CN216484649U - Magnetic control micromanipulation device and magnetic control equipment - Google Patents

Abstract

The application provides a magnetic control micromanipulation device and magnetic control equipment, and the magnetic control micromanipulation device includes: an inverted microscope including a microscope body and a first objective lens formed on the microscope body; the coil assembly is distributed at intervals with the first objective lens and forms a magnetic control space; the alternating power supply is electrically connected with the coil assembly to control the coil assembly to generate a magnetic field; a transfer mechanism capable of transferring the culture dish to move the culture dish into or out of the magnetic control space; wherein, under the state that the culture dish moved into the magnetic control space, the culture dish can be located the imaging range of first objective, and the magnetism micro-nano machinery in the culture dish can directional delivery sample sperm cell to supply sample sperm cell and sample oocyte to combine. The magnetic control equipment comprises a magnetic micro-nano machine and a magnetic control micromanipulation device. By adopting the technical scheme, no external instrument is required to invade the sample oocyte, and the damage to the sample oocyte is reduced.

Description

Magnetic control micromanipulation device and magnetic control equipment

Technical Field

The application belongs to the technical field of medical instruments, and particularly relates to a magnetic control micromanipulation device and magnetic control equipment.

Background

Intracytoplasmic Sperm Injection (ICSI) refers to a technique for fertilizing an egg by injecting a single Sperm into the egg with the aid of a micromanipulation system.

The traditional mechanical device adopting ICSI generally depends on mechanical movement to complete the micromanipulation process, specifically, sample oocytes are fixed at the position of a first pole body at 12 o ' clock or near 6 o ' clock, an injection needle enters the sample oocytes from 3 o ' clock direction to inject sample sperm cells into the sample oocytes, and the fertilization of the sample oocytes and the sample sperm cells is realized; the micromanipulation process adopts a pure mechanical invasive method to invade the sample oocyte, and the damage to the sample oocyte is larger.

SUMMERY OF THE UTILITY MODEL

One of the purposes of the embodiment of the application is as follows: provides a magnetic control micromanipulation device, aiming at solving the technical problem that in the prior art, an injection needle invades a sample oocyte to cause damage to the sample oocyte.

In order to solve the technical problem, the embodiment of the application adopts the following technical scheme:

there is provided a magnetically controlled micromanipulation apparatus comprising:

an inverted microscope including a microscope body and a first objective lens formed on the microscope body;

the coil assembly is distributed at intervals with the first objective lens and forms a magnetic control space;

the alternating power supply is electrically connected with the coil assembly to control the coil assembly to generate a magnetic field;

a transfer mechanism capable of transferring a culture dish to move the culture dish into or out of the magnetically controlled space;

wherein, under the state that the culture dish moved into the magnetic control space, the culture dish can be located the imaging range of first objective, just magnetic micro-nano machinery in the culture dish can the directional sample sperm cell that delivers, for sample sperm cell and sample oocyte combine.

In one embodiment, the magnetically controlled micromanipulation apparatus further comprises a laser assembly for projecting a laser beam at a target location capable of lysing the sample oocyte.

In one embodiment, the laser assembly comprises a laser light source and a second objective lens, and the second objective lens is arranged on the microscope body and is spaced from the first objective lens; and the second objective is connected with the laser light source optical path so that the laser beam emitted by the laser light source is projected to the target position of the sample oocyte through the second objective.

In one embodiment, the first objective lens is disposed within the magnetron space.

In one embodiment, the coil assembly comprises three sets of coils, each set of coils comprising two of the coils; the three groups of coils are respectively arranged oppositely along a first direction, a second direction and a third direction and jointly enclose to form the magnetic control space; wherein the first direction, the second direction and the third direction are mutually perpendicular in pairs.

In one embodiment, the transfer mechanism comprises a support platform and an object stage capable of holding the culture dish, wherein the object stage is movably arranged on the support platform so as to move the culture dish into or out of the magnetic control space;

the objective table is provided with an observation hole penetrating through the objective table along a first direction, and the first objective lens can be over against the observation hole along the first direction under the state that the culture dish is moved into the magnetic control space.

In one embodiment, the transfer mechanism further comprises a first guide rail and a second guide rail, the first guide rail is arranged on the support table, the second guide rail is arranged on the first guide rail in a sliding manner along a second direction, and the object stage is arranged on the second guide rail in a sliding manner along a third direction so as to move into or out of the magnetic control space; wherein the first direction, the second direction and the third direction are mutually perpendicular in pairs.

In one embodiment, the magnetic-control micromanipulation device further comprises an upper computer which is electrically connected to the alternating power supply and the transfer mechanism respectively; the upper computer is provided with a first controller and a second controller, the first controller can control alternating current output by the alternating power supply so as to control a magnetic field generated by the coil assembly, and the second controller can control the transfer mechanism.

In one embodiment, the inverted microscope further comprises:

the camera is electrically connected to the upper computer; the camera is arranged on the microscope body, and an optical path is connected with the first objective lens so as to acquire imaging content of the first objective lens;

and the display is electrically connected with the upper computer to display the imaging content of the first objective lens in real time.

The embodiment also provides a magnetic control device, which comprises a magnetic micro-nano machine and the magnetic control micromanipulation device, wherein the magnetic micro-nano machine can be matched with the coil assembly to combine the sample sperm cells in a targeted manner and deliver the sample sperm cells to the sample oocytes.

The magnetic control micromanipulation device provided by the embodiment of the application has the beneficial effects that: compared with the prior art, in the application, when the micromanipulation is carried out, the culture dish is moved into the magnetic control space by the transfer mechanism, at the moment, the culture dish can be positioned in the imaging range of the first objective lens, the magnetic micro-nano machine, the sample sperm cells and the sample oocytes in the culture dish are microscopically observed through the ocular lens of the microscope main body, the alternating current output by the alternating power supply is correspondingly controlled, and the adjustment of the magnetic field generated by the coil assembly is realized, so that the magnetic micro-nano machine is combined with the sample sperm cells in a targeted manner under the magnetic control action of the coil assembly, then the sample sperm cells are directionally delivered to the sample oocytes, and the sample sperm cells are released, so that the combination of the sample sperm cells and the sample oocytes is realized; the magnetic control micromanipulation device provided in this embodiment, through the magnetic micro-nano mechanical cooperation coil subassembly, realize the combination of sample sperm cell and sample oocyte, it has simulated the normal fertilization process of sample sperm cell and sample oocyte, need not during external instrument invades sample oocyte, has reduced the damage to sample oocyte. The magnetic control device provided by the embodiment also has the advantage of reducing the damage to the sample oocyte of the magnetic control micromanipulation device.

Drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the embodiments or the prior art descriptions will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise.

FIG. 1 is a first structural diagram of a magnetic-control micromanipulation apparatus provided in an embodiment of the present application in a first operating state;

FIG. 2 is a partial block diagram of the magnetic micromanipulation apparatus provided in FIG. 1 in a second operating state;

FIG. 3 is a block diagram of an inverted microscope of the magnetic micromanipulation apparatus provided in FIG. 1;

FIG. 4 is a block diagram of a coil assembly of the magnetically controlled micromanipulation apparatus provided in FIG. 1;

fig. 5 is a structural view of a transfer mechanism of the magnetic micromanipulation apparatus provided in fig. 1.

Wherein, in the figures, the respective reference numerals:

10-inverted microscope; 11-a microscope body; 111-a lens barrel; 112-rotating the cover; 12-a first objective lens; 13-ocular lens; 20-a coil assembly; 201-magnetic control space; 21-a coil; 21 a-a first coil; 21 b-a second coil; 21 c-a third coil; 22-a connecting rod; 22 a-first connecting rod; 22 b-a second connecting rod; 22 c-a third connecting rod; 23-a support bar; 24-a base; 30-an alternating power supply; 40-a transfer mechanism; 401-a viewing aperture; 41-a support table; 42-a stage; 43-a first guide rail; 44-a second guide rail; 45-a first motor; 46-a second motor; 50-a laser assembly; 51-a laser light source; 52-second objective lens; 60-an upper computer; 70-a first manipulator; 80-a second manipulator; 90-a camera; 100-a display; z-a first direction; x-a second direction; y-the third direction.

Detailed Description

Reference will now be made in detail to embodiments of the present application, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are exemplary and intended to be used for explaining the present application and should not be construed as limiting the present application.

In the description of the present application, it is to be understood that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present application and simplifying the description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present application.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present application, "a plurality" means two or more unless specifically limited otherwise, wherein two or more includes two.

In this application, unless expressly stated or limited otherwise, the terms "mounted," "connected," "secured," and the like are to be construed broadly and can include, for example, fixed connections, removable connections, or integral parts; can be mechanically or electrically connected; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art as appropriate.

The following detailed description is made with reference to the accompanying drawings and examples:

referring to fig. 1 to 3, the magnetic-control micromanipulation apparatus provided in the embodiment of the present application can cooperate with a magnetic micro-nano machine to perform micromanipulation, so as to combine a sample sperm cell and a sample oocyte; of course, the magnetic control micromanipulation device is matched with the magnetic micro-nano machine, and can also be used for realizing that a ferritin receptor or other receptors enter target cells. It should be noted that the magnetic micro-nano machine can move under the action of the magnetic field, and when the magnitude and the frequency of the magnetic field are different, the moving direction of the magnetic micro-nano machine is different, so that the magnetic micro-nano machine can realize directional movement under the magnetic control action of different magnetic fields; the magnetic micro-nano machine refers to a micro machine made of a magnetic nano material, for example, a shell of the micro machine is made of the magnetic nano material.

The magnetic-control micromanipulation apparatus includes an inverted microscope 10, a coil block 20, an alternating power supply 30, and a transfer mechanism 40. The inverted microscope 10 comprises a microscope body 11 and a first objective lens 12, wherein the microscope body 11 is arranged on a plane; wherein, the ocular 13 and the first objective 12 on the microscope body 11 are formed on the microscope body 11 at intervals, and the ocular 13 is connected with the first objective 12; it is understood that the user can observe the imaging content of the first objective lens 12 through the eyepiece 13. The coil assembly 20 is disposed on the plane and spaced apart from the first objective lens 12 and the ocular lens 13, and a magnetic control space 201 is formed in the coil assembly 20. The alternating power source 30 is electrically connected to the coil assembly 20 to control the coil assembly 20 to generate a magnetic field. The transfer mechanism 40 can transfer the culture dish to move the culture dish into or out of the magnetron space 201.

In order to realize the combination of the sample sperm cells and the sample oocytes, in this embodiment, the culture dish contains the magnetic micro-nano machine, the sample sperm cells and the sample oocytes; of course, when it is desired to achieve binding of ferritin receptors or other receptors to cells, magnetic micro-nano-machines, ferritin receptors or other receptors, and cells should be contained in the culture dish. Under the state that the culture dish is moved into the magnetic control space 201, the culture dish can be positioned in the imaging range of the first objective lens 12 through the transfer action of the transfer mechanism 40 on the culture dish, and the magnetic micro-nano machine in the culture dish can directionally deliver the sample sperm cells under the magnetic control action of the magnetic field generated by the coil assembly 20 so as to combine the sample sperm cells with the sample oocytes.

It should be noted that the alternating current power supply 30 is electrically connected to the coil assembly 20 to control the coil assembly 20 to generate the magnetic field; as can be appreciated, the alternating power supply 30 provides an alternating current to the coil assembly 20 such that the coil assembly 20 generates a magnetic field under the drive of the alternating current; wherein, under the drive of different alternating currents, the frequency and the size of the magnetic field generated by the coil assembly 20 are different, so that the adjustment effect on the frequency and the size of the magnetic field generated by the coil assembly 20 can be realized by changing the alternating current output by the alternating power supply 30; therefore, by adjusting the frequency and the size of the magnetic field, the magnetic micro-nano mechanical target can be combined with the sample sperm cells, the sample sperm cells are directionally delivered to the oocytes, and finally the sample sperm cells are released, so that the combination of the sample sperm cells and the sample oocytes is realized.

It should be noted that the transfer mechanism 40 can transfer the culture dish to move the culture dish into or out of the magnetron space 201; it can be understood that, when the transfer mechanism 40 moves the culture dish into the magnetic control space 201, the transfer mechanism 40 can continue to transfer the culture dish in the magnetic control space 201 to adjust the specific position of the culture dish in the magnetic control space 201, so that the magnetic micro-nano machine, the sample sperm cell and the sample oocyte in the culture dish are all within the imaging range of the first objective lens 12, which is helpful for a user to observe the specific position of the magnetic micro-nano machine, the sample sperm cell and the sample oocyte in the culture dish through the eyepiece 13, thereby facilitating the smooth proceeding of the micromanipulation. As shown in fig. 1, fig. 1 shows that the culture dish has been moved into the magnetron space 201 by the transfer of the transfer mechanism 40, and the culture dish is located within the imaging range of the first objective lens 12, and at this time, the culture dish is located above the first objective lens 12.

In this embodiment, the operation principle of the magnetic-control micromanipulation apparatus is as follows: placing a magnetic micro-nano machine, sample sperm cells and sample oocytes in a culture dish, and placing the culture dish on a transfer mechanism 40; the transfer mechanism 40 moves the culture dish into the magnetically controlled space 201 of the coil assembly 20, the user observes the imaging content of the first objective lens 12 through the eyepiece 13, and controls the transfer mechanism 40 to continue transferring the culture dish until the culture dish is located within the imaging range of the first objective lens 12, that is, until the user can clearly observe the magnetic micro-nano machine, the sample sperm cell and the sample oocyte in the culture dish through the eyepiece 13, at this time, the culture dish is located above the first objective lens 12, as shown in fig. 1; a user continues to observe the imaging content of the first objective lens 12 through the ocular lens 13, and adjusts the magnetic field generated by the coil assembly 20 by correspondingly controlling the alternating power supply 30 output by the alternating power supply 30, so that the magnetic micro-nano machine directionally moves under the magnetic control action of the magnetic field to combine with the sample sperm cells in a targeted manner, then directionally delivers the sample sperm cells to the sample oocytes, and releases the sample sperm cells to combine with the sample oocytes to realize fertilization; finally, the transfer mechanism 40 is controlled to move the culture dish out of the magnetron space 201, that is, out of the coil assembly 20, as shown in FIG. 2.

In this embodiment of the application, when performing micromanipulation, the transfer mechanism 40 moves the culture dish into the magnetic control space 201, at this time, the culture dish can be located the imaging range of the first objective 12, the magnetic micro-nano machine, the sample sperm cell and the sample oocyte in the culture dish are microscopically observed through the eyepiece 13 of the microscope main body 11, and the alternating current output by the alternating power supply 30 is correspondingly controlled, the adjustment of the magnetic field generated by the coil component 20 is realized, so, under the magnetic control effect of the coil component 20, the magnetic micro-nano machine is combined with the sample sperm cell in a targeted manner, then the sample sperm cell is directionally delivered to the sample oocyte, and the sample sperm cell is released, thereby the combination of the sample sperm cell and the sample oocyte is realized. Therefore, the magnetic control micromanipulation device provided by the embodiment, through the magnetic micro-nano mechanical matching coil component 20, the combination of the sample sperm cell and the sample oocyte is realized, the normal fertilization process of the sperm cell and the oocyte is simulated in the embodiment, on one hand, an external instrument is not required to invade the sample oocyte, the damage to the sample oocyte is reduced, on the other hand, the magnetic micro-nano mechanical can directionally deliver the sample sperm cell to the sample oocyte under the magnetic control effect, the posture of the oocyte is not required to be fixed, thereby the damage to the sample oocyte is further reduced, and the micromanipulation to the sample sperm cell and the sample oocyte is simplified.

In one embodiment, referring to FIG. 1, the magnetic micromanipulation apparatus further comprises a laser assembly 50, the laser assembly 50 being adapted to project a laser beam capable of lysing a target site of an oocyte of the sample. It should be noted that, when performing the micromanipulation, the laser assembly 50 projects a laser beam to the target position of the oocyte in a directional manner, and the zona pellucida at the target position of the oocyte is dissolved under the effect of the laser beam, so that the dissolved position of the oocyte is thinned or dissolved to form an opening; thus, when micromanipulation is carried out, the magnetic micro-nano mechanical orientation delivers the sample sperm cells to the dissolution position of the sample oocytes and releases the sample sperm cells, and the sample sperm cells enter the oocytes through the dissolution position of the oocytes, so that the combination of the sample sperm cells and the sample oocytes is realized.

Therefore, by adopting the technical scheme, the laser assembly 50 can directionally dissolve the transparent band at the target position of the sample oocyte, so that a channel is opened for delivering the sample sperm cells into the sample oocyte by the magnetic micro-nano machine, the sample sperm cells are assisted to pass through the transparent band of the sample oocyte and enter the sample oocyte for fertilization, the sample sperm cells without activity can smoothly enter the sample oocyte for fertilization, and the fertilization rates of the sample sperm cells and the sample oocyte are improved; and moreover, as the zona pellucida at the target position of the oocyte is dissolved, the possibility that the magnetic micro-nano machine enters the sample oocyte is further avoided, and the damage to the sample oocyte is further reduced.

In a possible embodiment, when the laser assembly 50 projects the laser beam, the culture dish is moved by the transfer function of the transfer mechanism 40 to adjust the position of the sample oocyte in the culture dish, so that the target position of the sample oocyte is located on the optical path of the laser assembly 50, and the laser beam can be directionally projected to the target position of the target sample oocyte, thereby improving the precise dissolution of the target position of the sample oocyte by the laser beam.

In a possible embodiment, the projection direction of the laser beam of the laser assembly 50 is adjustable to achieve a directed projection of the laser beam and a directed dissolution operation.

In one embodiment, referring to fig. 1 and fig. 3, the laser assembly 50 includes a laser light source 51 and a second objective lens 52, the second objective lens 52 is disposed on the microscope body 11 and spaced apart from the first objective lens 12; the second objective lens 52 is optically connected to the laser light source 51, so that the laser beam emitted from the laser light source 51 is projected to the target position of the sample oocyte through the second objective lens 52. It should be noted that, when performing the micromanipulation, the transfer mechanism 40 transfers the culture dish into the magnetic space 201, and the culture dish is located within the projection range of the second objective lens 52, specifically, the culture dish is located above the second objective lens 52; the laser light source 51 emits a laser beam, and the laser beam is directed to the target location of the sample oocyte through the second objective lens 52, so that the zona pellucida at the target location of the sample oocyte is dissolved.

In a possible embodiment, when the laser light source 51 projects a laser beam, the culture dish is moved by the transfer mechanism 40 to adjust the position of the sample oocyte in the culture dish so that the target position of the sample oocyte is located on the optical path of the second objective lens 52, and the laser beam can directionally and accurately dissolve the zona pellucida at the target position of the target sample oocyte through the second objective lens 52.

In a possible embodiment, the second objective lens 52 is movably provided on the microscope body 11, so that the second objective lens 52 can be moved to adjust the optical path direction thereof, so that the target location of the sample oocyte is located on the optical path of the second objective lens 52.

In a possible embodiment, the microscope body 11 is provided with a lens barrel 111, the lens barrel 111 is provided with a rotating cover 112, the first objective lens 12 and the second objective lens 52 are arranged on the rotating cover 112 of the microscope body 11 at intervals, and the rotating cover 112 rotates relative to the lens barrel 111 to realize the rotation of the second objective lens 52 on the rotating cover 112, so as to realize the position adjustment of the second objective lens 52, thereby enabling the target position of the sample oocyte to be located on the optical path of the second objective lens 52; moreover, the first objective lens 12 may be at least two, and generally, the magnifications of at least two first objective lenses 12 are different, when the rotating cover 112 rotates relative to the lens barrel 111, the rotation of at least two first objective lenses 12 on the rotating cover 112 can be realized, so as to realize the alternate use of at least two first objective lenses 12, that is, to make the culture dish located in the magnetron space 201 alternately located in the imaging range of at least two first objective lenses 12.

In one embodiment, referring to fig. 1 to 3, the first objective lens 12 is disposed in the magnetron space 201. It should be noted that the coil assembly 20 is disposed around the first objective lens 12, and a portion of the first objective lens 12 extends into the magnetron space 201, so that the magnetron space 201 of the coil assembly 20 and the imaging range of the first objective lens 12 can coincide, and thus, when the culture dish is moved into the magnetron space 201 by the transfer mechanism 40, the culture dish is substantially within the imaging range of the first objective lens 12, as long as the transfer mechanism 40 finely adjusts the specific position of the culture dish in the magnetron space 201, i.e. the culture dish is positioned in the magnetically controlled space 201 and in the imaging range of the first objective lens 12, and thus, by adopting the technical scheme, when the magnetic field generated by the coil component 20 controls the magnetic micro-nano mechanical to move, the imaging content of the magnetic micro-nano machine, the sample sperm cells and the sample oocytes can be observed, and smooth micro-operation is guaranteed.

In one embodiment, referring to fig. 1 and 4, the coil assembly 20 includes three sets of coils 21, each set of coils 21 includes two coils 21; the three groups of coils 21 are respectively arranged oppositely along a first direction z, a second direction x and a third direction y, and jointly enclose to form a magnetic control space 201; the first direction z, the second direction x and the third direction y are perpendicular to each other two by two, where perpendicular refers to substantially perpendicular, and it is understood that there may be a deviation between the two perpendicular directions.

The three groups of coils 21 are a first coil 21a, a second coil 21b, and a third coil 21 c; of the three sets of coils 21, two first coils 21a of the first set of coils 21 are spaced apart and opposed to each other along the first direction z, two second coils 21b of the second set of coils 21 are spaced apart and opposed to each other along the second direction x, two third coils 21c of the third set of coils 21 are spaced apart and opposed to each other along the third direction y, and two first coils 21a, two second coils 21b and two third coils 21c of the three groups of coils 21 together enclose the magnetic control space 201, based on the arrangement that the first direction z, the second direction x and the third direction y are mutually perpendicular in pairs, the magnetic control space 201 is a three-dimensional space, under the magnetic control action of the three groups of coils 21, the magnetic micro-nano machine can move in a three-dimensional space, and can be understood, under the action of magnetic control, the magnetic micro-nano machine can move in three directions which are mutually vertical in pairs respectively. Therefore, by adopting the technical scheme, the flexibility of the magnetic micro-nano machine moving under the driving of the magnetic field is improved, the magnetic micro-nano machine can be pertinently combined with the sample sperm in a targeted manner by controlling the alternating current output by the alternating power supply 30, and the sample sperm are delivered to the target sample oocyte in a directional manner, so that the degree of simulating the normal fertilization of the sperm cells in the embodiment is further improved, the damage to the sample oocyte is reduced, and the fertilization rates of the sample sperm cells and the sample oocyte are improved.

It should be further noted that the magnetic control space 201 is an overlapped portion of a space formed by two first coils 21a at intervals, a space formed by two second coils 21b at intervals, and a space formed by two third coils 21c at intervals, so that it is ensured that the magnetic micro-nano machines located in the magnetic control space 201 can be respectively driven by three groups of coils 21, that is, the magnetic micro-nano machines respectively move in three directions which are two by two and perpendicular to each other.

As shown in fig. 4, the first direction z is a vertical direction, and the second direction x and the third direction y are horizontal directions.

Optionally, in a specific embodiment, the connection rod 22 is connected between two coils 21 of each group of coils 21, and the number of the connection rods 22 between each group of coils 21 is at least two; the connecting rods 22 connected to the three coils 21 are respectively a first connecting rod 22a, a second connecting rod 22b and a third connecting rod 22 c. The two first coils 21a are spaced and oppositely arranged along the first direction z, at least two first connecting rods 22a distributed at intervals are connected between the two first coils 21a, and the first connecting rods 22a extend along the first direction z; the two second coils 21b are spaced and oppositely arranged along the second direction x, at least two second connecting rods 22b which are distributed at intervals are connected between the two second coils 21b, and the second connecting rods 22b extend along the second direction x; the two third coils 21c are spaced and oppositely arranged along the third direction y, at least two third connecting rods 22c are connected between the two third coils 21c and are distributed at intervals, and the third connecting rods 22c extend along the third direction y. The arrangement of the first connecting rod 22a, the second connecting rod 22b and the third connecting rod 22c improves the structural stability of each set of coils 21.

Optionally, in a specific embodiment, the first coil 21a and the first connecting rod 22a are both disposed between the two second coils 21b, and the two second coils 21b and the at least two second connecting rods 22b are commonly disposed around the outer peripheries of the first coil 21a and the first connecting rod 22 a; the second coil 21b and the second connecting rod 22b are arranged between the two third coils 21c, and the two third coils 21c and the at least two third connecting rods 22c are arranged around the outer peripheries of the second coil 21b and the second connecting rod 22 b; it is understood that the two third coils 21c and the at least two third connection bars 22c are commonly provided around the outer circumferences of the first coil 21a, the first connection bar 22a, the second coil 21b, and the second connection bar 22 b. Like this, support each other between three group's coils 21, improved the holistic structural stability of coil pack 20, guaranteed that three group's coils 21 respectively along first direction z, second direction x and the relative setting of third direction y to enclose jointly and close and form foretell magnetic control space 201, thereby guaranteed that coil pack 20 receives mechanical magnetic control effect a little to magnetism.

Optionally, the coil assembly 20 further includes a support rod 23 and a base 24, the base 24 is disposed on the plane, the support rod 23 is disposed on the base 24, and one of the coils 21 is disposed at one end of the support rod 23 away from the base 24, so that the support of the first coil 21a is realized by the arrangement of the support rod 23 and the base 24, the support effect of the whole coil assembly 20 is realized, and the magnetic control effect of the coil assembly 20 is ensured.

Optionally, the coil 21 is a helmholtz coil.

In one embodiment, referring to fig. 1, fig. 2 and fig. 5, the transfer mechanism 40 includes a support platform 41 and a stage 42 capable of holding the culture dish, the stage 42 is movably disposed on the support platform 41 to transfer the culture dish, so as to move the culture dish into or out of the magnetron space 201; the objective table 42 is provided with an observation hole 401, the observation hole 401 is a through hole, the observation hole 401 penetrates through the objective table 42 along the first direction z, and the first objective lens 12 can be over against the observation hole 401 along the first direction z in a state that the culture dish is moved into the magnetron space 201.

Note that the culture dish is placed in the observation hole 401 of the stage 42, and the stage 42 is movable on the support table 41 to transfer the culture dish; when the culture dish moves into the magnetron space 201 under the transferring action of the object stage 42, the object stage 42 may continue to transfer the culture dish to adjust the specific position of the culture dish, so that the culture dish is transferred to the upper side of the first objective lens 12 under the transferring action of the object stage 42, at this time, the first objective lens 12 is directly opposite to the observation hole 401 along the first direction z, and the culture dish is directly opposite to the culture dish along the first direction z through the observation hole 401, so that the culture dish is within the imaging range of the first objective lens 12.

In a possible embodiment, when the first objective lenses 12 are arranged in at least two, the at least two first objective lenses 12 can be rotated by the rotating cover 112 to be alternately rotated to be arranged opposite to the observation hole 401 along the first direction z, so as to realize the alternate use of the at least two first objective lenses 12; of course, when the target position of the sample oocyte needs to be dissolved by the laser, the second objective lens 52 may also be driven by the rotating cover 112 to rotate to the observation hole 401, so that the laser beam emitted by the laser source 51 may be projected to the target position of the sample oocyte sequentially through the second objective lens 52 and the observation hole 401, and the target position of the sample oocyte may be dissolved.

By adopting the above technical scheme, the arrangement of the objective table 42 and the observation hole 401 thereof can not only realize that the culture dish is transferred into the magnetic control space 201, but also enable the first objective lens 12 to image the culture dish through the observation hole 401 when the culture dish is transferred into the magnetic control space 201.

In one embodiment, referring to fig. 1, fig. 2 and fig. 5, the transfer mechanism 40 further includes a first guide rail 43 and a second guide rail 44, the first guide rail 43 is disposed on the support platform 41, the second guide rail 44 is slidably disposed on the first guide rail 43 along the second direction x, and the stage 42 is slidably disposed on the second guide rail 44 along the third direction y to move into or out of the magnetron space 201; the first direction z, the second direction x, and the third direction y are mutually perpendicular, and the first direction z, the second direction x, and the third direction y may refer to the description in the above embodiments, and are not described herein in detail.

The support 41 and the coil assembly 20 are sequentially distributed along the third direction y, the first guide rail 43 extends along the second direction x, and the second guide rail 44 extends along the third direction y. In operation, the object stage 42 is slidably disposed on the second guide rail 44 along the third direction y, so as to move the culture dish on the object stage 42 into the magnetron space 201; then, the object stage 42 is continuously slidably disposed on the second guide rail 44 along the third direction y, and at this time, the second guide rail 44 is slidably disposed on the first guide rail 43 along the second direction x, so that the object stage 42 is driven by the second guide rail 44 to move in the second direction x, thereby achieving position adjustment of the object stage 42 and the culture dish thereon in the second direction x and the third direction y, respectively, and facilitating the culture dish on the object stage 42 to move into the imaging range of the first objective lens 12.

By adopting the above technical scheme, the arrangement of the first guide rail 43 and the second guide rail 44 enables the objective table 42 to move in the second direction x and the third direction y respectively, so that the culture dish on the objective table 42 can move into or out of the magnetron space 201, and the position adjustment of the culture dish on the objective table 42 in the magnetron space 201 can be realized, so that the culture dish is located in the imaging range of the first objective lens 12.

Optionally, the transfer mechanism 40 further comprises a first motor 45 and a second motor 46; the first motor 45 is arranged between the first guide rail 43 and the second guide rail 44 to drive the second guide rail 44 to move on the first guide rail 43 along the second direction x; the second motor 46 is disposed between the second rail 44 and the stage 42 to drive the stage 42 to move on the second rail 44 along the third direction y.

In one embodiment, referring to fig. 1, the magnetic-control micromanipulation apparatus further includes an upper computer 60, the upper computer 60 is electrically connected to the alternating power source 30, the upper computer 60 is provided with a first manipulator 70 and a second manipulator 80, the first manipulator 70 can control the alternating current output by the alternating power source 30 to control the magnetic field generated by the coil assembly 20, and the second manipulator 80 can control the transfer mechanism 40.

It should be noted that, during the micromanipulation, the second manipulator 80 controls the transfer mechanism 40, so that the transfer mechanism 40 transfers the culture dish into the magnetron space 201, and adjusts the specific position of the culture dish in the magnetron space 201, so that the culture dish is located within the imaging range of the first objective lens 12; the alternating current output by the alternating power supply 30 is controlled by the first manipulator 70 to control the magnetic field generated by the coil assembly 20, so that the magnetic micro-nano machine directionally moves under the magnetic control action of the magnetic field to target and combine the sample sperm cells, then directionally delivers the sample sperm cells to the sample oocytes, and releases the sample sperm cells, so that the sample sperm cells and the sample oocytes are combined to realize fertilization. Therefore, by adopting the technical scheme, the operation convenience of the micromanipulation is improved, the efficiency of the micromanipulation is improved, and the fertilization effect of the sample sperm cells and the sample ova is improved.

When the second manipulator 80 operates, the upper computer 60 receives an operation signal of the second manipulator 80 and outputs an electrical signal to the transfer mechanism 40; in this embodiment, the upper computer 60 is electrically connected to the first motor 45 and the second motor 46. When the first manipulator 70 operates, the upper computer 60 receives an operation signal of the first manipulator 70 and outputs an electric signal to the ac power supply 30, thereby controlling the ac current output from the ac power supply 30.

Alternatively, the first manipulator 70 and the second manipulator 80 may be both configured as a handle or a key or the like.

Optionally, the transfer mechanism 40 is controlled by the second manipulator 80, so that the transfer mechanism 40 locates the target position of the sample oocyte in the culture dish on the optical path of the laser assembly 50, which can realize that the laser assembly 50 can accurately dissolve the target position of the sample oocyte, and can help to assist the sample sperm cell to enter the sample oocyte through the dissolution position of the sample oocyte.

In one embodiment, referring to fig. 1, the inverted microscope 10 further comprises a camera 90 and a display 100; the camera 90 is electrically connected to the upper computer 60, the camera 90 is arranged on the microscope body 11, and the optical path is connected to the first objective lens 12 to obtain the imaging content of the first objective lens 12; the display 100 is electrically connected to the host computer 60 to display the imaging content of the first objective lens 12 in real time. It should be noted that, when the culture dish is located within the imaging range of the first objective lens 12, based on the optical path of the camera 90 connected to the first objective lens 12, the camera 90 can acquire the imaging content of the first objective lens 12 in real time, and the display 100 displays the imaging content of the first objective lens 12 in real time; the imaging content of the first objective lens 12 is a culture dish, a magnetic micro-nano machine, sample sperm cells and sample ova on the culture dish. Thus, by adopting the technical scheme, when carrying out the micromanipulation, a user can directly obtain the specific conditions of the culture dish and the magnetic micro-nano machine, the sample sperm cells and the sample ova thereon in real time through the display 100, and then control the magnetic field of the coil assembly 20 by controlling the alternating power supply 30, so that the magnetic micro-nano machine directionally delivers the sample sperm cells to the sample ova, and thus, the micromanipulation convenience of the magnetic control micromanipulation device is improved.

In this embodiment, the operation principle of the magnetic-control micromanipulation apparatus is as follows: the magnetic micro-nano machine, the sample sperm cells and the sample oocytes are placed in a culture dish, and the culture dish is placed on an objective table 42 of the transfer mechanism 40; by operating the second manipulator 80, the stage 42 moves the culture dish into the magnetron space 201; observing the imaging content of the first objective lens 12 through the display 100, and continuously controlling the objective table 42 to transfer the culture dish until the culture dish is located within the imaging range of the first objective lens 12, that is, until a user can clearly observe the magnetic micro-nano machine, the sample sperm cells and the sample oocytes in the culture dish through the display 100, at this time, the culture dish is located above the first objective lens 12, as shown in fig. 1; continuing to observe the imaging content of the first objective lens 12 through the display 100 and continuing to control the stage 42 to move the culture dish so that the target position of the sample oocyte is located on the optical path of the second objective lens 52, and the laser light source 51 emits a laser beam so that the laser beam is projected from the second objective lens 52 to the target position of the sample oocyte and dissolves the transparent band of the target position of the sample oocyte; continuing to observe the imaging content of the first objective lens 12 through the display 100, and controlling the first manipulator 70 to correspondingly control the alternating power supply 30 output by the alternating power supply 30 to realize the adjustment of the magnetic field generated by the coil assembly 20, so that the magnetic micro-nano machine directionally moves under the magnetic control action of the magnetic field to target and combine the sample sperm cells, then directionally delivers the sample sperm cells to the dissolution position of the sample oocytes, and releases the sample sperm cells, thereby enabling the sample sperm cells to enter the sample oocytes through the dissolution position of the sample oocytes to realize fertilization; finally, the second manipulator 80 is manipulated to control the stage 42 to move the culture dish out of the magnetron space 201, i.e. out of the coil assembly 20, as shown in FIG. 2.

The embodiment also provides magnetic control equipment, which comprises a magnetic micro-nano machine and the magnetic control micromanipulation device of the embodiment. It should be noted that the magnetic micro-nano mechanism can cooperate with the coil assembly 20 to target and deliver sample sperm cells to the sample oocytes under the magnetic control of the magnetic field generated by the coil assembly 20. The magnetic micro-nano machine and the magnetic control micromanipulation device in this embodiment are the same as those in the previous embodiment, and specific reference is made to the description of the magnetic micro-nano machine and the magnetic control micromanipulation device in the previous embodiment, which is not repeated herein.

Through adopting above-mentioned technical scheme, make the magnetic micro-nano machinery cooperate with the coil subassembly 20 of the micro-manipulation device of magnetic control, realize the combination of sample sperm cell and sample oocyte, the process of sperm cell and oocyte normal fertilization has been simulated to this embodiment, on the one hand, need not in the external instrument invasion sample oocyte, the damage to sample oocyte has been reduced, on the other hand, the magnetic micro-nano machinery can directionally deliver sample sperm cell to sample oocyte under the magnetic control effect, need not the gesture of fixed oocyte, thereby further reduced the damage of sample oocyte, and simplified the micro-manipulation to sample sperm cell and sample oocyte.

The above description is only exemplary of the present application and should not be taken as limiting the present application, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims (10)

1. A magnetically controlled micromanipulation apparatus, comprising:

an inverted microscope including a microscope body and a first objective lens formed on the microscope body;

the coil assembly is distributed at intervals with the first objective lens and forms a magnetic control space;

the alternating power supply is electrically connected with the coil assembly to control the coil assembly to generate a magnetic field;

a transfer mechanism capable of transferring a culture dish to move the culture dish into or out of the magnetically controlled space;

wherein, under the state that the culture dish moved into the magnetic control space, the culture dish can be located the imaging range of first objective, just magnetic micro-nano machinery in the culture dish can the directional sample sperm cell that delivers, for sample sperm cell and sample oocyte combine.

2. The magnetically controlled micromanipulation apparatus of claim 1, wherein said magnetically controlled micromanipulation apparatus further comprises a laser assembly for projecting a laser beam capable of lysing a target site of said sample oocyte.

3. The magnetically controlled micromanipulation apparatus of claim 2, wherein said laser assembly comprises a laser source and a second objective lens, said second objective lens being disposed on said microscope body and spaced apart from said first objective lens; and the second objective is connected with the laser light source optical path so that the laser beam emitted by the laser light source is projected to the target position of the sample oocyte through the second objective.

4. The magnetically controlled micromanipulation apparatus of claim 1, wherein said first objective lens is disposed within said magnetically controlled space.

5. The magnetically controlled micromanipulation apparatus according to any of claims 1 to 4, wherein the coil assembly comprises three sets of coils, each set of coils comprising two of said coils; the three groups of coils are respectively arranged oppositely along a first direction, a second direction and a third direction and jointly enclose to form the magnetic control space; wherein the first direction, the second direction and the third direction are mutually perpendicular in pairs.

6. The magnetic control micromanipulation apparatus of any one of claims 1 to 4, wherein said transfer mechanism comprises a support base and a stage capable of holding said culture dish, said stage being movably provided on said support base to move said culture dish into or out of said magnetic control space;

the objective table is provided with an observation hole penetrating through the objective table along a first direction, and the first objective lens can be over against the observation hole along the first direction under the state that the culture dish is moved into the magnetic control space.

7. The magnetically controlled micromanipulation apparatus according to claim 6, wherein the transfer mechanism further comprises a first rail and a second rail, the first rail being provided on the support stage, the second rail being slidably provided on the first rail in the second direction, and the stage being slidably provided on the second rail in the third direction to move in or out of the magnetically controlled space; the first direction, the second direction and the third direction are mutually perpendicular in pairs.

8. The magnetically controlled micromanipulation apparatus of any one of claims 1 to 4, wherein said magnetically controlled micromanipulation apparatus further comprises an upper computer electrically connected to said alternating power supply and said transfer mechanism, respectively; the upper computer is provided with a first controller and a second controller, the first controller can control alternating current output by the alternating power supply so as to control a magnetic field generated by the coil assembly, and the second controller can control the transfer mechanism.

9. The magnetically controlled micromanipulation apparatus of claim 8, wherein the inverted microscope further comprises:

the camera is electrically connected to the upper computer; the camera is arranged on the microscope body, and an optical path is connected with the first objective lens so as to acquire imaging content of the first objective lens;

and the display is electrically connected with the upper computer to display the imaging content of the first objective lens in real time.

10. A magnetic control device comprising a magnetic micro-nanomachinery capable of engaging the coil assembly to target sample sperm cells and deliver the sample sperm cells to a sample oocyte, and a magnetically controlled micromanipulation apparatus according to any one of claims 1 to 9.

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