WO2021245952A1

WO2021245952A1 - Micro screw punch system

Info

Publication number: WO2021245952A1
Application number: PCT/JP2020/022448
Authority: WO
Inventors: 衛平藤; 克之城口; 一郎富永
Original assignee: ヨダカ技研株式会社; 国立研究開発法人理化学研究所
Priority date: 2020-06-05
Filing date: 2020-06-05
Publication date: 2021-12-09

Abstract

[Problem] TO provide a micro screw punch system configured such that cells can be "collected" one at a time. [Solution] This micro screw punch system comprises a needle part, a drive part for driving the needle part, and a control part for controlling the drive part, the needle part being moved forward and backward in a state of being rotated via the drive part by the control part.

Description

Micro screw punch system

The present invention relates to a microscrew punch for "collecting" a specific cell from a living tissue (organ or organ, cell mass such as embryo or organoid).

Ultra-fine liquid volume manipulation is very important from the viewpoint of high sensitivity and labor saving because most of the compounds that make up living organisms are liquids. Among them, the technique of "collecting" cells one by one under a microscope can be a technique that brings about dramatically higher accurate results from the conventional bio-research. This is because, in experiments dealing with cell populations or individual organs as in the past, since the average data of those populations is represented, (1) the existence of unique cells (unique phenomena) existing in the population is overlooked. It is possible that 2) individual cells miss different peculiar signals over time, and (3) peculiar signals that differ depending on their position in an organ are missed. The technology to find new phenomena by comparing such peculiar cells with other cells is attracting attention in the world because it leads to correct and essential understanding especially in "basic research" in the medical and diagnostic fields. ..

Currently, mainly in the United States, the "Human Cell Atlas" project, which looks at human whole body cells at the single cell level, has been promoted since 2016, and in Europe, the one-cell project "Life Time initiative" has been started in 2019. One-cell research is gaining momentum in life science research.
In Japan as well, in September 2018, JST-CRDS (Japan Science and Technology Agency-Research and Development Strategy Center) published a report called "Live Cell Atlas" that emphasizes technological development at the single cell level.

The concept of "collecting" one cell under a microscope, which is definitely necessary here, exists only in Japan and Germany due to its historical background. The reasons are (1) the world's four largest manufacturers of microscopes (Olympus, Nikon, Carl Zeiss, Leica), and (2) the world's two largest manufacturers of in vitro fertilization manipulators (Narikige).・ The existence of Eppendorf) can be mentioned. Therefore, in the conventional environment of US-led development of scientific research equipment, it was difficult to develop a device that "collects" only one cell, and it was difficult to understand its importance.

However, in the analysis to investigate the mechanism, it is necessary to investigate the moment when the cell changes with time (so-called dynaix analysis), and it is necessary to "collect" one cell at that moment under microscopic observation. This method can be the mainstream for investigating the mechanisms that occur in the body such as diseases.

A specific example of the need to "collect" a single cell or a cell mass with certain common characteristics from living tissue is several organs (spleen, lung, lymph node) from experimental animals such as mice. Etc.) to cut out certain cells that are present. Then, when it becomes possible to perform a comprehensive analysis of such cells, it becomes clear that the difference in function between the peculiar part and the other part is larger than the result derived by the conventional experimental method. Therefore, the essential understanding will be advanced, and it will lead to the application in the field of drug discovery and diagnosis in medical treatment.

For example, the spleen is a hematopoietic / lymphatic organ on the left flank, and plays a role in immunity such as destruction of aged red blood cells and processing of foreign substances in blood. Most of the spleen tissue is called the red pulp and is occupied by venous sinuses filled with red blood cells. In the white pulp scattered in the red pulp, dendritic cells and macrophage cells, which are immune cells, present antigens and promote antibody production from lymphocyte cells. In order to analyze in detail the immune function related to antigen presentation that occurs here, it is necessary to efficiently excise the white pulp. These macrophage cells are not only involved in the immune response, but also play a role in tissue reconstruction and tissue repair after the inflammatory response, and their analysis is important.

In addition, the alveoli, which control the main function of the lungs, are essential organs for the survival of the human body, which is responsible for gas exchange. A healthy person breathes about 20,000 liters of air a day. The air contains harmful bacteria, viruses and chemical substances. The immune system in the lungs functions normally against these harmful substances to prevent the onset of infectious diseases, cancer, allergies, asthma, and the like. The site called alveoli (several hundred mm) at the end of the lung may be the target of infectious diseases, and to elucidate the defense mechanism of the living body here, only the alveoli are "collected" and analyzed. The method of doing is desirable.

Furthermore, in the lymph node, there are stromal cells called stromal cells in addition to immune cells such as B cells, and these cells play a role in the skeleton structure. To put it simply, it is like a soft sponge fiber. Immune cells that reach the lymph nodes through the lymph vessels gather at different sites in the lymph nodes, but probably stromal cells play a role, and depending on the type, the sites where each immune cell gathers also differ. Conceivable.

It is currently known that the brain has a multi-layered structure consisting mainly of 6 types of cells. Research is often done on what kind of reaction is occurring in which place in brain wave experiments, but the reality is that the function in more detailed parts is not understood at all. Sections of dissected and removed organs in an analysis to find out more about what is happening in the cerebrum, cerebellum, pituitary gland, hypothalamus, hippocampus, or any particular part of those organs in the brain. It can be imagined that the results are very different between the sample once fixed with formalin and the sample taken raw from the creature.

An embryo is a cell population that has just been split from a fertilized egg, and its initial stage is called cleavage, but when it reaches 8 to 16 cleavages, each cell develops as a living body at that point. At that time, the fate of which organ it will be and where it will be placed begins to be made. At present, it is very difficult to cut out one cell in the cleavage, but if this one cell can be cut out, the analysis of the "body plan" will proceed, and the evolutionary research that will be the basis of biology. It can be expected to have a ripple effect in various fields such as regenerative medicine and gene therapy.

In particular, research development in the field of regenerative medicine is remarkable, but in reality, cells and organs produced in vitro cannot overcome the wall of "body plan" unless research on the mechanism of fate of such developmental processes is done. It has been pointed out that malformed species may be formed and immune from the living body to be eliminated or become cancerous, and various methods for suppressing tumor formation have been developed.
https://www.jstage.jst.go.jp/article/cytometryresearch/21/2/21_D-11-00018/_pdf
In order to solve this problem, it is necessary to take out the cells in the cleavage one by one and perform gene expression analysis in detail. It leads to the prediction that "this cell", "at this timing", "by this gene working", and "it can become this organ in the future", and it is a "material list" like only the gene sequence information currently known. It is possible to find not only the information as a true "design drawing" but also the information as a true "design drawing".

Conventionally, the work of sucking a single cell or a minute cell mass from such a raw tissue is difficult, so that it is rarely performed. Instead, a "laser microdissection" has been used that cuts out only the target site of a sample immobilized with formalin or the like using a local laser combined with the focus function of a microscope.
https://patents.google.com/patent/JP5467254B2/en
Laser cutting of such immobilized samples can certainly cut out what is of interest, but it is far from alive and unreliable, especially for protein and metabolite information.

Against this background, in order to meet the needs of the market, the inventor has been performing "collection" work for many years using glass microtubules and suction pumps with a small amount of liquid. Actually, it was very difficult to collect only the target cells with the current technology, but after several challenges, the problem to solve it became clear.
As a solution, (1) the needle is rotated, (2) the sharpness is sharpened by making it thinner than the current glass needle, and (3) it is necessary to change to a metal needle to make it thinner. 4) In addition to that, it is conceivable to attach a fine piece of glass that imitates a saw-like structure at the tip.

Japanese Unexamined Patent Publication No. 2017-129735

However, assuming that the tip of the needle is rotated while being sucked by the pump as in (1) above, the pump is placed at a position away from the needle, the pump and the needle are connected by a long tube, and the needle is rotated. You have to do that, but doing so will cause the tube to twist. Moreover, when the pump tries to suck or discharge through the tube from such a distant position, the volume from the inside of the pump to the needle increases, the controllability of the internal pressure deteriorates, and the tube also vibrates due to the rotational movement. , The sucked minute objects (cells, etc.) do not stay at the tip of the needle.

Therefore, it is ideal that the pump and needle are as close as possible, and it is best to integrate them as much as possible, but in that case, a small pump is required, and even if the pump is small, the pump is electrically controlled. It is assumed that the electric cable is twisted or entangled by rotating itself.

Therefore, we use a pump technology that is compact and capable of minute suction and discharge control. In addition, regarding the rotational movement, when the needle is fixed to the rotating shaft and continuous rotation is performed in one direction, rotational blurring occurs in the minute region as assumed this time, and it does not shake according to the central axis. It is very difficult to rotate. In order to solve this, the idea of cutting out by operating it by switching it half a turn or one turn to the left and right, and by connecting it with a tube, when a moray eel etc. eats the prey, press the prey against a rock or the seabed etc. I came up with the idea of imitating the movement of eating (death roll) by rotating my body while keeping it fixed. Further, as a method of preventing center shake, a method of first pressing a cylindrical guide along the outer circumference of the needle tip against the sample and then inserting the needle in that state is also conceivable.
Further, by introducing a thin-walled manufacturing technique for metal needles instead of glass needles, it is possible to install metal needles having a tip diameter of 0.1 mm or less.
It is also assumed that even if it is a glass needle, the sharpness can be increased by adhering a piece to the cut end.

In addition, by transmitting the rotational force to the needle through the tube in this way, the problem of internal pressure controllability can be solved because the pump can be installed as close as possible to the position where it does not interfere with the optical system of the microscope observation unit. However, it is possible to take a structure that does not adversely affect microscopic observation.

The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a microscrew punch system capable of finely driving a needle portion.

The microscrew punch system according to the present invention includes a needle unit, a drive unit that drives the needle unit, and a control unit that controls the drive unit. The needle unit is the drive unit by the control unit. It can move in the front-back direction while being rotated through the device.

Further, in the microscrew punch system according to the present invention, the needle portion, the pump portion that sucks the fluid through the needle portion, the needle portion, the drive portion that drives the pump portion, and the drive portion. A control unit for controlling the pump unit is provided, and the needle unit is driven by the control unit in conjunction with the pump unit driven via the drive unit.

Further, in the microscrew punch system according to the present invention, the pump portion is configured to be rotatable and movable in the front-rear direction, and the needle portion is rotated in conjunction with the pump portion in the front-rear direction. It is something that is moved.

Further, the microscrew punch system according to the present invention is provided with a support portion (guide) that pivotally supports the tip portion of the needle portion, and the control unit drives the support portion via the drive portion to drive the support portion and the needle. It is for aligning the parts.

Further, in the microscrew punch system according to the present invention, the inner diameter of the tip of the needle portion is set to 5 μm or more and 1000 μm or less.
Further, the microscrew punch system according to the present invention has a saw-like structure in which fine pieces of 1 μm or less are adsorbed on the tip surface of the needle portion.

Further, in the microscrew punch system according to the present invention, the control unit rotates the needle unit 180 degrees or more left and right and 5 reciprocations / minute or more to 6000 reciprocations / minute or less in the front-rear direction via the drive unit. It moves a distance of 1 μm to 1000 μm at 5 round trips / minute or more to 6000 round trips / minute.

Further, in the microscrew punch system according to the present invention, a container in which a recess is formed and a sample accessed by the needle portion is held in the recess, and a lid in which a penetration portion is formed and placed on the upper portion of the container are formed. And, the sample is one whose movement is restricted by the recess and the lid.

Since the microscrew punch system according to the present invention is configured to be movable in the front-rear direction while the needle portion is rotated, the drive of the needle portion can be finely controlled, and cells can be obtained from a sample accessed by the needle portion. It is possible to "collect" one by one.

In the microscrew punch system according to the present invention, since the needle portion is driven in conjunction with the pump portion, the drive of the needle portion can be finely controlled, and the drive control of the needle portion becomes simple.

It is a schematic block diagram which shows the system configuration of the microscrew punch system which concerns on embodiment of this invention. It is a schematic diagram for demonstrating the container and the lid of the microscrew punch system which concerns on embodiment of this invention. It is a schematic diagram which shows roughly two structural examples of the needle part of the microscrew punch system which concerns on embodiment of this invention. It is explanatory drawing for demonstrating operation of the microscrew punch system which concerns on embodiment of this invention. It is explanatory drawing for demonstrating the Example of the microscrew punch system which concerns on embodiment of this invention. It is the schematic which shows the part of the sample enlarged and schematic.

FIG. 1 is a schematic configuration diagram schematically showing a system configuration of a microscrew punch system 100 (hereinafter referred to as a system 100) according to an embodiment of the present invention. FIG. 2 is a schematic diagram for explaining the container 60 and the lid 70 of the system 100. FIG. 3 is a schematic diagram schematically showing two configuration examples of the needle portion 40 of the system 100. The configuration of the system 100 will be described with reference to FIGS. 1 to 3.

The system 100 has a control unit 10, a drive unit 20, a pump unit 30, a needle unit 40, a support unit 50, a retaining unit 55, a container 60, a lid 70, and a microscope 80, and each cell is contained one by one. It has a structure that makes it possible to cut out.
The system 100 "collects" cells from sample S held in a container 60 placed on a support (not shown). The picked up cells are discharged into a capillary or the like (not shown) placed in a place different from the container 60.

The control unit 10 controls the drive of the drive unit 20, the pump unit 30, and the support unit 50. Further, the state of the cells observed by the microscope 80 is sent to the control unit 10 as image data. The control unit 10 has, for example, a storage unit for storing programs and information, a communication unit for transmitting and receiving information to and from an external communication device, an arithmetic unit for processing information input / output, display, communication, program execution, and the like. There is.
When picking up the cells, the control unit 10 controls the drive unit 20 to position the tip of the needle unit 40 in the container 60, as shown in FIG. Then, the control unit 10 drives the pump unit 30 to pick up the cells. The specific operation of the control unit 10 will be described with reference to FIG.

The drive unit 20 drives the needle unit 40, the pump unit 30, and the support unit 50 by the control unit 10 that receives the operation support from the joystick or the touch panel (not shown). The drive unit 20 can drive the needle unit 40 in the front-rear direction or rotationally drive it via, for example, a motor or a gear. Further, the drive unit 20 drives the pump unit 30 to suck and discharge the fluid through the needle unit 40. Further, the drive unit 20 drives or rotates the support unit 50 in the left-right direction (X direction), the front-rear direction (Y direction), and the up-down direction (Z direction) via, for example, a motor or a gear. By driving the support portion 50 by the drive portion 20, the tip of the needle portion 40 can access the sample S.

As shown in FIG. 1, in the configuration in which the needle portion 40 and the pump portion 30 are integrally assembled, the drive portion 20 drives the needle portion 40 by driving the pump portion 30. .. That is, if the pump unit 30 is driven, the needle unit 40 is driven together. However, when the needle portion 40 and the pump portion 30 are not integrally assembled, for example, when the drive portion 20 in which the extension tube 41 is installed is interposed between the needle portion 40 and the pump portion 30. The drive unit 20 may drive the needle unit 40 and the pump unit 30 separately.

The drive unit 20 is composed of, for example, three actuator stages having a stroke of up to 15 mm or more on each side and a small rotary motor for driving the actuator stages. Specifically, the three actuator stages are assembled so as to move at a maximum JOG speed of 10 μm / sec or more and 50 mm / sec or less in the left-right direction (X direction), the front-back direction (Y direction), and the up-down direction (Z direction). After that, a plate (support portion 50) having a mechanism for holding the cutting blade (that is, the tip of the needle portion 40) and a rotary motor are attached to the tip thereof.

By doing so, the support portion 50 can be driven in the XYZ direction and the rotation direction (rotation angle 0 to 90 degrees, in increments of 0.1 degrees or less). The resolution of this actuator shall be at least 1 μm or less. If the resolution is coarse and large, it cannot be installed near the observation part of the microscope, and it causes shaking. Therefore, by setting the resolution to 1 μm or less, it is possible to move with high resolution without vibration even though it is small.

The configuration of the pump unit 30 is not particularly limited, but it may be configured to be, for example, a pump unit that can be controlled by a minute volume (liquid amount in the range of 100 pL to 1000 nL). As shown in FIG. 1, the pump portion 30 may be installed on the other end side of the needle portion 40 and may be integrally configured with the needle portion 40. Alternatively, the extension tube 41 connected to the other end side of the needle portion 40 may be lengthened, and the pump portion 30 may be installed at a position on the downstream side of the drive portion 20 after passing through the drive portion 20.

By realizing the miniaturization of the pump unit 30, it has become possible to realize the integration of the pump unit 30 and the needle unit 40. Therefore, since the drive of the needle unit 40 can also be controlled by controlling the drive of the pump unit 30, the drive control of the needle unit 40 is simpler than that of directly controlling the drive of the needle unit 40. It became a thing.

The fact that the needle portion 40 and the pump portion 30 are integrally configured means that the pump portion 30 is directly installed at the other end of the needle portion 40 and is connected to the other end of the needle portion 40. It is also assumed that the pump portion 30 is installed in the extension tube 41 or the like. That is, when the drive of the pump unit 30 can be transmitted to the needle unit 40, in other words, when the needle unit 40 is interlocked with the pump unit 30, it can be said that the needle unit 40 and the pump unit 30 are integrally configured. The extension tube 41 is lengthened so that another member, for example, a drive unit 20 is physically interposed between the needle unit 40 and the pump unit 30, and the pump unit 30 is driven although the extension tube 41 is connected in terms of flow path. If the above cannot be transmitted, it cannot be said that the needle portion 40 and the pump portion 30 are integrally configured.

The needle portion 40 is composed of a tubular member with both ends open, the open end portion located on the "collecting" side is the tip end, and the open end portion connected to the pump portion 30 is the other end. 1 and 2 show an example in which the extension tube 41 is connected to the other end. However, as shown in FIG. 3, the pump unit 30 may be installed directly at the other end. Further, the needle portion 40 may be formed linearly as shown in FIG. 3 (A) or may be formed by being curved as shown in FIG. 3 (B), thereby illuminating from above. Does not interfere with observation.

The tip of the needle portion 40 is driven by the drive portion 20 so that the sample S held in the container 60 can be accessed. The other end is connected to the pump portion 30 via the extension tube 41 in an airtight state. The extension tube 41 may be lengthened and connected to indirectly connect the pump portion 30. Since the other end of the needle portion 40 is connected to the pump portion 30 in an airtight state, the sample S held in the container 60 from the tip in response to the drive of the pump portion 30, that is, the suction or discharge of the fluid, is 1 You can pick up cells one by one.

It is desirable that the tip of the needle portion 40 has a sharper blade than the existing glass needle or metal needle. Specifically, it is desirable that the inner diameter of the tip of the needle portion 40 is 1 μm or more and 1000 μm or less. Further, the thin structure at the tip of the needle portion 40 is important when cutting elastic and flexible materials such as skin, and the inner diameter is 85% or more with respect to the outer diameter of the needle tip. Is desirable. Therefore, a case where the needle portion 40 is manufactured from a metal microneedle will be considered. In the case of such a metal microneedle, the original mother tube has a thin structure as described above, that is, an inner diameter of 85 with respect to the outer diameter of the needle tip. It is desirable to use a material of% or more, and by using this material, metal heating forming, which is one of the plastic working techniques, can be adopted to produce a fine tapered shape. The material of the metal microneedles is preferably titanium, but SUS or brass may also be used.

By pulling the originally thin metal pipe with a certain predetermined force by metal heating forming, it is possible to manufacture the needle portion 40 having a thin tip structure, and it is also possible to control the inner diameter of the tip depending on the conditions. However, the configuration of the needle portion 40 is not particularly limited, and the needle portion 40 may be manufactured with a glass needle as long as a sharp tip having a thin structure can be manufactured.
Further, a saw-like structure may be formed in which fine pieces of 1 μm or less are adsorbed on the tip surface of the needle portion 40. By doing so, the blade becomes sharper.

The support portion 50 pivotally supports the tip portion of the needle portion 40. That is, the support portion 50 is formed with a hole portion that penetrates the tip portion of the needle portion 40 and rotatably supports the support portion 50, and the support portion 50 is the tip portion of the needle portion 40 located in the hole portion of the support portion 50. Is configured so as not to restrict the rotation of the needle portion 40 while fixing the needle portion 40 to some extent. The diameter of the hole is larger than the tip of the needle 40 and smaller than the body of the needle 40.

The retaining portion 55 functions to prevent the tip portion of the needle portion 40 from coming out of the hole portion of the support portion 50. That is, the retaining portion 55 serves as a stopper for the needle portion 40.

The container 60 is made of, for example, PDMS (polydimethylsiloxane = silicone rubber). The container 60 is formed with a plurality of recesses 61 in which the sample S can be held. For example, FIG. 2 shows a case where four recesses 61 are formed as an example. The recess 61 has a predetermined depth and functions to prevent the sample S from slipping or escaping in the horizontal direction (direction parallel to the bottom surface of the container 60). Therefore, the sample S housed in the recess 61 is held by the recess 61. The sample S will be described in the subsequent examples.

The dimensions of the container 60 are as follows, for example.
The outer dimensions of the container 60, that is, length x width x height, are 20 mm x 20 mm x 5 mm.
When four recesses 61 are formed with respect to the container 60 having the above dimensions, the length × width × depth of the recesses 61 is 5 mm × 5 mm × 1 mm.
When nine recesses 61 are formed in a container 60 having the above dimensions, the length × width × depth of the recesses 61 is 1 mm × 1 mm × 0.3 mm.
When 16 recesses 61 are formed with respect to the container 60 having the above dimensions, the length × width × depth of the recesses 61 is 0.5 mm × 0.5 mm × 0.2 mm.

The container 60 can be molded by making an aluminum mold or an acrylic mold by cutting using a large NC milling cutter, polishing it, and then using it. Depending on the dimensions of the container 60, a photomask may be made, a resist mold may be made, and molding may be performed using the photomask.

The lid 70 is made of, for example, PDMS or the like, is placed on the upper part of the container 60, and covers the recess 61 of the container 60. That is, the lid 70 functions to restrict the upward movement of the sample S held in the recess 61 of the container 60 by being placed on the upper part of the container 60. However, a plurality of penetrating portions 71 are formed through the lid 70 so that the needle portion 40 can access the sample S. The opening shape of the penetrating portion 71 may be circular, polygonal, or slit-shaped. FIG. 2 shows an example in which eight penetrating portions 71 having a square opening shape are formed in the lid 70 with respect to one recess 61 of the container 60.

The dimensions of the lid 70 are as follows, for example.
The outer dimensions of the lid 70, that is, length x width x height, are 20 mm x 20 mm x 0.5 mm.
When forming 100 penetrating portions 71 with respect to the lid 70 having the above dimensions, for example, the following two dimensions can be considered.
(1) The length × width × depth of the penetrating portion 71 is 1 mm × 1 mm × 0.5 mm.
(2) The length × width × depth of the penetrating portion 71 is set to 0.3 mm × 0.3 mm × 0.5 mm.
When the height of the lid 70 is 0.2 mm and 100 penetration portions 71 are formed, the length × width × depth of the penetration portions 71 is 0.2 mm × 0.2 mm × 0.2 mm.

The microscope 80 observes the sample S held in the container 60. The sample S observed by the microscope 80 is sent to the control unit 10 as image data. The microscope 80 preferably has performance (specs) suitable for detailed observation and analysis of cells. Further, by connecting the microscope 80 to a display or the like, observation may be performed on a magnified screen.

FIG. 4 is an explanatory diagram for explaining the operation of the system 100. The operation of the system 100 will be described with reference to FIG. In the system 100, the control unit 10 controls the operation of each member in an integrated manner based on an instruction from the user. The user gives an instruction to the system 100 by using an operation unit such as a touch panel or a joystick.

In the system 100 to which the instruction is given, as shown in FIG. 4 (1), the control unit 10 moves the support unit 50 to align the needle unit 40 with the sample S. Specifically, as described above, the support portion 50 is moved in the X direction, the Y direction, and the Z direction, and the support portion 50 is rotated to determine the position of the needle portion 40. At the same time, the control unit 10 also performs overall positioning of the pump unit 30 and the needle unit 40 via the drive unit 20.

Next, in the system 100, the control unit 10 rotates the pump unit 30. That is, as shown in FIG. 4 (2), the control unit 10 rotates the needle unit 40 via the pump unit 30. Since the needle portion 40 is pivotally supported by the support portion 50 and is prevented from coming off by the retaining portion 55, the needle portion 40 rotates in a positioned state. Depending on the installation position of the pump unit 30, the rotation of the pump unit 30 may not be transmitted to the needle unit 40. In this case, the control unit 10 rotates and drives the needle unit 40 independently.

The control unit 10 has a high-speed reciprocating rotation setting (for example, a setting of repeating a rotation of 180 degrees or more to the left and right at a high speed (5 reciprocations / minute or more to 6000 reciprocations / minute or less)), a rotation movement distance setting, a rotation speed setting, and an acceleration setting. The rotation of the pump unit 30 is controlled based on the above. These settings may be saved in the control unit 10 in advance, or may be added later. In addition, the settings can be changed. The rotation distance of the pump unit 30 is set to 0 to 720 degrees.

Next, in the system 100, the control unit 10 actually moves the needle unit 40 in the front-rear direction at a rate of 5 reciprocations / minute or more to 6000 reciprocations / minute or less to actually access the sample S ((3) shown in FIG. 4). That is, the needle portion 40 moves in the front-rear direction in a rotated state. As a result, the sample S is picked up at the tip of the needle portion 40. By pushing or pulling the needle portion 40, the tip of the needle portion 40 can be made into a three-dimensionally complicated movement. Optimal cutting can be realized by complicating the movement of the tip of the needle portion 40 that functions as a blade. The front-back movement of the pump unit 30 has a maximum stroke of 15 mm or less.

<Example>
FIG. 5 is an explanatory diagram for explaining an embodiment of the system 100. FIG. 6 is a schematic diagram schematically showing an enlarged part of the sample S. An embodiment of the system 100 will be described with reference to FIGS. 5 and 6. This example shows an example in which a hole (hole H) can be made in a fish egg skin by using a fish egg skin (tarako skin) as a sample S.

It was found that the hole H could not be formed on the skin of the roe simply by pressing the needle portion 40 against the roe. Further, it was found that even if the needle portion 40 is rotated, the hole H cannot be formed in the skin of the roe just by repeating the situation where the rotation angle is small (for example, around 90 degrees).
Therefore, as described above, by pressing the needle portion 40 against the fish egg, which is the sample S, while rotating the needle portion 40 at a predetermined rotation angle or more, a hole H can be formed in a part of the skin of the fish egg, and from there. I was able to collect the fish eggs inside.

The control content executed by the control unit 10 of the system 100 may be realized by a logic circuit (hardware) formed in an integrated circuit (IC chip) or the like, or may be realized by software (program). ..
For example, when the control content is executed by software, the control unit 10 is a computer (one or more processors, a computer having a memory for storing the program) that executes an instruction of a program that is software that realizes each function. It is equipped with.

As the processor, for example, a CPU (Central Processing Unit) can be used. As the memory, for example, in addition to a ROM (Read Only Memory) or the like, a tape, a disk, a card, a semiconductor memory, a programmable logic circuit, or the like can be used. Further, a RAM (Random Access Memory) for expanding the program may be further provided.

The present invention is not limited to the above-described embodiment, and various modifications can be made within the scope of the claims, and the present invention can be obtained by appropriately combining the technical means disclosed in the different embodiments. The form is also included in the technical scope of the present invention. The numerical values shown are not particularly limited, and various changes can be made within the range shown in the claims.
The present invention can be widely used in various cell analyzes. For example, collection of white pulp scattered in the red pulp, collection of only alveoli from the lungs, site-specific collection of stromal cells, site-specific collection from the brain, fluorescence-labeled single cells from embryos. It can be applied to collection, etc.

10: Control unit 20: Drive unit 30: Pump unit 40: Needle unit 41: Extension tube 50: Support unit 55: Retaining unit 60: Container 61: Recessed 70: Lid 71: Penetration unit 80: Microscope 100: Microscrew punch System S: Sample H: Hall

Claims

Needle part and
The drive unit that drives the needle unit and
A control unit that controls the drive unit is provided.
The needle part is
A microscrew punch system that is moved in the front-rear direction by the control unit while being rotated via the drive unit.
Needle part and
A pump unit that sucks fluid through the needle unit and
The needle part, the drive part that drives the pump part, and
The drive unit and the control unit that controls the pump unit are provided.
The needle part is
A microscrew punch system driven by the control unit in conjunction with the pump unit driven via the drive unit.
The pump unit
It is configured to be rotatable and movable in the front-back direction.
The needle part is
The microscrew punch system according to claim 2, wherein the microscrew punch system is moved in the front-rear direction while being rotated in conjunction with the pump unit.
A support portion that pivotally supports the tip portion of the needle portion is provided.
The microscrew punch system according to any one of claims 1 to 3, wherein the control unit drives the support unit via the drive unit to align the needle unit.
The microscrew punch system according to any one of claims 1 to 4, wherein the inner diameter of the tip of the needle portion is 5 μm or more and 1000 μm or less.
The microscrew punch system according to any one of claims 1 to 5, which has a saw-like structure in which fine pieces of 1 μm or less are adsorbed on the tip surface of the needle portion.
The control unit
The needle unit is rotated 180 degrees or more left and right and 5 reciprocations / minute to 6000 reciprocations / minute or less via the drive unit, and at a distance of 1 μm to 1000 μm in the front-rear direction at 5 reciprocations / minute to 6000 reciprocations / minute. The microscrew punch system according to any one of claims 1 to 6, which can be moved.
A container in which a recess is formed and a sample accessed by the needle portion is held in the recess.
With a lid on which a penetration is formed and placed on top of the container,
The sample is
The microscrew punch system according to any one of claims 1 to 7, wherein the movement is restricted by the recess and the lid.