Sperm screening device and method

Abstract

The sperm screening device is sequentially provided with a sperm sampling component, a first filtering component, a sperm screening component, a second filtering component and a sperm collecting component from bottom to top, a sperm storage cavity is formed in the top surface of the sperm sampling part, the sperm screening part is provided with a vertically-through mucus storage cavity, and the sperm collecting part is provided with a vertically-through culture medium storage cavity; the first filtering part is provided with a plurality of first through holes penetrating up and down, and the two ends of the first filtering part are in contact with the sperm storage cavity and the mucus storage cavity respectively; the second filtering part is provided with a plurality of second through holes penetrating up and down, and the two ends of the second filtering part are in contact with the mucus storage cavity and the sperm collecting part respectively. The invention further provides a screening method using the sperm screening device. According to the sperm screening device and the using method thereof, sperms with the ultralow DNA fragmentation rate can be screened out, and the pregnancy rate and the offspring quality can be improved.

Description

Technical Field

[0001] The present application relates to the technical field of assisted reproductive equipment, and in particular to a sperm screening device and screening method. Background Art

[0002] Under the influence of today's fast-paced, high-pressure lifestyle and various other factors, the incidence of infertility has increased, which has promoted the development of assisted reproductive technology.

[0003] Common sperm selection methods used in in vitro fertilization (IVF) include swim-up and density gradient centrifugation (DGC), typically targeting sperm with good motility. However, procedures such as centrifugation and heating during these techniques can generate reactive oxygen species (ROS), which can increase the DNA fragmentation index (DFI) of sperm.

[0004] High sperm DNA fragmentation rates are increasingly recognized as a significant factor in infertility. Sperm DNA integrity is crucial for the effective transmission of genetic information and forms the biological basis for fertilization and embryonic development. Sperm with a high DFI are less likely to achieve successful fertilization, and even if fertilization is successful, the resulting embryo is more likely to fail to develop or result in miscarriage. Therefore, screening for sperm with ultra-low DNA fragmentation rates is crucial for improving pregnancy success rates. Summary of the Invention

[0005] In order to solve the above technical problems, the first purpose of the present invention is to provide a sperm screening device; the second purpose of the present invention is to provide a method for screening using the above sperm screening device; the sperm screening device provided in this application and its use method simulate multiple physiological characteristics of the female reproductive tract microenvironment, comprehensively reproduce the complete biological functions of the female reproductive tract, make the entire screening process closer to real physiological screening, and screen out sperm with ultra-low DNA fragmentation rate, which helps to improve the conception rate and offspring quality.

[0006] The technical solutions provided by the present invention are as follows: A sperm screening device is provided with a sperm sampling component, a first filtering component, a sperm screening component, a second filtering component and a sperm collecting component in order from bottom to top; The top surface of the sperm injection component is provided with a sperm storage cavity, the sperm screening component is provided with a mucus storage cavity running through it from top to bottom, and the sperm collecting component is provided with a culture medium storage cavity running through it from top to bottom; The first filter component is provided with a plurality of first through holes running through it from top to bottom, and the two ends of the first filter component are respectively in contact with the sperm storage chamber and the mucus storage chamber; the second filter component is provided with a plurality of second through holes running through it from top to bottom, and the two ends of the second filter component are respectively in contact with the mucus storage chamber and the sperm collecting component.

[0007] Preferably, the apertures of the first and second through holes are 5-20 μm; and / or, at least one guide is provided in the mucus storage cavity, and a mucus flow channel is formed between adjacent guides; and the sidewalls of the guide are at least partially curved.

[0008] Preferably, the cross section of the guide member is wavy; and / or, The guides have gaps therebetween so that the mucus flow channels communicate with each other.

[0009] Preferably, a main channel and a plurality of branch channels are provided in the mucus storage cavity, the main channel passes through the mucus storage cavity in a horizontal direction, and the guide members are located on both sides of the main channel so that the branch channels are located on both sides of the main channel.

[0010] Preferably, the side wall of the sperm storage chamber has at least one step; and / or, The inner diameter of the sperm storage cavity increases from bottom to top.

[0011] Preferably, the side walls of the sperm storage chamber are connected by continuous steps; and / or, The angle between the step slope and the horizontal plane is 130-140°.

[0012] Preferably, the sperm sampling component is further provided with a sperm sampling inlet communicated with the bottom of the sperm storage chamber; the sperm screening component is further provided with a mucus sampling inlet communicated with the mucus storage chamber; Moreover, the sperm collecting component and the sperm screening component are respectively provided with a first channel connected to each other, and the sperm sampling inlet is connected to the top surface of the device through the first channel; the sperm collecting component is also provided with a second channel, and the mucus sampling inlet is connected to the top surface of the device through the second channel.

[0013] Preferably, the volume of the sperm storage chamber is 0.1-2 ml; and / or, The thickness of the mucus storage cavity is 0.5-5 mm; and / or, The side of the culture medium storage chamber is also provided with a recess for collecting sperm.

[0014] Preferably, the sperm sampling component, sperm screening component, and sperm collecting component are optionally made of any one or more of light-curing resin, polymethyl methacrylate, polystyrene, polycarbonate, cycloolefin copolymer, and polydimethylsiloxane; The first filter component and the second filter component are optionally made of any one or more of polycarbonate and polyethylene terephthalate; The mucus injected into the sperm screening component is methylcellulose solution or hyaluronic acid solution.

[0015] The method for screening using any of the above-mentioned sperm screening devices comprises the following steps: S1, injecting the liquefied semen sample into the sperm storage chamber, then injecting the mucus into the mucus storage chamber, and then injecting the culture medium into the culture medium storage chamber; S2. Incubate and then collect the culture medium to obtain the screened sperm.

[0016] To address the above-mentioned issues, the present application provides a sperm screening device, which comprises, from bottom to top, a sperm sampling component, a first filter component, a sperm screening component, a second filter component, and a sperm collecting component. The top surface of the sperm sampling component is provided with a sperm storage chamber, the sperm screening component is provided with a mucus storage chamber extending vertically therethrough, and the sperm collecting component is provided with a culture medium storage chamber extending vertically therethrough. The first filter component is provided with a plurality of first through-holes extending vertically therethrough, and the two ends of the first filter component are in contact with the sperm storage chamber and the mucus storage chamber, respectively. The second filter component is provided with a plurality of second through-holes extending vertically therethrough, and the two ends of the second filter component are in contact with the mucus storage chamber and the sperm collecting component, respectively. The sperm screening device provided in the present application simulates the microenvironment of the female reproductive tract from multiple dimensions. After a sperm sample is injected into the sperm storage chamber of the sperm sampling component, the sperm, by utilizing its countercurrent and edge-contact swimming characteristics, is filtered by the first filter component, filtered by the mucus environment in the sperm screening component, and filtered again by the second filter component during its upward swimming process before finally reaching the culture medium in the sperm collecting component. Sperm with good quality and high DNA integrity have better motility, while sperm with high DNA fragmentation rate are intercepted by the above-mentioned structures. The screening process utilizes the sperm's own motility to reduce the probability of damage by external forces, thereby screening out sperm with ultra-low DNA fragmentation rate and high motility. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments recorded in this application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0018] Figure 1 Schematic diagram of an explosion of a sperm screening device according to an embodiment of the present invention; Figure 2 This is a schematic diagram of the assembled structure of the sperm screening device according to an embodiment of the present invention; Figure 3 Schematic diagram of the structure of the sperm sampling component in the sperm screening device according to an embodiment of the present invention; Figure 4 Schematic diagram of the structure of the sperm screening component in the sperm screening device in an embodiment of the present invention; Figure 5 Schematic diagram of the structure of the sperm collecting component in the sperm screening device according to an embodiment of the present invention; Figure 6 Figure 2 is the result of DNA damage rate test before and after screening; Figure 7 This is the result diagram of sperm motility parameter detection; Figure 8 A comparison chart of sperm motility between the screening device with and without the sperm screening component; Figure 9 The figure shows the comparison of sperm motility between the screening device with and without the guide.

[0019] Figure markings: 1-sperm sampling component; 11-sperm storage chamber; 111-step; 12-sperm sampling inlet; 2-first filtering component; 21-first through hole; 3-sperm screening component; 31-mucus storage chamber; 32-guide; 33-mucus flow channel; 331-main channel; 332-branch flow channel; 34-mucus sampling inlet; 4-second filtering component; 41-second through hole; 5-sperm collecting component; 51-culture medium storage chamber; 52-recess; 6-first channel; 7-second channel; 8-sealing bottom membrane. DETAILED DESCRIPTION

[0020] In order to help those skilled in the art better understand the technical solutions in this application, the technical solutions in the embodiments of this application will be clearly and completely described below. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making any creative efforts shall fall within the scope of protection of this application.

[0021] It should be noted that when an element is referred to as being “fixed on” or “set on” another element, it can be directly on the other element or indirectly set on the other element; when an element is referred to as being “connected to” another element, it can be directly connected to the other element or indirectly connected to the other element.

[0022] It should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on this application.

[0023] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of technical features indicated. Thus, a feature specified as "first" or "second" may explicitly or implicitly include one or more of such features. Throughout the description of this application, "plurality" or "several" means two or more, unless otherwise specifically defined.

[0024] It should be noted that the structures, proportions, sizes, etc. illustrated in the drawings of this specification are only used to match the contents disclosed in the specification for people familiar with this technology to understand and read, and are not used to limit the conditions under which this application can be implemented. Therefore, they have no substantive technical significance. Any structural modification, change in proportional relationship or adjustment of size should still fall within the scope of the technical content disclosed in this application without affecting the efficacy and purpose that can be achieved by this application.

[0025] As shown in the figure, an embodiment of the present invention provides a sperm screening device, which is provided with a sperm sampling component 1, a first filtering component 2, a sperm screening component 3, a second filtering component 4 and a sperm collecting component 5 in order from bottom to top; The top surface of the sperm injection component 1 is provided with a sperm storage cavity 11, the sperm screening component 3 is provided with a mucus storage cavity 31 extending vertically therethrough, and the sperm collecting component 5 is provided with a culture medium storage cavity 51 extending vertically therethrough; The first filter component 2 is provided with a plurality of first through holes 21 running through it from top to bottom, and the two ends of the first filter component 2 are in contact with the sperm storage chamber 11 and the mucus storage chamber 31 respectively; the second filter component 4 is provided with a plurality of second through holes 41 running through it from top to bottom, and the two ends of the second filter component 4 are in contact with the mucus storage chamber 31 and the sperm collecting component 5 respectively.

[0026] The DNA fragmentation rate of sperm is related to both sperm quality and damage caused by sperm selection procedures. Furthermore, during the selection process, prolonged contact between motile sperm and immature sperm and cellular debris can lead to the production of reactive oxygen species (ROS), which in turn cause DNA fragmentation and further increase the sperm DNA fragmentation rate.

[0027] In response to the above problems, the present application provides a sperm screening device, which is provided with a sperm sampling component 1, a first filter component 2, a sperm screening component 3, a second filter component 4 and a sperm collecting component 5 from bottom to top; the top surface of the sperm sampling component 1 is provided with a sperm storage chamber 11, the sperm screening component 3 is provided with a mucus storage chamber 31 running through it from top to bottom, and the sperm collecting component 5 is provided with a culture medium storage chamber 51 running through it from top to bottom; the first filter component 2 is provided with a plurality of first through holes 21 running through it from top to bottom, and the two ends of the first filter component 2 are in contact with the sperm storage chamber 11 and the mucus storage chamber 31 respectively; the second filter component 4 is provided with a plurality of second through holes 41 running through it from top to bottom, and the two ends of the second filter component 4 are in contact with the mucus storage chamber 31 and the sperm collecting component 5 respectively. The sperm screening device provided herein simulates the microenvironment of the female reproductive tract from multiple dimensions. After a sperm sample is injected into the sperm storage chamber 11 of the sperm injection component 1, it utilizes the sperm's countercurrent and side-swimming characteristics to cause it to swim upward, passing through filtration in the first filter component 2, screening in the mucus environment of the sperm screening component 3, and further filtration in the second filter component 4 before finally reaching the culture medium in the sperm collection component 5. High-quality sperm with high DNA integrity have improved motility, while sperm with high DNA fragmentation rates are trapped by these various structures. Furthermore, the screening process utilizes the sperm's inherent motility to reduce the probability of damage from external forces, thereby selecting sperm with ultra-low DNA fragmentation rates and high motility.

[0028] The sperm screening device provided in this application simulates multiple physiological characteristics of the female reproductive tract microenvironment, comprehensively reproduces the complete biological functions of the female reproductive tract, makes the entire screening process closer to real physiological screening, and can screen out sperm with ultra-low DNA fragmentation rates, which helps to improve the conception rate and offspring quality.

[0029] Specifically, the first filter component 2 and the second filter component 4 use the microchannels formed by the through holes to block the deformed sperm outside, while the normal sperm pass through smoothly, which not only achieves preliminary screening, but also separates the immature sperm and cell fragments from the normal sperm in time, avoiding the generation of reactive oxygen species and increasing the DNA fragmentation rate of normal sperm.

[0030] In the sperm screening component 3, mucus storage chamber 31 is filled with mucus, simulating the mucus environment of the female reproductive tract. Utilizing mucus-penetrating technology, the sperm screened are closer to physiologically high-quality sperm. The mucus also effectively maintains sperm motility and motility, minimizing breakage and inactivation.

[0031] The sperm screening device provided herein comprises a sperm sampling component 1, a first filter component 2, a sperm screening component 3, a second filter component 4, and a sperm collecting component 5, arranged sequentially from top to bottom. This refers to the assembled state of the sperm screening device during use. The assembly of these components can be achieved through methods known in the art, such as snap-fitting and gluing. The vertical and horizontal positions of the components herein are also determined based on their state during use.

[0032] A sperm storage chamber 11 is provided on the top surface of the sperm sampling component 1. Specifically, a recessed groove is formed downward from the top surface of the sperm sampling component 1, forming the sperm storage chamber 11. The sperm storage chamber 11 does not penetrate the sperm sampling component 1, thus preventing reagents from leaking from the bottom surface. However, to prevent leakage caused by machining accuracy, a sealing bottom membrane 8 can be added below the sperm sampling component 1.

[0033] In this application, the mucus storage chamber 31 provided within the sperm screening component 3 extends vertically through the sperm screening component 3. Specifically, the top and bottom surfaces of the mucus storage chamber 31 are formed by the end surfaces of the first filter component 2 and the second filter component 4, respectively. Mucus has a certain density and viscosity, and during use, it is retained within the mucus storage chamber 31, defined by the two filter components, without leaking downward. Similarly, the bottom surface of the culture medium storage chamber 51 is also defined by the top surface of the second filter component 4.

[0034] In the present application, both ends of the first filter component 2 are in contact with the sperm storage cavity 11 and the mucus storage cavity 31 respectively, which means that the end surface of the filter component participates in forming the edge of the cavity, thereby fully contacting the sample / solution injected into the cavity.

[0035] Preferably, the apertures of the first through holes 21 and the second through holes 41 are 5-20 μm; and / or, At least one guide member 32 is provided in the mucus storage chamber 31 , and a mucus flow channel 33 is formed between adjacent guide members 32 ; at least a portion of the sidewall of the guide member 32 is a curved surface.

[0036] Preferably, the aperture of the first through hole 21 and the second through hole 41 is 5-20 μm. This aperture allows only sperm with normal motility to pass through, while sperm with poor motility / abnormality are trapped and separated.

[0037] The pore sizes of the two filter components can be the same or different. More preferably, the pore size of the first filter component 2 is smaller than that of the second filter component 4. This eliminates most deformed and low-motility sperm as they pass through the first filter component 2, improving the overall quality of the screened sperm. The second filter component 4 primarily separates the mucus and culture medium, preventing the complete mixing of the two reagents, which can lead to the inconvenience of extracting the sperm-containing culture medium. It also serves a certain purpose in re-screening and ensuring sperm quality.

[0038] In the present application, mucus is placed in the mucus storage chamber 31 to simulate and guide the mucus environment and improve the screening quality; while the culture medium provides a collection and storage environment to ensure the normal survival of sperm after screening.

[0039] Preferably, at least one guide member 32 is further provided in the mucus storage chamber 31 to divide the mucus storage chamber 31 into different mucus flow channels 33; and the side wall of the guide member 32 is at least partially curved, that is, the guide member 32 adopts a bionic design, taking advantage of the fact that sperm like to swim on curved walls, thereby increasing the sperm swimming distance and allowing multiple sperm to swim in different mucus flow channels 33 for screening, thereby increasing the flux.

[0040] The side wall of the guide member 32 refers to the wall extending from the top surface of the first filter component 2 to the bottom surface of the second filter component 4. After mucus is added to the mucus storage chamber 31, the side wall of the guide member 32 is immersed in the mucus, which is conducive to the sperm swimming along the wall.

[0041] Preferably, the cross section of the guide member 32 is wavy; and / or, There are gaps between the guide members 32 so that the mucus flow channels 33 communicate with each other.

[0042] The guide member 32 preferably has a wavy cross-section with a rich variety of curvatures. This wavy shape better simulates the physiological environment, more closely resembles the tortuous path in the fallopian tube, and is more consistent with natural selection mechanisms. The wavy channel's periodic curvature forces sperm to frequently adjust their direction of movement, significantly differentiating sperm of varying motility. Highly motile sperm actively adapt to path changes, utilizing the flexibility of their flagella to achieve steering and preferentially pass through the channel. Low-motility or abnormal sperm, however, are prone to becoming stuck in corners or lingering in curved areas due to insufficient steering ability or morphological defects.

[0043] The cross section refers to cutting the sperm screening component 3 along the horizontal plane, and the curvature of the guide 32 changes along the horizontal plane, which is conducive to guiding the sperm to swim in the horizontal direction first and then swim toward the second filter component 4; this design can maintain a large flux even when the thickness of the sperm screening component 3 is relatively thin, thereby ensuring the screening quality.

[0044] Preferably, there are gaps between the guides 32 so that the mucus flow channels 33 are connected to each other, which is more similar to the vaginal environment, allowing sperm to swim more freely, and when adding the mucus reagent from any position, the mucus can be distributed to each mucus flow channel 33.

[0045] More preferably, the vertical height of the guide member 32 is the same as the height of the sperm screening component 3 , to ensure that the sperm can always swim along the side wall of the guide member 32 .

[0046] Preferably, a main channel 331 and multiple branch channels 332 are provided in the mucus storage cavity 31 . The main channel 331 runs through the mucus storage cavity 31 in a horizontal direction. The guide members 32 are located on both sides of the main channel 331 , so that the branch channels 332 are located on both sides of the main channel 331 .

[0047] More preferably, the multiple guide members 32 are arranged so that a main channel 331 or multiple branch channels 332 are formed within the mucus storage chamber 31. The main channel 331 is the portion in the center of the mucus storage chamber 31 where the guide members 32 do not extend; the branch channels 332 are separated by the guide members 32 on either side of the main channel 331. This creates a "snake-like skeleton structure" that simulates the vaginal environment and improves screening quality.

[0048] The number of branch flow channels 332 is determined by the number of guide members 32. The number of guide members 32 is set as needed, and can be 1-100, more preferably 4-50, and even more preferably 8-30.

[0049] Preferably, the side wall of the sperm storage chamber 11 has at least one step 111; and / or, The inner diameter of the sperm storage chamber 11 increases from bottom to top.

[0050] Preferably, the side walls of the sperm storage chamber 11 are connected by continuous steps 111; and / or, The angle between the slope of the step 111 and the horizontal plane is 130-140°.

[0051] The sidewall of the sperm storage chamber 11 preferably has at least one step. A step refers to a change in the vertical plane from the horizontal plane at at least one portion of the sidewall. The angle between the slope of the step 111 and the horizontal plane is 130-140°. This means that sperm travel from the slope of the step 111 to the horizontal plane above it, and then through the slope above to the horizontal plane even higher. The slopes they pass through are all more gradual than right angles (angles of 130-140°). This allows for screening without affecting sperm's upstream movement due to abrupt changes in the slope, thereby assisting in the selection of high-quality sperm. More preferably, the angle between the slope of the step 111 and the horizontal plane is 135-138°.

[0052] Preferably, the inner diameter of the sperm storage chamber 11 increases from bottom to top, and can be increased uniformly or unevenly. The change in the inner diameter of the sperm storage chamber 11 and the step 111 can be provided at the same time, or only one of them can be provided.

[0053] More preferably, the side walls of the sperm storage chamber 11 are connected by continuous steps 111 , and in this case, the inner diameter of the sperm storage chamber 11 also increases from bottom to top.

[0054] Preferably, the sperm sampling component 1 is further provided with a sperm sampling inlet 12 connected to the bottom of the sperm storage chamber 11; the sperm screening component 3 is further provided with a mucus sampling inlet 34 connected to the mucus storage chamber 31; Moreover, the sperm collecting component 5 and the sperm screening component 3 are respectively provided with a first channel 6 connected to each other, and the sperm sampling inlet 12 is connected to the top surface of the device through the first channel 6; the sperm collecting component 5 is also provided with a second channel 7, and the mucus sampling inlet 34 is connected to the top surface of the device through the second channel 7.

[0055] Preferably, the sperm sampling component 1 and the sperm screening component 3 are further provided with a sperm sampling inlet 12 and a mucus sampling inlet 34, respectively, and the sperm sampling inlet 12 is connected to the bottom of the sperm storage chamber 11, ensuring that the sperm sample first enters the bottom of the sperm storage chamber 11, and the sperm contained therein are screened upstream in the sperm storage chamber 11.

[0056] Furthermore, the sperm sampling inlet 12 and the mucus sampling inlet 34 are both connected to the top surface of the device (i.e., the top surface of the sperm collecting component 5) through channels, so the entire device can be assembled before injecting samples and reagents, which is easy to operate.

[0057] Specifically, the sperm collecting component 5 and the sperm screening component 3 are each provided with a first channel 6 that is interconnected, and the first channel 6 is connected to the sperm sampling inlet 12. Thus, a sperm sample is injected through the opening of the first channel 6 on the top surface of the sperm collecting component 5, and can flow through the first channel 6 into the sperm sampling inlet 12 and ultimately into the sperm storage chamber 11. Similarly, mucus enters the mucus sampling inlet 34 through the second channel 7 and ultimately enters the mucus storage chamber 31.

[0058] Since the sperm injection component 1 and the sperm screening component 3 have different vertical heights, and the first channel 6 and the second channel 7 have different lengths, providing auxiliary markings at the channel entrances can help the operator accurately inject the corresponding sample or reagent.

[0059] Preferably, the volume of the sperm storage chamber 11 is 0.1-2 ml; and / or, The thickness of the mucus storage cavity 31 is 0.5-5 mm; and / or, The side of the culture medium storage chamber 51 is further provided with a recess 52 for collecting sperm.

[0060] The volume of the sperm storage chamber 11 is preferably 0.1-2 ml, more preferably 0.5-1 ml, which is sufficient to accommodate a sample for sperm screening. Furthermore, this volume range of the sperm storage chamber 11 is suitable for the sperm sample volume that can be collected from most patients, ensuring that the sample can fill the chamber for efficient screening.

[0061] The thickness of the mucus storage chamber 21 is preferably 0.5-5 mm, which ensures the quality of screening without adversely affecting healthy sperm.

[0062] The side of the culture medium storage chamber 51 is also provided with a recess 52 for collecting sperm. The recess 52 means that the wall of the sperm collecting component 5 is thinner here, and the diameter of the culture medium storage chamber 51 is larger, forming a fixed position for sucking culture medium for collection, ensuring the reproducibility of the operation.

[0063] There is no particular limitation on the volume of the culture medium storage chamber 51, but from the perspective of cost and operational convenience, it can be set to the same volume as the sperm storage chamber 11, that is, the volume of the culture medium storage chamber 51 is also 0.1-2 ml, more preferably 0.5-1 ml.

[0064] Preferably, the sperm sampling component 1, the sperm screening component 3, and the sperm collecting component 5 are optionally made of any one or more of light-curing resin, polymethyl methacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), and polydimethylsiloxane (PDMS); The first filter component 2 and the second filter component 4 are optionally made of any one or more of polycarbonate and polyethylene terephthalate; The mucus injected into the sperm screening component 3 is a methylcellulose solution or a hyaluronic acid solution.

[0065] The sperm sampling component 1, sperm screening component 3, and sperm collecting component 5 can be made of commercially available materials that are non-toxic to sperm. For example, the sperm sampling component 1, sperm screening component 3, and sperm collecting component 5 can be made of any one or more of photocurable resin, polymethyl methacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), and polydimethylsiloxane (PDMS).

[0066] The first filter component 2 and the second filter component 4 are optionally made of any one or more of polycarbonate (PC) and polyethylene terephthalate (PET).

[0067] The mucus injected into the sperm screening component 3 can be a sorting liquid product known in the art that simulates the reproductive tract environment. Methylcellulose solution or hyaluronic acid solution, or other compounded formulas can be selected.

[0068] The method for screening using any of the above-mentioned sperm screening devices comprises the following steps: S1, injecting the liquefied semen sample into the sperm storage chamber 11, then injecting the mucus into the mucus storage chamber 31, and then injecting the culture medium into the culture medium storage chamber 51; S2. Incubate and then collect the culture medium to obtain the screened sperm.

[0069] The present application also provides a method for screening using any of the sperm screening devices described above, comprising the following steps: S1, injecting a liquefied semen sample into the sperm storage chamber 11, then injecting mucus into the mucus storage chamber 31, and then injecting a culture medium into the culture medium storage chamber 51; S2, incubating, and then extracting the culture medium from the sperm collection chamber 52 to obtain screened sperm. The screening method provided in the present application sequentially injects a sperm sample (the sperm sample can be liquefied or otherwise treated according to conventional procedures in the art before injection), mucus, and culture medium into corresponding components, incubates, and collects the sperm after it is enriched in the culture medium to obtain screened sperm. The obtained sperm is transferred to a collection device for standby use.

[0070] The incubation time is preferably 15-60 min, more preferably 30-40 min, to give the sperm sufficient time to swim.

[0071] The culture medium can be collected by drawing it out with a syringe. When the sperm collection component 5 is provided with a recess 52, the sample can be fixed at the recess 52 to ensure the stability of the operation. The operation of injecting the sample and reagent is preferably performed slowly to give the liquid sufficient time to flow and avoid gushing out from the narrow channel. In addition, the slow injection operation can reduce damage to the sperm sample. The injected sample and reagent need to fill each cavity separately to ensure a continuous liquid environment for sperm to swim.

[0072] The sperm screening device provided in the present application needs to be sterilized before use, and can be sterilized by ethylene oxide sterilization, high temperature and high pressure sterilization or other methods commonly used in the medical field.

[0073] Example 1 A sperm screening device is provided with a sperm sampling component 1, a first filtering component 2, a sperm screening component 3, a second filtering component 4 and a sperm collecting component 5 in order from bottom to top; The top surface of the sperm injection component 1 is provided with a sperm storage chamber 11. The inner diameter of the sperm storage chamber 11 increases from bottom to top, and the side walls of the sperm storage chamber 11 are connected by five consecutive steps 111. The angle between adjacent faces of the steps 111 is 45 degrees. The volume of the sperm storage chamber 11 is 1 ml. The sperm screening component 3 has a mucus storage chamber 31 extending vertically through the chamber. Twelve guide members 32 are positioned within the chamber, with gaps between each guide member 32. Adjacent guide members 32 form a mucus flow channel 33, comprising a main channel 331 and multiple branch channels 332. The main channel 331 extends horizontally through the chamber 31, with the guide members 32 positioned on either side of the main channel 331, such that the branch channels 332 are positioned on either side of the main channel 331. The sidewalls of the guide members 32 are curved, and the cross-section of the guide members 32 is wavy. The thickness of the mucus storage chamber 31 is 2 mm. The sperm collecting component 5 is provided with a culture medium storage chamber 51 which runs through the upper and lower parts. A recess 52 for collecting sperm is also provided on the side of the culture medium storage chamber 51. The volume of the culture medium storage chamber 51 is 1.4 ml. The first filter component 2 is provided with a plurality of first through holes 21 extending vertically therethrough, and the two ends of the first filter component 2 are in contact with the sperm storage chamber 11 and the mucus storage chamber 31 respectively; the pore size of the first through holes 21 is 14 μm; The second filter component 4 is provided with a plurality of second through holes 41 extending vertically therethrough, and the two ends of the second filter component 4 are in contact with the mucus storage chamber 31 and the sperm collecting component 5 respectively; the pore size of the second through holes 41 is 20 μm; The sperm sampling component 1 is also provided with a sperm sampling inlet 12 connected to the bottom of the sperm storage chamber 11; the sperm screening component 3 is also provided with a mucus sampling inlet 34 connected to the mucus storage chamber 31; and the sperm collecting component 5 and the sperm screening component 3 are respectively provided with a first channel 6 connected to each other, and the sperm sampling inlet 12 is connected to the top surface of the device through the first channel 6; the sperm collecting component 5 is also provided with a second channel 7, and the mucus sampling inlet 34 is connected to the top surface of the device through the second channel 7.

[0074] The sperm sampling component 1, sperm screening component 3, and sperm collection component 5 are each made of white, transparent, biocompatible resin IF3165, using a microArch™ S140 3D printer manufactured by Chongqing Mofang Precision Technology Co., Ltd. The first filter component 2 and the second filter component 4 are made of polycarbonate.

[0075] The mucus injected into the sperm screening component 3 is a methylcellulose solution.

[0076] The method for screening using any of the above-mentioned sperm screening devices comprises the following steps: S1, take 1 ml of liquefied semen sample and inject it into sperm storage chamber 11, take 0.75 ml of mucus and inject it into mucus storage chamber 31, take 1 ml of culture medium and inject it into culture medium storage chamber 51; S2. Incubate for 30 minutes, then use a 1 ml syringe to extract the culture medium from the depression 52 to obtain the screened sperm.

[0077] The DNA damage rate of the collected sperm samples was tested, and the experimental results were as follows: Figure 6 Furthermore, CASA (Computer Assisted Sperm Analysis) was used to detect the motility parameters of sperm. The experimental results are shown in Figure 7 The results show that the female reproductive tract organ chip of the present invention can screen sperm with ultra-low DNA fragmentation rate while ensuring high sperm vitality and motility.

[0078] Comparative Example 1 The sperm screening device does not include the sperm screening component 3 and does not inject mucus. Other aspects are the same as those of Example 1.

[0079] Effect comparison Figure 8 shown. Figure 8 It can be seen from the figure that setting a mucus cavity and injecting mucus has better effects than not setting a mucus cavity.

[0080] Comparative Example 2 The mucus storage chamber 31 is not provided with the guide member 32 , and the rest is the same as that of the first embodiment.

[0081] Effect comparison Figure 9 shown. Figure 8 It can be seen from the figure that the effect of providing the guide member 32 is better than that of not providing the guide member 32.

[0082] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A sperm screening device, characterized in that: From bottom to top, a sperm sampling component (1), a first filtering component (2), a sperm screening component (3), a second filtering component (4) and a sperm collecting component (5) are sequentially provided; The top surface of the sperm sampling component (1) is provided with a sperm storage cavity (11), the sperm screening component (3) is provided with a mucus storage cavity (31) extending vertically therethrough, and the sperm collecting component (5) is provided with a culture medium storage cavity (51) extending vertically therethrough; The first filter component (2) is provided with a plurality of first through holes (21) extending vertically therethrough, and the two ends of the first filter component (2) are in contact with the sperm storage chamber (11) and the mucus storage chamber (31), respectively; the second filter component (4) is provided with a plurality of second through holes (41) extending vertically therethrough, and the two ends of the second filter component (4) are in contact with the mucus storage chamber (31) and the sperm collecting component (5), respectively.

2. The sperm screening device according to claim 1, characterized in that: The apertures of the first through hole (21) and the second through hole (41) are 5-20 μm; and / or, At least one guide member (32) is provided in the mucus storage cavity (31), and a mucus flow channel (33) is formed between adjacent guide members (32); at least a portion of the side wall of the guide member (32) is a curved surface.

3. The sperm screening device according to claim 2, characterized in that: The cross section of the guide member (32) is wavy; and / or, There are gaps between the guide members (32) so that the mucus flow channels (33) are connected to each other.

4. The sperm screening device according to claim 3, characterized in that: The mucus storage cavity (31) is provided with a main channel (331) and a plurality of branch channels (332). The main channel (331) runs through the mucus storage cavity (31) in a horizontal direction. The guide member (32) is located on both sides of the main channel (331), so that the branch channels (332) are located on both sides of the main channel (331).

5. The sperm screening device according to claim 1, characterized in that: The side wall of the sperm storage chamber (11) has at least one step (111); and / or, The inner diameter of the sperm storage chamber (11) increases from bottom to top.

6. The sperm screening device according to claim 5, characterized in that: The side walls of the sperm storage chamber (11) are connected by continuous steps (111); and / or, The angle between the slope of the step (111) and the horizontal plane is 130-140°.

7. The sperm screening device according to any one of claims 1 to 6, characterized in that: The sperm sampling component (1) is further provided with a sperm sampling inlet (12) connected to the bottom of the sperm storage chamber (11); the sperm screening component (3) is further provided with a mucus sampling inlet (34) connected to the mucus storage chamber (31); Furthermore, the sperm collecting component (5) and the sperm screening component (3) are respectively provided with a first channel (6) that is connected to each other, and the sperm sampling inlet (12) is connected to the top surface of the device through the first channel (6); the sperm collecting component (5) is also provided with a second channel (7), and the mucus sampling inlet (34) is connected to the top surface of the device through the second channel (7).

8. The sperm screening device according to claim 1, characterized in that: The volume of the sperm storage chamber (11) is 0.1-2 ml; and / or, The thickness of the mucus storage cavity (31) is 0.5-5 mm; and / or, The side of the culture medium storage chamber (51) is also provided with a recess (52) for collecting sperm.

9. The sperm screening device according to claim 1, characterized in that: The sperm sampling component (1), sperm screening component (3), and sperm collecting component (5) are optionally made of any one or more of light-curing resin, polymethyl methacrylate, polystyrene, polycarbonate, cycloolefin copolymer, and polydimethylsiloxane; The first filter component (2) and the second filter component (4) are optionally made of any one or more of polycarbonate and polyethylene terephthalate; The mucus injected into the sperm screening component (3) is a methylcellulose solution or a hyaluronic acid solution.

10. A method for screening using the sperm screening device according to any one of claims 1 to 9, characterized in that: The following steps are involved: S1, injecting the liquefied semen sample into the sperm storage chamber (11), then injecting the mucus into the mucus storage chamber (31), and then injecting the culture medium into the culture medium storage chamber (51); S2. Incubate and then collect the culture medium to obtain the screened sperm.

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