A device and method for combined activation of early embryos

Abstract

The application relates to the technical field of embryo engineering, and discloses a combined activation device for early embryos, which comprises a culture dish used for storing early embryos, a cell holding mechanism used for adjusting the pose of the early embryos and fixing the early embryos, and a combined activation mechanism comprising a capillary micro-needle and a first needle holder, wherein the capillary micro-needle comprises a liquid metal channel and a chemical substance channel; liquid metal and a wire arranged in the liquid metal channel form a liquid metal electrode used for electrically activating the early embryos; and the chemical substance channel is used for releasing chemical substances to chemically activate the early embryos. The combined activation mechanism integrates the functions of electrical activation and chemical activation, improves the convenience of combined activation of the early embryos, the capillary micro-needle can realize precise combined activation of local parts, such as nuclear material regions, of a single early embryo, reduces excessive electrical damage or chemical damage to other parts of the early embryo, and thus improves the activation rate of the early embryos.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of embryo engineering, in particular to a combined activation device and method for early embryos. BACKGROUND

[0002] In the field of embryo engineering, early embryo activation is a common means at each stage of the early embryo micro-operation process. In the process of natural fertilization, the cytoplasmic activation of the oocyte is completed by the entry of sperm and the induction of calcium oscillation. In parthenogenetic activation (PA), intracytoplasmic sperm injection (ICSI), somatic cell nuclear transfer, artificial assisted activation of oocytes is essential. The currently known artificial assisted activation methods mainly include single activation and combined activation. Common single activation methods mainly include mechanical activation, electrical activation, and chemical activation (calcium ion carrier A23187, ionomycin, and ethanol, etc.); combined activation is a method of first pure physical activation or chemical activation, and then combined treatment with protein synthesis inhibitors, protein phosphorylation inhibitors, or cytochalasin B. More and more studies have shown that combined activation is better than single electrical activation or chemical activation.

[0003] At present, the commonly used combined activation is to first perform electrical activation on the early embryo and then immerse the early embryo in a solution containing chemicals to perform chemical activation on the early embryo. The device is relatively rough and has low precision. Electrical activation uses an activation chamber with two parallel plate electrodes to perform electrical activation on a batch of early embryos. Due to the large spacing of the macroscopic parallel plate electrodes, the electrical stimulation voltage applied to a single early embryo is also large and not uniform enough, which can easily cause excessive electrical damage to the embryo and cannot complete precise electrical stimulation on specific parts of the early embryo. It is impossible to complete the combined activation process of electrical activation and chemical activation on the early embryo with a set of activation device.

[0004] Therefore, how to stimulate specific parts of the early embryo and how to complete the combined activation of the early embryo with a set of activation device to improve the activation rate of the early embryo are problems that need to be solved by those skilled in the art. SUMMARY

[0005] The purpose of the present application is to provide a combined activation device and method for early embryos, which can stimulate specific parts of the early embryo, including electrical stimulation and chemical stimulation, and complete the combined activation of the early embryo with a set of activation device, thereby improving the activation rate of the early embryo.

[0006] To solve the above technical problems, the present application provides a combined activation device for early embryos, comprising:

[0007] A culture dish for storing early embryos;

[0008] A cell holding mechanism is used to adjust the position of the early embryo and fix the early embryo.

[0009] The combined activation mechanism includes a capillary microneedle and a first needle holder, the capillary microneedle being connected to the first needle holder; the capillary microneedle includes a liquid metal channel and a chemical substance channel; the liquid metal channel contains liquid metal and a wire, the liquid metal being located at the tip of the capillary microneedle, the wire being used to connect to an excitation power source, the liquid metal and the wire constituting a liquid metal electrode for electro-activating the early embryo; the chemical substance channel is used to release chemical substances for chemical activation of the early embryo.

[0010] Preferably, the capillary needle includes a plurality of liquid metal channels and a chemical substance channel, wherein the plurality of liquid metal channels are arranged around the chemical substance channel.

[0011] Preferably, the bottom of the culture dish is provided with an array of micropits, which are used to prevent the early embryo from moving.

[0012] Preferably, the first needle holder includes a first cap, a second cap, a first connecting seat, a third cap, and a first fixing rod;

[0013] The first cap is threadedly connected to the second cap, the second cap and the third cap are both threadedly connected to the first connecting seat, and the first fixing rod is threadedly connected to the third cap;

[0014] The capillary needle's tail extends through the first and second caps, and the first connecting seat is provided with a pneumatic drive inlet. The chemical substance channel in the capillary needle is connected to the pneumatic drive inlet.

[0015] Preferably, the cell holding mechanism includes a cell holding needle and a second needle holder, the cell holding needle being connected to the second needle holder, the second needle holder having an air inlet communicating with the cell holding needle.

[0016] Preferably, the diameter of the liquid metal channel is 7 μm.

[0017] Preferably, the diameter of the chemical substance channel is 10 μm.

[0018] Preferably, the cell-holding needle has an inner diameter of 15 μm and an outer diameter of 100 μm.

[0019] Preferably, the micropit has a diameter of 150 μm and a depth of 50 μm.

[0020] This application also provides a method for the combined activation of early embryos, applied to the combined activation device for said early embryos, comprising:

[0021] After the cell holding mechanism fixes the early embryo, the combined activation mechanism continuously supplies high-voltage DC pulses to the target site of the early embryo to electroactivate the early embryo.

[0022] After the early embryo is electrically activated, the combined activation mechanism is controlled to release chemicals to chemically activate the early embryo.

[0023] This application provides a combined activation device for early embryos, comprising: a culture dish for storing early embryos; a cell holding mechanism for adjusting the posture of early embryos and fixing them; and a combined activation mechanism including a capillary microneedle and a first needle holder, the capillary microneedle being connected to the first needle holder; the capillary microneedle includes a liquid metal channel and a chemical substance channel; the liquid metal channel contains liquid metal and a wire, the liquid metal being located at the tip of the capillary microneedle, the wire being used to connect to an excitation power source, the liquid metal and the wire constituting a liquid metal electrode for electro-activating the early embryo; the chemical substance channel is used to release chemical substances for chemical activation of the early embryo. The capillary microneedle of this application can achieve precise combined activation of localized areas of a single early embryo, such as the nuclear material region, reducing excessive electrical or chemical damage to other parts of the early embryo, thereby improving the activation rate of early embryos; furthermore, a single combined activation mechanism integrates electro-activation and chemical activation, improving the convenience of combined activation of early embryos; the cell holding mechanism can quickly adjust the cell posture, reducing time and minimizing factors that cause cell death or developmental arrest due to cell posture adjustments.

[0024] The method and apparatus for the combined activation of early embryos provided in this application have the effects described above. Attached Figure Description

[0025] To more clearly illustrate the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 A structural diagram of a combined activation device for early embryos provided in an embodiment of this application;

[0027] Figure 2 A structural diagram of a petri dish provided in an embodiment of this application;

[0028] Figure 3 A structural diagram of a combined activation mechanism provided in an embodiment of this application;

[0029] Figure 4 A diagram illustrating the tip structure of a capillary needle provided in an embodiment of this application;

[0030] Figure 5 A schematic diagram of the cross-sectional area of ​​the tip of a capillary needle provided in an embodiment of this application;

[0031] Figure 6 An internal structural diagram of a capillary needle provided in an embodiment of this application;

[0032] Figure 7 A process flow diagram for preparing the tip of a capillary needle is provided for embodiments of this application;

[0033] Figure 8 A structural diagram of a cell holding mechanism provided in an embodiment of this application;

[0034] Figure 9 A flowchart illustrating a combined activation method for early embryos provided in this application embodiment;

[0035] The attached figures are labeled as follows: 1 is a culture dish, 2 is a combined activation mechanism, 3 is a cell holding mechanism, 4 is a cell, 101 is a micropit, 201 is a capillary needle, 202 is the first cap, 203 is the second cap, 204 is the first connector, 205 is the third cap, 206 is the first fixing rod, 207 is the pneumatic drive inlet, 208 is the wire outlet, 209 is the first annular washer, 210 is the second annular washer, and 211 is a chemical conduit. 2011 is the liquid metal channel, 2012 is the chemical substance channel, 2013 is the wire, 301 is the cell holding needle, 302 is the fourth cap, 303 is the fifth cap, 304 is the second connector, 305 is the sixth cap, 306 is the second fixing rod, 307 is the gas inlet, 308 is the gas pipe, 309 is the third annular washer, 310 is the fourth annular washer, A is the tip of the capillary needle, and B is the tip of the cell holding needle. Detailed Implementation

[0036] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of this application.

[0037] Currently, much research has been conducted on the activation of early mammalian embryos, with methods evolving from single activation to combined approaches, achieving significant progress. Electroactivation is a commonly used method, favored by researchers due to its ease of operation, high activation rate, and lack of chemical toxicity. The principle of electroactivation is that under the influence of a brief high-voltage direct current pulse, the stability of the phosphodiester bimolecular structure of the early embryonic membrane changes, forming numerous recoverable micropores on the cell membrane. This allows extracellular Ca+ to enter the cell, increasing the intracellular Ca+ concentration. The increased intracellular Ca2+ concentration leads to the loss of CSF activity, rapid degradation of cyclin B, and loss of MPF activity, activating the cell to complete the second meiotic division and enter the next cell cycle. Chemical activation mainly includes calcium ion carrier A23187, iomycin, ethanol activation, protein synthesis inhibitors, and protein phosphorylation inhibitors. Calcium ion carrier A23187 (CaA) primarily activates early embryos through the release of intracellular Ca2+. Iomycin, another calcium ion carrier, also functions through the release of intracellular Ca2+ in early embryos. However, it doesn't directly promote the release of Ca2+ from the early embryo. Instead, it first utilizes Ca2+ channels on the cell membrane to allow Ca2+ to flow from the extracellular space into the cell, and then activates Ca2+ in the endogenous endoplasmic reticulum to enter the early embryonic cytoplasm. Ethanol's activation of the early embryo mainly involves the formation of IP3 in the cell membrane. Through IP3, receptors mediate the release of endogenous Ca2+, causing an early activation response in the early embryo. Protein cytokines such as maturation-promoting factor (MPF) and cell quiescence factor (CSF) are regulators of the cell cycle; it is under their influence that oocytes arrest in the MII phase. These factors are highly sensitive to Ca2+; when the Ca2+ level in the activated oocyte cytoplasm rises to a certain level, MPF and CSF become inactive or disappear. Using protein synthesis inhibitors to activate the early embryo does not work because it causes fluctuations in Ca2+ concentration, but because it inhibits the synthesis of these protein cytokines, thus allowing the early embryo to leave the MII phase and resume the second meiotic division. Protein phosphorylation inhibitors can prevent protein phosphorylation, thereby inhibiting the activity of MPF and CSF, and also inhibit the release of the second polar body, ensuring that the chromosomes of parthenogenetically activated oocytes are diploid.

[0038] The core of this application is to provide a combined activation device and method for early embryos.

[0039] To enable those skilled in the art to better understand the present application, the following description is provided in conjunction with the accompanying drawings (…). Figures 1-8 The present application will be further described in detail below with reference to the specific embodiments.

[0040] Figure 1 A structural diagram of a combined activation device for early embryos provided in this application embodiment is shown below.Figure 1 As shown, 1 is a culture dish, 2 is a combined activation mechanism, 3 is a cell holding mechanism, and 4 is a cell. The culture dish 1 is used to store early embryos; the cell holding mechanism 3 is used to adjust the position of the early embryos and fix them in place; the combined activation mechanism 2 includes a capillary needle 201 and a first needle holder, with the capillary needle 201 connected to the first needle holder; the capillary needle 201 includes a liquid metal channel 2011 and a chemical substance channel 2012; the liquid metal channel 2011 contains liquid metal and a wire 2013, with the liquid metal located at the tip of the capillary needle 201, and the wire 2013 used to connect to an excitation power source; the liquid metal and the wire 2013 constitute liquid metal for electro-activation of the early embryos; the chemical substance channel 2012 is used to release chemical substances for chemical activation of the early embryos.

[0041] This application provides a combined activation device for early embryos, comprising: a culture dish for storing early embryos; a cell holding mechanism for adjusting the posture of early embryos and fixing them; and a combined activation mechanism including a capillary microneedle and a first needle holder, the capillary microneedle being connected to the first needle holder; the capillary microneedle includes a liquid metal channel and a chemical substance channel; the liquid metal channel contains liquid metal and a wire, the liquid metal being located at the tip of the capillary microneedle, the wire being used to connect to a power source, the liquid metal and the wire forming an electrode for electro-activating the early embryo; the chemical substance channel is used to release chemical substances for chemical activation of the early embryo. The capillary microneedle of this application can achieve precise combined activation of local areas of a single early embryo, such as the nuclear material region, reducing excessive electrical or chemical damage to other parts of the early embryo, thereby improving the activation rate of early embryos; furthermore, a single combined activation mechanism integrates both electro-activation and chemical activation functions, improving the convenience of combined activation of early embryos; the cell holding mechanism can quickly adjust the cell posture, reducing time and minimizing factors that cause cell death or developmental arrest due to cell posture adjustments.

[0042] The embodiments of this application do not specifically limit the shape and size of the petri dish 1. Figure 2 A structural diagram of a petri dish provided in an embodiment of this application is shown below. Figure 2 The bottom of the culture dish 1 is provided with an array of micropits 101, each with a diameter of 150 μm and a depth of 50 μm. The culture dish 1 serves as the operating table for the entire device. Cells 4 are placed in the culture dish 1, and the micropits 101 at the bottom prevent early embryos from easily moving, making them easy to grasp.

[0043] Figure 3 A structural diagram of a combined activation mechanism provided in an embodiment of this application is shown below. Figure 3As shown, the combined activation mechanism 2 includes a capillary needle 201 and a first needle holder. The first needle holder includes a first cap 202, a second cap 203, a first connecting seat 204, a third cap 205, a first fixing rod 206, a pneumatic drive inlet 207, a wire outlet 208, a first annular washer 209, a second annular washer 210, and a chemical conduit 211. A represents the tip portion of the capillary needle 201. The first cap 202 is threaded to the second cap 203, and both the second cap 203 and the third cap 205 are threaded to the first connecting seat 204. The first fixing rod 206 is threaded to the third cap 205. The tail of the capillary needle 201 passes through the first cap 202 and the second cap 203. The first connecting seat 204 is provided with a pneumatic drive inlet 207, and the chemical substance channel 2012 in the capillary needle 201 is connected to the pneumatic drive inlet 207 through the chemical conduit 211. Of course, a through hole is provided on the side wall of the capillary needle 201 near the tail, and the corresponding second cap 203 is provided with a wire outlet 208 to facilitate the lead-out of the wire 2013 in the liquid metal channel 2011. This application embodiment does not specifically limit the number of chemical substance channels 2012 and liquid metal channels 2011 in the capillary needle; the capillary needle 201 may include multiple liquid metal channels 2011 and one chemical substance channel 2012. The pneumatic drive inlet 207 can be connected to a microinjection pump, which increases the gas pressure in the chemical substance channel 2012 to release the chemicals in the chemical substance channel 2012. Figure 4 This is a diagram illustrating the tip structure of a capillary needle provided in an embodiment of this application. Figure 5 This is a schematic diagram of the cross-sectional area of ​​the tip of a capillary needle provided in an embodiment of this application, combined with... Figure 4 and Figure 5 It includes six liquid metal channels 2011 and one chemical substance channel 2012, with the six liquid metal channels 2011 arranged around the chemical substance channel 2012; the diameter of the liquid metal channels 2011 is 7 μm and the diameter of the chemical substance channel 2012 is 10 μm. Figure 6 An internal structural diagram of a capillary needle provided in an embodiment of this application is shown below. Figure 6As shown, the liquid metal channel 2011 contains liquid metal and a wire 2013. The liquid metal is located at the tip of the capillary needle 201, and the wire 2013 extends from the needle tip to a through hole near the needle tail. The wire 2013 is used to connect to a power source. The liquid metal and the wire 2013 form an electrode that can electrically activate cells. To facilitate the position adjustment of the combined activation mechanism 2, the first fixing rod 206 of the first needle holder can be connected to a robotic arm (not shown in the figure), and the position adjustment of the combined activation mechanism can be achieved by controlling the robotic arm. The first annular washer 209 and the second annular washer 210 in the first needle holder are used to deform and fix the tail of the capillary needle 201 when squeezed by the cap. In this embodiment, the capillary needle 201 is detachably connected to the first needle holder, which facilitates the replacement of the capillary needle 201.

[0044] To gain a clearer understanding of the structure of the aforementioned joint activation mechanism, Figure 7 A process flow chart for preparing a capillary needle tip is provided in the embodiments of this application. The following is in conjunction with... Figure 7 This section introduces the fabrication process of the capillary needle tip in the combined activation mechanism:

[0045] (1) Drawing a glass tube to form capillary needles. Preferably, a capillary needle drawing instrument is used to heat and draw the glass tube to a predetermined shape and size. Before drawing, the glass tube is prefabricated, with a central chemical substance channel of 1 mm diameter and six microtubes (liquid metal channels) of 0.7 mm diameter surrounding the chemical substance channel. The glass tube is heated and drawn by the drawing instrument to form a 10 μm chemical substance channel and six 7 μm liquid metal channels.

[0046] (2) Liquid metal is injected from the end of the capillary needle glass tube into six glass microtubes with a diameter of 7 μm. Preferably, a high-precision syringe is used to inject the liquid metal from the end of the capillary needle. In this device, the liquid metal is gallium-based, but the liquid metal is not limited to gallium-based liquid metal. The chemical substance channels need to be blocked during liquid metal injection to prevent liquid metal from flowing into the chemical substance channels.

[0047] (3) Throw the liquid metal toward the tip of the capillary needle. As a preferred option, use the huge centrifugal force generated by the high speed of the centrifuge to throw the liquid metal toward the tip of the capillary needle until the liquid metal fills the needle tip without air bubbles when observed under a microscope. Before the centrifuge is started, set the speed of the centrifuge to 6500 r / min and the duration to 1-2 minutes. The speed and time can also be adjusted according to the diameter of the capillary needle.

[0048] (4) Trimming the tip of the capillary needle electrode. Preferably, the tip of the capillary needle is trimmed using a needle forging machine to ensure the trimmed tip diameter meets requirements. After forging and polishing, the tip ultimately forms a 10 μm chemical channel and a 7 μm liquid metal channel. Before the liquid metal oxidizes and solidifies, six wires are led out from the tail of the capillary needle glass tube to connect to a power source, forming a liquid metal capillary needle electrode. The liquid metal exposed to air quickly oxidizes, forming a thin solid oxide film of approximately 1 nm. This helps stabilize the shape of the liquid metal capillary needle electrode and prevents liquid metal from flowing out from the tip, thus affecting the electrode's performance.

[0049] Figure 8 As shown in Figure 8, a structural diagram of a cell holding mechanism provided in this application embodiment is provided. The cell holding mechanism includes a cell holding needle 301 and a second needle holder. The cell holding needle 301 is connected to the second needle holder, and the second needle holder is provided with an air inlet 307, which communicates with the cell holding needle 301. The second needle holder includes a fourth cap 302, a fifth cap 303, a second connecting seat 304, a sixth cap 305, a second fixing rod 306, an air inlet 307, a gas pipe 308, a third annular washer 309, and a fourth annular washer 310. B represents the tip of the cell holding needle. This application does not specifically limit the cell holding needle 301. The tip of the cell holding needle 301 is made of a prefabricated glass tube with an inner diameter of 15 μm and an outer diameter of 100 μm. During operation, it uses the principle of negative pressure to hold early embryos, keeping the cells in a relatively stable state. The cell holding mechanism 3 can be lowered or held at any time. More importantly, when the cells are placed on the culture dish, the cell holding mechanism 3 can be moved to different positions around the cells and then held, achieving the purpose of adjusting the cell posture, which is very convenient and has high convenience and repeatability. To facilitate the position adjustment of the cell holding mechanism 3, the second fixing rod 306 of the second needle holder can be connected to a robotic arm (not shown in the figure), and the position adjustment of the cell holding mechanism 3 can be achieved by controlling the robotic arm. The third annular washer 309 and the fourth annular washer 310 in the second needle holder are used to deform and fix the tail of the cell holding needle 301 when squeezed by the cap.

[0050] In the above embodiments, the combined activation device for early embryos has been described in detail. This application also provides embodiments corresponding to the combined activation method for early embryos.

[0051] Figure 9 A flowchart of a combined activation method for early embryos provided in this application embodiment is shown below. Figure 9 As shown, the combined activation methods for early embryos include:

[0052] S10: After the cell holding mechanism fixes the early embryo, the combined activation mechanism continuously supplies high-voltage DC pulses to the target site of the early embryo to electrically activate the early embryo.

[0053] S11: After the early embryo is electrically activated, the combined activation mechanism is controlled to release chemicals to chemically activate the early embryo.

[0054] The above method can be controlled by a controller connected to the cell-holding mechanism and the combined activation mechanism. Target areas in early embryos include the nuclear material region, etc. The specific process is as follows:

[0055] (1) Early embryo fixation stage: Mouse or pig oocytes are fused with sperm in vitro to form fertilized eggs. The early embryos are placed on a culture dish and then fixed with a cell holding mechanism 3 to prevent the early embryos from moving or rotating.

[0056] (2) Activation stage of early embryo: The early embryo is activated using the combined activation mechanism 2. During the electro-activation process, a high voltage DC pulse is continuously applied, with a voltage of 3.2V and a pulse width of 50-100μs. When the early embryo is electro-activated, the permeability of the cell membrane increases. At this time, the chemical solution is released and enters the early embryo through the cell membrane, rapidly activating a series of metabolic reactions in the early embryo.

[0057] (3) Early embryo position adjustment stage: After activating one side of the cell membrane of the early embryo using the combined activation mechanism 2, the cell position should be changed. At this time, the cell holding mechanism 3 (based on negative pressure) should be used to adjust the position of the early embryo. When the early embryo is placed on the culture dish, the cell holding mechanism 3 is moved to different positions around the early embryo, and then the early embryo is held to achieve the purpose of adjusting the position of the embryo. After the adjustment is completed, the operation of the embryo activation stage is repeated.

[0058] The present application provides a method for the combined activation of early embryos. By electroactivating the cell membrane of early embryos, the stability of the phosphodiester bimolecular structure of the membrane is altered, and many reversible micropores are formed on the cell membrane. At this time, calcium ion carriers and ionomycin released by chemical activation enter the cell through the micropores, activating a series of metabolic reactions in the early embryo, thereby greatly increasing the survival rate of embryo development. This method is of great significance for the in vitro development of early embryos.

[0059] The foregoing provides a detailed description of a combined activation apparatus and method for early embryos provided in this application. The various embodiments in the specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since it corresponds to the method disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to in the method section. It should be noted that those skilled in the art can make several improvements and modifications to this application without departing from the principles of this application, and these improvements and modifications also fall within the protection scope of the claims of this application.

[0060] It should also be noted that, in this specification, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

Claims

1. A combined activation device for early embryos, characterized in that, include: Petri dishes are used to store early-stage embryos; A cell holding mechanism is used to adjust the position of the early embryo and fix the early embryo. The combined activation mechanism includes a capillary microneedle and a first needle holder, the capillary microneedle being connected to the first needle holder; the capillary microneedle includes a liquid metal channel and a chemical substance channel; the liquid metal channel contains liquid metal and a wire, the liquid metal being located at the tip of the capillary microneedle, the wire being used to connect to an excitation power source, the liquid metal and the wire constituting a liquid metal electrode for electro-activating the early embryo; the chemical substance channel is used to release chemical substances for chemical activation of the early embryo. The first needle holder includes a first cap, a second cap, a first connecting seat, a third cap, and a first fixing rod; The first cap is threadedly connected to the second cap, the second cap and the third cap are both threadedly connected to the first connecting seat, and the first fixing rod is threadedly connected to the third cap; The tail of the capillary needle passes through the first cap and the second cap. The first connecting seat is provided with a pneumatic drive inlet. The chemical substance channel in the capillary needle is connected to the pneumatic drive inlet. The cell holding mechanism includes a cell holding needle and a second needle holder. The cell holding needle is connected to the second needle holder, and the second needle holder is provided with an air guide port, which is in communication with the cell holding needle. The capillary needle includes a plurality of liquid metal channels and a chemical substance channel, wherein the plurality of liquid metal channels are arranged around the chemical substance channel; The bottom of the culture dish is provided with an array of micropits, which are used to prevent the early embryos from moving. The diameter of the liquid metal channel is 7 μm; The diameter of the chemical substance channel is 10 μm; The cell holding needle has an inner diameter of 15 μm and an outer diameter of 100 μm. The micro-pit has a diameter of 150 μm and a depth of 50 μm.

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