Intracytoplasmic sperm injection support device, intracytoplasmic sperm injection support system, intracytoplasmic sperm injection support program, and egg retention device
The microinsemination support device and system simplify the automation of sperm injection by using an egg retention device and control unit to manage stage movement based on positional relationships, improving efficiency and success rates in intracytoplasmic sperm injection.
Patent Information
- Application Number
- JP2024154443
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2024-09-09
- Publication Date
- 2024-12-09
- Estimated Expiration
- 2044-09-09
AI Technical Summary
Current microinsemination technologies, such as intracytoplasmic sperm injection (ICSI), require significant time to master and often involve complex device configurations for automating sperm injection tools, necessitating a simpler and more efficient support system.
A microinsemination support device and system that utilize an egg retention device with a recess and suction port, combined with a control unit that acquires positional relationships between the sperm injection tool and egg, allowing for precise movement of the stage to perform microinsemination without direct control of the sperm injection tool, and includes an egg retention device with a recess and suction port for holding eggs.
Enables a simpler device configuration for microinsemination, allowing for high-precision automated sperm injection into eggs with reduced reliance on individual skills, enhancing efficiency and success rates.
Smart Images

Figure 0007596002000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to an intracytoplasmic sperm injection support apparatus, an intracytoplasmic sperm injection support system, an intracytoplasmic sperm injection support program, and an egg holding device. [Background technology]
[0002] Intracytoplasmic sperm injection (ICSI), in which sperm are directly injected into the cytoplasm of an egg to fertilize it, has been developed and put into practical use as one of the infertility treatments. In ICSI, sperm immobilization, sperm inhalation, and sperm injection into the egg are performed while observing the sperm and egg under a microscope, so ICSI is also called microinsemination.
[0003] Currently, ICSI is performed by embryologists, but since it takes a long time to become proficient in ICSI, technology to support ICSI is required. For example, Patent Document 1 discloses a control device for moving surgical tools manually operated by embryologists to desired positions. [Prior art documents] [Patent documents]
[0004] [Patent Document 1] Patent Publication No. 2021-029453 Summary of the Invention [Problem to be solved by the invention]
[0005] However, at present, technology to support ICSI is still under development. For example, when trying to automate the movement of a sperm injection tool, the device configuration may become complicated as shown in Patent Document 1. Therefore, the present invention aims to provide an ICSI support device, ICSI support system, ICSI support program, or egg holding device having a simple device configuration. [Means for solving the problem]
[0006] An intracytoplasmic sperm injection support device according to one aspect of the present disclosure is an intracytoplasmic sperm injection support device that supports intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held by an egg holding device, and includes an acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, and a control unit that controls movement of a stage on which the egg holding device is positioned to inject sperm into the egg to perform intracytoplasmic sperm injection based on the information acquired by the acquisition unit.
[0007] This ICSI support device supports ICSI by moving the stage based on the acquired information including the relative positional relationship between the sperm injection tool and the egg. Therefore, unlike a device that supports ICSI by controlling the movement of the sperm injection tool such as that in Patent Document 1, for example, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.
[0008] An egg holding device according to one aspect of the present disclosure includes a recess for accommodating an egg and a suction port for holding the egg in the recess. Such an egg holding device is disposed in the above-mentioned ICSI support apparatus for use.
[0009] Such an egg holding device allows the ICSI support apparatus to fix and rotate the egg contained therein, so that, for example, a sperm injection tool can be inserted into the egg from an appropriate direction without controlling the movement of the sperm injection tool.
[0010] An ICSI support system according to one aspect of the present disclosure includes an ICSI support device according to one aspect of the present disclosure and a sperm injection tool.
[0011] An aspect of the present disclosure provides an ICSI support program that supports ICSI injecting sperm held in a sperm injection tool into an egg held by an egg holding device, and causes a computer to function as an acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, and a control unit that controls the movement of a stage on which the egg holding device is positioned to inject sperm into the egg and perform ICSI, based on the information acquired by the acquisition unit.
[0012] The ICSI support system and ICSI support program support ICSI by moving the stage based on the acquired information including the relative positional relationship between the sperm injection tool and the egg. Therefore, unlike a device that supports ICSI by controlling the movement of the sperm injection tool such as that in Patent Document 1, for example, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.
[0013] In addition, a program relating to one aspect of the present disclosure can be installed or loaded into a computer and / or device through various recording media such as optical disks such as CD-ROMs, magnetic disks, and semiconductor memories, or by downloading via a communication network, etc.
[0014] In this specification, the term "unit" does not simply mean a physical component, but also includes cases where the function of the component is realized by software. Also, the function of one component may be realized by two or more physical components, and the functions of two or more components may be realized by one physical component. Effect of the Invention
[0015] According to the present invention, it is possible to provide an ICSI support apparatus, an ICSI support system, an ICSI support program, or an egg holding device, etc., having a simple device configuration. [Brief description of the drawings]
[0016] [Figure 1] 1 is an overall conceptual diagram of an intracytoplasmic sperm injection support system according to an embodiment of the present invention. [Diagram 2] FIG. 2 is an example of a functional block diagram of the ICSI support device according to the present embodiment. [Diagram 3] 2 is an example of a physical configuration of the ICSI supporting device according to the present embodiment. [Figure 4] FIG. 1A is a schematic perspective view and FIG. 1B is an enlarged plan view of an egg holding device according to this embodiment. [Diagram 5] 1 is a flowchart showing an example of steps of an ICSI method according to the present embodiment. [Figure 6] FIG. 2 is a schematic perspective view of another example of an egg holding device according to the present embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0017] Hereinafter, a mode for carrying out the present invention (hereinafter referred to as "the present embodiment") will be described in detail with reference to the drawings, but the present invention is not limited thereto, and various modifications are possible without departing from the gist of the present invention. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference symbols. The drawings are schematic and do not necessarily correspond to actual dimensions, ratios, etc. The drawings may also include parts with different dimensional relationships and ratios.
[0018] [Intracytoplasmic sperm injection support system] An ICSI supporting system 1 according to this embodiment will be described with reference to Fig. 1. Here, Fig. 1 is an overall conceptual diagram of the ICSI supporting system 1 according to this embodiment.
[0019] The ICSI support system 1 according to this embodiment includes an ICSI support device 2 according to this embodiment and a sperm injection tool 3. Details of the ICSI support device 2 according to this embodiment will be described later.
[0020] As shown in Fig. 1, the ICSI support device 2 is connected to a sperm injection tool 3, a driving unit 12 for moving a stage 11, and an imaging unit 13 for imaging a sample placed on the stage 11. In Fig. 1, the ICSI support device 2 is connected to other components by wires, but the ICSI support device 2 may be connected to other components wirelessly or may be physically integrated with other components. Therefore, one or more of the stage 11, the driving unit 12, and the imaging unit 13 may be included in the ICSI support device 2 as a part of the ICSI support device 2.
[0021] A container 14 containing a sample is placed on the stage 11. The container 14 is, for example, a glass or resin dish. In FIG. 1, a sperm pool PS and an egg pool PO are provided in the container 14. The container 14 and / or the stage 11 may be provided with a temperature control means for maintaining the sperm pool PS and / or the egg pool PO at a temperature suitable for ICSI. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function of measuring the temperature in the container 14. The temperature suitable for ICSI is, for example, around 37°C, and may be 33 to 40°C, 35 to 38°C, 36 to 37°C, or 37°C.
[0022] The sperm pool PS contains sperm obtained from patients or subjects who wish to undergo ICSI. The sperm pool PS may contain, in addition to sperm, a sperm culture medium or a highly viscous liquid that inhibits sperm motility (e.g., a polyvinylpyrrolidone (PVP) solution). The egg pool PO contains eggs obtained from patients or subjects who wish to undergo ICSI.
[0023] The egg pool PO may contain eggs and a culture solution for eggs. The culture solution for sperm and eggs is not particularly limited, but may be physiological saline (salt containing 0.9 w / v% sodium chloride). The egg pool PO is provided on or adjacent to the egg holding device so that the egg holding device can hold the eggs.
[0024] The stage 11 includes a driving unit 12 for moving the stage. The driving unit 12 may move the stage 11 in the in-plane directions of the stage 11 (x and y directions in FIG. 1), but it is preferable that the driving unit 12 can also move the stage 11 in the direction perpendicular to the plane of the stage 11 (z direction in FIG. 1). In other words, the stage 11 is preferably a stage that includes the driving unit 12 and can move in three axial directions. The driving unit 12 may rotate the stage around each of the x, y, and z axes. In this case, the driving unit 12 can control the translational movement and rotational movement about the x-axis, y-axis, and z-axis, resulting in a total of six degrees of freedom of movement.
[0025] The driving unit 12 is not particularly limited as long as it can move the stage 11 under the control of the ICSI support device 2, and may be, for example, an electrically controllable motor. The stage 11 and the driving unit 12 may be, for example, an electrically controllable automatic stage provided in a microscope.
[0026] The imaging unit 13 acquires captured images or captured video of the sample on the stage 11 and the sperm injection tool 3. In Fig. 1, the imaging unit 13 captures an image of the sample on the stage 11 in a planar view from a vertically upward direction of the stage 11. The imaging unit 13 also captures images so that the viewing angle includes at least the portion of the sperm injection tool 3 for suctioning and injecting sperm, so that positional information of this portion can be acquired. Note that the imaging unit 13 does not necessarily have to be provided vertically upward of the stage 11, as long as it can acquire an image or video including the positional relationship between the sample on the stage 11 and the sperm injection tool 3.
[0027] The imaging unit 13 may be configured with an imaging device equipped with, for example, a CCD camera or a CMOS sensor. The imaging unit 13 may image the sample on the stage 11 and the sperm injection tool 3 through an optical microscope. The observation method using an optical microscope is not particularly limited, but may include bright-field observation, dark-field observation, phase contrast observation, polarized light observation, spindle observation, differential interference observation, and relief contrast observation. The magnification of the objective lens may also be appropriately adjusted, and may be, for example, 20x, 40x, 60x, etc. The data captured by the imaging unit 13 may be a still image or a moving image. In the following, a case where the imaging unit 13 acquires a moving image will be described, but it goes without saying that the imaging unit 13 can also support ICSI in the same way when acquiring multiple still images.
[0028] The sperm injection tool 3 is a tool for injecting a specific sperm into the cytoplasm of an egg. The sperm injection tool 3 may be, for example, an injection pipette commonly used in ICSI. It is preferable that the sperm injection tool 3 is capable of contacting the sperm pool PS and sucking the sperm. The sperm injection tool 3 may be provided with a means for immobilizing the sperm in the sperm pool PS. Examples of the means for immobilizing the sperm include a means for applying weak vibrations such as a piezoelectric element, and a laser light irradiation means. Alternatively, the sperm may be immobilized by applying pressure directly to the sperm using the tip (e.g., the inlet / outlet) of the sperm injection tool 3. The means for immobilizing the sperm may be provided in the ICSI support system 1 as a mechanism different from the sperm injection tool 3.
[0029] The sperm injection tool 3 may be equipped with a pressure control mechanism for aspirating and injecting sperm. The pressure control mechanism may adjust the output of a pump included in the sperm injection tool 3 or attached to the sperm injection tool 3 based on the control of the ICSI support device 2, and may aspirate sperm present near the inlet / outlet of the sperm injection tool 3, or discharge sperm aspirated and held in the sperm injection tool 3 from the inlet / outlet.
[0030] The sperm injection tool 3 is preferably provided with a fixed position relative to the imaging unit 13. According to this embodiment, even if the stage 11 is moved, the position of the sperm injection tool 3 does not move in the imaging field of the imaging unit 13, so that the relative positional relationship between the sample on the stage 11 and the sperm injection tool 3 can be easily adjusted.
[0031] The ICSI support device 2 supports ICSI based on captured moving images of the sample on the stage 11 and the sperm injection tool 3 acquired by the imaging unit 13. The ICSI support device 2 will be described in detail below.
[0032] (Intracytoplasmic sperm injection support device) 2 is a functional block diagram of the ICSI support device 2. The ICSI support device 2 includes an acquisition unit 21, a control unit 22, and an analysis unit 23. The ICSI support device 2 supports ICSI injecting sperm held in a sperm injection tool 3 into an egg held by an egg holding device.
[0033] The acquisition unit 21 acquires information including the relative positional relationship between the sperm injection tool 3 and the egg, which is acquired by the imaging unit 13 capturing images of the egg pool PO and the sperm injection tool 3 on the stage 11. The acquisition unit 21 only needs to acquire information including the relative positional relationship between the sperm injection tool 3 and the egg based on the captured image or captured video captured by the imaging unit 13, and does not need to acquire the captured image or captured video itself captured by the imaging unit 13.
[0034] In one embodiment, the acquisition unit 21 may acquire a captured image or a captured moving image captured by the imaging unit 13, the image including the sperm injection tool 3 and the egg in the imaging field of view. In one embodiment, the acquisition unit 21 may acquire information indicating the relative positional relationship between the sperm injection tool 3 and the egg, obtained by analyzing the captured image or the captured moving image captured by the imaging unit 13. The information indicating the relative positional relationship between the sperm injection tool 3 and the egg may be, for example, the distance between the entrance / exit of the sperm injection tool 3 and the egg, or the coordinates of the entrance / exit of the sperm injection tool 3 and the egg. The information indicating the relative positional relationship between the sperm injection tool 3 and the egg may be, for example, estimated from the relative positional relationship between the sperm injection tool 3 and a marker provided around the part of the egg holding device that contains the egg. The coordinates of the entrance / exit of the sperm injection tool 3 and the egg may be xy coordinates in the in-plane direction of the stage 11, and may further be xyz coordinates including the z direction perpendicular to the plane of the stage 11. The acquisition unit 21 may acquire the extension direction of the entrance / exit of the sperm injection tool 3, that is, the insertion direction when the sperm injection tool 3 is inserted into an egg.
[0035] The acquisition unit 21 may further acquire information including the position of the polar body of the egg. In ICSI, sperm injection into the cytoplasm of the egg is often performed while avoiding the polar body of the egg. This is because the spindle tends to be present near the polar body (first polar body) of the egg, and damage to the spindle due to insertion of the sperm injection tool 3 is suppressed. Therefore, the acquisition unit 21 may further acquire information including the position of the spindle of the egg.
[0036] Since the position of the polar body of the ovum can be acquired from an observed image of the ovum, the acquisition unit 21 may acquire information including the position of the polar body of the ovum by acquiring a captured image or a captured video of the ovum captured by the imaging unit 13. In one embodiment, the acquisition unit 21 may acquire information indicating the position of the polar body of the ovum, which is obtained by analyzing the captured image or the captured video captured by the imaging unit 13.
[0037] The acquisition unit 21 may further acquire information including the relative positional relationship between the sperm injection tool 3 and the sperm contained in the sperm pool PS arranged on the stage 11.
[0038] In one embodiment, the acquisition unit 21 may acquire a captured image or a captured video image captured by the imaging unit 13, the image including the sperm injection tool 3 and the sperm in the imaging field of view. In one embodiment, the acquisition unit 21 may acquire information indicating the relative positional relationship between the sperm injection tool 3 and the sperm, obtained by analyzing the captured image or the captured video image captured by the imaging unit 13. The information indicating the relative positional relationship between the sperm injection tool 3 and the sperm may be, for example, the distance between the entrance / exit of the sperm injection tool 3 and the sperm, or the coordinates of the entrance / exit of the sperm injection tool 3 and the sperm.
[0039] The acquisition unit 21 may be realized by a communication unit 2d described below.
[0040] The control unit 22 controls the movement of the stage 11 on which the egg holding device is placed to inject sperm into an egg for ICSI based on the information acquired by the acquisition unit 21. The control unit 22 may also control the movement of the stage 11 to hold the immobilized sperm in the sperm injection tool 3 based on the information acquired by the acquisition unit 21.
[0041] The control unit 22 may include an imaging control unit 221, a drive control unit 222, a sperm injection tool control unit 223, a suction device control unit 224, and a water supply device control unit 225 in order to hold sperm in the sperm injection tool 3 and inject the held sperm into an egg to perform intracytoplasmic sperm injection.
[0042] The imaging control unit 221 controls the imaging unit 13 and adjusts the imaging area of the imaging unit 13. The imaging control unit 221 may adjust the imaging area by adjusting the imaging field of view of the imaging unit 13. When the imaging unit 13 performs imaging via a microscope system, the imaging control unit 221 may adjust the settings of the microscope system attached to the imaging unit 13 in order to image sperm and / or eggs with high resolution. Such adjustment may be performed by the person who performs ICSI.
[0043] The drive control unit 222 controls the drive unit 12 to move the stage 11. The drive control unit 222 may move the stage 11 via an electrical mechanism included in the drive unit 12.
[0044] The sperm injection tool control unit 223 controls the sperm injection tool 3 to aspirate and discharge sperm. The sperm injection tool control unit 223 may control the pressure control mechanism of the sperm injection tool 3 to adjust the output of a pump included in or attached to the sperm injection tool 3. If the sperm injection tool 3 includes a means for immobilizing sperm, the sperm injection tool control unit 223 may control the sperm injection tool 3 to operate the means for immobilizing sperm and immobilize the sperm.
[0045] The suction device control section 224 and the water supply device control section 225 respectively control the suction device and the water supply device that may be connected to the egg holding device. The egg holding device will be described in detail later, but the egg is held in the egg holding device by the suction device. In addition, the egg held or contained in the egg holding device may be rotated by the water supply device.
[0046] The suction device control unit 224 and the water supply device control unit 225 respectively control the suction device and the water supply device to suck and rotate the ovum. The suction device control unit 224 and the water supply device control unit 225 suck the ovum and supply water to the ovum based on the information about the ovum acquired by the acquisition unit 21.
[0047] The water supplying device control unit 225 may control the water supplying device to rotate the egg so that the sperm is injected by the sperm injection tool from a direction where the polar body is not located, based on the information including the position of the polar body of the egg acquired by the acquisition unit 21. For this purpose, the water supplying device control unit 225 may rotate the egg by controlling the water supplying device to supply water to the egg so that the polar body of the egg is located at approximately 12 o'clock or 6 o'clock, with the direction in which the sperm injection tool 3 is located being the 3 o'clock direction. The water supplying device control unit 225 may control the temperature of the fluid supplied from the water supplying device so that the temperature in the container 14 is kept at a temperature suitable for ICSI. The temperature of the fluid is controlled, for example, by a temperature control means that may be provided in the water supplying device. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function of measuring the temperature of the fluid supplied from the water supplying device.
[0048] The suction device is not particularly limited as long as it is connected to the egg holding device and can suck up an egg located near the suction port of the egg holding device. The suction device may be, for example, a pump whose pressure can be controlled by the suction device control unit 224.
[0049] The water supplying device is not particularly limited as long as it is connected to the egg holding device and can supply fluid from the water supply port of the egg holding device. The water supplying device may be, for example, a pump capable of controlling the flow rate of the fluid to be supplied by the water supplying device control unit 225. The water supplying device may include a temperature control means for maintaining the temperature of the fluid to be supplied within a certain range. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function of measuring the temperature of the fluid supplied from the water supplying device. The temperature of the fluid is preferably maintained at a temperature suitable for ICSI, and the temperature is, for example, around 37°C, and may be 33 to 40°C, 35 to 38°C, 36 to 37°C, or 37°C. The temperature control means may control the temperature of the fluid to be supplied so that the temperature in the container 14 is maintained at a temperature suitable for ICSI.
[0050] The control unit 22 may be realized by a program stored in a RAM 2b or a ROM 2c, which will be described later, and executed by a CPU 2a. Instructions from the control unit 22 are transmitted to each unit and device via a communication unit 2d.
[0051] The analysis unit 23 analyzes the information acquired by the acquisition unit 21 and assists the control by the control unit 22. In this embodiment, the analysis unit 23 is provided in the ICSI support device 2, but may be provided in a unit or device other than the ICSI support device 2, such as the imaging unit 13 or a computer connected to the imaging unit 13. The analysis unit 23 may include, for example, a sperm recognition unit 231, an egg recognition unit 232, a sperm evaluation unit 233, and an egg evaluation unit 234.
[0052] The sperm recognition unit 231 recognizes sperm by analyzing the information acquired by the acquisition unit 21. When the acquisition unit 21 acquires a captured image or a captured video, methods for recognizing sperm from the image or video include a method of preparing a plurality of representative images showing typical shapes of sperm and performing pattern matching using the representative images for each frame in the image or video, and a method of using a learning model trained using sperm observation images as teacher data.
[0053] The ovum recognition unit 232 analyzes the information acquired by the acquisition unit 21 and recognizes the ovum. When the acquisition unit 21 acquires a captured image or a captured video, methods for recognizing the ovum from the image or video include a method of preparing a plurality of representative images showing a typical shape of an ovum and performing pattern matching using the representative images for each frame in the image or video, and a method of using a learning model trained using observation images of an ovum as teacher data. Alternatively, the ovum may be recognized based on a marker attached to the ovum holding device.
[0054] The sperm evaluation unit 233 analyzes the information acquired by the acquisition unit 21 and evaluates the quality of each sperm. Sperm quality means the properties of each sperm related to the fertilization success rate, blastocyst achievement rate, implantation rate, and / or birth success rate, etc., when used in ICSI. High sperm quality means that the fertilization success rate, blastocyst achievement rate, implantation rate, and / or birth success rate, etc., when used in ICSI are relatively high. The sperm evaluation unit 233 may quantify the sperm quality by calculating at least one index related to the sperm quality.
[0055] At least one index relating to sperm quality includes, but is not limited to, the indexes described in the WHO laboratory manual for the examination and processing of human semen; Sixth Edition published by the World Health Organization (WHO). Such indexes include, for example, at least one of sperm motility, sperm morphology, and the degree of occurrence of sperm DNA fragmentation, or an index calculated from two or more of these.
[0056] The sperm evaluation unit 233 may calculate at least one index related to sperm quality by various methods. For example, sperm motility can be indexed by the speed of movement at a predetermined time interval, the linearity of the movement trajectory, etc. The sperm evaluation unit 233 can track sperm at a predetermined time interval and calculate the speed of movement and the linearity of the movement trajectory based on the position information of the sperm in each frame. The sperm motility may be calculated using a learning model that is trained using the sperm quality and movement as teacher data.
[0057] The sperm morphology can be indexed based on the morphology of the sperm captured in each frame of the captured image or captured video. The sperm evaluation unit 233 may index the morphology of one sperm based on multiple frames and calculate an index by averaging these values. The sperm morphology can be indexed based on, for example, the shape of the sperm head, the shape of the sperm tail, and the balance of their defects and sizes. The sperm motility may be calculated using a learning model that is trained using the sperm quality and morphology as teacher data.
[0058] The degree of occurrence of DNA fragmentation of sperm can be indexed by comprehensively considering the sperm's movement such as the speed of movement in a predetermined time interval and the linearity of the movement trajectory, and the morphology of the sperm captured in each frame of the captured image or captured video. The degree of occurrence of DNA fragmentation of sperm may be calculated using a learning model that is trained using the degree of occurrence of DNA fragmentation of sperm and the movement and / or morphology of sperm as teacher data. The degree of occurrence of DNA fragmentation of sperm can be measured using a stained image in which sperm with DNA fragmentation are selectively stained.
[0059] The sperm evaluation unit 233 may calculate an index that comprehensively evaluates the quality of sperm by considering two or more of the above-mentioned indices. The sperm evaluation unit 233 may calculate an index by arbitrarily weighting the indices related to the sperm motility, sperm morphology, and the degree of occurrence of sperm DNA fragmentation, and then averaging them. In this case, if any of the indices falls below a threshold, a penalty may be imposed by subtracting a certain number from the calculated index.
[0060] The egg evaluation unit 234 analyzes the information acquired by the acquisition unit 21 and evaluates the quality of each egg. Egg quality refers to the properties of each egg related to the fertilization success rate, blastocyst achievement rate, implantation rate, and / or birth success rate, etc., when used in ICSI. High egg quality refers to a relatively high fertilization success rate, blastocyst achievement rate, implantation rate, and / or birth success rate, etc., when used in ICSI. The egg evaluation unit 234 may quantify the egg quality by calculating at least one index related to the egg quality.
[0061] The ovum evaluation unit 234 may evaluate the quality of the ovum based on, for example, the positions, shapes, and sizes of the polar bodies, spindles, and smooth endoplasmic reticulum, the degree of turbidity of the cytoplasm, etc. The ovum evaluation unit 234 may evaluate the quality of the ovum using a learning model trained using the quality and morphology of the ovum as teacher data.
[0062] The analysis unit 23 may be realized by a program stored in the RAM 2b or ROM 2c described below and executed by the CPU 2a. The analysis result by the analysis unit 23 may be used by the control unit 22, may be transmitted to each unit and device via the communication unit 2d, and may be displayed on the display unit 2f.
[0063] Next, the physical configuration of the ICSI support device 2 will be described with reference to FIG. 3. FIG. 3 is a diagram showing an example of the physical configuration of the ICSI support device 2. The ICSI support device 2 has a CPU (Central Processing Unit) 2a equivalent to a processor, a RAM (Random Access Memory) 2b and a ROM (Read only Memory) 2c equivalent to a storage unit, a communication unit 2d, an input unit 2e, and a display unit 2f. These components are connected to each other via a bus so that data can be transmitted and received. In this example, the function of the ICSI support device 2 is described as being configured by one computer, but the function of the ICSI support device 2 may be realized by combining multiple computers. In addition, the configuration shown in FIG. 3 is an example, and the ICSI support device 2 may have components other than these, or may not have some of these components.
[0064] The CPU 2a controls the execution of programs stored in the RAM 2b or the ROM 2c and calculates and processes data. The CPU 2a is a calculation unit that executes programs that cause the computer to function as the acquisition unit 21, the control unit 22, and the analysis unit 23. The CPU 2a receives various data from the input unit 2e and the communication unit 2d, and displays the calculation results of the data on the display unit 2f or stores them in the RAM 2b or the ROM 2c.
[0065] The RAM 2b is a rewritable part of the storage unit, and may be composed of, for example, a semiconductor memory element. The RAM 2b may store a program executed by the CPU 2a. Note that these are merely examples, and the RAM 2b may store data other than these.
[0066] The ROM 2c is a storage unit from which data can be read, and may be configured, for example, with a semiconductor memory element. The ROM 2c may store, for example, data that is not rewritten.
[0067] The communication unit 2d is an interface that connects the ICSI support device 2 to other units and devices, such as the sperm injection tool 3, the driving unit 12, the imaging unit 13, the suction device, and the water supply device. The communication unit 2d may be connected to a network by wire or wirelessly.
[0068] The input unit 2e receives data input from a user, and may include, for example, a keyboard and a touch panel.
[0069] The display unit 2f visually displays the results of the calculations performed by the CPU 2a and may be configured with, for example, an LCD (Liquid Crystal Display). The display unit 2f may display information acquired by the acquisition unit 21, for example, a captured image or a captured video image acquired by the imaging unit 13.
[0070] The ICSI support program according to this embodiment may be provided by being stored in a computer-readable storage medium such as RAM 2b or ROM 2c, or may be provided via a communication network connected by the communication unit 2d. In the ICSI support device 2, the CPU 2a executes the program according to this embodiment, thereby realizing the functions described with reference to FIG. 2. These physical configurations are merely examples, and do not necessarily have to be independent configurations. For example, the ICSI support device 2 may include an LSI (Large-Scale Integration) in which the CPU 2a and the RAM 2b and / or ROM 2c are integrated together.
[0071] (Egg Retention Device) Next, an egg holding device for use in the ICSI support system 1 will be described with reference to Fig. 4. The egg holding device according to this embodiment is used to efficiently carry out control by the ICSI support apparatus 2 according to this embodiment. The egg holding device according to this embodiment may be made of, for example, resin.
[0072] FIG. 4 is a schematic perspective view (FIG. 4(A)) and an enlarged plan view (FIG. 4(B)) of an egg holding device D1 according to this embodiment. As shown in FIGS. 4(A) and (B), the egg holding device D1 includes recesses 151a, 151b, and 151c for accommodating eggs O1, O2, and O3, respectively, and suction ports 154a, 154b, and 154c for holding the eggs O1, O2, and O3 in the recesses 151a, 151b, and 151c, respectively. FIG. 4(B) is an enlarged plan view of the egg O1 held in the recess 151a. The egg holding device D1 further includes water supply ports 153a, 153b, and 153c for rotating the eggs O1, O2, and O3 in the recesses 151a, 151b, and 151c.
[0073] In Fig. 4(A), three eggs O1, O2, O3 are respectively held in three recesses 151a, 151b, 151c, but the egg holding device D1 only needs to have a structure for holding and holding one or more eggs. In the following, a case where three eggs O1, O2, O3 are respectively held in three recesses 151a, 151b, 151c as in Fig. 4(A) will be described, but the number of eggs held and held in the egg holding device D1 is not particularly limited.
[0074] In the following, when there is no need to distinguish between the three eggs O1, O2, and O3, they will be collectively referred to as the eggs O. The same applies to other configurations, and in Fig. 4(A), the symbols a, b, and c are assigned to the components of the egg holding device D1 in correspondence with the three eggs O1, O2, and O3, respectively, but when there is no need to distinguish between the components corresponding to the three eggs O1, O2, and O3, the symbols a, b, and c will be omitted. For example, the three recesses 151a, 151b, and 151c corresponding to the three eggs O1, O2, and O3 may be collectively referred to as recess 151.
[0075] In addition, the egg holding device D1 according to this embodiment may be provided as the egg pool PO in FIG. 1, or may be provided adjacent to the egg pool PO. That is, each recess of the egg holding device D1 may be used as an egg pool PO, or an egg pool PO containing eggs may be provided separately from the recess of the egg holding device D1. Therefore, the egg holding device D1 according to this embodiment may move following the stage 11. When the sperm injection tool 3 is fixed to the imaging unit 13, the sperm injection tool 3 is substantially fixed in the imaging field of the imaging unit 13 by moving the stage 11, and only the egg holding device D1 can be moved. Thereby, by moving the stage 11, ICSI can be performed with high accuracy.
[0076] Returning to Fig. 4, an egg O is held in the recess 151 of the egg holding device D1. The recess 151 is not particularly limited as long as it can hold the egg O in a predetermined area. The recess 151 may have a width and a length of, for example, 100 to 1000 µm, preferably 150 to 500 µm, in a plan view. The recess 151 may have a depth of, for example, 100 to 1000 µm, preferably 150 to 500 µm.
[0077] The recess 151 may be a recess surrounded on the bottom and all four sides, and having an opening on the top. One of the four surroundings forming the recess 151 may be partially removed. By partially removing one of the surroundings on the four sides forming the recess 151 in this manner, it is possible to make it easier for the egg O to come into contact with the sperm injection tool 3.
[0078] In one embodiment, the recess 151 may be formed by being surrounded by a bottom surface and a wall portion extending upward from the bottom surface, and at least a part of the wall portion may be configured to be lower in height than the other wall portions. For example, the part of the wall portion may have a height of, for example, 100 to 1000 μm, preferably 150 to 500 μm, and the relatively low wall portion may have a height of, for example, 20 to 200 μm, preferably 50 to 150 μm. The relatively low wall portion may be located on the opposite side to the wall portion in which the suction port described below is provided.
[0079] A suction port 154 is provided on the wall portion forming the recess 151 of the egg holding device D1. The egg O can be held in the egg holding device D1 by sucking the egg O through the suction port 154. With the egg O sucked through the suction port 154, sperm can be injected into the egg O by bringing the entrance / exit of the sperm injection tool 3 into contact with the egg O. In other words, the suction port 154 plays the role of a holding pipette in a conventional ICSI operation.
[0080] Therefore, the suction port 154 may have a shape similar to that of the suction port of the holding pipette. For example, as shown in FIG. 4(B), the suction port 154 may have a generally tapered shape in which the diameter decreases as it approaches the recess 151. The shape of the opening of the suction port 154 is not particularly limited, and may be, for example, a generally circular shape, a generally elliptical shape, or a rounded rectangular shape. By using such a shape, it is possible to reduce damage to the ovum O when the ovum O is sucked. Furthermore, the circle-equivalent diameter d of the opening of the suction port 154 is, for example, 10 to 150 μm, and preferably 15 to 100 μm. The circle-equivalent diameter means the diameter of a circle having the same area as the shape of the opening.
[0081] The suction port 154 is connected to a suction device for sucking the ovum O through the suction port 158. The suction port 154 and the suction port 158 are connected by a flow path inside the ovum holding device D1. A plurality of suction ports 158 may be provided corresponding to the plurality of suction ports 154a, 154b, and 154c, and one or a plurality of suction ports 158 connected to each of the plurality of suction ports 154a, 154b, and 154c may be provided. In FIG. 4(A), one suction port 158 connected to each of the plurality of suction ports 154a, 154b, and 154c is provided. Therefore, in FIG. 4(A), when the suction device connected to the suction port 158 is operated to suck the ovum O, all of the ovum O1, O2, and O3 contained in the recesses 151a, 151b, and 151c are sucked in at the same time.
[0082] 4(B), when the egg O is sucked through the suction port 158, a fluid flow F1 is generated from the opening of the suction port 154 toward the suction port 158, and the egg O is sucked into the opening of the suction port 154 and comes into contact with the opening. By maintaining suction in this state of contact with the opening, the egg O can be held at the opening of the suction port 154.
[0083] The wall portion forming the recess 151 of the ovum holding device D1 is further provided with a water supply port 153. By supplying a fluid from the water supply port 153, the ovum held in the recess 151 can be moved or rotated in the recess 151.
[0084] As described above, in ICSI, it is preferable to avoid the polar body when inserting the sperm injection tool into the ovum in order to avoid damaging the spindle. As shown in Fig. 4(B), by supplying water to the ovum O from the water supply port 153 while the acquisition unit 21 acquires the position information of the polar body PB of the ovum O, the polar body can be moved to an appropriate position and held at the opening of the suction port 154 in this state.
[0085] In the embodiment shown in Figure 4(B), since the sperm injection tool 3 is inserted in the opposite direction to the suction port 154, i.e., from below in Figure 4(B), it is preferable that the pole body PB is positioned in the direction of the water supply port 153 or the water drainage port 155, i.e., to the left or right in Figure 4(B).
[0086] The shape of the water supply port 153 is not particularly limited as long as it can supply a fluid to the recess 151. The fluid supplied from the water supply port 153 is typically a liquid such as water or culture medium, but a gas such as air may be supplied to the recess 151.
[0087] The water supply port 153 is connected to a water supply device for supplying water to the ovum O through the water supply port 157. The water supply port 153 and the water supply port 157 are connected by a flow path inside the ovum holding device D1. A plurality of water supply ports 157 may be provided corresponding to the plurality of water supply ports 153a, 153b, and 153c, and one or a plurality of water supply ports 157 connected to each of the plurality of water supply ports 153a, 153b, and 153c may be provided. In FIG. 4(A), one water supply port 157 connected to each of the plurality of water supply ports 153a, 153b, and 153c is provided. Therefore, in FIG. 4(A), when the water supply device connected to the water supply port 157 is operated and the ovum O is sucked, water is supplied to the recesses 151a, 151b, and 151c.
[0088] As shown in FIG. 4(B), when water is supplied to the recess 151 through the water supply port 157, a fluid flow F2 is generated from the water supply port 157 toward the opening of the water supply port 153.
[0089] A drain port 155 may be provided in a wall portion forming the recess 151 of the ovum holding device D1. The drain port 155 is provided as a discharge path for the fluid supplied from the water supply port 153. When the upper portion of the recess 151 is formed as an opening as in Fig. 4(A), the drain port 155 can be omitted.
[0090] The drain outlet 155 may be connected to a drainage device through a drain port 159. The drain outlet 155 and the drain port 159 are connected by a flow path inside the egg holding device D1. A plurality of drain ports 159 may be provided corresponding to the plurality of drain outlets 155a, 155b, 155c, or one or a plurality of drain ports 159 connected to each of the plurality of drain outlets 155a, 155b, 155c may be provided. As shown in FIG. 4(B), when draining through the drain port 159, a fluid flow F3 is generated from the opening of the drain outlet 155 toward the drain port 159.
[0091] A marker 152 that assists in identifying the recess 151 and the egg O may be provided around the recess 151 of the egg holding device D1. There may be one or more markers 152. In order to facilitate contact between the egg O and the sperm injection tool 3, it is preferable that the marker 152 is provided on the wall opposite to the wall provided with the suction port 154. In this case, the control unit 22 can recognize the marker 152 and perform control so as to insert the sperm injection tool 3 into the egg O from the direction of the marker 152. The marker 152 may be provided around the recess 151, and in this case, the analysis unit 23 can recognize the marker 152 and recognize the rough position where the egg O is located.
[0092] [Intracytoplasmic sperm injection method] Hereinafter, a method for carrying out ICSI using the ICSI support system according to this embodiment will be described. Since the ICSI method according to this embodiment uses the ICSI support system according to this embodiment, at least a part of the ICSI process can be automated. In particular, since the process of injecting sperm into an egg can be automated, ICSI can be carried out efficiently and with a high success rate without relying on the individual skills of the embryologist.
[0093] Fig. 5 is a flow chart showing an example of the steps of the ICSI method according to this embodiment. Although not shown in Fig. 5, the ICSI practitioner (typically an embryologist) places a container 14 containing a sample on the stage 11 of the ICSI support system 1 according to this embodiment, and sets up the sample and the entrance and exit of the sperm injection tool 3 in the imaging field of the imaging unit 13.
[0094] The following describes a method in which the ICSI support system 1 automatically performs ICSI without the intervention of the ICSI practitioner, but some or all of the following steps can also be performed manually by the ICSI practitioner.
[0095] 5, in the ICSI method according to the present embodiment, first, the imaging field of view of the imaging unit 13 is moved to the sperm pool PS (hereinafter, also referred to as "step S1"). In step S1, the imaging control unit 221 controls the imaging unit 13 and / or the drive control unit 222 controls the drive unit 12 to move the stage 11, so that the imaging unit 13 images the sperm pool PS on the stage 11.
[0096] In step S1, the position of the sperm pool PS may be stored in the ICSI support device 2, and the stored position of the sperm pool PS may be called and the imaging area of the imaging unit 13 may be moved to the sperm pool PS. Alternatively, a marker indicating the position of the sperm pool PS may be provided around the sperm pool PS, and the marker may be recognized by the analysis unit 23, and the imaging area of the imaging unit 13 may be moved to the sperm pool PS.
[0097] Next, the sperm to be used in ICSI are selected and immobilized (hereinafter also referred to as "Step S2"). In Step S2, first, good sperm suitable for use in ICSI are selected. Specifically, the sperm recognition unit 231 recognizes each sperm in the sperm pool PS, and the sperm evaluation unit 233 evaluates the quality of each sperm. The sperm evaluation unit 233 selects good sperm from the sperm whose quality has been evaluated. The sperm evaluation unit 233 may select sperm whose quality has been evaluated as being relatively high from the sperm whose quality has been evaluated, or may select sperm whose quality exceeds a pre-established threshold value.
[0098] In step S2, the selected sperm are then immobilized. The sperm may be immobilized by the sperm injection tool control unit 223 controlling the immobilization means provided in the sperm injection tool 3, or the control unit 22 may control an immobilization device different from the sperm injection tool 3. When the sperm injection tool control unit 223 controls the immobilization means provided in the sperm injection tool 3 to immobilize the sperm, the drive control unit 222 may control the drive unit 12 to move the stage 11 in order to set the selected sperm and the immobilization means provided in the sperm injection tool 3 in a positional relationship appropriate for immobilization. When immobilizing the sperm by directly pressing the entrance / exit of the sperm injection tool 3 against the sperm, the drive control unit 222 may control the drive unit 12 to move the stage 11 in order to appropriately bring the entrance / exit of the sperm injection tool 3 into contact with the sperm.
[0099] Next, the sperm selected and immobilized in step S2 are aspirated (hereinafter also referred to as "step S3"). In step S3, the drive control unit 222 controls the drive unit 12 to move the stage 11 so that the sperm to be aspirated approaches the entrance / exit of the sperm injection tool 3. Next, the sperm injection tool control unit 223 controls the sperm injection tool 3 to aspirate the sperm from the entrance / exit and hold the sperm in the sperm injection tool 3.
[0100] Next, the imaging field of view of the imaging unit 13 is moved to the egg pool (hereinafter also referred to as "step S4"). In step S4, the imaging control unit 221 controls the imaging unit 13 and / or the drive control unit 222 controls the drive unit 12 to move the stage 11, so that the imaging unit 13 images the egg pool PO on the stage 11.
[0101] In step S4, the position of the egg pool PO may be stored in the ICSI support device 2, and the stored position of the egg pool PO may be called up and the imaging area of the imaging unit 13 may be moved to the egg pool PO. Alternatively, a marker indicating the position of the egg pool PO may be provided around the egg pool PO, and the marker may be recognized by the analysis unit 23, and the imaging area of the imaging unit 13 may be moved to the egg pool PO. The analysis unit 23 may recognize the egg holding device, or may recognize a marker attached to the egg holding device.
[0102] Next, eggs to be used for ICSI are recognized and selected (hereinafter also referred to as "Step S5"). In Step S5, good eggs suitable for use in ICSI are selected. Specifically, the egg recognition unit 232 recognizes each egg in the egg pool PO, and the egg evaluation unit 234 evaluates the quality of each egg. The egg evaluation unit 234 selects good eggs from among the eggs whose quality has been evaluated. The egg evaluation unit 234 may select eggs that have been evaluated to be of relatively high quality from among the eggs whose quality has been evaluated, or may select eggs that exceed a pre-established threshold value.
[0103] In addition, in ICSI, the number of cells in the prepared egg is often less than the number of cells in the sperm. Therefore, it is preferable to inject high-quality sperm into high-quality eggs to increase the fertilization success rate. In FIG. 5, steps S4 and S5 may be performed before step S1 to adjust the quality of the sperm selected in step S2 according to the quality of the selected egg.
[0104] For example, if good quality eggs are selected in step S5, sperm with relatively high quality may be selected in step S2, or the threshold for sperm to be selected may be set higher than the normal setting to select good quality sperm.
[0105] Alternatively, in ICSI, sperm are often injected into all of the prepared eggs, so evaluation of egg quality may be omitted.
[0106] Alternatively, if an egg of poor quality is selected in step S5, for example an egg with a quality index below a threshold, the automation of sperm injection may be canceled and the practitioner of the ICSI may be notified to prompt them to perform manual injection.
[0107] Next, the orientation of the ovum selected in step S5 is adjusted (hereinafter also referred to as "step S6"). In step S6, first, the analysis unit 23 determines a preferred orientation of the ovum based on the positional relationship between the sperm injection tool 3 and the ovum acquired by the acquisition unit 21. For example, the analysis unit 23 recognizes the position of the polar body of the ovum acquired by the acquisition unit 21, and determines the orientation of the ovum such that the polar body of the ovum is positioned perpendicular to the direction in which the sperm injection tool 3 is inserted.
[0108] Next, the egg facing the direction determined in step S5 is held in the egg holding device (hereinafter also referred to as "step S7"). In step S7, the water supply device control unit 225 controls the water supply device while the suction device control unit 224 controls the suction device, so that the egg facing in the appropriate direction is held in the egg holding device.
[0109] Next, the sperm aspirated in step S3 are injected into the egg held in step S7 (hereinafter also referred to as "step S8"). In step S8, first, the egg is brought close to the entrance / exit of the sperm injection tool 3 in order to inject the sperm into the egg and perform ICSI. At this time, the drive control unit 222 controls the drive unit 12 to move the stage 11. Next, the sperm injection tool control unit 223 controls the sperm injection tool 3 to inject the sperm into the egg from the entrance / exit. After the injection is completed, the sperm injection tool 3 is removed from the egg, completing the ICSI.
[0110] Next, it is determined whether or not sperm injection into all of the eggs has been completed (hereinafter also referred to as "Step S9"). Step S9 only needs to be performed when the number of egg cells prepared is small, and can be omitted when a large number of eggs are prepared. By storing the eggs into which sperm have been injected, the ICSI support device 2 returns to step S1 when it determines that there are eggs into which sperm have not been injected (Step S9: No). At this time, the number of eggs into which sperm have not been injected may be displayed on the display unit 2f. When it is determined that sperm injection into all of the eggs has been completed (Step S9: Yes), the process ends.
[0111] In each of the above steps, the acquisition unit 21 may optionally acquire information including the relative positional relationship between the entrance / exit of the sperm injection tool 3 and the egg, and / or information including the relative positional relationship between the entrance / exit of the sperm injection tool 3 and the sperm. For example, in step S3, information including the relative positional relationship between the sperm injection tool 3 and the sperm is acquired, and the sperm is sucked by the sperm injection tool 3 based on this. In addition, in step S8, information including the relative positional relationship between the entrance / exit of the sperm injection tool 3 and the egg is acquired, and the sperm injection tool 3 is inserted into the egg based on this. In addition, in step S6, the acquisition unit 21 further acquires information including the position of the polar body or spindle of the egg. In addition, when the acquisition unit 21 acquires a captured image or a captured moving image from the imaging unit 13, in each step, if at least one of the sperm injection tool 3, the egg, and the sperm is included in the imaging field of view, the coordinates of at least one of the sperm injection tool 3, the egg, and the sperm may be acquired based on the captured image or the captured moving image.
[0112] [Variations] Although an example of this embodiment has been described above, the present invention is not limited to the above. For example, the examples and / or preferred aspects (preferred, more preferred, even more preferred, even more preferred, etc.) in the description of each component and step can be arbitrarily combined to form this embodiment, unless otherwise specified. For example, for each embodiment, an embodiment described as a preferred aspect may be combined with an embodiment described as a preferred aspect, or an embodiment described as a preferred aspect may be combined with a configuration described as a more preferred embodiment (or even more preferred embodiment, etc.). Furthermore, each component and step can be omitted as appropriate as long as it does not impair the effects of this embodiment.
[0113] For example, in the ICSI support system 1 shown in Fig. 1, the egg pool PO and sperm pool PS are arranged in the same container 14, but the egg pool PO and sperm pool PS may be provided in different containers. Also, when the ICSI support system 1 is used only for injecting sperm into eggs, a sperm pool does not need to be provided in the stage 11. In this case, a user of the ICSI support system 1 (typically, an embryologist) can perform ICSI using a sperm injection tool 3 that holds sperm. In this case, steps S1 to S3 in the flowchart shown in Fig. 5 can be omitted.
[0114] In the above description, the sperm injection tool 3 is fixed to the imaging unit 13, but a mechanism for moving the sperm injection tool 3 may be added. Therefore, the ICSI support device 2 according to this embodiment may control the movement of the sperm injection tool 3 in the sperm injection tool control unit 223. In this case, the movement of the stage 11 may be used as a main moving means (for example, a translational alignment means between the egg and the entrance / exit of the sperm injection tool 3), and the movement of the sperm injection tool 3 may be used as a supplementary moving means (for example, a rotational alignment means for adjusting the direction in which the entrance / exit of the sperm injection tool 3 is inserted into the egg).
[0115] In addition, in the ICSI method according to the present embodiment, before, after, or during each step, the ICSI practitioner may accept processing. For example, in step S2, the ICSI practitioner may select sperm to be aspirated, or may immobilize the sperm.
[0116] In step S3, the practitioner of ICSI may specify a method of aspirating sperm. For example, the practitioner of ICSI may select whether to aspirate sperm from the head side or the tail side.
[0117] In addition, in step S5, the person performing the ICSI may select the egg into which the sperm is injected.
[0118] In addition, the person who performs the ICSI may adjust the injection of sperm into the egg in steps S6 to S8. For example, the person who performs the ICSI may specify which part of the egg the sperm injection tool 3 should be inserted into, from which direction, and to what part.
[0119] Furthermore, before or during each step, in order to capture high-resolution images of sperm and / or eggs, the imaging control unit 221 may adjust the settings of the imaging unit 13 and / or the microscope system attached to the imaging unit 13. Such adjustments may be performed by the person who performs the ICSI. For example, the observation method and magnification of the optical microscope may be adjusted according to the imaging target and purpose of each step, so that each step is performed appropriately.
[0120] In addition, before each step, a confirmation step may be included in which the practitioner of ICSI confirms whether or not to proceed to the next step. In addition, when an abnormality is detected in each step, it is also possible to switch to processing by the practitioner of ICSI. Examples of such abnormalities include a case where the state of the ovum is different from normal, such as a case where the perivitelline space is filled and the cytoplasm cannot be confirmed, or a case where the shape of the zona pellucida is abnormal. In addition, when an abnormality is detected, a notification may be displayed to the practitioner of ICSI to check the setup of the ICSI support system 1.
[0121] Moreover, the egg holding device may be an embodiment shown in Fig. 6 in addition to the embodiment shown in Fig. 4. The egg holding device D2 shown in Fig. 6 differs from the egg holding device D1 shown in Fig. 4 in that the first recess 251a, the second recess 251b, and the third recess 251c each have a different role.
[0122] That is, in the egg holding device D1 shown in Fig. 4, the three recesses 151a, 151b, and 151c are equivalent and have the same configuration. On the other hand, in the egg holding device D2 shown in Fig. 6, the first recess 251a serves as a pool of eggs that have not yet been injected with sperm (i.e., the egg pool PO), the second recess 251b serves as a recess for holding eggs when sperm are injected (i.e., the recess 151 of the egg holding device D1 shown in Fig. 4), and the third recess 251c serves as a pool of eggs after sperm injection has been completed.
[0123] With the ovum holding device D2, it is easy to distinguish between ovum that have not been injected with sperm and ovum that have already been injected with sperm, and the decision in step S9 in the flowchart shown in FIG. 5 is easy.
[0124] The egg holding device D2 shown in Figure 6 includes a first recess 251a, a second recess 251b, and a third recess 251c for accommodating eggs O1, O2, and O3, respectively, a suction port 254 for holding the egg O2 in the second recess 251b, and a second water supply port 253b for rotating the egg O2 in the second recess 251b.
[0125] In FIG. 6, ovum O1 is an ovum that has not yet been injected with sperm, ovum O2 is an ovum that is about to be injected with sperm, and ovum O3 is an ovum that has already been injected with sperm.
[0126] The egg holding device D2 further includes a first water supply port 253a for transferring the egg O1 held in the first recess 251a to the second recess 251b. In the egg holding device D2, the egg O1 held in the first recess 251a can be transferred to the second recess 251b by supplying a fluid from the first water supply port 253a. This allows sperm injection into the egg O1 to be performed subsequently after sperm injection into the egg O2 is completed.
[0127] In the egg holding device D2, the second water supply port 253b has a role not only for rotating the egg O2 in the second recess 251b but also for transferring the egg O2 to the third recess 251c after the sperm injection into the egg O2 is completed. By adjusting the amount and speed of the fluid supplied from the second water supply port 253b, it is possible to distinguish between a case where the egg O2 is rotated in the second recess 251b and a case where the egg O2 is transferred to the third recess 251c.
[0128] Similarly to the egg holding device D1, the first water supply port 253a and the second water supply port 253b are connected to a water supply device via a water supply port 257. Similarly to the egg holding device D1, the first water supply port 253a and the second water supply port 253b may be connected to the same water supply port 257 or different water supply ports 257.
[0129] Furthermore, the egg holding device D2 has a marker 252, a suction port 254, a drain port 255, a suction port 258, and a drain port 259, but the configurations thereof may be similar to the marker 152, the suction port 154, the drain port 155, the suction port 158, and the drain port 159 of the egg holding device D1.
[0130] [Note] The present disclosure includes the following embodiments. [1] An ICSI support device that supports ICSI by injecting sperm held in a sperm injection tool into an egg held by an egg holding device, comprising: an acquisition unit that acquires information including a relative positional relationship between the sperm injection tool and the egg; A control unit that controls the movement of a stage on which the egg holding device is placed to inject the sperm into the egg and perform ICSI based on the information acquired by the acquisition unit; An in vitro fertilization support device comprising: [2] The acquisition unit further acquires information including a relative positional relationship between the sperm injection tool and the sperm contained in the sperm pool arranged on the stage, The control unit further controls the movement of the stage to hold the immobilized sperm in the sperm injection tool based on the information acquired by the acquisition unit. [1] The ICSI support device described in [1]. [3] an imaging unit that images the egg, the sperm, and the sperm injection tool; a drive unit for moving the stage based on an instruction from the control unit; Further comprising: The ICSI support device according to [1] or [2]. [4] the egg holding device is connected to a suction device for holding the egg in the egg holding device; The control unit further controls the suction device. The ICSI support device according to any one of [1] to [3]. [5] the egg holding device is connected to a water pump for rotating the egg in the egg holding device; The control unit further controls the water supply device. The ICSI support device according to any one of [1] to [4]. [6] The acquisition unit further acquires information including a position of the polar body of the egg, The control unit controls the water supply device to rotate the egg so that the sperm is injected by the sperm injection tool from a direction in which the polar body is not located. [5] The in vitro fertilization support device described in. [7] The water supply device is provided with a temperature control means for maintaining the temperature of the water supply fluid within a certain range. The ICSI support device described in [5] or [6]. [8] The sperm injection tool is fixed to the imaging unit. The ICSI support device according to any one of [3] to [7]. [9] An ovum holding device to be placed in the ICSI support device according to any one of [1] to [8], a recess for receiving an egg; a suction port for holding an ovum in the recess; Equipped with Egg retention device.
[10] Further comprising a water supply port for rotating the egg in the recess. [9] An egg holding device as described in the above.
[11] [1] to [8], and an ICSI support device according to any one of the above. The sperm injection tool; Equipped with Intracytoplasmic sperm injection support system.
[12] A microinsemination support program for supporting microinsemination in which sperm held in a sperm injection tool are injected into an egg held by an egg holding device, comprising: Computer, an acquisition unit that acquires information including a relative positional relationship between the sperm injection tool and the egg; A control unit that controls the movement of a stage on which the egg holding device is placed to inject the sperm into the egg and perform ICSI based on the information acquired by the acquisition unit; To function as program. [Explanation of symbols]
[0131] 1... ICSI support system, 2... ICSI support device, 3... sperm injection tool, 11... stage, 12... drive unit, 13... imaging unit, 14... container, 21... acquisition unit, 22... control unit, 23... analysis unit, 151, 251... recess, 152, 252... marker, 153, 253... water supply port, 154, 254... suction port, 155, 255... drainage port, 157, 257... water supply port, 158, 258...suction port, 159, 259...drainage port, 221...imaging control unit, 222...drive control unit, 223...sperm injection tool control unit, 224...suction device control unit, 225...water supply device control unit, 231...sperm recognition unit, 232...egg recognition unit, 233...sperm evaluation unit, 234...egg evaluation unit, D1, D2...egg holding device, O...egg, PO...egg pool, PS...sperm pool.
Claims
1. An ICSI support device that supports ICSI by injecting sperm held in a sperm injection tool into an egg held by an egg holding device, comprising: A sperm pool for accommodating the sperm and an egg holding device for holding the egg are placed on a stage; The ICSI support device comprises: An acquisition unit that acquires information including a relative positional relationship between the sperm injection tool and the egg, and information including a relative positional relationship between the sperm injection tool and the sperm contained in the sperm pool; A control unit that controls the movement of the stage to hold the immobilized sperm in the sperm injection tool based on the information acquired by the acquisition unit, and controls the movement of the stage to inject the sperm into the egg and perform ICSI; An in vitro fertilization support device comprising:
2. an imaging unit that images the egg, the sperm, and the sperm injection tool; a drive unit for moving the stage based on an instruction from the control unit; Further comprising: The ICSI support device according to claim 1.
3. the egg holding device is connected to a suction device for holding the egg in the egg holding device; The control unit further controls the suction device. The ICSI support device according to claim 1.
4. the egg holding device is connected to a fluid supply for rotating the egg in the egg holding device; the fluid supplying device supplies a fluid to the egg placed in the egg holding device to rotate the egg; The control unit further controls the fluid supply device. The ICSI support device according to claim 1.
5. The acquisition unit further acquires information including a position of the polar body of the egg, The control unit controls the fluid supply device to rotate the egg so that the sperm is injected by the sperm injection tool from a direction in which the polar body is not located. The ICSI support device according to claim 4.
6. The fluid supply device includes a temperature control means for maintaining the temperature of the fluid to be supplied within a certain range. The ICSI support device according to claim 4.
7. The sperm injection tool is fixed to the imaging unit. The ICSI support device according to claim 2.
8. An ovum holding device for placing on the stage connected to the ICSI support apparatus according to any one of claims 1 to 7, a recess for receiving an egg; a suction port for holding an ovum in the recess; Equipped with Egg retention device.
9. and a fluid supply port for rotating the egg in the recess.
9. An egg holding device according to claim 8.
10. The ICSI support device according to any one of claims 1 to 7, The sperm injection tool; Equipped with Intracytoplasmic sperm injection support system.
11. A microinsemination support program for supporting microinsemination in which sperm held in a sperm injection tool are injected into an egg held by an egg holding device, comprising: A sperm pool for accommodating the sperm and an egg holding device for holding the egg are placed on a stage; Computer, An acquisition unit that acquires information including a relative positional relationship between the sperm injection tool and the egg, and information including a relative positional relationship between the sperm injection tool and the sperm contained in the sperm pool; A control unit that controls the movement of the stage to hold the immobilized sperm in the sperm injection tool based on the information acquired by the acquisition unit, and controls the movement of the stage to inject the sperm into the egg and perform ICSI; To function as program.
Citation Information
Patent Citations
Manipulator system and method for manipulating microscopic object to be manipulated
CN102959452A
Micromanipulator
JP2001330781A
Stage device and minute manipulation equipment
JP2020126126A
Intracytoplasmic sperm injection training device
JP2020185007A
Micro-insemination apparatus and position control method of micro-insemination surgical instrument
JP2021029453A
Cited By
Sperm sorting assistance device, projection device, and microscope system
JP7751345B1
Information processing device, method, and program for tracking sperm
JP7840606B1
