In-vitro fertilization and embryo co-culture device capable of automatically changing liquid

Abstract

The utility model discloses an in vitro fertilization and embryo co-culture device capable of automatically changing liquid, which comprises a substrate and a fertilization culture area arranged on the substrate, the fertilization culture area comprises at least two liquid cabins, at least two micro-channels and at least two culture units, and the culture units are recessed inwards to the upper surface of the substrate. Every two adjacent culture units are communicated with each other, the culture units are positioned between the two liquid cabins, and the culture units and the liquid cabins are communicated with each other through micro-channels. The embryo co-culture device integrates external fertilization and embryo co-culture, can realize automatic replacement of a culture solution, optimizes the embryo culture environment, improves the development success rate of embryos, improves the development quality of embryos, and is time-saving and labor-saving.

Description

Technical Field

[0001] The utility model relates to the field of assisted reproduction, and particularly relates to an in vitro fertilization and embryo co-culture device capable of automatically changing liquid. Background Art

[0002] According to the assessment of the World Health Organization, about 1 in every 7 couples has reproductive disorders. A recent survey in China shows that the number of infertile couples accounts for 10% of the number of married couples, more than doubling the 4.8% surveyed in 1984, and the incidence rate is on the rise. Affected by the concept of carrying on the family line in China, most families are eager to have children, which makes infertile couples bear great psychological pressure and even leads to family and social problems such as divorce and extramarital affairs. The direct effect of assisted reproductive technology (ART) is to enable infertile couples to realize the wish of pregnancy and childbirth, and the related problems caused by infertility will naturally be solved accordingly.

[0003] In the in vitro fertilization-embryo transfer (IVF-ET) technology in assisted reproductive technology (ART), which is currently a widely used technology with a relatively high acceptance rate among the public, the traditional embryo culture method in the in vitro fertilization-embryo transfer (IVF-ET) technology is to place the fertilized eggs in a culture dish, add a drop of culture medium of about 30 to 50 microliters, cover it with a layer of culture oil for heat preservation, and then observe the development of the embryos under a microscope. Frequent observation and replacement of the new culture medium are required, which has relatively high requirements for operators, does not form an integrated culture process, and has low efficiency.

[0004] Therefore, it is necessary to develop an embryo culture device that can not only achieve co-culture of multiple embryos, but also realize in vitro fertilization and embryo culture, which is multifunctional, easy to operate, and has a high success rate of embryo development. Summary of the Utility Model

[0005] The technical solution adopted by the utility model to solve the above technical problems is as follows:

[0006] An in vitro fertilization and embryo co-culture device capable of automatically changing liquid, comprising a base and a fertilization and culture area arranged on the base. The fertilization and culture area includes a liquid chamber, a microchannel, and a culture unit. The culture unit is recessed inward to the upper surface of the base. There are at least 2 liquid chambers and 2 culture units respectively. Each adjacent two culture units are communicated with each other. The culture unit is located between two liquid chambers, and the culture unit and the liquid chamber are mutually penetrated through the microchannel.

[0007] Furthermore, it further includes an inclined seat, which is detachably installed at the bottom of the base, and the inclination angle of the inclined seat is 5° to 30°.

[0008] Preferably, the inclination angle of the inclined seat is 10° to 15°, the inclined seat is intelligently electrically controlled, and an anti-slip pad is provided on the surface of the inclined seat.

[0009] Furthermore, the fertilization and culture area has 4 liquid compartments and 16 culture units. Every 2 liquid compartments and every 8 culture units are interconnected through microchannels to form independent culture groups, and there are 2 culture groups in total.

[0010] Furthermore, the microchannel is in the shape of a flared opening, with the large end connecting to the liquid compartment and the small end connecting to the culture unit.

[0011] Furthermore, the base is made of mirror glass material, the liquid compartment has a top cover, and a sampling hole is opened on the top cover.

[0012] Furthermore, the base is made of any one of polypropylene, polycarbonate, or polystyrene, which has high transparency.

[0013] Furthermore, the liquid compartment, the microchannel, and the culture unit are all made of polydimethylsiloxane material, and the addition ratio of the curing agent in the polydimethylsiloxane is 10% to 30%.

[0014] Furthermore, the liquid compartment, the microchannel, and the culture unit are all made of one of silica gel, polycarbonate, polypropylene, or polystyrene.

[0015] Furthermore, a water storage compartment is opened in the fertilization and culture area, water is contained in the water storage compartment, and an upper cover is provided above the culture unit. The upper cover is made of polydimethylsiloxane material.

[0016] The beneficial effects of the present utility model are as follows:

[0017] The communication design between the culture units enables the co-culture of multiple embryos to achieve interaction and communication, which has a positive impact on the development of embryos and improves the development quality of embryos;

[0018] The design of the liquid compartment and the microchannel completely changes the culture method, realizes the automatic microfluid replacement of the culture solution, eliminates the need for frequent manual replacement, and can effectively discharge waste liquid;

[0019] The base of the mirror glass has good light transmittance, enabling the development of embryos to be clearly observed in real time under a microscope during the culture process, and timely adjustments can be made;

[0020] The selection of polydimethylsiloxane material can automatically adjust the pH value and play a certain protective role for embryos. Description of the Drawings

[0021] Figure 1 is a three-dimensional perspective schematic diagram of the present utility model;

[0022] Figure 2 is a front structural schematic diagram of the present utility model;

[0023] Figure 3 is a partially enlarged front structural schematic diagram of the present utility model;

[0024] Figure 4 is a side sectional view of the present utility model;

[0025] Figure 5 is a partially enlarged side sectional view of the present utility model.

[0026] As shown in the figure: 1. Substrate; 2. Liquid chamber; 3. Sampling hole; 4. Microchannel; 5. Culture unit; 6. Water storage chamber; 7. Upper cover. Specific embodiments

[0027] The present utility model will be further described below in conjunction with the accompanying drawings and embodiments, but it is not intended to limit the present utility model.

[0028] As Figures 1 to 4 shown, the present utility model is an in vitro fertilization and embryo co-culture device with automatic liquid change based on continuous liquid supply through a microchannel and co-culture of multiple embryos. It includes a substrate 1 and a fertilization and culture area. The fertilization and culture area is arranged on the substrate 1. The fertilization and culture area includes a liquid chamber 2, a microchannel 4, and a culture unit 5. There are at least two liquid chambers 2. One of them is used for sampling fresh embryo culture medium or semen, and the other is used for storing the discarded and nutrient-depleted embryo culture medium. The culture unit 5 is located between the two liquid chambers 2. Specifically, as Figure 3 shown, there are at least two culture units 5, and the adjacent culture units 5 are connected. As Figure 4 shown, the culture unit 5 is recessed inward to the upper surface of the substrate 1, and the culture unit 5 and the liquid chamber 2 are interconnected through the microchannel 4.

[0029] The principle of its in vitro fertilization is as follows: Place the mature oocytes into the culture unit 5, and then inject the capacitated sperm into one liquid chamber 2 or inject the capacitation solution and uncapacitated sperm into the liquid chamber 2 together. Since the liquid chamber 2, the microchannel 4, and the culture unit 5 are all connected, the sperm will flow and swim along the microchannel 4 towards the culture unit 5 and the other liquid chamber 2 under the pressure difference. When the sperm swims to the culture unit 5 containing the mature oocytes, in vitro fertilization can be achieved. Then, it can be observed under a microscope. If fertilization is successful, the fertilized eggs can be transferred to the corresponding culture device for culture. Of course, it is also possible to directly suck away all other substances except the fertilized eggs in the entire device, inject embryo culture medium into one liquid chamber 2, and directly perform perfusion culture of the fertilized eggs in the culture unit 5 through the microchannel 4.

[0030] The principle of its embryo co-culture is as follows: An embryo is placed inside the culture unit 5, and embryo culture medium is injected into a liquid chamber 2. The embryo culture medium slowly flows into the culture unit 5 through the microchannel 4, providing fresh nutrients for the embryo, achieving microfluidic control for the replacement of the embryo culture medium. Moreover, after the embryo culture medium flows into the culture unit 5, a backflow is bound to form inside the culture unit 5. Therefore, the embryo can rotate slightly inside the culture unit 5. The continuous rotation process is equivalent to "taking a bath", flushing away some dirt or toxic substances released by the embryo. The discarded substances washed away flow along the microchannel 4 to another liquid chamber 2 for collecting waste liquid. Compared with the traditional method of manually replacing and adding culture medium drops, it is more convenient and efficient. Moreover, the traditional method cannot effectively remove dirt and harmful substances, which has a significant adverse impact on the development survival rate of the embryo. Furthermore, because adjacent culture units 5 are connected, the embryos inside can interact during the culture and development process, releasing or absorbing information factors to "communicate" with each other, thereby achieving the purpose of co-culture and improving the development success rate of the embryo.

[0031] Furthermore, in order to enable better flow and control of liquids such as embryo culture medium between the liquid chamber 2, the microchannel 4, and the culture unit 5, the present utility model further includes an inclined seat detachably installed at the bottom of the base 1. The inclination angle of the inclined seat is 5° - 30°. Without the inclined seat, the normal flow is very slow. If you want a faster flow, you can use the inclined seat to achieve the desired slope to ensure that liquids such as embryo culture medium flow at a certain speed. The optimal inclination angle of the inclined seat is 10° - 15°. Additionally, the inclined seat can be designed to be intelligently electrically controlled, so that different inclination angles can be matched according to the setting to achieve the most accurate, simple, and efficient purpose. Moreover, an anti-slip pad can be set on the surface of the inclined seat or anti-slip patterns can be engraved to improve the safety of the culture equipment.

[0032] As Figure 2 shown, in a specific embodiment, the fertilization and culture area has 4 liquid chambers 2 and 16 culture units 5. Every 2 liquid chambers 2 and every 8 culture units 5 are interconnected through the microchannel 4 to form independent culture groups, and there are a total of 2 culture groups. One group can be used for in vitro fertilization, and the other group can be used for embryo culture.

[0033] Preferably, the microchannel 4 is designed in the shape of a flared mouth. Its large end is connected to the liquid chamber 2, and its small end is connected to the culture unit 5.

[0034] In one embodiment, the substrate 1 is made of mirror glass material, and its light transmittance and transparency are much higher than those of traditional polymer material substrates. The light transmittance of the mirror glass substrate 1 can reach more than 99.5%, while the light transmittance of traditional polymer material substrates is 95% or 96%. The mirror glass substrate 1 enables the operator to quickly observe the development of each embryo under the microscope.

[0035] In addition to being made of mirror glass material, the substrate 1 can also be made of materials with high transparency such as polypropylene, polycarbonate, or polystyrene, which can also achieve good observation conditions.

[0036] As Figure 1 shown, in another embodiment, the liquid chamber 2 has a top cover, and a sample injection hole 3 is provided on the top cover. Liquids such as embryo culture medium can be injected into the liquid chamber 2 through the sample injection hole 3.

[0037] In a specific embodiment, the liquid chamber 2, the microchannel 4, and the culture unit 5 in the fertilization and culture area are all made of, but not limited to, polydimethylsiloxane material. The addition ratio of the curing agent in polydimethylsiloxane is 10% to 30%. The polydimethylsiloxane material has thermal stability, chemical inertness, dielectric properties, and excellent biocompatibility, and is flexible and breathable, similar to the skin, with a respiratory effect. Carbon dioxide can penetrate through the polydimethylsiloxane, enabling the pH value of the embryo culture medium in the fertilization and culture area to be maintained at 7.3.

[0038] For traditional materials such as plastics, a lot of oil needs to be covered on the embryo culture medium, which will cause waste of oil. Some toxicity or harmful substances may also be carried in the oil. Using polydimethylsiloxane material does not require oil and can provide an embryo culture environment with low oxygen and high carbon dioxide.

[0039] At the same time, the polydimethylsiloxane material has a certain flexibility and elasticity. When the embryo touches the soft wall of the polydimethylsiloxane in the culture unit 5, it will not cause damage to the embryo, and the environmental comfort during the embryo development process will be better.

[0040] In addition to being made of polydimethylsiloxane material, the liquid chamber 2, the microchannel 4, and the culture unit 5 in the fertilization and culture area can also be made of one of materials such as silica gel, polycarbonate, polypropylene, or polystyrene. These materials can also protect the embryo well, and their cost is relatively lower than that of polydimethylsiloxane. Polydimethylsiloxane can be used as a solution for the best embodiment.

[0041] During the process of embryo culture, the humidity of the culture environment is crucial. In order to provide a certain humidity supplement to the culture environment and reduce the water evaporation of the embryo culture solution, a water storage tank 6 is also provided in the fertilization and culture area. Water is contained in the water storage tank 6. When the embryo is cultured and developed, the water storage tank 6 can increase a certain humidity to the entire culture environment, which is more conducive to embryo culture, improving its success rate and quality. The number of water storage tanks 6 can be set according to different requirements, and preferably, two water storage tanks 6 are provided.

[0042] In addition, further, a top cover 7 can be covered above the culture unit 5. The top cover 7 is made of polydimethylsiloxane material. If the embryo is cultured for a long time, the top cover 7 can be covered to reduce the water evaporation of the culture solution in the culture unit 5 and also avoid the pollution of the external environment to the culture environment.

[0043] The present utility model is not limited to the above embodiments. Any other products identical or similar to the present utility model obtained by anyone under the inspiration of the present utility model shall fall within the protection scope of the present utility model.

Claims

1. An in vitro fertilization and embryo co-culture device capable of automatically changing liquid, comprising a substrate and a fertilization culture area arranged on the substrate, characterized in that: The fertilization culture area includes a liquid tank, a microfluidic channel and a culture unit. The culture unit is recessed inwardly to the upper surface of the base. There are at least two liquid tanks and at least two culture units. Every two adjacent culture units are connected. The culture unit is located between the two liquid tanks. The culture unit and the liquid tank are interconnected through the microfluidic channel.

2. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: The utility model also comprises an inclined seat which is detachably mounted on the bottom of the base and has an inclination angle of 5° to 30°.

3. The in vitro fertilization and embryo co-culture device capable of automatically changing liquid according to claim 2, characterized in that: The tilting angle of the tilting seat is 10° to 15°, the tilting seat is intelligently electrically controlled, and an anti-slip pad is arranged on the surface of the tilting seat.

4. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: The fertilization culture area has 4 liquid tanks and 16 culture units. Every 2 liquid tanks and every 8 culture units are interconnected through microfluidics to form independent culture groups. There are 2 culture groups in total.

5. The in vitro fertilization and embryo co-culture device capable of automatically changing fluid according to claim 1, characterized in that: The microchannel is in the shape of a trumpet, with the large end connected to the liquid chamber and the small end connected to the culture unit.

6. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: The base is made of a mirror glass material, and the liquid chamber is provided with a top cover, on which a sampling hole is provided.

7. The in vitro fertilization and embryo co-culture device capable of automatically changing liquid according to claim 1, characterized in that: The substrate is made of any one of polypropylene, polycarbonate or polystyrene having high transparency.

8. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: The liquid chamber, microfluidic channel and culture unit are all made of polydimethylsiloxane material, and the curing agent added in the polydimethylsiloxane is added in a ratio of 10% to 30%.

9. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: The fluid chambers, microfluidic channels, and culture units are all made of one of silicone, polycarbonate, polypropylene, or polystyrene.

10. The in vitro fertilization and embryo co-culture device capable of automatically exchanging fluid according to claim 1, characterized in that: A water storage tank is provided in the fertilization culture area. The water storage tank is filled with water. An upper cover is provided above the culture unit. The upper cover is made of polydimethylsiloxane material.

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