Functional filter test cartridge and use thereof

Abstract

The application provides a functional filter test filter element and application thereof, and comprises a filter element body with a three-stage step structure with a porosity of 51-75% which is made of thermoplastic polymer microspheres through sintering or chemical bonding, ultraviolet crosslinking, the thermoplastic polymer microspheres are pretreated before preparation and molding, the filter element body is surface treated after preparation and molding, a hydrophilic group is added to the surface of the filter element body and grafting is carried out to connect molecules, groups or functional groups, and a plurality of through holes with staggered hole positions are formed in the upper end and the lower end of the filter element body respectively. The filter element has a great specific surface area, effectively increases the filtering and capturing capacity in a limited space, and can sensitively capture the target analyte during use; in addition, the filter element is surface hydrophilic treated, has strong hydrophilicity, has small resistance when liquid passes through, and can pass through at 100%; various chemical modifications or grafting are carried out on the surface of the filter element, so that the filter element is suitable for a variety of detections and is all-purpose.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pipette tips, in particular to a functional filter test filter element and application thereof. BACKGROUND

[0002] A pipette or pipette gun is an experimental instrument commonly used in the fields of life science, medicine, biology, etc. The accessory pipette tip is used in a large number of experiments, and various filter elements are usually arranged in the pipette tip. Some types of commonly used filter elements are used to prevent the suctioned liquid from entering the pipette or pipette gun used for suction, thereby preventing cross contamination and protecting the suction device. Some other types of filter elements are used to adsorb or capture certain target analytes. For example, in a ChIP assay, a specially treated tip filter element can be used to adsorb or capture certain specific DNA fragments, RNA fragments, etc. in a chromatin solution, and then the specific DNA fragments, RNA fragments are separated from the tip filter element and recovered for DNA or RNA analysis and research.

[0003] However, the existing tip filter element for adsorbing or capturing target analytes has a small specific surface area and can adsorb or capture a small amount of target analytes. Moreover, the tip filter element is hydrophobic and prone to clogging, poor flowability, and inconvenience in use.

[0004] One existing Chinese patent with the title of pipette tip and method of using the same (CN107073474B) discloses that a rigid porous matrix comprises a sintered thermoplastic polymer, the matrix is modified after sintering to provide a chemically reactive surface, such as a functionalized surface, which provides pendant functional groups suitable for connecting ligands to the surface, optionally via a linker, and the matrix has a porosity of about 50%.

[0005] The tip filter element of the above-mentioned patent has a small specific surface area when the pore size of the through hole is small, and air bubbles are easily generated in the filter element during suction, which causes the tip filter element to be clogged. Therefore, the porosity of the tip filter element cannot reach 50% due to the clogging problem in actual use, and the flowability cannot meet the use requirements, which is inconvenient to use. SUMMARY

[0006] The present application aims to provide a functional filter test filter element with a specific surface area expanded by 3-15 times, excellent solution flowability, and no clogging, and application thereof.

[0007] To achieve the above-mentioned purpose, the present application proposes the following technical solutions:

[0008] The utility model provides a functional filter test filter core, including filter core body, the filter core body is made of thermoplastic polymer microsphere that is pretreated into SOS ball structure, and the porosity of filter core body is improved through SOS ball structure, and the porosity of filter core body is 51 %-75 %;

[0009] The structure of the filter core body is a three-section stepped structure, including a middle cylinder and first and second cones of the same structure connected to opposite ends of the middle cylinder, the first and second cones are respectively provided with the same number of first and second through holes, and the surface area of the filter core body is increased through the first and second through holes.

[0010] The first through holes are arranged parallel to the axial direction of the first cone, and the second through holes are arranged parallel to the axial direction of the second cone, and the first and second through holes on the same filter core body are not connected to each other; when the number of the first and second through holes is at least two, the first and second through holes are arranged in a staggered manner.

[0011] As a preferred technical solution of the utility model, the filter core body is made of thermoplastic polymer microspheres and SiO2 mesoporous microspheres treated into SOS ball structure.

[0012] As a preferred technical solution of the utility model, the thermoplastic polymer microspheres are any one or a mixture of two of PS microspheres and PMMA microspheres.

[0013] The thermoplastic polymer microspheres are any one or more than one of solid spheres and mesoporous spheres.

[0014] The diameter of the thermoplastic polymer microspheres is 20-150 microns.

[0015] As a preferred technical solution of the utility model, the filter core body is prepared and formed by sintering, chemical bonding or ultraviolet cross-linking.

[0016] When the filter core body is prepared and formed by sintering, the sintering temperature is 120-220℃, the sintering duration is 3-20 minutes, and after sintering, the filter core body is naturally cooled to obtain the filter core body.

[0017] When the filter core body is prepared and formed by chemical bonding, the filter core body is bonded together by an adhesive, and after the adhesive solidifies, the filter core body is obtained.

[0018] When the filter core body is prepared and formed by ultraviolet cross-linking, the filter core body is first bonded together by an ultraviolet curing agent, and then ultraviolet light is irradiated by an ultraviolet curing device to obtain the filter core body.

[0019] As a preferred technical scheme of the present application, the SOS ball is a large-diameter thermoplastic polymer microsphere with a plurality of small-diameter thermoplastic polymer microspheres uniformly attached to the surface of the large-diameter thermoplastic polymer microsphere.

[0020] As a preferred technical scheme of the present application, the SOS ball is a large-diameter SiO2 mesoporous microsphere with a plurality of small-diameter thermoplastic polymer microspheres uniformly attached to the surface of the large-diameter SiO2 mesoporous microsphere and / or a large-diameter thermoplastic polymer microsphere with a plurality of small-diameter thermoplastic polymer microspheres uniformly attached to the surface of the large-diameter thermoplastic polymer microsphere.

[0021] As a preferred technical scheme of the present application, the content of the SiO2 mesoporous microspheres in the filter core body is 15%-20%, and the rest is thermoplastic polymer microspheres;

[0022] The SiO2 mesoporous microspheres are prepared by a SiO2 mesoporous microsphere preparation process, and the prepared SiO2 mesoporous microspheres are subjected to particle size screening treatment to screen out SiO2 mesoporous microspheres with a particle size difference of 1-2 microns, thereby obtaining monodisperse SiO2 mesoporous microspheres.

[0023] As a preferred technical scheme of the present application, the filter core body is subjected to surface treatment to make the filter core body have hydrophilicity and the function of adsorbing or capturing target analytes, which includes:

[0024] Before the filter core body is prepared and formed, the surface of the thermoplastic polymer microspheres is subjected to hydrophilic treatment and chemical modification treatment;

[0025] Or after the filter core body is prepared and formed, the surface of the filter core body is subjected to hydrophilic treatment and chemical modification treatment;

[0026] Or before the filter core body is prepared and formed, the surface of the thermoplastic polymer microspheres is subjected to first hydrophilic treatment and chemical modification treatment, and after the filter core body is prepared and formed, the surface of the filter core body is subjected to second hydrophilic treatment and chemical modification treatment;

[0027] The hydrophilic treatment is to add a hydrophilic group to the surface of the filter core body, and the hydrophilic group includes a hydroxyl group, a carboxyl group, an amino group, a quaternary amino group, and an acrylic acid;

[0028] The chemical modification treatment is to graft to connect molecules, groups or functional groups, and the molecules, groups or functional groups include SiO2 molecules, biotin, avidin, oligonucleotides, receptors, antibodies, and IDA groups.

[0029] As a preferred technical scheme of the present application, the diameter of the intermediate cylinder is greater than the maximum diameter of the first cone or the second cone;

[0030] The first and second cones are integrally connected to the middle column, and the diameters of the first and second cones gradually decrease from the end close to the middle column to the end away from the middle column.

[0031] The first and second through holes have a pore size of 10-50 microns, wherein the pore size of the first and second through holes of the filter core body containing single-specification thermoplastic polymer microspheres is relatively uniform.

[0032] The application of the functional filter test core, as described above, is applied to protein purification, assay diagnosis and life science research.

[0033] The technical scheme of the present application provides a functional filter test core, which pre-treats thermoplastic polymer microspheres and SiO2 mesoporous microspheres into SOS ball structures before being made into a fixed shape, so that the sintered filter core has a porosity of 51%-75%, a through hole pore size of 10-50 microns, and a hole position on the upper and lower ends of the filter core is staggered, which significantly increases the surface area of the filter core and increases the effective adsorption and capture capacity in a limited space, so that it can sensitively adsorb or capture the target analyte during use; in addition, the thermoplastic polymer microspheres and the filter core are subjected to surface hydrophilic treatment, so that they have strong hydrophilicity, the resistance is small when the liquid passes through, and it can pass through 100%; various chemical modifications or grafting are performed on the surface of the filter core, various molecules, groups or functional groups are connected, so that the filter core is suitable for various detections and has relatively all-purpose application.

[0034] It should be understood that all combinations of the foregoing concepts and additional concepts described in greater detail below can be seen as being part of the subject matter of the present disclosure as long as such concepts are not mutually inconsistent.

[0035] The foregoing and other aspects, embodiments and features of the present teachings can be better understood from the following description of the present teachings taken in conjunction with the accompanying drawings. Other aspects, embodiments and features of the present teachings will be apparent from the description that follows and from the claims. BRIEF DESCRIPTION OF DRAWINGS

[0036] The drawings are not drawn to scale. In the drawings, each same or like component that is shown in various figures can be represented by a same reference numeral. For the sake of clarity, not every component can be labeled in every figure. Embodiments of various aspects of the present teachings will now be described, by way of example only, with reference to the accompanying drawings in which:

[0037] Figure 1 Structure diagram of a filter core with a diameter of 10 microns;

[0038] Figure 2 This is a schematic diagram of the structure of a filter element with a diameter of 15 micrometers.

[0039] Figure 3 This is a schematic diagram of the structure of a filter element with a diameter of 25 micrometers.

[0040] Figure 4 This is a schematic diagram of the structure of a filter element with a diameter of 35 micrometers.

[0041] Figure 5 This is a schematic diagram of the structure of a Φ35 micrometer filter element from another direction;

[0042] Figure 6 This is a schematic diagram of the structure of a filter element with a diameter of 50 micrometers.

[0043] Figure 7 This refers to the state of the SOS balls when they are bonded together. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention without creative effort are within the scope of protection of the present invention. Unless otherwise defined, the technical or scientific terms used herein should have the ordinary meaning understood by those skilled in the art.

[0045] The terms "first," "second," and similar words used in the specification and claims of this patent application do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Similarly, unless the context clearly indicates otherwise, the singular forms of "an," "a," or "the," etc., do not indicate a quantity limitation, but rather indicate the presence of at least one. Terms such as "comprising" or "including" indicate that the element or object preceding "comprising" encompasses the features, wholes, steps, operations, elements, and / or components listed following "comprising" or "including," and do not exclude the presence or addition of one or more other features, wholes, steps, operations, elements, components, and / or sets thereof. Terms such as "upper," "lower," "left," and "right" are used only to indicate relative positional relationships; when the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0046] Example 1

[0047] This invention provides a functional filtration test filter element, including a filter element body. The filter element body is prepared by a filter element molding method using thermoplastic polymer microspheres, and the prepared filter element body has a porosity of 51%-75%. The larger porosity significantly increases the specific surface area of ​​the filter element body, increasing the ability to effectively adsorb and capture target analytes within a limited space. This allows for the adsorption or capture of more target analytes when liquids pass through, even in dilute solutions. This improves the sensitivity of the filter element body during use. Subsequently, a smaller volume of eluent can be used to elute the target analytes from the filter element body, resulting in a solution with a higher concentration of the target analytes, thus significantly increasing the concentration of the target analytes in the eluent.

[0048] In this embodiment of the invention, the thermoplastic polymer microspheres have a diameter of 20-150 micrometers and include any one or a mixture of two of PS microspheres and PMMA microspheres, wherein PS is polystyrene and PMMA is polymethyl methacrylate. For example, the filter element body can be made using pure PS microspheres; the filter element body can be made using pure PMMA microspheres; or the filter element body can be made by uniformly mixing PS microspheres and PMMA microspheres and then forming them using a filter element preparation method. The thermoplastic polymer microspheres are any one or more of solid spheres and mesoporous spheres. Specifically, the PS microspheres are one or more of solid spheres and mesoporous spheres; the PMMA microspheres are one or more of solid spheres and mesoporous spheres. When both PS microspheres and PMMA microspheres are present, their spherical structures can be the same or different, i.e., it can be a combination of PS solid microspheres + PMMA solid microspheres, or a combination of PS mesoporous microspheres + PMMA solid microspheres, or a combination of PS mesoporous microspheres + PMMA mesoporous microspheres, etc.

[0049] Before the filter element body is fabricated, the thermoplastic polymer microspheres are pretreated, including preparing the thermoplastic polymer microspheres into SOS spheres, so as to maximize the porosity of the fabricated filter element body. Figure 7 As shown, the SOS ball is a thermoplastic polymer microsphere with a large diameter, on which several smaller thermoplastic polymer microspheres are uniformly attached. The unique connection structure of the SOS ball ensures that the thermoplastic polymer microspheres bond primarily through the surfaces between the smaller diameter microspheres, resulting in a minimal contact surface between the SOS balls and preventing the larger diameter microspheres from contacting each other. This creates larger pores between the larger diameter microspheres, thereby increasing the overall porosity of the prepared filter cartridge. The porosity can be calculated using existing porosity calculation formulas combined with the structural characteristics of the SOS ball in this embodiment.

[0050] In the prior art, the thermoplastic polymer microspheres are generally mixed uniformly and then bonded to form a minimum unit of microspheres, irregular spheres or mesoporous spheres, without treating the microspheres before bonding to form a microsphere combination unit with a large porosity, and then mixing and bonding the microsphere combination unit, so that the final filter core body has a small porosity, which cannot meet the use requirements. The preparation and treatment of the SOS spheres in the embodiments of the present application require certain means, such as selecting appropriate diameter large-diameter microspheres and small-diameter microspheres and appropriate quantity ratio of large-diameter microspheres and small-diameter microspheres, so that the small-diameter microspheres and the small-diameter microspheres are in a tangential connection state, and the porosity of the SOS sphere combined by the small-diameter microspheres and the large-diameter microspheres can be as large as possible. The microspheres without special pretreatment cannot naturally form a special structure such as the SOS sphere, so the SOS sphere structure in the embodiments of the present application is realized by brainpower technical means.

[0051] In the embodiments of the present application, the thermoplastic polymer microspheres may contain PS microspheres and PMMA microspheres, so the larger-diameter thermoplastic polymer microspheres and the smaller-diameter thermoplastic polymer microspheres may be the same kind of thermoplastic polymer microspheres, such as both being PS microspheres or both being PMMA microspheres; or two different kinds of thermoplastic polymer microspheres, for example, the larger-diameter thermoplastic polymer microspheres are PS microspheres and the smaller-diameter thermoplastic polymer microspheres are PMMA microspheres, or vice versa.

[0052] In the embodiments of the present application, the filter core body is prepared by a filter core forming preparation method, including but not limited to any one of sintering, chemical bonding, ultraviolet crosslinking. The combination state between the adjacent microspheres or microsphere combination units of the thermoplastic polymer microspheres in the prepared filter core body is in a tangential state or a partially fused connection state. The arrangement mode of the single microspheres or microsphere combination units (such as SOS spheres) of the thermoplastic polymer microspheres in the prepared filter core body can be all in a disordered state between the microspheres or SOS spheres, can form a horizontal and vertical arrangement in a straight line, or can form a spiral structure of the stacked arrangement between the microspheres or SOS spheres. The ordered or disordered arrangement between the microspheres or SOS spheres further improves the porosity of the filter core body.

[0053] When the filter core body is prepared by sintering, the method comprises the following steps: firstly, a certain amount of thermoplastic polymer microspheres are placed in a specific mold; then, heating is started, and the thermoplastic polymer microspheres are melted and bonded together under their own characteristics, wherein the sintering temperature is 120-220 DEG C, the sintering duration is 3-20 minutes, and the sintering is naturally cooled after being finished.

[0054] When the filter core body is prepared by chemical bonding, the method comprises the following steps: firstly, a certain amount of thermoplastic polymer microspheres are poured into a specific mold; then, an adhesive is added to the mold to bond the thermoplastic polymer microspheres together, and the adhesive is solidified to obtain the filter core body.

[0055] When the filter core body is prepared by ultraviolet crosslinking, the method comprises the following steps: firstly, a certain amount of thermoplastic polymer microspheres are poured into a specific mold; then, an ultraviolet curing agent is added to the mold to bond the thermoplastic polymer microspheres together; and finally, ultraviolet light is irradiated by using an ultraviolet curing device to solidify the ultraviolet curing agent to obtain the filter core body.

[0056] In the embodiment of the present application, after the filter core body is prepared, surface treatment is performed on the filter core body to make the filter core body have hydrophilicity and the function of adsorbing or capturing the analyte, including but not limited to the following methods:

[0057] The first method is to perform hydrophilic treatment and chemical modification treatment on the surface of the thermoplastic polymer microspheres before the filter core body is prepared; the second method is to perform hydrophilic treatment and chemical modification treatment on the surface of the filter core body after the filter core body is prepared; and the third method is to first perform first hydrophilic treatment and chemical modification treatment on the surface of the thermoplastic polymer microspheres before the filter core body is prepared, and then perform second hydrophilic treatment and chemical modification treatment on the surface of the filter core body after the filter core body is prepared.

[0058] The hydrophilic treatment comprises adding a hydrophilic group to the surface of the thermoplastic polymer microspheres or the filter core body. The hydrophilic group includes but is not limited to a hydroxyl group, a carboxyl group, an amino group, a quaternary amino group and acrylic acid. By adding the hydrophilic group, the filter core body has strong hydrophilicity, so that the liquid can smoothly pass through the filter core body, the resistance is small, and the filter core body is not blocked, and the time of the solution passing through the filter core body is shortened, so that the test time is shortened and the detection or test efficiency is improved.

[0059] The chemical modification treatment includes grafting on the surface of the thermoplastic polymer microspheres or the surface of the filter core body to connect molecules, groups or functional groups, which include SiO2 molecules, biotin, avidin, oligonucleotides, receptors, antibodies and IDA groups, but are not limited to the above molecules, groups or functional groups. In practical applications, suitable molecules, groups or functional groups can be grafted on the surface of the filter core body as needed for adsorption or capture of corresponding target analytes that can be adsorbed or captured. Among them, the filter core body is chemically grafted, when SiO2 molecules are grafted, the filter core body can be used for biomolecule detection; when antibodies are grafted, the filter core body can be used for chemiluminescence detection, single antibody screening; when IDA groups are grafted, the filter core body can be used for protein purification; therefore, the filter core body can be grafted on the surface of the filter core body as needed.

[0060] In the embodiment of the present application, the structure of the filter core body after molding is a three-section stepped structure, including a middle cylinder and first and second cones of the same structure connected to opposite ends of the middle cylinder. The first and second cones are integrally formed and connected to the middle cylinder, the diameters of the first and second cones gradually decrease from the end close to the middle cylinder to the end away from the middle cylinder, and the diameter of the middle cylinder is greater than the maximum diameter of the first or second cone.

[0061] The first and second cones on the same filter core body are respectively provided with the same number of first and second through holes that are not connected to each other. The first and second through holes are both arranged parallel to the axial direction of the middle cylinder, the first through hole extends from the end of the first cone to the connection between the first cone and the middle cylinder, and does not extend through the middle cylinder to the second cone; similarly, the second through hole extends from the end of the second cone to the connection between the second cone and the middle cylinder, and does not extend through the middle cylinder to the first cone, and no through hole is provided in the middle cylinder.

[0062] As shown in Figure 1 or Figure 2 When only one first through hole is provided in the first cone, only one second through hole is provided in the second cone, at this time, the hole positions of the first and second through holes correspond and are both located in the middle of the filter core body; when two first through holes are provided in the first cone, two second through holes are also provided in the second cone, that is, the number of first and second through holes located on the same filter core body is the same. As can be seen, the structures of the first and second cones at both ends of the middle cylinder are completely the same, therefore, it can be said that the entire filter core body has no upper and lower structures, and the advantage of such design is that it can facilitate the installation of the filter core body, that is, there is no need to distinguish the upper end or lower end of the filter core body, and the filter core body can be directly installed into a suction head or the like after being taken out, which is fast and efficient.

[0063] As shown in Figures 3 to 5 , when the number of the first through holes and the second through holes is at least two, the first through holes and the second through holes are staggered. As shown in Figure 3 , the filter core body is 25 microns, and the first taper and the second taper are respectively provided with 3 first through holes and 3 second through holes, and the hole positions of the 3 first through holes and the 3 second through holes are staggered. As shown in Figure 4 and Figure 5 , the filter core body is 35 microns, and the first taper and the second taper are respectively provided with 4 first through holes and 4 second through holes, and the hole positions of the 4 first through holes and the 4 second through holes are also staggered.

[0064] In the embodiment of the present application, in addition to the through holes, the filter core body can also be provided with through grooves, that is, in addition to the first taper and the second taper being respectively provided with staggered first through holes and second through holes, the first taper and the second taper are respectively provided with first through grooves and second through grooves on the side surfaces thereof, and the number of the first through grooves and the second through grooves is also the same and staggered. As shown in Figure 6 , the filter core body is 50 microns, the first through groove is parallel to the central axis of the first taper and is arranged on the side surface thereof, and the first through groove extends linearly from the end of the first taper to one end of the middle column but does not communicate with the middle column; the second through groove is parallel to the central axis of the second taper and is arranged on the side surface thereof, and the second through groove extends linearly from the end of the second taper to one end of the middle column but does not communicate with the middle column.

[0065] The filter core body of the embodiment of the present application is provided with a three-section stepped structure, and first through holes and second through holes are arranged inside both ends thereof, and first through grooves and second through grooves are arranged on the surface thereof, so that the surface area of the filter core body can be effectively increased, the surface area is 8-10 times larger than that of the conventional filter core which is not provided with through holes inside and through grooves on the surface, the surface area of the filter core is greatly increased in limited space, more target analytes can be adsorbed or captured when the solution passes through, the sensitivity of the filter core body is greatly improved, the filtering speed is greatly increased, the probability of particle blockage is reduced, and the effect of not delaying the filtration in limited cross-sectional area is realized.

[0066] For the traditional filter core, no through hole is formed in its interior at both ends, so when sucking, the solution first contacts the end face of the traditional filter core, then under the continuous negative pressure, is sucked into the pores in the interior of the traditional filter core, and then enters the lumen of the washing liquid device (pipette) through the pores in the interior, and the target analyte in the solution is adsorbed or captured when flowing through the interior of the traditional filter core. As can be seen, the surface of the traditional filter core that can contact the solution is only the cross-sectional area of the end, which is very easy to cause the end face to be blocked by particulate matter in the solution during filtration.

[0067] The filter core body of the present application can increase the surface area by setting a plurality of through holes and through grooves to achieve the technical effect of improving adsorption and capture. Because, as known from common knowledge, the pore characteristics of porous materials are that the pores are closed in the interior of the material, or are communicated with the outside at the surface of the material, the former is called closed pores, and the latter is called open pores; some pores are separated in the interior of the material, or some pores are interconnected in the interior of the material. For the technical effect of the embodiment of the present application, open pores and the two types of interconnected pores in the material are required, the internal surface of these open pores is in a bare state and can directly contact the solution, so as to have the opportunity to adsorb or capture the target analyte, and the internal surface of the closed pores cannot directly contact the solution, so there is no opportunity to contact the target analyte, and then adsorb or capture the target analyte. Therefore, the through holes are formed in the interior of the filter core body and the through grooves are formed on the surface, thereby cutting and damaging part of the closed pores in the interior of the filter core body, destroying the original closed property, changing the independent closed pores separated in the interior of the material into open pores with exposed internal surface, thereby creating the opportunity to contact the solution, and then adsorbing and capturing the target analyte in the solution. Therefore, one of the purposes of setting the through holes and the through grooves in the embodiment of the present application is to change the closed pores in the interior of the filter core body into open pores, thereby increasing the surface area and improving the adsorption and capture effect.

[0068] In the embodiment of the present application, the first through hole and the second through hole have a pore size of 10-50 microns. By controlling the pore size of the through hole, air cannot enter the filter core body, avoiding the situation of blockage caused by the formation of air bubbles in the filter core body, but at the same time allowing the solution to pass through, so that the target analyte in the solution is adsorbed or captured by the functional groups or groups on the surface of the filter core body. Therefore, when the solution is being drawn, it is difficult for air to enter the through hole, and when the solution passes through the through hole and enters the inside of the filter core body, the solution must also pass through the intermediate cylinder between the first cone and the second cone. At this time, the intermediate cylinder is not easy to produce air bubbles, just like a traditional filter core without a through hole, thereby limiting the generation of air bubbles. In addition, if air bubbles are generated in the through hole, because the other end of the through hole is a closed structure, the suction force applied when drawing is greater than when the solution first enters the through hole. At this time, the air bubbles in the through hole will be squeezed and broken under the vertical upward force of the solution, so that the air bubbles cannot persist in the inside of the filter core body, thereby avoiding blockage caused by air bubbles. Moreover, one of the conditions for the generation of air bubbles is the sudden increase in the permeability of the porous material. However, the embodiment of the present application is just the opposite, that is, for the entire filter core body, the permeability of the through hole cone section is greater than that of the intermediate cylinder section located in the middle, that is, for the solution, the flow direction of the entire filter core body is from the section with greater permeability to the section with smaller permeability, which is a condition for the sudden decrease in the permeability of the porous material, which is contrary to the condition for the generation of air bubbles. Therefore, it is proved that the embodiment of the present application actually does not generate air bubbles. Among them, the first through hole and the second through hole of the filter core body containing single-specification thermoplastic polymer microspheres have a relatively uniform pore size.

[0069] Embodiment 2

[0070] The difference between embodiment 2 and embodiment 1 is that the microspheres used to make the filter core body also contain SiO2 mesoporous microspheres. Therefore, in the embodiment 2 of the present application, the thermoplastic polymer microspheres are any one or a mixture of two of PS microspheres and PMMA microspheres, and the filter core body can be made by mixing PS microspheres and SiO2 mesoporous microspheres; can be made by mixing PMMA microspheres and SiO2 mesoporous microspheres; or can be made by uniformly mixing PS microspheres, PMMA microspheres and SiO2 mesoporous microspheres. Similarly, before the filter core body is prepared and formed, the thermoplastic polymer microspheres and SiO2 mesoporous microspheres are pretreated, specifically, the thermoplastic polymer microspheres and SiO2 mesoporous microspheres are prepared into SOS balls.

[0071] In the embodiment 2 of the present application, because the SiO2 mesoporous microspheres do not have the property of adhesion, in this case, the SOS spheres are a large-diameter SiO2 mesoporous microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres, or a large-diameter thermoplastic polymer microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres, so that when sintering is used to prepare the molding, the thermoplastic polymer microspheres can be used to bond the SOS spheres together. The combination type of the SOS spheres can be divided into: first, only the SOS spheres with a large-diameter SiO2 mesoporous microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres; second, the SOS spheres with a large-diameter SiO2 mesoporous microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres, and the SOS spheres with a large-diameter thermoplastic polymer microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres.

[0072] In addition, the special connection structure of the SOS spheres allows the SOS spheres to be bonded only by the surface of the small-diameter thermoplastic polymer microspheres, so that the contact surface of the bonded SOS spheres is extremely small, and the large-diameter SiO2 mesoporous microspheres do not contact each other, thereby leaving a larger pore between the large-diameter SiO2 mesoporous microspheres, and further improving the overall porosity of the prepared filter core body. As shown in Figure 6 In the optimal bonding case, that is, when the SOS spheres are bonded to each other, the bonding between each adjacent two SOS spheres is only through the tangent surface connection between the small-diameter thermoplastic polymer microspheres, so that the SOS spheres, the SiO2 mesoporous microspheres, the thermoplastic polymer microspheres, or any different types and structures of microspheres are in a state of maximum porosity, thereby maximizing the porosity of the prepared filter core body.

[0073] When in the embodiment 2 of the present application, only the SOS spheres with a large-diameter SiO2 mesoporous microsphere surface uniformly attached to several small-diameter thermoplastic polymer microspheres exist, and the thermoplastic polymer microspheres are all mesoporous spheres, the pore formed by the optimal bonding of the SiO2 mesoporous microspheres, the thermoplastic polymer microspheres, and the SOS spheres, combined with the through hole on the filter core body, can make the porosity of the prepared filter core body reach 75%, which is much better than the porosity of the existing filter core.

[0074] It is known that the greater the porosity, the greater the specific surface area for the same volume. For filter cartridges used for adsorbing or capturing analytes, the greater the porosity, the greater the specific surface area for the same filter cartridge volume, and thus the greater the surface area of the filter cartridge body that can be surface treated, and the greater the number of functional groups, radicals, etc. attached to the surface, so that the filter cartridge can adsorb or capture more analytes of interest. Therefore, in the present embodiment 2, the filter cartridge body is treated to achieve a porosity of 75% by treating the structure of the SiO2 mesoporous microspheres and the thermoplastic polymer microspheres as described above, which has a higher effective adsorption or capture capacity, a higher adsorption or capture efficiency, and a higher sensitivity than existing filter cartridges. A large amount of analytes of interest in a solution can be adsorbed or captured on the filter cartridge body, overcoming the problem that the adsorption or capture amount of the filter cartridge is limited by volume, and significantly reducing the adsorption or capture time, greatly shortening the implementation time, or in a solution containing very few analytes of interest, the analytes of interest can also be adsorbed or captured, and after elution with a small amount of eluent (smaller volume), a solution with significantly increased analyte of interest concentration can be obtained.

[0075] Embodiment 3

[0076] Functional filter test cartridge for protein purification

[0077] Monodisperse PS microspheres with a diameter of 30 microns were mixed uniformly with monodisperse SiO2 mesoporous microspheres with a diameter of 120 microns, sintered at 150°C for 5 minutes, and after cooling, a filter cartridge body according to the present application was prepared, which had a porosity of about 70-75%. The filter cartridge body was about 1 cm long, and the first cone, the second cone and the middle column almost equally divided the filter cartridge body, wherein the first cone and the second cone were respectively provided with 3 first through holes and 3 second through holes, and the first through holes and the second through holes were arranged in a staggered manner, and the pore size of the first through holes and the second through holes was 25 microns. According to the ISO / DIS5636-5 Gurley test method, the air flow of 300 cubic centimeters of air passing through the filter cartridge body was 400-500 seconds, indicating that it was very difficult for air to enter the filter cartridge body.

[0078] Embodiment 4

[0079] Application of a functional filter test cartridge, the functional filter test cartridge of embodiment 1 or embodiment 2 described above is applied to protein purification, assay diagnosis and life science research.

[0080] Specifically, for example, when applied to protein purification, specific polypeptide fragments or proteins, or heparin-binding proteins, cell wall proteins, etc. can be separated and purified; when applied to determination and diagnosis, it can be used for DNA / RNA separation, streptavidin purification or biotin purification, etc.; when applied to life science research, it can be used as an in vitro diagnostic product or CRO research.

[0081] Although the present application has been disclosed in the above with preferred embodiments, it is not intended to limit the present application. Those skilled in the art can make various modifications and improvements without departing from the spirit and scope of the present application. Therefore, the scope of protection of the present application shall be subject to the scope defined by the claims.

Claims

1. A functional filtration test filter element, comprising a filter element body, characterized in that, The filter element body is made of thermoplastic polymer microspheres pretreated into an SOS sphere structure. The porosity of the filter element body is increased by the SOS sphere structure, and the filter element body has a porosity of 51%-75%. The filter element body has a three-stage stepped structure, including a middle column and a first cone and a second cone with the same structure connected to opposite ends of the middle column. The first cone and the second cone are respectively provided with the same number of first through holes and second through holes, which increase the surface area of ​​the filter element body. The first through hole is arranged parallel to the axial direction of the first cone, and the second through hole is arranged parallel to the axial direction of the second cone. The first through hole and the second through hole on the same filter element body are not connected to each other. When there are at least two of the first through hole and the second through hole, the first through hole and the second through hole are staggered.

2. The functional filter test cartridge as described in claim 1, characterized in that, The filter element body is made of thermoplastic polymer microspheres and SiO2 mesoporous microspheres that have been processed into SOS sphere structures.

3. The functional filter element for testing as described in claim 1 or 2, characterized in that, The thermoplastic polymer microspheres are any one or a mixture of two of PS microspheres and PMMA microspheres; The thermoplastic polymer microspheres are any one or more of solid spheres and mesoporous spheres; The diameter of the thermoplastic polymer microspheres is 20-150 micrometers.

4. The functional filter element for testing as described in claim 1 or 2, characterized in that, The filter element body is prepared and shaped by sintering, chemical bonding, or ultraviolet cross-linking. When the filter element body is prepared by sintering, the sintering temperature is 120-220℃, the sintering duration is 3-20 minutes, and the filter element is left to cool naturally after sintering. When the filter element body is prepared by chemical bonding, it is bonded together with an adhesive, and the filter element is obtained after the adhesive solidifies. When the filter element body is prepared by ultraviolet crosslinking, it is first bonded together with an ultraviolet curing agent, and then cured by ultraviolet light irradiation using an ultraviolet curing device.

5. The functional filter test cartridge as described in claim 1, characterized in that, The SOS ball is a thermoplastic polymer microsphere with a large diameter on its surface, with several smaller thermoplastic polymer microspheres uniformly attached.

6. The functional filter test cartridge as described in claim 2, characterized in that, The SOS ball is a SiO2 mesoporous microsphere with a large diameter on its surface uniformly coated with several smaller diameter thermoplastic polymer microspheres and / or a thermoplastic polymer microsphere with a large diameter on its surface uniformly coated with several smaller diameter thermoplastic polymer microspheres.

7. The functional filter test cartridge as described in claim 2, characterized in that, The content of SiO2 mesoporous microspheres in the filter element body is 15%-20%, and the remainder is thermoplastic polymer microspheres; The SiO2 mesoporous microspheres are prepared using a SiO2 mesoporous microsphere preparation process. The prepared SiO2 mesoporous microspheres are then subjected to particle size sieving to separate SiO2 mesoporous microspheres with a particle size difference of 1-2 micrometers, thus obtaining monodisperse SiO2 mesoporous microspheres.

8. The functional filter test cartridge as described in claim 1, characterized in that, The filter element body undergoes surface treatment to make it hydrophilic and to adsorb or capture the target analyte, including: Before the filter element body is formed, the surface of the thermoplastic polymer microspheres is subjected to hydrophilic treatment and chemical modification treatment; Alternatively, after the filter element body is manufactured, the surface of the filter element body can be subjected to hydrophilic treatment and chemical modification treatment; Alternatively, before the filter element body is formed, the surface of the thermoplastic polymer microspheres may undergo a first hydrophilic treatment and chemical modification treatment, and after the filter element body is formed, the surface of the filter element body may undergo a second hydrophilic treatment and chemical modification treatment. The hydrophilic treatment involves adding hydrophilic groups to the surface of the thermoplastic polymer microspheres or the filter element body. The hydrophilic groups include hydroxyl, carboxyl, amino, quaternary amino, and acrylic acid groups. The chemical modification treatment involves grafting onto the surface of the thermoplastic polymer microspheres or the filter element body to connect molecules, groups, or functional groups, including SiO2 molecules, biotin, avidin, oligonucleotides, receptors, antibodies, and IDA groups.

9. The functional filter test cartridge as described in claim 1, characterized in that, The diameter of the intermediate column is greater than the maximum diameter of the first cone or the second cone; The first cone and the second cone are integrally formed and connected to the intermediate column. The diameters of the first cone and the second cone gradually decrease from the end closer to the intermediate column to the end farther away from the intermediate column. The pore diameters of the first and second through holes are 10-50 micrometers, wherein the pore diameters of the first and second through holes in the filter body containing thermoplastic polymer microspheres of a single specification are relatively uniform.

10. An application of a functional filter testing cartridge, characterized in that, The functional filter cartridge as described in any one of claims 1-9 is used for protein purification, assay and diagnosis.

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