Chemical delivery system and method

Abstract

The present application belongs to the technical field of chemical delivery. In order to solve the problems of difficult operation and poor stability in the process of chemical delivery in the process of oocyte / embryo freezing treatment by using the existing method, the present application discloses a chemical delivery system and method, wherein the system comprises a carrier and a chip; the carrier is provided with a groove for containing a solution; the chip is provided with an interval and the chemical to be delivered is arranged in the interval, and the coverage area of the interval is greater than the opening area of the groove; the chip and the carrier can move relative to each other, the chemical to be delivered in the interval can fully cover and contact the solution in the groove, and a free diffusion is formed between them. By the present application, the difficulty of the operation can be reduced, and the stability and reliability of the operation process can be improved in the process of chemical delivery in the process of oocyte / embryo freezing treatment.

Description

Technical Field

[0001] This invention belongs to the field of chemical delivery technology, specifically relating to a chemical delivery system and method for delivering chemicals to biological materials or solutions. Background Technology

[0002] Accurately delivering chemicals to biological materials or base solutions to ensure specific interactions and reactions is crucial in many applications and research. For example, in the cryopreservation of oocytes / embryos, after retrieval, the oocytes / embryos undergo sequential contact with basic culture medium (BS), equilibrium solution (ES), and vitrification solution (VS) before being placed in liquid nitrogen for freezing.

[0003] During the process of handling eggs / embryos with different chemicals, it is necessary to accurately control the contact time between the eggs / embryos and different chemicals according to the concentration of the chemicals to ensure the final freezing effect of the eggs / embryos. For example, regarding the control of the contact time between eggs / embryos and vitrification solution, because vitrification solution is highly toxic, the process of transferring eggs / embryos from the equilibration solution to and from the vitrification solution using traditional methods with glass pipettes needs to be strictly controlled within 60 seconds. This requires operators to accurately deliver the chemicals to the eggs / embryos within a limited time to ensure that the carrier containing the eggs / embryos and residual solution can be placed into liquid nitrogen in time for subsequent freezing treatment.

[0004] However, since eggs / embryos are only about 0.1–0.2 mm in size, practically invisible to the naked eye, operators need to use a microscope to aspirate them from the solution and transfer them to the next container containing a different solution. During this aspiration and retrieval process, it's inevitable that some solution from the previous solution will be carried into the next, affecting the concentration and composition of the new solution. Therefore, when observing the position of the eggs / embryos in real time under a microscope, it's crucial to accurately control not only the timing of aspiration and retrieval but also to prevent excessive solution from being drawn into the glass pipette. This traditional method places extremely high demands on the operator and results in very inconsistent operational outcomes. To address this, Genea Limited of Australia has disclosed an automated egg / embryo vitrification platform (Gavi) to replace manual operators in automatically adding different chemicals during the egg / embryo cryopreservation process, thereby reducing the difficulty and instability of manual operation.

[0005] When using an automated oocyte / embryo vitrification platform (Gavi), after the oocytes / embryos are placed on the appropriate carrier, the robotic arm of the Gavi platform sequentially adds and aspirates different chemicals into the basal solution containing the oocytes / embryos within a specified time period, according to pre-programmed settings and motion positioning, thus automating the process. However, during this automated operation, because the vitrification fluid is denser than water, the oocytes / embryos are usually suspended in the vitrification fluid and easily move with the fluid flow. They can only sink to the bottom of the carrier by their own gravity. Therefore, when the robotic arm adds and aspirates chemicals through the pipette, there is a risk of accidentally dislodging or aspirating the oocytes / embryos. Therefore, this method reduces the amount of solution aspirated, leaving more solution in the carrier to decrease the risk of accidental aspiration of eggs / embryos. However, excessive solution residue in the carrier can lead to an increase in thermal mass, affecting the subsequent freezing rate, adversely impacting vitrification, and even causing the freezing of eggs / embryos to fail.

[0006] Furthermore, because the automated oocyte / embryo vitrification platform (Gavi) uses a robotic arm structure, the overall size of the platform is very large, requiring a large laboratory space for installation and use. This increases the construction and maintenance costs of the laboratory, which is not conducive to its widespread use and reducing the cost of oocyte / embryo freezing. Summary of the Invention

[0007] The main objective of this invention is to provide a chemical delivery system and method to solve the aforementioned problems existing in the prior art, wherein:

[0008] According to one aspect of the present invention, a chemical delivery system is provided, comprising: a carrier and a chip; the carrier having a groove for holding a solution; the chip having a section and a chemical to be delivered within the section, the coverage area of ​​the section being larger than the opening area of ​​the groove; the chip and the carrier being movable relative to each other, the chemical to be delivered located in the section being able to make full-coverage contact with the solution in the groove, and forming free diffusion between the two.

[0009] When the chemical to be dispensed is a solution, a gel is selected to hold the chemical and is embedded and fixed within the area of ​​the chip.

[0010] The lower end of the interval is provided with a permeable membrane, forming a groove-shaped structure; the membrane is used to provide support for the chemical to be released.

[0011] The permeable membrane is selected from perforated membranes, mesh membranes, or dialysis membranes.

[0012] The permeable film is selected from water-soluble films.

[0013] The chip has a plate-like frame structure and multiple sequentially arranged sections for fixing the chemicals to be released.

[0014] The chip has an open structure at both ends.

[0015] The chip includes at least two support plates and at least one partition plate; wherein the support plates are arranged in parallel to each other, and the partition plate is located between two adjacent support plates and divides the area between two adjacent support plates into independent intervals.

[0016] The partition and the support plate are connected movably, and the size of the interval can be freely adjusted.

[0017] The opposing surfaces of two adjacent support plates are provided with sliding grooves, and the end of the partition is located in the sliding groove and can slide freely in the sliding groove.

[0018] Wherein, the included angle between the groove wall and the groove bottom in the groove is ≤90°.

[0019] The system also includes a substrate; the substrate is used to place and fix the carrier and is provided with two parallel tracks; the tracks provide support and fixation for the chip, so that the lower surface of the chip is in contact with the upper surface of the carrier.

[0020] The track and the chip are detachably attached and fixed together.

[0021] The track and the chip are connected by magnetic adsorption, wherein the track is made of ferromagnetic metal and the chip is equipped with a magnet.

[0022] The substrate has a light-transmitting area that allows light to pass through, and the light-transmitting area corresponds to the area where the groove is located.

[0023] The light-transmitting area has a hollow structure.

[0024] The light-transmitting area adopts a light-transmitting heating plate structure.

[0025] The system also includes a base, and a drive unit is provided on the base; wherein the carrier is kept relatively fixed to the base, and the drive unit is connected to the chip for driving the chip to slide horizontally relative to the carrier.

[0026] The system also includes a base, on which a drive unit is provided; wherein the chip is fixed relative to the base, and the drive unit is connected to the carrier for driving the carrier to slide horizontally relative to the chip.

[0027] The base also has a hollow area; the hollow area is used to transmit light and corresponds to the area where the groove is located.

[0028] According to another aspect of the present invention, a chemical delivery method is also provided, comprising:

[0029] Step S1, fix the carrier for holding the solution: fix the carrier with the groove horizontally, so that the groove is kept with the opening facing upward, wherein the angle between the groove wall and the bottom of the groove is ≤90°;

[0030] Step S2, setting up the chip containing the chemical to be applied: placing the chip containing the chemical to be applied on the carrier, so that the chemical to be applied is in contact with the upper surface of the carrier and the chip is spaced apart from the groove to avoid the chip covering the groove;

[0031] Step S3: Add the solution into the groove of the carrier, and make the liquid level of the solution higher than the groove.

[0032] Step S4: Drive the carrier and the chip to move relative to each other, so that the chemical to be added comes into direct contact with the solution and forms free diffusion between them, thus completing the addition of the chemical into the groove.

[0033] The chip has multiple sections, each containing a different chemical to be dispensed in a specific order. The contact time between each chemical and the solution in the groove is controlled by adjusting the size of the sections and the speed of the chip's movement.

[0034] By employing the above-described technical solution of the present invention, the difficulty of chemical administration during the freezing of eggs / embryos can be reduced, the embryos can be protected during the chemical administration process, and the stability and reliability of the operation can be improved. Attached Figure Description

[0035] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings:

[0036] Figure 1 This is a schematic diagram of the chemical delivery system in Example 1;

[0037] Figure 2This is a schematic diagram of the external structure of the carrier in Example 1;

[0038] Figure 3 This is a schematic diagram of the external structure of the chip in Example 1;

[0039] Figure 4 This is a schematic diagram of the chemical delivery process during the cryopreservation of embryo glass using the chemical delivery system in Example 1;

[0040] Figure 5(a) shows the situation along... Figure 1 A partial schematic diagram of the chip's partition plate and groove first contacting each other in the H-direction;

[0041] Figure 5(b) shows the route along Figure 1 A partial schematic diagram of the initial contact between the gel and the groove in the chip along the H-direction;

[0042] Figure 6 for Figure 2 Enlarged schematic diagram of the local structure at point A;

[0043] Figure 7 This is a schematic diagram of the chemical delivery system in Example 2;

[0044] Figure 8 This is a schematic diagram of the external structure of the substrate in Example 2;

[0045] Figure 9 This is a schematic diagram of the chemical delivery system in Example 3. Detailed Implementation

[0046] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings and examples of the addition of different chemical solutions during the vitrification and freezing of embryos.

[0047] Example 1

[0048] Combination Figure 1 As shown in this embodiment, the chemical delivery system for the glass freezing process of embryos includes a carrier 1 and a chip 2, wherein the carrier 1 is used to hold the embryos to be processed and related solutions, and the chip 2 is used to carry different chemical solutions for sequential delivery.

[0049] Combination Figure 2 As shown, the carrier 1 is a strip-shaped structure, including a handle 11, a thin sheet 12, and a groove 13. The groove 13 is located near the front end of the thin sheet 12 and is used to hold the embryos to be processed and related solutions. The size of the groove 13 can be adjusted according to the number and size of the embryos to be processed and the amount of solution to be held. In this embodiment, the size of the groove is directly designed based on the amount of solution remaining during subsequent freezing treatment, thereby precisely controlling the final amount of solution remaining in the groove.

[0050] In this embodiment, the entire carrier adopts a strip-shaped structure to facilitate embryo freezing operations with existing cryopreservation systems, improving the compatibility of the carrier with existing equipment. Simultaneously, the handle portion of the carrier is preferably designed with sufficient width to allow for labeling of relevant information on the embryos to be processed. The sheet is made of a uniformly thick, transparent, biocompatible plastic material with good thermal conductivity, ensuring suitability for holding embryos and the speed of heat transfer during subsequent freezing. Similarly, in other embodiments, depending on the operating conditions and requirements, the carrier can also be designed with other grooved structures, such as a flat plate structure.

[0051] Combination Figure 3 As shown, chip 2 adopts a plate-like frame structure and has multiple sequentially arranged intervals 22 for fixing the chemicals to be added. In this embodiment, chip 2 adopts a frame structure composed of two support plates 20 and two partitions 21. The two support plates 20 are parallel, the two partitions 21 are parallel, and the two partitions 21 are located between the two support plates 20, dividing the area between the two support plates 20 into three independent intervals 22, each used to set different chemicals to be added. In this embodiment, for the chemical solutions to be added during the embryo vitrification process, the basal culture medium is directly placed into the groove along with the embryo beforehand. The three intervals 22 in chip 2 are respectively provided with pre-equilibration solution, equilibration solution, and vitrification solution. The pre-equilibration solution has the lowest concentration of cryoprotectant, and the vitrification solution has the highest concentration of cryoprotectant. The pre-equilibration solution, equilibration solution, and vitrification solution are all placed on chip 2 in the form of gel 23.

[0052] Furthermore, in this embodiment, with the basal culture medium pre-added directly to the groove, three sections are created on the chip to hold solutions of cryoprotectants with different concentrations, thereby accurately controlling the concentration relationship of different solutions sequentially added to the embryo and ensuring the precision of solution addition. Similarly, in other embodiments, the number of sections on the chip can be arbitrarily adjusted according to the type and quantity of chemicals to be added and the concentration control requirements, accurately controlling the concentration gradient between chemicals in adjacent sections and ensuring the precision of chemical addition.

[0053] Preferably, the partition 21 and the support plate 20 in the chip 2 can be designed to be movably connected, so that the size of the interval 22 can be freely adjusted. For example, by providing grooves on the opposite sides of the two support plates 20, the end of the partition 21 can be inserted into the groove, so that the position of the partition 21 can be freely adjusted in the groove, thereby realizing the adjustment of the size of the interval and meeting the requirements for carrying different amounts of chemicals.

[0054] Combination Figures 1 to 4 As shown, the specific steps for adding different solutions during the cryopreservation of embryos using the chemical delivery system of this embodiment are as follows:

[0055] Step S1: Fix the carrier used to hold the embryos to be processed and the basic culture medium. Place the carrier 1 with the groove 13 horizontally and fix it, keeping the opening of the groove 13 facing upward.

[0056] Step S2: Set the chip containing the chemical to be added.

[0057] First, the pre-equilibration solution, equilibration solution, and vitrification cryosol are each prepared into gel structures and fixed in the three corresponding regions of the chip according to the order of addition. The gels can be prepared using conventional physical hydrogel preparation methods, such as those for sodium alginate, gelatin, or agarose gels, or conventional chemical hydrogel preparation methods, such as those for PEGDA or GelMA hydrogels.

[0058] Then, the chip 2 with gel is placed horizontally on the carrier 1, so that the gel 23 is in contact with the upper surface of the carrier 1, and a certain horizontal distance is maintained between the chip 2 and the groove 13 to avoid the chip 2 covering the groove 13 at this time.

[0059] Step S3: The embryo to be processed is transferred into the groove 13 of the carrier 1, and the groove 13 is filled with basic culture medium. The surface tension of the liquid causes the top of the basic culture medium to form a hemispherical structure and extend to the outside of the groove 13.

[0060] In step S4, the chip 2 is moved along the length of the carrier 1, allowing the three gels carrying different chemicals on the chip 2 to slide sequentially over the groove 13. When the gel 23 on the chip 2 comes into contact with the solution above the groove 13, the solution in the gel and the solution in the groove merge, and under the influence of the concentration difference, solution exchange begins. This allows the solution in the gel to gradually diffuse into the groove 13 and eventually enter the embryo, thus completing the chemical delivery into the groove 13. Simultaneously, because the coverage area of ​​the gel 23 is larger than the opening size of the groove 13, the groove remains covered by the gel during the exchange of solutions, preventing the embryo from overflowing. Furthermore, during the above process, the movement and pausing of the chip can be controlled at any time as needed to maintain the effective concentration difference between the solution in the gel and the solution in the groove, improving the delivery speed and efficiency of the solution from the gel into the groove.

[0061] Combination Figure 3As shown, in this embodiment, the intervals at both ends of the chip 2 are designed as open structures and the width of the partition between the intervals is reduced. This allows the chip to contact the solution in the groove first, rather than the partition, when it moves relative to the carrier. Furthermore, the chip can quickly pass through the partition position during the movement, thus shortening the contact time and contact area between the partition and the solution in the groove.

[0062] As shown in Figure 5(a), when the partition 21 and the sheet 12 form a corresponding "contact" relationship, the partition 21 and the sheet 12 cannot be completely flat and there are actually gaps. At this time, when the gel 23 comes into contact with the solution in the groove 13, the gap between the partition 21 and the sheet 12 will form a capillary effect on the solution in the groove 13, causing the solution in the groove 13 to fill the gap. In this way, during the diffusion and exchange process between the gel 23 and the solution in the groove 13, there is also a risk that the embryo may be carried out of the groove due to the solution in the groove 13 flowing to the gap between the partition 21 and the sheet 12.

[0063] Conversely, as shown in Figure 5(b), when gel 23 comes into contact with sheet 12, since there is a thin layer of solution on the surface of gel 23, the surface solution of gel 23 will form a close contact with the surface of sheet 12, eliminating the gap between gel 23 and sheet 12. In this way, when gel 23 and sheet 12 are in close contact, when gel 23 comes into contact with the solution in groove 13, the solution in groove 13 will no longer be affected by capillary action and flow, so that diffusion exchange between gel 23 and solution in gel 23 can be carried out stably, so that the embryo can remain stably in groove 13, thereby improving the protection of the embryo in groove.

[0064] Preferred, combined Figure 6 As shown, in this embodiment, the angle between the bottom 131 and the wall 132 of the groove 13 is designed as a 90° vertical structure. This reduces the risk of the embryo gradually "climbing out" of the groove along the wall as the solution flows within it, thus improving control over the embryo's position within the groove. Similarly, the angle between the wall and the bottom of the groove can be further designed as an acute angle less than 90°, thereby further increasing the difficulty for the embryo to "climb out" of the groove along the wall.

[0065] Furthermore, in other embodiments, the chip and the carrier can even employ other forms of relative movement, such as a composite movement including relative horizontal and vertical movement. This allows the area on the chip to contact and detach from the groove in the vertical direction, completely avoiding horizontal contact movement between the chip and the carrier, thereby further reducing the risk of the embryo being accidentally carried out of the groove horizontally. Alternatively, the carrier and chip can be arranged vertically, creating relative movement in the vertical direction. This allows for quick and convenient transfer of the vertically arranged carrier to the freezing equipment, improving the ease of carrier transfer.

[0066] Preferably, the gel preparation process involves directly preparing the pre-equilibration liquid, equilibration liquid, and vitrification liquid within the chip's compartment. This allows the gel to be directly integrated with the chip during formation, improving operational efficiency. First, the chip is placed horizontally on a worktable. The lower end of the compartment is temporarily sealed using the worktable, creating a groove-shaped structure. Then, the relevant solutions and reagents for preparing the gel-formed chemical are sequentially added into the compartment. As the gel forms within the compartment, it simultaneously establishes a fixed connection with the chip, thus completing the preparation of the chip containing the gel-formed chemical in one step. To enhance the bonding strength between the gel and the chip, a fixing groove can be pre-formed on the inner surface of the compartment within the chip. The formed gel portion is positioned within this groove, creating an embedded connection between the gel and the chip, further strengthening the bond.

[0067] In other embodiments, the pre-equilibration solution, equilibration solution, and vitrification cryosol can also be fixed on the chip in other forms to complete subsequent diffusion exchange with the solution in the groove. For example, a perforated membrane, mesh, or dialysis membrane of appropriate thickness and pore size can be placed on the lower surface of the chip, and the solution to be added can be directly added into the groove. The perforated membrane, mesh, or dialysis membrane provides support for the solution to be added. In this way, while the perforated membrane, mesh, or dialysis membrane forms a cover over the groove to prevent embryo leakage, when both sides of the perforated membrane, mesh, or dialysis membrane are in contact with the solution, solution penetration can occur to complete the diffusion exchange of solutions on both sides.

[0068] Furthermore, although only one groove is provided on the carrier given in this embodiment, in actual use, multiple grooves can be provided on the carrier at the same time depending on the number of embryos to be processed. This allows multiple embryos to be processed on the same carrier at the same time, thereby improving processing efficiency.

[0069] Example 2

[0070] Combination Figure 7 and Figure 8As shown, in this embodiment, the chemical delivery system used in the glass cryopreservation process for embryos also includes a carrier 1 and a chip 2, and further includes a substrate 3. The substrate 3 is a channel steel structure, wherein the middle area of ​​the substrate 3 is used to support and fix the carrier 1, and the two sidewalls along its length can serve as tracks 31 to provide support and adsorption fixation for the support plate 20 of the chip 2. By changing the height of the tracks 31, the positional relationship between the chip 2 and the upper surface of the carrier 1 can be adjusted, thereby ensuring effective contact between the gel and the solution in the groove.

[0071] Similarly, in other embodiments, a guide step can be provided on each of the two tracks. This way, when the chip is placed between the two guide steps, the guide steps can guide the chip's movement, thereby improving the directional accuracy of the chip's movement on the substrate.

[0072] Combination Figure 3 and Figure 8 As shown, the track 31 and the chip 2 are detachably fixedly connected by magnetic adsorption. For example, the track 31 is made of ferromagnetic metal and magnets 24 are provided at corresponding positions on the support plate 20, thereby forming a magnetic adsorption fixed connection between the track 31 and the chip 2. More preferably, the track can also adopt an electromagnet structure, so that the rapid connection and disconnection between the substrate and the chip can be achieved through electrical control, improving the convenience of operation.

[0073] In this embodiment, by setting a substrate, not only can the carrier be supported and fixed, for example by adhesive or snap-fit ​​connection between the substrate and the carrier, ensuring the stability of the carrier position during the entire operation, but the chip can also be supported and fixed, maintaining effective contact between the chip and the carrier, and preventing accidental detachment during relative movement of the chip and the carrier, which would affect the normal operation. At the same time, the substrate can also collect the solution flowing to the outside of the groove, preventing the solution from overflowing and causing pollution to the surrounding environment.

[0074] Combination Figure 8 As shown, in this embodiment, a light-transmitting area 32 is also provided in the middle of the substrate 3. That is, the area in the substrate 3 corresponding to the groove 13 is formed by selecting a light-transmitting material to create a light-transmitting area. At this time, with the help of the light transmitted through the light-transmitting area, the carrier and chip as a whole can be moved through the substrate to be directly observed under a microscope, realizing real-time observation of the chemical dispensing process and accurately controlling the dispensing progress of the chemicals.

[0075] Furthermore, depending on the actual operational needs, the light-transmitting area can either use conventional light-transmitting materials to meet the light transmission requirements alone, or it can use light-transmitting materials with heating functions, such as heated glass, so as to simultaneously meet the purposes of light transmission and temperature control.

[0076] Furthermore, although only one carrier and one chip are set on the substrate in this embodiment, in actual operation, multiple carriers can be set side by side on the substrate at the same time, depending on the number of embryos to be processed and the width of the chip, i.e. the coverage width of the gel. Thus, during a single movement of the chip, the chemical delivery operation to the embryos on multiple carriers can be completed simultaneously, improving operational efficiency.

[0077] Example 3

[0078] Combination Figure 9 As shown, in this embodiment, the chemical delivery system for the glass cryopreservation process of embryos includes, in addition to the carrier 1, chip 2, and substrate 3, a base 4 for directly supporting and fixing the substrate 3. A drive unit consisting of a stepper motor 41, a lead screw 42, and a push rod 43 is mounted on the base 4. The substrate 3 is located on the base 4 and is parallel to the lead screw 42. The push rod 43 is sleeved on the lead screw 42 and can reciprocate along the lead screw 42 under the drive of the stepper motor 41. The push rod 43 is also fixedly connected to the chip 2.

[0079] At this point, by driving the push rod 43 to move horizontally back and forth along the lead screw 42 via the stepper motor 41, the chip 2 can be moved horizontally back and forth relative to the carrier 1. This controls the gel in different sections of the chip 2 to contact the solution in the groove 13 sequentially, achieving automated control. Furthermore, by controlling the movement of the stepper motor 41, the contact time between different gels in the chip 2 and the solution in the groove 13 can be precisely controlled, thereby accurately controlling the dispensing time of the solution in the gel and the contact time between the embryo and different solutions, further improving the accuracy of dispensing different solutions to the embryo.

[0080] In addition, in other embodiments, a track slider structure can be used to replace the lead screw and push rod to form a drive unit, and the chip can be moved relative to the carrier by the reciprocating movement of the slider along the track.

[0081] Combination Figure 9 As shown, an optical axis 44 is also provided on the base 4 in this embodiment. The optical axis 44 is parallel to the lead screw 42 and connected to the free end of the push rod 43. It is used to provide auxiliary guidance for the reciprocating movement of the push rod 43, improve the stability of the push rod 43 driving the chip 2 to move, and improve the stability of the contact process between the gel and the solution in the groove.

[0082] Preferred, combined Figure 9As shown, a hollow area 45 is also provided in the middle of the base 4, that is, the area corresponding to the light-transmitting area of ​​the chip 2 is a hollow structure. This ensures that light can pass smoothly through the base 4 and be projected onto the light-transmitting area of ​​the chip 2, ensuring the normal use of the microscope. Similarly, depending on the actual use in different environments, the hollow area can also be made of a light-transmitting material, such as light-transmitting glass, to achieve the purpose of light transmission. Alternatively, a light-transmitting material with heating function, such as heated glass, can be selected to simultaneously satisfy the purposes of light transmission and temperature control.

[0083] Furthermore, although the above-described embodiments 1, 2, and 3 all use the operation of adding different chemical solutions during the vitrification and freezing of embryos as examples to introduce the technical solution of the present invention, those skilled in the art can fully apply the chemical delivery system to the operation of accurately delivering chemicals to other biological materials or base solutions based on the concept of the present invention. For example, when adding powdered chemicals to a solution, a water-soluble film can be used to temporarily support the amount of chemicals added at one time. During the movement of the chip relative to the carrier, when the water-soluble film comes into contact with the solution and dissolves, a quantitative amount of chemicals can be directly released into the solution, thereby completing the accurate delivery of chemicals.

[0084] The present invention has at least one of the following beneficial effects:

[0085] 1. In this invention, embryos and basal culture medium are pre-placed on a carrier with grooves. All chemicals to be added are sequentially fixed onto a chip with designated sections, where the coverage area of ​​the chemicals in each section is larger than the opening area of ​​the groove. As the chip moves relative to the carrier surface, the chemicals slide across the chip and contact the solution within the groove, allowing for free diffusion. This displacement between the chemicals and the solution in the groove facilitates the sequential addition and removal of different chemicals. Thus, even when the chemicals cover the entire groove, the solution displacement between the chemicals and the solution avoids the risk of the embryo being washed out due to large-scale flow of the solution within the groove. It also avoids the risk of accidentally removing the embryo when using suction to remove the solution from the groove, thereby protecting the embryo during chemical addition and improving the reliability and stability of the entire operation.

[0086] 2. In this invention, by making the chemical solution into a gel structure, it is not only easy to fix and connect it to the chip, improving the convenience of operation, but also ensures effective diffusion and replacement between the solution in the gel and the solution in the groove when the gel comes into contact with the solution in the groove, ensuring the effective delivery and discharge of the chemical.

[0087] 3. In this invention, by controlling the size of the groove, the residual amount of solution in the groove can be precisely controlled when the solution is drained by replacing the solution in the groove with chemicals, thereby ensuring the effect and quality of subsequent embryo freezing.

[0088] 4. The chemical delivery system of the present invention is not only simple in structure, small in space and low in manufacturing cost, but also can simultaneously process multiple groups of biological materials to achieve higher processing efficiency and lower cost.

[0089] The above description is merely an embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of the claims of the present invention.

Claims

1. A chemical delivery system, characterized in that, The device includes a carrier and a chip. The carrier has a groove for holding a solution. The chip has a section and a chemical to be dispensed is placed within the section. The coverage area of ​​the section is larger than the opening area of ​​the groove. The chip covers the carrier, and the chip and the carrier move relative to each other. The chemical to be dispensed in the section makes full contact with the solution in the groove, so that the chemical to be dispensed in the section keeps in contact with the upper surface of the carrier and forms free diffusion between them. When the chemical to be dispensed is a solution, a hydrogel is used to hold the chemical and embed it within the area of ​​the chip; or a permeable film is provided at the lower end of the area to form a groove-shaped structure; the film is used to provide support for the chemical to be dispensed.

2. The chemical delivery system according to claim 1, characterized in that, The permeable membrane may be a perforated membrane, a mesh membrane, or a dialysis membrane.

3. The chemical delivery system according to claim 1, characterized in that, The permeable membrane is selected from water-soluble membranes.

4. The chemical delivery system according to claim 1, characterized in that, The chip has a plate-like frame structure and multiple sequentially arranged sections for fixing the chemicals to be released.

5. The chemical delivery system according to claim 4, characterized in that, The chip has an open structure at both ends.

6. The chemical delivery system according to claim 4, characterized in that, The chip includes at least two support plates and at least one partition plate; wherein the support plates are arranged in parallel to each other, and the partition plate is located between two adjacent support plates and divides the area between two adjacent support plates into mutually independent intervals.

7. The chemical delivery system according to claim 6, characterized in that, The partition and the support plate are connected movably, and the size of the interval can be freely adjusted.

8. The chemical delivery system according to claim 7, characterized in that, The opposing surfaces of two adjacent support plates are provided with sliding grooves, and the end of the partition is located in the sliding groove and can slide freely in the sliding groove.

9. The chemical delivery system according to claim 1, characterized in that, The included angle between the groove wall and the groove bottom is ≤90°.

10. The chemical delivery system according to any one of claims 1-9, characterized in that, The system also includes a substrate for placing and fixing the carrier, and is provided with two parallel tracks; the tracks provide support and fixation for the chip, so that the lower surface of the chip is in contact with the upper surface of the carrier.

11. The chemical delivery system according to claim 10, characterized in that, The track and the chip are detachably attached by adsorption.

12. The chemical delivery system according to claim 11, characterized in that, The track and the chip are connected by magnetic adsorption, wherein the track is made of ferromagnetic metal and the chip is equipped with a magnet.

13. The chemical delivery system according to claim 10, characterized in that, The substrate has a light-transmitting area that allows light to pass through, and the light-transmitting area corresponds to the area where the groove is located.

14. The chemical delivery system according to claim 13, characterized in that, The light-transmitting area adopts a hollow structure.

15. The chemical delivery system according to claim 13, characterized in that, The light-transmitting area adopts a light-transmitting heating plate structure.

16. The chemical delivery system according to any one of claims 1-9, characterized in that, The system also includes a base, on which a drive unit is provided; wherein the carrier is fixed relative to the base, and the drive unit is connected to the chip for driving the chip to slide horizontally relative to the carrier.

17. The chemical delivery system according to any one of claims 1-9, characterized in that, The system also includes a base, on which a drive unit is provided; wherein the chip is fixed relative to the base, and the drive unit is connected to the carrier for driving the carrier to slide horizontally relative to the chip.

18. The chemical delivery system according to claim 16, characterized in that, The base also has a hollow area; the hollow area is used to transmit light and corresponds to the area where the groove is located.

19. The chemical delivery system according to claim 17, characterized in that, The base also has a hollow area; the hollow area is used to transmit light and corresponds to the area where the groove is located.

20. A chemical delivery method for the chemical delivery system of claim 1, characterized in that, include: Step S1, fix the carrier for holding the solution: fix the carrier with the groove horizontally, so that the groove is kept with the opening facing upward, wherein the angle between the groove wall and the bottom of the groove is ≤90°; Step S2, setting up the chip containing the chemical to be applied: placing the chip containing the chemical to be applied on the carrier, so that the chemical to be applied is in contact with the upper surface of the carrier and the chip is spaced apart from the groove to avoid the chip covering the groove; Step S3: Add the solution into the groove of the carrier, and make the liquid level of the solution higher than the groove. Step S4: Cover the chip on the carrier, drive the carrier and the chip to move relative to each other, so that the chemical to be added comes into direct contact with the solution, so that the chemical to be added in the interval keeps in contact with the upper surface of the carrier and forms free diffusion between the two, thus completing the addition of the chemical into the groove.

21. The chemical delivery method according to claim 20, characterized in that, The chip has multiple sections, each containing a different chemical to be dispensed in a specific order. By adjusting the size of the sections and the chip's moving speed, the contact time between each chemical and the solution in the groove can be controlled.

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