is a micro region in which a micro section of a biological sample is collected.

In the system of the present invention, the hollow sampling needle is moved at least in the axial direction perpendicular to the plane formed by the biological sample holder. In this specification, this direction is referred to as the Z axis, and the plane direction orthogonal to the Z axis is referred to as the XY plane. The biological specimen is placed on a biological specimen holder that is movable in a direction other than the Z-axis direction, for example, in the XY plane direction, and the biological specimen sampling site is moved to the sampling position on the movement axis of the hollow sampling needle. Then, the hollow collection needle is moved in the Z-axis direction to the lower limit to cut and collect the collection site of the biological sample, thereby collecting a microsection sample. In addition, the hollow sampling needle may move in the direction of another axis or two axes orthogonal to the Z axis when storing the collected microsection sample. Alternatively, the biological sample holder may be fixed and the hollow sampling needle may be moved in the three directions of XYZ.

Hereinafter, embodiments of the present invention will be described with reference to the attached FIGS. 1 to 17. The examples described below do not limit the content of the invention described in the claims. Moreover, not all of the configurations described below are essential requirements of the present invention. The upper and lower sides in FIGS. 1, 3 to 8, 10, 10, 13, 16 and 17 will be described as the upper and lower sides of the present sampling system.

1 and 2 show a schematic diagram of the entire configuration of the hollow collection needle system for collecting biological microsections of the present embodiment and a photograph of one example. A sampling mechanism is fixed on the stage 8A of the microscope 8. The sampling mechanism unit includes a sampling needle unit 1, a movable arm 2, a sampling needle driving Z-axis actuator 3, a titer plate 4 for accommodating a microsection collected from a biological sample, a sampling needle system substrate 5, and a biological sample. A biological sample holding table 6 to be placed and a biological sample holding table driving XY actuator 7 are provided. A high-resolution camera 9 is attached to the microscope 8 so that an image of a biological sample (not shown) placed on the biological sample holder 6 can be taken and viewed on the monitor screen 12A of the computer 12. .. The hollow collection needle system for collecting biological micro-sections of this embodiment comprises a collection mechanism section, a power supply control section 11, and a computer 12. The present embodiment mainly relates to a sampling needle unit 1 in a sampling mechanism section and a movable arm 2 holding the sampling needle unit 1. The information of the high resolution camera 9 is sent to the computer 12 and used for determining the sampling position. Reference numeral 10 shown in FIG. 1 is a light source for illumination.

The biological sample 201 is placed on the biological sample holding table 6 directly or through a placing container (see FIGS. 9 to 14) such as a petri dish 202 or a slide glass 203. When the table 6 and the mounting container are made of a hard material such as glass, the hollow sampling needle 101 may be damaged when the tip 101A of the hollow sampling needle 101 comes into contact with the table. In order to avoid this, in the present embodiment, a spring mechanism that alleviates collision damage is attached to the sampling needle unit 1 or the sampling mechanism portion that holds the hollow sampling needle 101. The hollow sampling needle 101 has a cylindrical shape, and the inner diameter thereof is constant, but the outer diameter thereof is tapered conically at the tip portion 101A. The curvature of the knife end of the tip 101A is 10 microns or less.

The hollow collection needle 101 is attached to the collection needle holder 102, and constitutes the collection needle unit 1 together with the collection needle holder cover 103. The sampling needle unit 1 is attached to a movable arm 2 of a sampling needle driving Z-axis actuator 3. The biological sample 201 is placed on the biological sample holding table 6 and then set at a predetermined position of the biological sample holding table driving XY actuator 7. In order to determine the lowering limit of the sampling needle unit 1 and confirm the sampling position, the hollow sampling needle 101 is first collected until the tip 101A of the hollow sampling needle 101 touches the dish 202 or the slide glass 203 before placing the biological sample 201. It is lowered by the drive Z-axis actuator 3. Since the relative position of the sampling needle driving Z-axis actuator 3 is displayed on the monitor screen 12A of the control computer 12, the hollow sampling needle 101 is lowered while confirming the image displayed on the monitor screen 12A.

FIG. 3 is a schematic sectional view when the sampling needle unit 1 according to the present embodiment is attached to the movable arm 2. The sampling needle unit 1 includes a hollow sampling needle 101, a sampling needle holder 102, a sampling needle holder cover 103, a slit cover 104, a compression coil spring 105 that is an elastic body, an eccentricity preventive body 106, a holding cover 107, a lower stopper 108 and an upper stopper. It has a stopper 109. The sampling needle unit 1 includes a hollow metal sampling needle 101 having an inner diameter of 0.2 mm and a sampling needle holder 102 having an outer diameter of 1.0 mm, and is mounted on a movable arm 2 movable in the Z-axis direction. To be done. Needless to say, a metal hollow sampling needle having an inner diameter of 0.1 mm or a sampling needle holder 102 having an outer diameter of 1.1 mm and different from 1.0 mm may be used. The movable arm 2 is equipped with a motor 112 that rotates and a solenoid 117 that is a push-out portion drive mechanism that drives a push-out rod 114 as a push-out portion.

The hollow collection needle 101 is fixed to the collection needle holder 102 formed in a cylindrical shape by being pushed inward from the lower side. The collection needle holder 102 is inserted into a collection needle holder cover 103 formed in a cylindrical shape, and can slide inside the collection needle holder cover 103. The lower portion 103A of the collection needle holder cover 103 is inserted and held in a slit cover 104 formed in a cylindrical shape. The upper part 103B of the sampling needle holder cover 103 is inserted and held by a holding cover 107 formed in a cylindrical shape. The upper end 104B of the slit cover 104 and the lower end 107A of the holding cover 107 are in contact with each other. The sampling needle unit 1 is attached to the movable arm 2 by fixing the holding cover 107 to the movable arm 2. Further, the lower end side of the sampling needle holder 102 is inserted into the compression coil spring 105. A stopper 108 is attached to the lower end portion 102A of the sampling needle holder 102 to prevent the compression coil spring 105 from falling off. The compression coil spring 105 can pass a sampling needle holder 102 having an inner diameter of 1.28 mm, an outer diameter of 1.92 mm and an outer diameter of 1.0 mm. The sampling needle holder cover 103 has an inner diameter slightly larger than the outer diameter of the sampling needle holder 102, and since the sampling needle holder cover 103 has an outer diameter of 2.0 mm, it serves as a stopper on the upper end side of the compression coil spring 105. .. However, it fits inside the slit cover 104 having an inner diameter of 2.0 mm. The compression coil spring 105 is sandwiched between the stopper 108 and the sampling needle holder cover 103. Further, in order to restrict the collection needle holder 102 from moving downward relative to the collection needle holder cover 103, the collection needle holder 102 is provided with a stopper 109 on the upper outlet side of the collection needle holder cover 103. Has been. By adjusting this position, the elastic force of the compression coil spring 105 can be controlled.

A rotating mechanism 111 that rotates the sampling needle holder 102 about its axis is mounted above the portion of the sampling needle holder 102 to which the stopper 109 is mounted. A gear or a pulley is used as the rotating mechanism 111. Further, a T-shaped joint 113 is attached to the upper end portion 102B of the sampling needle holder 102, and a tube 115 and a push rod 114 that form a solution flow path are attached via the T-shaped joint 113. That is, the sampling needle holder 102 holds the hollow sampling needle 101 at the tip (lower end) and can rotate about the central axis. This rotation is supported by a sampling needle holder cover 103 having an inner diameter approximately the same as the outer diameter of the sampling needle holder 102, and an eccentricity preventive body 106 for preventing the hollow sampling needle 101 from rotating during rotation is provided at the lower end of the slit cover 104. It is attached to 104A.

When the push rod 114 is not used, the tube 115 is attached via an L-shaped joint (not shown). The L-shaped or T-shaped joint 113 is provided with a rotation preventing mechanism (not shown) using an O-ring or the like so that the tube 115 does not rotate even if the sampling needle holder 102 rotates via the rotation mechanism 111. There is. The push rod 114 is slidable in the collection needle holder 102 in the axial direction (longitudinal direction). The tube 115 that forms the solution flow path is connected to the solution discharge mechanism 116. When collecting the collected micro-sections into a reaction cell (not shown), the solution flow from the discharge mechanism 116 passes through the tube 115, the collection needle holder 102, and the hollow collection needle 101 and from the tip (lower end) of the hollow collection needle 101. It is ejected in the form of pushing out a minute section. Further, the push rod 114 is also connected to the solenoid 117 that is a push unit driving mechanism, and can perform a push operation when collecting microsections.

Below, we will explain according to the procedure of collecting microsections. The hollow sampling needle 101 is pushed and fixed in the sampling needle holder 102 through a slit 106A (pore) formed in the eccentricity prevention body 106 at the tip of the slit cover 104. The sampling needle unit 1 is attached to a movable arm 2 equipped with a rotation mechanism 111. Next, the sampling mechanism is initialized. The petri dish 202 or slide glass 203 before the biological sample 201 is placed is placed on the biological sample holder 6. Next, the sampling needle unit 1 is gradually lowered until the tip portion 101A of the hollow sampling needle 101 comes into contact with the surface of the petri dish 202 or the slide glass 203. The point at which 0.2 mm lower than the point of contact is set as the lowering limit of the sampling needle unit 1. When the hollow sampling needle 101 is lowered to the lower limit, it collides with the petri dish 202 or the slide glass 203. However, when an external force is applied to the tip 101A of the hollow sampling needle 101, the compression coil spring 105 contracts. Since the hollow collecting needle 101 is raised relative to the collecting needle holder cover 103 and the external force applied to the hollow collecting needle 101 is reduced, the hollow collecting needle 101 is protected from damage. Since the tip 101A of the hollow sampling needle 101 can be observed with the microscope 8 in this lowered state, the biological sample holder is placed on the central axis C of the hollow sampling needle 101 in the image of the microscope 8 displayed on the monitor screen 12A of the computer 12. Bring the position marker attached to 6. This is the sampling position of the micro section. Pull up the sampling needle unit 1 and return it to the standby position. The sampling needle unit 1 is stopped at the standby position except when collecting or collecting.

The biological specimen 201 is placed on the petri dish 202 or the slide glass 203. The position to be sampled by observing the image of the microscope 8 is determined on the monitor screen 12A of the computer 12. The position coordinates on the image of the collection site are converted into the coordinates of the biological sample holding table driving XY actuator 7 that moves the biological sample holding table 6 on which the biological sample 201 is placed. Using this information, the operation of the biological sample holder driving actuator 7 that moves the sampling site to the sampling position is determined.

Clicking Start Collection on the Controller tab (not shown) on the monitor screen 12A of the computer 12 will start the collection of microsections. When the sampling signal is obtained and the sampling needle unit 1 reaches the lower limit, the hollow sampling needle 101 rotates for a certain period of time to cut and collect a micro section from the biological sample 201. The rotation time is specified in advance, but is usually 1-2 seconds. When the biological specimen 201 has a large thickness or is hard, it is necessary to increase the rotation time. When the rotation is completed, the sampling needle unit 1 returns to the standby position. The cut and sampled microsection is held inside the tip portion 101A of the hollow sampling needle 101.

What is important in this rotary cutting and punching method is that the hollow sampling needle 101 rotates about the central axis C. The rotational power is transmitted from the external motor 112 to the sampling needle holder 102. At this time, the hollow sampling needle 101 is arranged on the rotation axis of the sampling needle holder 102, and the central axis C of the hollow sampling needle 101 and the rotation axis of the sampling needle holder 102 may be aligned, but this is not always the case. In such a case as well, the slit lower end 104B of the slit cover 104 has slits 106A (pores) of substantially the same size as the outer diameter of the hollow sampling needle 101 so that accurate rotation sampling from the sampling site of the biological sample 201 is possible. An eccentricity prevention body 106 is provided. This prevents the hollow sampling needle 101 from eccentrically rotating.

Next, the titer plate 4 is moved, and the reaction cell for collecting the microsection is arranged directly below the hollow sampling needle 101. The sampling needle unit 1 descends, and the tip 101A of the hollow sampling needle 101 stops at a position of about 5 mm from the bottom surface of the reaction cell. Next, the solution discharge mechanism 116 is driven, the solution flows inside the tube 115, the collection needle holder 102, and the hollow collection needle 101, and the solution flow is discharged from the tip portion 101A. At this time, the microsection held inside the hollow sampling needle 101 is pushed out into the reaction cell. When the thickness of the biological specimen 201 is large, the micro slice collected by the solution flow may not be discharged from the inside of the hollow sampling needle 101. In order to eliminate such a trouble, in this embodiment, a push rod 114 made of a tungsten wire is placed inside the hollow sampling needle 101. Since the push rod 114 arranged inside the hollow sampling needle 101 also acts as a resistance to the solution flow, the outer diameter is preferably 70% or less of the inner diameter of the hollow sampling needle 101. The pushing bar 114 mechanically pushes the micro-section out of the hollow sampling needle 101 from the tip 101A of the hollow sampling needle 101 almost simultaneously with the solution discharge. Since the solution is discharged almost at the same time as the microsection is extruded, the microsection is collected in the reaction cell. At this time, since the tip portion 101A of the hollow sampling needle 101 and the push rod 114 are washed with the solution, continuous sampling is possible.

When the collection of the micro section is completed, the sampling needle unit 1 returns to the standby position. The titer plate 4 equipped with the reaction cell also returns to the original standby position. The next collection site is located directly below the hollow collection needle 101 and the next collection operation is repeated. This sampling operation is repeated by the number of designated sampling sites.

Rotating the hollow sampling needle 101 has an advantage that the biological specimen 201 can be punched and cut even if the pushing force is weak. At the time of punching, the blade portion of the hollow sampling needle 101 collides with a hard Petri dish or the surface of a slide glass, but the force pressing against the surface is much weaker than in the case of being fixed because it is mediated by the compression coil spring 105. The blade of the sampling needle 101 is not damaged. That is, repeated sampling is possible.

If the biological specimen 201 is a thin pathological section, it is not necessary to use the rotation mechanism. The biological specimen 201 is placed on a Petri dish 202 or a slide glass 203 via a PDMS film or a thin silicon sheet. If the sampling needle unit 1 having a spring mechanism is used, it is possible to punch and collect a micro section without positioning the tip (lower end) of the hollow sampling needle 101 in detail. In this case as well, the tip 101A of the hollow sampling needle 101 collides with the surface of the petri dish 202 and the slide glass 203, but excessive pressure is not applied to the blade of the hollow sampling needle 101 by the compression coil spring 105. Will not be damaged.

The hollow sampling needle 101 of the present embodiment has a tip 101A whose end face is substantially flat, but this is not the case when a rotating mechanism is used. It is also possible to use a partly lacking part or a corrugated part.

In the above description, an example in which the biological specimen 201 is observed and a plurality of collection sites is determined and collected in advance is explained, but it is also possible to collect each time while observing the biological specimen 201. In this case, the hollow collection needle system for collecting biological microsections can be operated by a touch panel or the like.

In this embodiment, by increasing the length of the collection needle holder cover 103 that supports the collection needle holder 102, there is an advantage that the shake of the collection needle holder 102 itself can be reduced.

As shown in FIG. 4, in the present embodiment, the sampling needle holder 102 has a Teflon (registered trademark) tube 118 as a holding member in a stainless steel pipe (outer diameter 1.0 mm, inner diameter 0.7 to 0.8 mm). It uses the inserted shape. After inserting the hollow sampling needle 101 and inserting the Teflon tube 118 into the sampling needle holder 102 so that the hollow sampling needle 101 stops at a position of about 3 mm, a stop 118A as a positioning portion is provided at the tip (lower end) of the sampling needle holder 102 about 3 mm. The inner diameter is made smaller by inserting. As a result, the hollow sampling needle 101 can be pushed and fixed to the sampling needle holder 102 by a certain length while maintaining airtightness.

Needless to say, the hollow sampling needle 101 may be fixed and used in the form of a step connected to a metal pipe having a small outer diameter. In this case, the sampling needle holder 102 and the hollow sampling needle 101 are integrated.

In this embodiment, the collection needle holder cover 103, the compression coil spring 105, and the stopper 108 form a buffer mechanism.

As described above, the hollow microcollection needle system for collecting biological microsections according to the present embodiment is a hollow microcollection needle system for collecting microscopic sections from the biological specimen 201, and the microsections are cut from the biological specimen 201. The hollow sampling needle 101 to be sampled, the biological sample holding table 6 on which the biological sample 201 is placed, the slide glass 202 or the petri dish 203, and the hollow sampling needle 101, the biological sample holding table 6, the slide glass 202 or the microscopic sample at the time of sampling By providing the collection needle holder cover 103, the compression coil spring 105, and the stopper 108 that alleviate the impact caused by the collision when the petri dish 203 collides, an excessive external force is applied to the hollow collection needle 101. It is possible to avoid it and prevent the hollow sampling needle 101 from being damaged.

The hollow collection needle system for collecting living body micro-sections of this embodiment is a hollow collection needle system for collecting living body micro-sections that collects micro-sections from a living specimen 201, and a collection needle holder 102 that holds a hollow collection needle 101. And a collection needle holder cover 103 that movably inserts the collection needle holder 102, the buffer mechanism has a compression coil spring 105 that is deformable in the moving direction of the collection needle holder 102, and when collecting a microsection, When an external force of a predetermined amount or more is applied to the hollow sampling needle 101, the compression coil spring 105 deforms and the sampling needle holder 102 moves inside the sampling needle holder cover 103, so that an excessive external force is applied to the hollow sampling needle 101. Can be avoided, and the hollow collection needle 101 can be prevented from being damaged. Further, as a result, detailed adjustment is not required for setting the lower limit position of the hollow sampling needle 101 that descends when collecting a microsection from the biological specimen 201, and thus the lower limit position can be set easily.

In addition, the hollow collection needle system for collecting biological microsections of the present embodiment includes a rotating mechanism 111 that rotates the collection needle holder 102, and the collection needle holder 102 is rotatable about the axis C of the hollow collection needle 101. Thereby, even when the biological sample 201 is hard or a part of the hollow sampling needle 101 is missing, a micro section can be easily punched from the biological sample 201. Further, by rotating the hollow collecting needle 101, the hollow collecting needle 101 can be cut and punched without strongly pressing the blade of the hollow collecting needle 101 against the biological sample, so that the hollow collecting needle 101 can be prevented from being damaged and can last a long time.

In addition, the hollow collection needle system for collecting a living body micro-section of the present embodiment is provided with a solution discharge mechanism 116, causes the solution to flow in the hollow collection needle 101, and the micro-section held in the hollow collection needle 101 is externalized together with the solution. By discharging the solution into the hollow collecting needle 101 and the inside of the hollow collecting needle 101, the solution can be discharged simultaneously.

Further, the hollow collection needle system for collecting living body micro-sections of the present embodiment is provided with the pushing rod 114 and the solenoid 117 for moving the pushing rod 114, and pushes out the micro-section held in the hollow collecting needle 101. Thus, the micro-section can be reliably taken out from the hollow sampling needle 101 by being pushed out to the outside.

Further, in the hollow collection needle system for collecting biological micro-sections of the present embodiment, the elastic body is the compression coil spring 105, and the collection needle holder 102 is inserted into the compression coil spring 105, so that the hollow collection needle 101 and the collection needle holder. When the sampling needle unit 1 including the sampling needle holder cover 103 and the compression coil spring 105 is attached to the movable arm 2 that moves the sampling needle unit 1, the compression coil spring 105 contracts. It is possible to avoid applying an excessive external force to the hollow sampling needle 101 and move the sampling needle unit 1 to a desired position by the movable arm 2.

Further, in the hollow collection needle system for collecting living body micro-sections of the present embodiment, the collection needle holder 102 includes the Teflon tube 118 holding the hollow collection needle 101, and the Teflon tube 118 is formed with the aperture 118A for positioning the hollow collection needle 101. By doing so, the hollow sampling needle 101 can be positioned and fixed at a desired position with respect to the sampling needle holder 102.

Further, in the hollow collecting needle system for collecting living body micro-sections of the present embodiment, since the hollow collecting needle 101 is made of metal and the inner diameter is 0.5 mm to 0.2 mm, the raw living body sample and the thickness are 0.1. It is possible to punch and collect microsections from a thick biological specimen of 2 mm or more.

Further, in the hollow collection needle system for collecting biological microsections of the present embodiment, the hollow collection needle 101 is made of metal and the inner diameter is 0.2 mm to 0.05 mm, so that the detailed position of the thin biological specimen 201 can be determined. A microsection can be collected from a specified narrow area by designating it as a collection site.

FIG. 5 shows a second embodiment of the present invention, in which the same parts as those in the first embodiment are designated by the same reference numerals and detailed description thereof will be omitted. In this embodiment, the sampling needle holder 102 is supported by bearings 121A and 121B. Here, a sampling needle holder cover 103 having an inner diameter much larger than the outer diameter of the sampling needle holder 102 is used. Two bearings 121A and 121B are arranged in the collection needle holder cover 103 to support the collection needle holder 102. The sampling needle holder cover 103 also serves as the slit cover 104 in the first embodiment. The bearing 121A is fixed by a fixing member 122 so as not to move upward, and the bearing 121B is fixed by a fixing member 123 so as not to move downward. The sampling needle holder 102 can slide inside the bearings 121A and 121B. Two stoppers 108A and 108B fixed to the sampling needle holder 102 are arranged between the two bearings 121A and 121B, and a compression coil spring 105A, which is an elastic body, is arranged between the bearings 121A and 108A. A compression coil spring 105B, which is an elastic body, is arranged between the stopper 108B and the stopper 108B. Thereby, the spring action can be generated in the upward and downward directions.

The hollow collection needle 101 is inserted into the collection needle holder 102 through the slit 106A of the eccentricity prevention body 106 and fixed. The role of the eccentricity prevention body 106 is to prevent the hollow collection needle 101 from eccentric movement during rotation. Hereinafter, the basic operation is the same as that of the first embodiment.

In this embodiment, the compression coil spring 105A, the compression coil spring 105B, the stopper 108A, the stopper 108B, the bearing 121A, and the bearing 121B constitute a buffer mechanism.

As described above, the hollow collection needle system for collecting living body microsections according to the present embodiment is a hollow collection needle system for collecting living body microsections that collects a microsection from the living body specimen 201, and includes the hollow collection needle 101 and the hollow collection needle. A collection needle holder 102 that holds the needle 101, a collection needle holder cover 103 that movably inserts the collection needle holder 102, and compression coil springs 105A and 105B that are deformable in the moving direction of the collection needle holder 102 are provided. When an external force of a predetermined amount or more is applied to the hollow collection needle 101 during the collection of the microsection, the compression coil springs 105A and 105B are deformed, and the collection needle holder 102 moves inside the collection needle holder cover 103, It is possible to prevent an excessive external force from being applied to the hollow sampling needle 101 and prevent the hollow sampling needle 101 from being damaged. Further, as a result, detailed adjustment is not necessary for setting the lowering limit position of the hollow sampling needle 101 that descends when collecting a microsection from the biological specimen 201, so that the lowering limit position can be easily set.

6 and 7 show a third embodiment of the present invention. The same parts as those of the first and second embodiments are designated by the same reference numerals, and detailed description thereof will be omitted. This embodiment is an example of the sampling needle unit 1 having no rotation function. In this case, the eccentricity preventive body 106 and the slit cover 104 used in the first and second embodiments are unnecessary. In this case, the holding cover 107 may be removed and the sampling needle holder cover 103 may be directly attached to the movable arm 2 as shown in FIG. Further, as shown in FIG. 7, the compression coil spring 105 may be disposed inside the holding cover 107, and the lower side may be held by the stopper 108 and the upper side may be held by the stopper 109.

In this embodiment, since the rotating mechanism 111 is not used, the number of constituent parts of the sampling needle unit 1 is reduced, which is useful for cost reduction. It is suitable for punching thin biological specimens. In this case, since the micro section collected by the solution flow can be extruded, the extruding rod 114 is often unnecessary. In this embodiment, the collection needle holder 102 and the collection needle holder cover 103 are both made of stainless steel. Of course, other materials may be used.

In this embodiment, the collection needle holder cover 103, the compression coil spring 105, and the stopper 108 shown in FIG. 6 constitute a buffer mechanism. Further, the compression coil spring 105, the stopper 108, and the stopper 109 in FIG. 7 constitute a buffer mechanism.

As described above, the hollow collection needle system for collecting living body microsections according to the present embodiment is a hollow collection needle system for collecting living body microsections that collects a microsection from the living body specimen 201, and includes the hollow collection needle 101 and the hollow collection needle. A microscopic section is provided with a sampling needle holder 102 that holds the needle 101, a sampling needle holder cover 103 that movably inserts the sampling needle holder 102, and a compression coil spring 105 that is deformable in the moving direction of the sampling needle holder 102. When an external force of a predetermined amount or more is applied to the hollow collecting needle 101 at the time of collecting, the compression coil spring 105 is deformed, and the collecting needle holder 102 moves inside the collecting needle holder cover 103, so that the hollow collecting needle 101 It is possible to prevent an excessive external force from being applied to the hollow collection needle 101 and prevent the hollow collection needle 101 from being damaged. Further, as a result, detailed adjustment is not required for setting the lower limit position of the hollow sampling needle 101 that descends when collecting a microsection from the biological specimen 201, and thus the lower limit position can be set easily.

FIG. 8 shows a fourth embodiment of the present invention. The same parts as those of the first to third embodiments are designated by the same reference numerals, and detailed description thereof will be omitted. In this embodiment, the movable arm 2 is provided with a spring mechanism. The sampling needle holder cover 103 is fixed to the movable arm 2. Instead of the sampling needle holder cover 103, a part of the movable arm 2 may be hollowed out and used as a substitute. In this case, the length of the sampling needle holder cover 103 is shorter than that shown in FIG. The compression coil spring 105 is arranged between the stopper 108 fixed to the sampling needle holder 102 and the stopper 122 fixed to the upper surface of the arm 2. Since the diameter of the through hole 122A of the stopper 122 that is bored for inserting the sampling needle holder 102 is larger than the outer diameter of the sampling needle holder 102 and smaller than the outer diameter of the compression coil spring 105, the compression coil spring 105 However, the collection needle holder 102 can pass through the stopper 122 without resistance. When the sampling needle holder 102 is pushed up, the compression coil spring 105 contracts to reduce the pressure applied to the distal end portion 101A of the hollow sampling needle 101. In FIG. 8, the connection to the T-shaped joint 113 and the like is omitted. Of course, the tube 115, the push rod 114, etc. can also be attached.

When the rotation mechanism 111 is not required as in the present embodiment, the sampling needle cover 103 and the eccentricity prevention body 106 are not required, which is advantageous in that the configuration is simple.

In this embodiment, the compression coil spring 105, the stopper 108, and the stopper 124 form a buffer mechanism.

As described above, the hollow collection needle system for collecting living body microsections according to the present embodiment is a hollow collection needle system for collecting living body microsections that collects a microsection from the living body specimen 201, and includes the hollow collection needle 101 and the hollow collection needle. A microscopic section is provided with a sampling needle holder 102 that holds the needle 101, a sampling needle holder cover 103 that movably inserts the sampling needle holder 102, and a compression coil spring 105 that is deformable in the moving direction of the sampling needle holder 102. When an external force of a predetermined amount or more is applied to the hollow collecting needle 101 at the time of collecting, the compression coil spring 105 is deformed, and the collecting needle holder 102 moves inside the collecting needle holder cover 103, so that the hollow collecting needle 101 It is possible to prevent an excessive external force from being applied to the hollow collection needle 101 and prevent the hollow collection needle 101 from being damaged. Further, as a result, detailed adjustment is not required for setting the lower limit position of the hollow sampling needle 101 that descends when collecting a microsection from the biological specimen 201, and thus the lower limit position can be set easily.

9 to 17 show a fifth embodiment of the present invention. The same parts as those of the first to fourth embodiments are designated by the same reference numerals, and detailed description thereof will be omitted. The present embodiment is an example in which the cushioning mechanism is provided on the biological sample holding table 6 side. The biological sample 201 is placed on a placing container, which is a placing part such as a slide glass 202 or a petri dish 203, and then placed on the biological sample holding table 6. A sponge-like substance 204 having a thickness of about 1 mm, which is an elastic member, is attached to an end portion of the bottom surface of the mounting container. Therefore, when the placing container is placed on the biological sample holding table 6, only the sponge-like substance 204 comes into contact with the biological sample holding table 6, and the placing container does not come into contact with the biological sample holding table 6 and is placed on the biological sample holding table 6. The container is supported by the sponge-like substance 204. In this state, in order to cut and collect the microsection from the biological specimen 201, when the hollow sampling needle 101 is lowered, the hollow sampling needle 101 penetrates the biological specimen 201 and comes into contact with the mounting container, so that the hollow sampling needle 101 101 presses the mounting container. When this pressing force is an external force of a predetermined value or more, the sponge-like substance 204 is elastically deformed, and the mounting container is pushed down. Therefore, the impact on the tip portion 101A of the hollow sampling needle 101 due to the collision between the hollow sampling needle 101 and the mounting container is alleviated. In addition, when the biological sample 201 is hard, it is placed before the hollow sampling needle 101 penetrates the biological sample 201 (a state in which the hollow sampling needle 101 is in contact with the biological sample 201) or while cutting the biological sample 201. In some cases, the container for use is pushed down.

When the sponge-like substance 204 is attached to the rectangular slide glass 202, as shown in FIGS. 9 to 11, the sponge-like substance 204 is attached to the lower surfaces of the end portions 202A and 202B in the longitudinal direction of the slide glass 202 to form a circular petri dish. When it is attached to the 203, as shown in FIGS. 12 to 14, it is attached to the lower surface outer peripheral portion 203A of the petri dish 203 in an annular shape. It should be noted that the attachment position of the sponge-like substance 204 is such that, when the mounting container is pressed by the hollow collecting needle 101, the mounting container is pushed down without the lower surface of the mounting container being extremely inclined. , It may be in another position. Further, in this embodiment, two sponge-like substances 204 are attached to the slide glass 202 and one sponge-like substance 204 is attached to the petri dish 203, but three or more sponge-like substances 204 may be attached to the slide glass 202, Two or more sponge-like substances 204 may be attached to the petri dish 203. In this case, the sponge-like substances 204 may have the same shape or different shapes. Note that other members such as a gel-like member may be used instead of the sponge-like substance 204 as long as they can support the slide glass 202 and the petri dish 203 and are elastically deformable.

When the mounting container on which the biological sample 201 is mounted is fixed to the biological sample holding table 6 without using the sponge-like substance 204 and does not move, it is not easy to determine whether or not the hollow sampling needle 101 has reached the biological sample 201. .. However, in this embodiment, the placing container is lowered by the pressing force of the hollow sampling needle 101. Therefore, there is an advantage that it is possible to easily visually confirm that the hollow sampling needle 101 has touched the biological sample 201. An optical sensor (not shown), which is a position detection means for detecting the position of the mounting container, is provided to detect the movement of the mounting container, thereby detecting the hollow sampling needle 101 and the mounting container. Contact may be detected.

In the present embodiment, the sponge-like substance 204 is provided in the mounting container as a cushioning mechanism, but the biological sample holder 6 may be configured to descend due to the contraction of the compression coil spring 205. 15 and 16 show this example. The biological specimen holding table 6 is provided with a petri dish 203 and an arrangement hole 207 for arranging a spacer 206 which is a spring attachment member. The spacer 206 has a bottomed cylindrical main body 208 having an open top, and a spring mounting portion 209 extending radially outward from an upper end of the main body 208. Four compression coil springs 205 are fixed to the lower surface of the spring mounting portion 209 at equal intervals. The bottom portion 210 of the spacer 206 is provided with an observation hole 211 for observing the biological specimen 201 with the microscope 8. When the dish 203 is housed in the main body 208, a double structure is formed.

Around the placement hole 207 of the biological sample holding base 6, bottomed spring placement holes 213 for placing the compression coil springs 205 are formed at four locations. As shown in FIGS. 15 and 16, with the petri dish 203 accommodated in the body portion 208 of the spacer 206, the body portion 208 is arranged in the arrangement hole 207, and the compression coil spring 205 is arranged in the spring arrangement hole 213. To do. At this time, a gap D is formed between the upper surface of the biological sample holding base 6 and the lower surface of the spring attachment portion 209, and the compression coil spring 205 contracts, so that the petri dish 203 and the spacer 206 together with the length of the gap D. It is only possible to descend. The number of compression coil springs 205 can be appropriately changed as long as the spacer 206 accommodating the petri dish 203 is supported without tilting and can be lowered by the external force received from the hollow sampling needle 101. Further, the number of spring placement holes 213 may be equal to or larger than the number of compression coil springs 205 to be used, and the number of spring placement holes 213 in which the compression coil springs 205 are placed can be increased by forming more than the compression coil springs 205. You can

With the spacer 206 accommodating the petri dish 203 attached to the biological sample holder 6, in order to cut and collect a microsection from the biological sample 201, when the hollow sampling needle 101 is lowered, the hollow sampling needle 101 penetrates the biological sample 201. Then, the hollow collection needle 101 presses the petri dish 203 by contacting the petri dish 203. When this pressing force becomes an external force of a predetermined value or more, the compression coil spring 207 elastically deforms (contracts), and the mounting container is pressed down. Therefore, the impact on the tip portion 101A of the hollow sampling needle 101 due to the collision between the hollow sampling needle 101 and the mounting container is alleviated. In addition, when the biological sample 201 is hard, it is placed before the hollow sampling needle 101 penetrates the biological sample 201 (a state in which the hollow sampling needle 101 is in contact with the biological sample 201) or while cutting the biological sample 201. In some cases, the container for use is pushed down.

As described in the first embodiment, the hollow collecting needle 101 is fixed by being inserted into the collecting needle holder 102. The hollow collection needle 101 can be replaced as needed. The sampling needle holder 102 has a shape as shown in FIGS. 4 and 17. In this embodiment, as shown in FIG. 17, a diameter-expanded portion 102C is provided at the tip of the collection needle holder 102 to enlarge the inner diameter and outer diameter of the tip of the collection needle holder 102. Therefore, a step structure is formed by the sampling needle holder 102 and the enlarged diameter portion 102C, and the lower end surface portion 102D of the sampling needle holder 102 functions as a positioning portion. The Teflon tube 118 is also arranged inside the expanded diameter portion 102C continuously from the sampling needle holder 102, and airtightness is maintained. The hollow collecting needle 101 inserted in the expanded diameter portion 102C is held at a predetermined position by the lower end surface portion 102D which is a positioning portion.

Also in this embodiment, by providing the rotating mechanism 111 of the hollow sampling needle 101, the biological specimen 201 can be cut even with a weak force. The hollow sampling needle 101 is inserted into a slit 106A having an inner diameter slightly larger than the outer diameter of the hollow sampling needle 101 to prevent shaft shake during rotation. If the inner diameter of the slit 106A is larger than the outer diameter of the hollow sampling needle 101, the frictional resistance is small, and the hollow sampling needle 101 can be easily rotated, but the shaft is largely shaken. On the other hand, if the size is almost the same, the shaft shake is reduced, but the frictional resistance when the hollow sampling needle 101 moves up and down increases. Therefore, when a spring mechanism as a buffer mechanism is provided in the sampling needle unit 1 or the sampling mechanism, the spring mechanism may be affected by the frictional resistance between the hollow sampling needle 101 and the slit 106A. Providing a cushioning mechanism on the biological sample holding table 6 presented in this embodiment has an advantage that this problem can be solved. A spring mechanism may be provided in the collection needle unit 1 or the collection mechanism section, and a cushioning mechanism may be provided in the biological sample holder 6.

In this embodiment, the slide glass 202 and the sponge-like substance 204 in FIGS. 9 to 11 form a buffer mechanism. Further, the petri dish 203 and the sponge-like substance 204 in FIGS. 12 to 14 form a buffer mechanism. In addition, the biological sample holder 6, the compression coil spring 205, and the spacer 206 in FIGS. 15 and 16 form a buffer mechanism.

As described above, the hollow microcollection needle system for collecting biological microsections according to the present embodiment is a hollow microcollection needle system for collecting microscopic sections from the biological specimen 201, and the microsections are cut from the biological specimen 201. Hollow sampling needle 101 for sampling, slide glass 202 on which biological specimen 201 is placed, and slide glass for mitigating impact due to the collision when hollow sampling needle 101 collides with slide glass 202 during collection of microsections By including 202 and the sponge-like substance 204, it is possible to prevent the hollow collecting needle 101 from being damaged by the collision between the hollow collecting needle 101 and the slide glass 202.

The hollow collection needle system for collecting biological micro-sections of the present embodiment is a hollow collection needle system for collecting biological micro-sections from the biological specimen 201, and a hollow collection needle system for cutting and collecting the micro-sections from the biological specimen 201. The collection needle 101, the petri dish 203 on which the biological sample 201 is mounted, and the petri dish 203 and the sponge-like substance 204 that alleviate the impact caused by the collision when the hollow collection needle 101 and the petri dish 203 collide during the collection of microsections. By including the above, it is possible to prevent the hollow sampling needle 101 from being damaged due to the collision between the hollow sampling needle 101 and the petri dish 203.

The hollow collection needle system for collecting biological micro-sections of the present embodiment is a hollow collection needle system for collecting biological micro-sections from the biological specimen 201, and a hollow collection needle system for cutting and collecting the micro-sections from the biological specimen 201. The sampling needle 101, the petri dish 203 on which the biological specimen 201 is placed, and the biological specimen holder 6 that alleviates the impact caused by the collision when the hollow sampling needle 101 and the petri dish 203 collide with each other when the micro-section is sampled, compression. By providing the coil spring 205 and the spacer 206, it is possible to prevent the hollow sampling needle 101 from being damaged due to the collision between the hollow sampling needle 101 and the petri dish 203.

In addition, in the hollow collection needle system for collecting living body micro-sections of the present embodiment, the buffering mechanism has the sponge-like substance 204 holding the slide glass 202, and at the time of collecting the micro-sections, the external force of a predetermined amount or more is applied to the slide glass 202. When is added, the sponge-like substance 204 is deformed and the slide glass 202 moves, so that the hollow collection needle 101 can be prevented from being damaged due to the collision between the hollow collection needle 101 and the slide glass 202.

In addition, in the hollow collection needle system for collecting biological micro slices of the present embodiment, the buffering mechanism has the sponge-like substance 204 holding the petri dish 203, and an external force of a predetermined amount or more is applied to the petri dish 203 when the micro slices are collected. Then, the sponge-like substance 204 is deformed and the petri dish 203 moves, so that the hollow collection needle 101 can be prevented from being damaged due to the collision between the hollow collection needle 101 and the petri dish 203.

In addition, in the hollow collection needle system for collecting biological micro-sections of the present embodiment, the buffering mechanism has the compression coil spring 205 holding the Petri dish 203, and when collecting micro-sections, an external force above a predetermined level is applied to the slide glass 202. When added, the compression coil spring 205 is deformed and the petri dish 203 moves, so that the hollow collection needle 101 can be prevented from being damaged by the collision between the hollow collection needle 101 and the petri dish 203.

The present invention is not limited to the above embodiments, and various modifications can be made within the scope of the gist of the present invention. For example, in the above, an example of operating the hollow microneedle collecting system for collecting biological microsections on the inverted microscope 8 has been described, but the hollow microcollecting needle system for collecting biological microsections is independent of the microscope 8 and Hollow sampling needle system for collecting biological microsections for punching and sampling using only the biological sample image displayed on the monitor screen 12A of 12 and position information of the sampling site, and biological microsection sampling to be used by docking with a system other than the inverted microscope 8 The technique of the present invention can be similarly applied to the hollow hollow collecting needle system.

1 Sampling needle unit 2 Movable arm 3 Sampling needle driving Z-axis actuator 4 Titer plate 5 Sampling needle system substrate 6 Biological specimen holder (mounting part)
7 Living Specimen Holding Platform XY Actuator 8 Microscope 8A Stage 9 Camera 10 Illumination Light Source 11 Power Supply Control Unit 12 Computer 12A Monitor Screen 101 Hollow Sampling Needle 101A Tip 102 Sampling Needle Holder 102A Lower End 102B Upper End 103 Sampling Needle Holder Cover 103A Lower part 103B Upper part 104 Slit cover 104A Lower end part 1024 Upper end part 105 Compression coil spring (elastic body, buffer mechanism)
105A compression coil spring (elastic body, buffer mechanism)
105B Compression coil spring (elastic body, buffer mechanism)
106 Eccentricity Preventing Body 106A Slit 107 Holding Cover 107A Lower End 108 Stopper 108A Stopper 108B Stopper 109 Stopper 111 Rotating Mechanism 112 Motor 113 T-Join 114 Extrusion Bar (Extrusion Part)
115 Tube 116 Solution Discharging Mechanism 117 Solenoid (Extrusion Unit Driving Mechanism)
118 Teflon tube (holding member)
118A Aperture (positioning part)
121A bearing 121B bearing 122 fixing metal fitting 123 fixing metal fitting 124 stopper 124A through hole 201 biological sample 202 slide glass (mounting part)
202A end part 202B end part 203 Petri dish (placement part)
203A Lower surface outer peripheral portion 204 Sponge-like substance (elastic member, cushioning mechanism)
205 compression coil spring (elastic member, cushioning mechanism)
206 Spacer 207 Arrangement hole 208 Main body 209 Spring mounting portion 210 Bottom 211 Observation hole 212 Spring arrangement hole C Central axis (axis)
D gap

Claims (11)

A hollow collection needle system for collecting microscopic slices from a biological specimen,
A hollow collection needle for cutting and collecting the micro section from the biological specimen,
A mounting unit for mounting the biological specimen,
A hollow collection needle system for collecting biological micro-sections, comprising: a buffer mechanism that alleviates the impact caused by the collision when the hollow collection needle collides with the placement unit during collection of the micro section. .. A collection needle holder for holding the hollow collection needle,
A collection needle holder cover that movably inserts the collection needle holder,
The buffer mechanism has an elastic body that is deformable in the moving direction of the sampling needle holder,
When an external force of a predetermined amount or more is applied to the hollow collection needle at the time of collecting the micro section, the elastic body is deformed, and the collection needle holder moves inside the collection needle holder cover. The hollow collection needle system for collecting biological micro-sections according to claim 1. The elastic body is a compression coil spring,
The sampling needle holder is inserted through the compression coil spring,
A collection needle unit including the hollow collection needle, the collection needle holder, the collection needle holder cover, and the compression coil spring is attached to a movable arm that moves the collection needle unit. The hollow collection needle system for collecting biological microsections according to claim 2. A rotation mechanism for rotating the collection needle holder,
The hollow collection needle system for collecting biological microsections according to claim 2 or 3, wherein the collection needle holder is rotatable about an axis of the hollow collection needle. The cushioning mechanism has an elastic member that holds the mounting portion,
The living body according to claim 1, wherein, when an external force of a predetermined amount or more is applied to the placing portion during the collection of the microsection, the elastic member is deformed and the placing portion moves. Hollow collection needle system for microsection collection. A collection needle holder for holding the hollow collection needle,
A rotating mechanism for rotating the collection needle holder,
The hollow collection needle system for collecting biological microsections according to claim 5, wherein the collection needle holder is rotatable about an axis of the hollow collection needle. The collection needle holder comprises a holding member for holding the hollow collection needle,
The hollow collection needle system for collecting biological microsections according to any one of claims 2, 3, 4, and 6, wherein a positioning portion for positioning the hollow collection needle is formed on the holding member. Equipped with a solution discharge mechanism,
The living body according to any one of claims 1 to 7, characterized in that the solution is caused to flow in the hollow collecting needle, and the microsections held in the hollow collecting needle are discharged to the outside together with the solution. Hollow collection needle system for microsection collection. An extrusion unit, and an extrusion unit drive mechanism for moving the extrusion unit,
The hollow collection needle system for collecting biological micro slices according to any one of claims 1 to 7, wherein the micro section held in the hollow collection needle is pushed out by the pushing section. The hollow collection needle system for collecting biological microsections according to any one of claims 1 to 9, wherein the hollow collection needle is made of metal and has an inner diameter of 0.5 mm to 0.2 mm. The hollow collection needle system for collecting biological microsections according to any one of claims 1 to 9, wherein the hollow collection needle is made of metal and has an inner diameter of 0.2 mm to 0.05 mm.

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