Sealing process for well plate, high-throughput screening method, well plate heat sealing device, and high-throughput screening system

Abstract

The present application relates to the technical field of high-throughput chemical reactions, and in particular to a sealing process for a well plate, a high-throughput screening method, a well plate heat sealing device, and a high-throughput screening system. The sealing process for a well plate comprises: covering a blind well of a well plate with a film and then carrying out heat sealing, wherein the material for forming the film is consistent with the material of the part of the well plate in contact with the film, and the heat sealing conditions comprise: the heat sealing temperature is 5-65°C higher than the melting point of the material of the film, and the heat sealing time is 0.3-4.5 s. The sealing process can solve the problems of difficulty in single-well sealing of small volume wells in existing well plates and tolerance to only low temperatures of existing sealing processes. Thus, a well plate reaction device is allowed to expand its applicable ranges of reaction temperatures and reaction solvents in high-throughput screening, implementing heating and oscillating reactions, and also implementing chemical reactions under conditions exceeding the boiling points of solvents.

Description

Orifice plate sealing process, high-throughput screening method, orifice plate heat sealing device and high-throughput screening system

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This disclosure claims priority to Chinese patent application number 2023116888093, filed with the Chinese Patent Office on December 8, 2023, and entitled “Sealing process for well plate and high-throughput screening method thereof”;

[0003] And the priority of the Chinese patent application with application number 2023233596886 and titled "Well Plate Heat Sealing Device and High Throughput Screening System" filed with the Chinese Patent Office on December 8, 2023, the entire contents of which are incorporated by reference in this disclosure. Technical Field

[0004] The present disclosure belongs to the field of high-throughput chemical reaction technology, and specifically relates to a well plate sealing process, a high-throughput screening method, a well plate heat sealing device, and a high-throughput screening system. Background Art

[0005] Multi-channel well plates are mostly used in the fields of biology and biochemistry, for example, for the study of proteins, peptides and enzymes at room temperature or 37°C. Multi-channel well plates are rarely used in organic chemical reactions. Since organic chemical reactions use many types of solvents that are highly corrosive and have a wide reaction temperature range, glassware is generally used as reaction containers. Well plate reactors are important reaction devices in high-throughput screening, such as 48-well plates, 96-well plates and 384-well plates made of plastic. The heat sealing process of the well plate refers to covering the blind holes of the well plate with a film, heating the film and applying a certain pressure to the film to achieve the effect of sealing the reaction solution or solid in the blind holes of the well plate. At present, a variety of well plate heat sealing devices have been developed, such as using aluminum foil and polypropylene film as heat sealing films to achieve well plate heat sealing. However, traditional well plates have the problem of difficulty in sealing small-volume single holes.

[0006] Public content

[0007] The embodiments of the present disclosure provide a sealing process for an orifice plate, a high-throughput screening method, an orifice plate heat sealing device and a high-throughput screening system. The sealing process provided by the embodiments of the present disclosure can solve the problem that it is difficult to seal a single hole of a small volume in the existing orifice plate, and the problem that the existing sealing process can tolerate low temperature. Thereby solving the problem that the reaction temperature and reaction solvent are limited in the high-throughput screening method based on the orifice plate, the reaction cannot be carried out at a reaction temperature higher than the boiling point of the solvent, and the reaction conditions of heating and oscillation cannot be achieved. The orifice plate heat sealing device provided by the embodiments of the present disclosure can realize a high-temperature, fast (<5s) heat sealing process, ensuring that the temperature of the liquid or solid in the blind hole of the orifice plate is always lower than 30°C during the heat sealing process, improving the mechanical strength of the heat-sealed part of the orifice plate and ensuring that the seal does not fail in usage scenarios such as heating and / or oscillation.

[0008] In the first aspect, an embodiment of the present disclosure provides a sealing process for an orifice plate, comprising: covering a layer of film over the blind hole of the orifice plate and then performing heat sealing, wherein the material forming the film is consistent with the material of the contact portion between the orifice plate and the film, and the heat sealing conditions include: the heat sealing temperature is 5-65°C higher than the melting point of the film material, and the heat sealing time is 0.3-4.5s.

[0009] It should be noted that the above-mentioned well plate can be a commercially available multi-well plate, such as a 24-well, 48-well, 96-well and 384-well plate, or it can be a bubble cap well plate provided in the embodiments of the present disclosure.

[0010] Optionally, the heat sealing temperature is 10-55° C. higher than the melting point of the film material, preferably 10-50° C. higher than the melting point of the film material;

[0011] Optionally, the heat sealing time is 0.5-4 s; more preferably 0.5-3 s, further preferably 0.5-1 s or 1-3 s.

[0012] Optionally, the material forming the film is a thermoplastic material;

[0013] Optionally, the thermoplastic material is selected from any one of polyolefin materials, polyester materials, polyamide materials and polyurethane materials, or a composite material of a combination of at least two of them;

[0014] Optionally, the thermoplastic material is selected from any one of polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyethylene terephthalate, polybutylene terephthalate, polyarylate, polyisocyanate, polymethyl methacrylate, polycarbonate, nylon, polyperfluoroethylene propylene and polychlorotrifluoroethylene, or a composite material of a combination of at least two thereof.

[0015] Optionally, the thickness of the film is 0.04-0.18 mm; preferably 0.04-0.15 mm, more preferably 0.04-0.1 mm.

[0016] Optionally, the film is a PP film, and the thickness of the PP film is 0.04-0.18 mm, preferably 0.04-0.15 mm, and more preferably 0.04-0.1 mm;

[0017] The heat sealing temperature is 170-215° C., preferably 180-210° C.; the heat sealing time is 0.5-4.5 s; preferably 0.5-3 s, more preferably 1-3 s.

[0018] Optionally, the film is an FEP film, and the thickness of the FEP film is 0.04-0.18 mm, preferably 0.04-0.15 mm, and more preferably 0.04-0.1 mm;

[0019] The heat sealing temperature is 250-350° C., preferably 280-300° C.; the heat sealing time is 0.3-4.5 s; preferably 0.5-3 s, more preferably 0.5-1 s.

[0020] In a second aspect, an embodiment of the present disclosure provides a high-throughput screening method, which includes the sealing process of the well plate described in any of the aforementioned embodiments.

[0021] Optionally, the orifice plate comprises a bubble cap orifice plate;

[0022] Optionally, the cross-sectional shape of the blind hole of the bubble cap plate is one of circular, quasi-circular, elliptical and quasi-elliptical; more preferably circular;

[0023] Optionally, the blind holes of the bubble cap plate are in a shape of a semi-spherical body or a semi-ellipsoidal body as a whole; preferably, the blind holes are in a shape of a semi-spherical body.

[0024] Optionally, the method further comprises: performing a molding process on the thermoplastic material to form a blister hole plate;

[0025] Optionally, the method comprises: performing a thermoforming process on the thermoplastic material to form a blister hole plate;

[0026] Optionally, the molding process includes: any one of a blow molding process, a vacuum molding process or an injection molding process.

[0027] Optionally, the step of forming the blister plate includes: heating a thermoplastic material having a thickness of 0.15-0.8 mm to a temperature 5-30° C. lower than the melting point of the thermoplastic material, and then processing the thermoplastic material substrate into a mold shape by a blow molding process or a vacuum molding process to form the blister plate;

[0028] Optionally, the heating is performed to a temperature 5-25°C below the melting point of the thermoplastic material, more preferably 5-20°C below the melting point of the thermoplastic material.

[0029] Alternatively, the thermoplastic material is heated to a molten state, and then the thermoplastic material substrate is processed into a mold shape using an injection molding process to form a blister plate with a thickness of 0.15-0.8 mm;

[0030] Optionally, the thermoplastic material has a thickness of 0.2-0.6 mm.

[0031] Optionally, the step of forming the blister plate includes: heating a thermoplastic material having a thickness of 0.15-0.8 mm to a temperature 5-30° C. lower than the melting point of the thermoplastic material, and maintaining the temperature for 50-100 seconds, and then quickly feeding the thermoplastic material onto a mold, and then vacuum molding the thermoplastic material to form the blister plate;

[0032] Optionally, the thickness of the thermoplastic material is 0.2-0.6 mm;

[0033] Optionally, heating to a temperature 5-25° C. below the melting point of the thermoplastic material, more preferably 5-20° C. below the melting point of the thermoplastic material;

[0034] Optionally, the heating temperature is maintained for 70-90 seconds.

[0035] Optionally, the step of forming the blister plate includes: placing a thermoplastic material having a thickness of 0.15-0.8 mm on a mold, heating it to a temperature 5-30° C. lower than the melting point of the thermoplastic material, and then blow-molding the thermoplastic material under a certain pressure to form the blister plate;

[0036] Optionally, the thickness of the thermoplastic material is 0.2-0.6 mm;

[0037] Optionally, the heating is performed to a temperature 5-25°C below the melting point of the thermoplastic material, more preferably 5-20°C below the melting point of the thermoplastic material.

[0038] Optionally, the thermoplastic material is selected from any one of polyolefin materials, polyester materials, polyamide materials and polyurethane materials, or a composite material of a combination of at least two of them;

[0039] Optionally, the thermoplastic material is selected from any one of polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyethylene terephthalate, polybutylene terephthalate, polyarylate, polyisocyanate, polymethyl methacrylate, polycarbonate, nylon, polyperfluoroethylene propylene and polychlorotrifluoroethylene, or a composite material of a combination of at least two thereof.

[0040] Optionally, the thermoplastic material is a PP material, and the molding process comprises: heating the PP material to 130-165° C., maintaining the temperature for 50-100 seconds, and performing vacuum molding in a vacuum environment, wherein the thickness of the PP material is 0.15-0.8 mm;

[0041] Optionally, the thickness of the PP material is 0.2-0.6 mm; optionally, the heating temperature is 150-155° C.; optionally, the heating temperature is maintained for 70-90 seconds;

[0042] Alternatively, the steps of the molding process include: heating the PP material to 130-165° C. and blow molding the PP material at a pressure of not less than 0.4 MPa, wherein the thickness of the PP material is 0.15-0.8 mm;

[0043] Optionally, the thickness of the PP material is 0.2-0.6 mm; optionally, the heating temperature is 140-150°C.

[0044] Optionally, the thermoplastic material is an FEP material, and the molding process comprises: heating the FEP material to 220-260° C., maintaining the temperature for 50-100 seconds, and performing vacuum molding in a vacuum environment, wherein the thickness of the FEP material is 0.15-0.8 mm; optionally, the thickness of the FEP material is 0.2-0.6 mm; optionally, the heating temperature is 240-250° C.; optionally, the heating temperature is maintained for 70-90 seconds;

[0045] Alternatively, the molding process includes heating the FEP material to 220-260°C and blow molding it at a pressure of not less than 0.4 MPa, wherein the thickness of the FEP material is 0.15-0.8 mm; optionally, the thickness of the FEP material is 0.2-0.6 mm; optionally, the heating temperature is 240-250°C.

[0046] Optionally, the method includes: after forming the bubble cap plate, adding the reaction solution and / or solid into the blind hole of the bubble cap plate, and then sealing the plate according to the sealing process of the plate, then heating and / or shaking, and then analyzing the reaction system.

[0047] Optionally, during the sealing process, a sealing ring is formed at the opening of each blind hole of the bubble hole plate; optionally, the shape of the sealing ring is the same as the shape of the blind hole of the bubble hole plate; optionally, a space for forming the sealing ring is provided between two adjacent blind holes; optionally, the inner contour line of the sealing ring covers the outer contour line of the blind hole or is flush with the outer contour line of the blind hole.

[0048] Optionally, a boss is provided on the device for achieving heating and / or oscillation, and when the heating temperature is higher than the boiling point of the solvent, the boss contacts the sealed bubble hole plate to perform secondary reinforcement sealing on the blind hole of the bubble hole plate; the diameter of the boss is between the outer diameter and the inner diameter of the sealing ring at the opening of the blind hole of the bubble hole plate.

[0049] In a third aspect, an embodiment of the present disclosure provides a hole plate heat sealing device, comprising a bracket, a transfer plate, and a heating element, wherein the transfer plate and the heating element are both connected to the bracket, and the transfer plate and the heating element can selectively contact each other;

[0050] The heating element includes a thermal compression head mounting plate and at least one thermal compression head, each of the thermal compression heads is an annular structure, one end of each thermal compression head is connected to the thermal compression head mounting plate, a side of the thermal compression head mounting plate relatively close to the thermal compression head can selectively contact the transfer plate, and the other side of the thermal compression head mounting plate is connected to the bracket.

[0051] Optionally, the thermal compression head mounting plate includes a thermal compression head mounting plate body, at least one spring and at least one sleeve, each of the springs and each of the sleeves are arranged in the thermal compression head mounting plate body, one end of a sleeve is connected to the thermal compression head mounting plate body, and the other end is connected to a thermal compression head, and one of the springs is sleeved outside the sleeve.

[0052] Optionally, at least one cavity is provided on the thermal compression head mounting plate body, and one of the springs and one of the sleeves are both disposed in one of the cavity.

[0053] Optionally, the heating element further includes a heating rod configured to heat the thermal compression head, and the heating rod is disposed in the thermal compression head mounting plate body.

[0054] Optionally, the transfer plate includes a hole plate transfer plate, a lower mold plate and a film pressing frame, the hole plate transfer plate is connected to the lower mold plate, and the film pressing frame is connected to the lower mold plate, so that the heat-sealing film is evenly covered on the multi-channel hole plate and ensures that the heat-sealing film will not shift during the heat sealing process; the lower mold plate is connected to the bracket, and the film pressing frame selectively contacts the hot pressing head mounting plate.

[0055] Optionally, a receiving cavity configured to place the orifice plate transfer plate is provided in the lower mold plate.

[0056] Optionally, mounting parts are provided along the four sides of the lower mold plate, and the film pressing frame is connected to the lower mold plate through the mounting parts, so that the heat-sealing film is evenly covered on the multi-channel orifice plate and ensures that the heat-sealing film does not deviate during the heat-sealing process.

[0057] Optionally, the bracket includes a telescopic device connected to the thermal pressure head mounting plate to push the heating element and the transfer plate into selective contact.

[0058] Optionally, the bracket includes a fixed mold sliding base plate and a bottom fixed plate, the fixed mold sliding base plate is connected to the transfer plate; a slide rail is provided on the bottom fixed plate, and the fixed mold sliding base plate is slidably connected to the bottom fixed plate via the slide rail.

[0059] In a fourth aspect, an embodiment of the present disclosure provides a high-throughput screening system, which includes the well plate heat sealing device described in any one of the aforementioned embodiments.

[0060] Compared with the existing technology, the advantages of the examples disclosed herein include, for example:

[0061] The disclosed embodiment achieves single-hole sealing of small-volume holes by covering a layer of film over the blind holes of the orifice plate and then performing heat sealing, thereby expanding the applicable range of reaction temperature and reaction solvent of the high-throughput screening method based on the orifice plate, achieving reactions under high-temperature conditions and conditions above the boiling point of the solvent, and realizing reaction conditions of heating and oscillation.

[0062] The orifice plate heat sealing device provided by the embodiment of the present disclosure realizes a high-temperature, fast (<5s) heat sealing process, thereby ensuring that the temperature of the liquid or solid in the blind hole of the orifice plate is always lower than 30°C during the heat sealing process, and the temperature change of the liquid or solid will not affect the subsequent high-pass screening, and the properties of the heat-sensitive liquid or solid will not change due to temperature changes; the mechanical strength of the heat-sealed part of the orifice plate is improved to ensure that the seal does not fail in subsequent heating and / or oscillation usage scenarios; and the uniformity of the sealing of the multi-channel orifice plate is ensured. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present disclosure and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without creative work.

[0064] FIG1 is a diagram of a conventional high-throughput screening device according to an embodiment of the present disclosure;

[0065] FIG2 is a diagram showing a sealing method of a conventional orifice plate reaction device provided by an embodiment of the present disclosure;

[0066] FIG3 is a schematic diagram of a high-throughput screening method according to an embodiment of the present disclosure;

[0067] FIG4 is a partial schematic diagram of the blister plate sealing method provided in Example 1 of the present disclosure;

[0068] FIG5 is an apparent kinetic curve diagram provided by Example 1 of the present disclosure;

[0069] FIG6 is a diagram showing the blister plate forming results provided in Comparative Example 1 of the present disclosure;

[0070] FIG7 is a diagram showing the blister plate forming results provided in Comparative Example 2 of the present disclosure;

[0071] FIG8 is a diagram showing the blister plate forming results provided in Comparative Example 3 of the present disclosure;

[0072] FIG9 is a diagram showing the heat sealing results of Comparative Example 4 of the present disclosure;

[0073] FIG10 is a diagram showing the heat sealing results of Comparative Example 5 of the present disclosure;

[0074] FIG11 is a diagram showing the heat sealing results of Comparative Example 6 of the present disclosure;

[0075] FIG12 is a diagram showing the heat sealing results of Comparative Example 7 of the present disclosure;

[0076] FIG13 is a diagram showing the heat sealing results of Comparative Example 8 of the present disclosure;

[0077] FIG14 is a diagram showing the heat sealing results of Comparative Example 9 of the present disclosure;

[0078] FIG15 is a diagram showing the heating oscillation heat sealing results provided in Comparative Example 10 of the present disclosure;

[0079] FIG16 is a diagram showing the blister plate forming results provided in Comparative Example 11 of the present disclosure;

[0080] FIG17 is a diagram showing the blister plate forming results provided in Comparative Example 12 of the present disclosure;

[0081] FIG18 is a diagram showing the blister plate forming results provided in Comparative Example 13 of the present disclosure;

[0082] FIG19 is a schematic structural diagram of a hole plate heat sealing device provided in an embodiment of the present disclosure;

[0083] FIG20 is a schematic structural diagram of a heating element provided in an embodiment of the present disclosure;

[0084] FIG21 is a schematic structural diagram of a thermal compression head mounting plate provided in an embodiment of the present disclosure;

[0085] FIG22 is a schematic structural diagram of a transfer plate provided in an embodiment of the present disclosure;

[0086] FIG23 is an exploded view of a transfer plate provided in an embodiment of the present disclosure;

[0087] FIG24 is a schematic structural diagram of a thermal compression head mounting plate and a transfer plate in contact with each other according to an embodiment of the present disclosure;

[0088] FIG25 is a partial schematic diagram of the thermal compression head mounting plate and the transfer plate in contact position provided by an embodiment of the present disclosure.

[0089] Icons: 100-orifice plate heat sealing device; 111-top fixing plate; 112-aluminum profile frame; 113-bottom fixing plate; 114-slide rail; 115-fixed mold sliding bottom plate; 120-telescopic device; 116-first connecting plate; 117-second connecting plate; 130-heating element; 140-transfer plate; 134-hot pressing head mounting plate; 132-spring; 133-hot pressing head; 131-sleeve; 135-hot pressing head mounting plate body; 141-orifice plate transfer plate; 142-lower mold plate; 143-film pressing frame; 144-mounting hole. DETAILED DESCRIPTION

[0090] In order to make the purpose, technical solutions and advantages of the embodiments of the present disclosure clearer, the technical solutions in the embodiments of the present disclosure will be clearly and completely described below in conjunction with the drawings in the embodiments of the present disclosure. Obviously, the described embodiments are part of the embodiments of the present disclosure, rather than all of the embodiments. The components of the embodiments of the present disclosure described and shown in the drawings herein can be arranged and designed in various different configurations. If specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0091] Therefore, the following detailed description of the embodiments of the present disclosure provided in the accompanying drawings is not intended to limit the scope of the present disclosure as claimed, but merely represents selected embodiments of the present disclosure. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present disclosure without creative effort shall fall within the scope of protection of the present disclosure.

[0092] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not need to be further defined or explained in subsequent drawings.

[0093] In the description of the present disclosure, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," "outer," etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the disclosed product is typically placed when in use. These terms are intended solely to facilitate the description of the present disclosure and to simplify the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on the present disclosure. Furthermore, the terms "first," "second," "third," etc., are used solely to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0094] Furthermore, terms such as "horizontal" and "vertical" do not necessarily mean that a component must be absolutely horizontal or overhanging, but rather that it can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical," and does not mean that the structure must be completely horizontal, but rather that it can be slightly tilted.

[0095] It should also be noted that, in the description of this disclosure, unless otherwise expressly specified or limited, the terms "disposed," "installed," "connected," and "connected" should be understood broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; mechanical connections or electrical connections; direct connections or indirect connections through an intermediate medium; and internal connections between two components. Those skilled in the art will understand the specific meanings of the above terms in this disclosure based on the specific circumstances.

[0096] Thermoplastics, also known as thermosoftening plastics or thermoplastics in the embodiments of this disclosure, are plastics that exhibit plasticity at a certain temperature, solidify upon cooling, and can undergo this process repeatedly. These plastics are selected from any one of polyolefins, polyesters, polyamides, and polyurethanes, or composite materials comprising a combination of at least two.

[0097] The polyolefin materials described in the present disclosure, whose English name is polyolefins, refer to a general term for a class of thermoplastic resins obtained by polymerizing or copolymerizing α-olefins such as ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, 4-methyl-1-pentene, and certain cycloolefins.

[0098] The polyester material described in the present disclosure, whose English name is Polyethylene terephthalate, refers to the general term for polymers obtained by condensation of polyols and polyacids.

[0099] The polyamide material disclosed in the present invention is composed of aliphatic, aromatic or mixed dibasic aliphatic aromatic carboxylic acids and aliphatic, aromatic or mixed dibasic aliphatic aromatic amines.

[0100] The polyurethane material disclosed in the present invention, whose English name is polyurethane, is composed of isocyanate (or polyisocyanate), polyol and some additives.

[0101] The FEP material described in the present disclosure, whose full name is Fluorinated ethylene propylene, and whose Chinese name is fluorinated ethylene propylene copolymer, is a polymer material formed by the copolymerization of tetrafluoroethylene and hexafluoropropylene.

[0102] The present disclosure provides a high-throughput screening method, as shown in FIG3 , comprising:

[0103] S1, forming a bubble cap hole plate;

[0104] The thermoplastic material is molded to form a blister plate; the steps of forming the blister plate specifically include:

[0105] A thermoplastic material of suitable thickness is heated to near the melting point of the thermoplastic material, and then the thermoplastic material substrate is processed into a mold shape through a molding process to form a blister hole plate.

[0106] The thickness of the thermoplastic material is 0.15-0.8 mm, for example, any value between 0.15-0.8 mm, such as 0.15 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm and 0.8 mm, or a range between any two values, for example, preferably 0.2-0.6 mm.

[0107] If the thermoplastic material thickness is higher or lower than the above-mentioned thickness, poor thermoforming may occur, resulting in the blister plate being unsuitable for subsequent heat sealing. When the thickness is lower than the preferred range, the plastic sheet softens significantly during thermoforming, causing some areas of the blister plate to be very thin and resulting in insufficient blind hole strength. When the thickness is higher than the preferred range, the plastic sheet cannot fully adhere to the mold during thermoforming, resulting in some areas of the blister plate lacking a complete, rounded blind hole structure.

[0108] The heating temperature is 5-30°C lower than the melting point of the thermoplastic material, for example, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, or any other value between 5-30°C or a range between any two values ​​below the melting point of the thermoplastic material. For example, the heating is preferably performed to a temperature 5-25°C lower than the melting point of the thermoplastic material, more preferably 5-20°C lower than the melting point of the thermoplastic material.

[0109] Heating temperatures above or below the above range may result in poor thermoforming results, making the resulting blister plate unsuitable for subsequent heat sealing. When the heating temperature is above the preferred range, the plastic sheet softens significantly during thermoforming, causing the blind hole structure to collapse in some or all areas of the blister plate. When the temperature is below the preferred range, the plastic sheet cannot fully adhere to the mold during thermoforming, resulting in some areas of the blister plate lacking a complete, rounded blind hole structure.

[0110] Alternatively, the thermoplastic material is heated to a molten state. The heating temperature is not particularly limited, as long as the thermoplastic material is in a molten liquid state. For example, the heating temperature may be any value such as 5°C, 10°C, 15°C, 20°C, 25°C, or 30°C above the melting point of the thermoplastic material. For example, the heating temperature is preferably 5-25°C above the melting point of the thermoplastic material, and more preferably 5-20°C above the melting point of the thermoplastic material.

[0111] Molding processes include, but are not limited to, thermoforming processes, and may include, for example, blow molding, thermoforming, or injection molding. For example, when the heating temperature is 5-30°C below the melting point of the thermoplastic material, blow molding or thermoforming may be used. Alternatively, when the thermoplastic material is heated to a molten state, injection molding may be used.

[0112] For example, in a vacuum forming process, a thermoplastic material of appropriate thickness is heated to near the melting point of the thermoplastic material and maintained at this temperature for a period of time. The thermoplastic material is quickly sent to the top of the mold and then vacuum formed in a vacuum environment.

[0113] There are no restrictions on the vacuum level and duration of the vacuum environment; the process can be continued until the thermoplastic material adheres to the mold. This is because the smooth metal mold provides mechanical protection against the blind hole, preventing damage if the vacuum is too high or maintained for too long. Preferably, the vacuum level should be no less than 0.07 MPa (negative pressure), and the vacuum duration should be no less than 5 seconds. Furthermore, the thicker the thermoplastic material, the higher the vacuum level.

[0114] In the blow molding process, a thermoplastic material sheet of appropriate thickness is placed on the mold, heated to near the melting point of the thermoplastic material, and blow-molded under a certain pressure.

[0115] There are no restrictions on the pressure parameters and hold time; simply blow mold until the thermoplastic material fits the mold. This is because the smooth metal mold provides mechanical protection against the blind hole, preventing damage from excessive pressure or prolonged hold time. Preferably, the pressure should be no less than 0.4 MPa, and the hold time should be no less than 10 seconds. The thicker the thermoplastic material, the longer the hold time and the higher the pressure.

[0116] It should be noted that, regardless of whether the above-mentioned vacuum molding or blow molding, the thickness and heating temperature of the thermoplastic material are the same as those defined above.

[0117] Specifically, thermoplastic materials include but are not limited to polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyarylate (PAR), polyisocyanurate (PPO), polymethyl methacrylate (PMMA), polycarbonate (PC), nylon (PA), polyperfluoroethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE) and composite materials (PCTFE and PVC composite double-layer material).

[0118] The following embodiments of the present disclosure are described using PP material molding as an example:

[0119] The steps of the molding process include: heating the PP material to 130-165° C., maintaining the temperature for 50-100 seconds, and maintaining it in a vacuum environment for 5 seconds or more. The thickness of the PP material is 0.15-0.8 mm.

[0120] When blistering PP material, the heating temperature is maintained for 50-100s, for example, 50s, 60s, 70s, 80s, 90s and 100s, or any value between 50-100s or a range value between any two values. For example, the heating temperature is preferably maintained for 70-90s.

[0121] When blistering PP material, the heating temperature is any value between 130-165°C, such as 130°C, 140°C, 150°C, 160°C and 165°C, or a range value between any two values, for example, preferably 150-155°C.

[0122] Alternatively, the molding process comprises heating the PP material to 130-165° C., and blow molding the PP material for 10 seconds or more at a pressure of not less than 0.4 MPa, wherein the thickness of the PP material is 0.15-0.8 mm.

[0123] When the above-mentioned PP material is blow-molded, the heating temperature is any value between 130-165°C, such as 130°C, 140°C, 150°C, 160°C and 165°C, or a range value between any two values, for example, preferably 140-150°C.

[0124] When the above-mentioned PP material is vacuum-formed or blow-molded, the thickness of the PP material is any value between 0.15-0.8mm, such as 0.15mm, 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm and 0.8mm, or a range value between any two values, for example, preferably 0.2-0.6mm.

[0125] The following embodiments of the present disclosure are described using FEP material as an example:

[0126] The steps of the molding process include: heating the FEP material to 220-260° C., maintaining the temperature for 50-100 seconds, and maintaining it in a vacuum environment for 5 seconds or more. The thickness of the FEP material is 0.15-0.8 mm.

[0127] When the above-mentioned FEP material is blister-formed, the heating temperature is maintained for 50-100s, for example, any value between 50-100s or a range value between any two values ​​such as 50s, 60s, 70s, 80s, 90s and 100s. For example, the heating temperature is preferably maintained for 70-90s.

[0128] Alternatively, the molding process comprises the steps of: heating the FEP material to 220-260° C., and blow molding the FEP material for 10 seconds or more at a pressure of not less than 0.4 MPa, wherein the thickness of the FEP material is 0.15-0.8 mm;

[0129] When the above-mentioned FEP material is vacuum-molded or blow-molded, the thickness of the FEP material is any value between 0.15-0.8 mm, such as 0.15 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm and 0.8 mm, or a range value between any two values, for example, preferably 0.2-0.6 mm.

[0130] When the above-mentioned FEP material is vacuum-molded or blow-molded, the heating temperature is any value between 220-260°C, such as 220°C, 230°C, 240°C, 250°C and 260°C, or a range between any two values, for example, preferably 240-250°C.

[0131] The blind holes of the bubble cap plate provided in the embodiment of the present disclosure are generally in the shape of a semi-spherical or semi-ellipsoidal body, preferably a semi-spherical body, and have a cross-sectional shape of a circle, a semi-circular, an elliptical, or a semi-elliptical body, more preferably a circle.

[0132] In order to achieve the effect of sealing a small hole or a single hole, a sealing ring needs to be formed at the opening of each blind hole, so a space for forming a sealing ring needs to be reserved between two adjacent blind holes.

[0133] Specifically, after heat sealing, a sealing ring is formed at the opening of the blind hole of the blister plate. The shape of the sealing ring is the same as that of the blind hole, i.e., when the blind hole cross-section is circular, the sealing ring is a circular ring; when the blind hole cross-section is elliptical, the sealing ring is an elliptical ring; and when the blind hole cross-section is quasi-circular, the sealing ring is a quasi-circular ring. At the same time, the opening of the blind hole should be completely covered by the heat-sealing ring, i.e., the inner contour of the sealing ring should completely cover the outer contour of the blind hole opening or be flush with the outer contour of the blind hole opening.

[0134] The outer contours of adjacent sealing rings should not intersect. The width of the sealing rings should be no less than 1mm. If the outer contours of adjacent sealing rings intersect, cross-contamination of adjacent blind holes is likely to occur. If the width of the sealing rings is less than 1mm, the mechanical strength of the seal is poor, making it easy for liquid to leak from the blind holes.

[0135] S2, adding materials;

[0136] The reaction solution and / or solids configured for a high-throughput screening chemical reaction are added to the blister plate. Specifically, a manual pipette or automated pipetting device can be used to sequentially add the prepared reaction solution to each blind well. For solid-liquid two-phase reactions, manual or automated weighing and consolidation can be used to sequentially add the solids required for the reaction to each blind well.

[0137] S3, heat sealing;

[0138] The blister plate to which the reaction reagents have been added is transferred to a heat sealing instrument, and a film of appropriate thickness is covered on the blind holes of the blister plate. The material forming the film is consistent with the material of the contact portion between the plate and the film. Then, the heat sealing temperature and heat sealing time of the heat sealing instrument are set. Here, after heat sealing, a sealing ring is formed at the opening of each blind hole of the blister plate.

[0139] Furthermore, the heat sealing conditions include: a heat sealing temperature of 5-65°C higher than the melting point of the film material, for example, any value between 5-65°C, such as 5°C, 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, and 65°C, or a range between any two values, preferably 10-55°C higher than the melting point of the film material, preferably 10-50°C higher than the melting point of the film material. The heat sealing temperature is limited to the above conditions. If the heat sealing temperature is higher than the above temperature, it cannot ensure that the temperature of the liquid in the blind hole remains below 30°C during the entire heat sealing process, and the heat sealing film is easily melted and ruptured, directly adhering to the heat sealing machine pressure head. Below this range, the heat sealing effect is poor, and the liquid in the blister plate leaks.

[0140] The heat sealing time is 0.3-4.5s, for example, any value between 0.3-4.5s or a range between any two values ​​such as 0.3s, 1s, 2s, 3s, 4s and 4.5s, for example, preferably 0.5-4s; more preferably 0.5-3s, further preferably 0.5-1s or 1-3s.

[0141] Heat sealing times longer or shorter than these may result in poor sealing performance, making the product unusable for subsequent reactions. If the heat sealing time exceeds the optimal range, the temperature of the liquid in the blind hole cannot be maintained below 30°C throughout the heat sealing process, and the heat sealing film is prone to melting and cracking, directly adhering to the heat sealer's pressure head. If the heat sealing time is shorter than this range, the heat sealing effect is poor and the liquid in the blister plate leaks.

[0142] The thickness of the film is 0.04-0.18 mm; for example, any value between 0.04-0.18 mm, such as 0.04 mm, 0.05 mm, 0.08 mm, 0.1 mm, 0.12 mm, 0.14 mm, 0.15 mm and 0.18 mm, or a range value between any two values, for example, preferably 0.04-0.15 mm, more preferably 0.04-0.1 mm.

[0143] If the film thickness is lower than that specified in the embodiments of the present disclosure, the film will easily melt and break during heat sealing. If the film thickness is too thick, the heat sealing effect of the film will be poor, the heat sealing time will be greatly extended, and it will not be possible to ensure that the temperature of the liquid in the blind hole remains below 30°C during the entire heat sealing process, which will adversely affect the control of the reaction temperature conditions. At the same time, according to the film thickness specified in the embodiments of the present disclosure, it can also ensure that the heat-sealed film formed after heat sealing can directly pierce the injection needle of the detection instrument for sampling, which is convenient to use.

[0144] Furthermore, the material forming the film is consistent with the material of the contact portion between the orifice plate and the film. That is, if the thermoplastic material forming the blister orifice plate is a single material, the material forming the film is also a single material, for example, both are PP. If the thermoplastic material forming the blister orifice plate is a composite homogeneous material, the material forming the film is also a composite homogeneous material, for example, both are acrylonitrile-butadiene-styrene copolymer / polycarbonate blend (PC / ABS). If the thermoplastic material forming the blister plate is a composite multilayer material, the material forming the film is selected to be a single material that is consistent with the material of one side of the outer layer of the composite multilayer material forming the blister plate. For example, the blister plate is selected from polyvinyl chloride / polyvinyl chloride (PVC / PVDC), and the material forming the film is selected from PVC material, and the film covers the PVC surface of the blister plate; or the material forming the film is selected from a composite multilayer material, wherein the material of one side of the outer layer is consistent with the material of one side of the outer layer of the composite multilayer material forming the blister plate. For example, the blister plate is selected from polyvinyl chloride / polyvinyl chloride (PVC / PVDC), and the material forming the film is selected from polytrifluoroethylene resin / polyvinyl chloride (PCTFE / PVC), and the PVC surface of the film covers the PVC surface of the blister plate. The PC / ABS, PVC / PVDC, and PCTFE / PVC are all existing materials.

[0145] Specifically, the film is a PP film, and the thickness of the PP film is 0.04-0.18 mm, for example, any value between 0.04-0.18 mm, such as 0.04 mm, 0.05 mm, 0.08 mm, 0.1 mm, 0.12 mm, 0.14 mm, 0.15 mm and 0.18 mm, or a range value between any two values, for example, preferably 0.05-0.15 mm, more preferably 0.04-0.1 mm.

[0146] The heat sealing temperature is 170-215°C, for example, any value between 150-215°C, such as 170°C, 180°C, 190°C, 200°C, 210°C and 215°C, or a range between any two values, preferably 180-210°C.

[0147] The heat sealing time is 0.5-4.5s; for example, any value between 0.5-4.5s or a range between any two values ​​such as 0.5s, 1s, 2s, 3s, 4s and 4.5s, for example, preferably 0.5-3s, more preferably 1-3s.

[0148] Taking FEP film as an example, the thickness of the FEP film is 0.04-0.18 mm, for example, 0.04 mm, 0.05 mm, 0.08 mm, 0.1 mm, 0.12 mm, 0.14 mm, 0.15 mm, 0.18 mm and 0.2 mm, etc., any value between 0.04-0.18 mm or a range value between any two values, for example, preferably 0.05-0.15 mm, more preferably 0.04-0.1 mm.

[0149] The heat sealing temperature is 250-350°C, for example, any value between 250-350°C, such as 250°C, 260°C, 270°C, 280°C, 290°C, 300°C, 310°C, 320°C, 330°C, 340°C and 350°C, or a range value between any two values, for example, preferably 280-300°C.

[0150] The heat sealing time is 0.3-4.5s, such as any value between 0.3-4.5s or a range between any two values ​​such as 0.3s, 1s, 2s, 3s, 4s and 4.5s, for example, preferably 0.5-3s, more preferably 0.5-1s.

[0151] S4, heating and / or shaking;

[0152] The heat-sealed blister plate is placed on a heating and / or shaking device, and the heating temperature and reaction time are set.

[0153] If the heating temperature is higher than the boiling point of the solvent during the heating and / or shaking process, the bubble cap plate needs to be reinforced and sealed for a second time to ensure that the bubble cap plate does not burst.

[0154] Specifically, the heating and / or oscillating device is provided with a boss. When the heating temperature is higher than the boiling point of the solvent, the boss contacts the sealed blister plate, thereby providing a secondary reinforcement seal to the blind holes of the blister plate. For example, when ethanol is used as the reaction solvent, if the heating temperature is higher than 85°C, further reinforcement should be provided by a forced sealing method, otherwise the blind holes will easily burst. If the heating temperature is lower than the boiling point of the solvent, secondary reinforcement sealing is not required.

[0155] It should be noted that when only oscillation is performed and heating is not involved, the device may not contain a boss.

[0156] The secondary reinforced seal described in the embodiment of the present disclosure refers to the blister plate formed after heat sealing in step S3, and then the blister plate is further sealed by contacting the boss with the sealed blister plate to prevent the blind holes from bursting. The diameter of the boss is between the outer diameter and inner diameter of the sealing ring at the opening of the blind hole of the blister plate. The blister plate can then be reinforced and sealed to ensure that the blind holes do not burst under conditions above the boiling point of the solvent.

[0157] The features and performance of the present disclosure are further described in detail below with reference to examples.

[0158] Example 1

[0159] This example uses the following chemical reaction as an example to perform a high-throughput screening method:

[0160] Specifically include:

[0161] The PP sheet was heated to 150°C and maintained at this temperature for 75 seconds. The thickness of the PP sheet was 0.4 mm. The vacuum degree of the blister was set to 0.08 MPa (negative pressure). The vacuum environment lasted for 10 seconds to obtain a blister plate. The cross-section of the blind hole of the blister plate was formed into a circle, and the whole was hemispherical. The diameter of the opening was 6 mm, and the distance between two adjacent blind holes (center to center) was 10 mm.

[0162] The reaction materials were added to each blind hole of the bubble cap plate obtained above. Specifically, the reaction solution in each blind hole had a concentration of 0.05 M of the reactant 3,4-difluoronitrobenzene, a concentration of 0.1 M of the reactant morpholine, a concentration of 0.25 M of the base triethylamine, and a volume of 50 μL of the solvent ethanol.

[0163] Then heat seal is performed. During the heat sealing process, the thickness of the PP heat sealing film is 0.04 mm, the heat sealing temperature is set to 200°C, and the heat sealing time is set to 2 seconds. After heat sealing, a sealing ring with a ring width of 1 mm and an inner diameter of 7 mm is formed. The sealing ring and the blind hole are concentrically distributed, and the outer contour lines of adjacent sealing rings do not intersect.

[0164] After heat sealing, the blister plate was placed on a heated oscillator, with reaction temperatures set at 60°C, 75°C, and 100°C, respectively, and an oscillation speed of 350 rpm. Every 30 minutes, the reaction liquid from one blind hole was withdrawn with a syringe for HPLC analysis. A partial schematic diagram of the heated oscillator, when heated at 100°C, is shown in Figure 4. As shown in Figure 4, a sealing ring 1 formed by heat-sealing a thin film is placed over the blind hole 3 of the blister plate. The boss 2 contacts the sealed blind hole 3 of the blister plate, providing a secondary seal.

[0165] The apparent kinetic curves at three reaction temperatures were drawn based on the chromatographic results (see Figure 5).

[0166] As shown in Figure 5, the heat-sealed blister plate can meet the different reaction conditions and equipment requirements of the above reaction formula. The reaction rate at a reaction temperature of 75°C is improved compared to that at 60°C. At the same time, at a heating temperature of 100°C, which is higher than the boiling point of ethanol, the reaction rate is greatly improved. This proves that the blister plate still has an excellent sealing effect at high temperatures, even above the boiling point of the solvent, and can be used for high-throughput screening.

[0167] Figure 5 also shows that the higher the reaction temperature, the greater the slope of the apparent kinetic curve, indicating a higher first-order reaction rate constant. The reaction was also completed using ethanol as the solvent at a reaction temperature of 100°C, demonstrating that the bubble cap plate reactor achieves the goal of intensifying the reaction by using it above the boiling point of the solvent.

[0168] The above reaction and all parameters were used to perform 48 24 h reactions at 100 °C. The experimental results are shown in Table 1.

[0169] Table 1 Test results

[0170] It can be seen that the reaction uniformity of the 48-well plate is good, and the standard deviation of the yield is 1.1%, indicating that the blister plate and the sealing process have good reaction uniformity for high-throughput screening.

[0171] Example 2

[0172] This example uses the chemical reaction provided in Example 1 as an example to perform a high-throughput screening method, including:

[0173] The FEP sheet was heated to 240°C and maintained at this temperature for 75 seconds. The thickness of the FEP sheet was 0.4 mm, the vacuum degree of the blister was set to 0.08 MPa (negative pressure), and the vacuum environment lasted for 10 seconds to obtain a blister plate. The cross-section of the blind hole of the blister plate was formed into a circle, and the whole was hemispherical. The diameter of the opening was 6 mm, and the distance between two adjacent blind holes (center to center) was 10 mm.

[0174] The reaction materials were added to each blind hole of the bubble cap plate obtained above. Specifically, the reaction solution in each blind hole was added with a concentration of 0.05 M of the reactant 3,4-difluoronitrobenzene, a concentration of 0.1 M of the reactant morpholine, a concentration of 0.25 M of the base triethylamine, and a volume of 50 μL of the solvent N,N-dimethylformamide (DMF).

[0175] Then heat seal is performed. During the heat sealing process, the thickness of the FEP heat sealing film is 0.04 mm, the heat sealing temperature is set to 280°C, and the heat sealing time is set to 1 second. After heat sealing, a sealing ring with a ring width of 1 mm and an inner diameter of 7 mm is formed. The sealing ring and the blind hole are concentrically distributed, and the outer contour lines of adjacent sealing rings do not intersect.

[0176] The heat-sealed blister plate was placed on a heating oscillator, and the reaction temperature was set to 100° C., the oscillation speed was set to 350 rpm, and the reaction time was set to 1 h.

[0177] The 48-well plate was placed directly into the HPLC sample injection tray and the sample was injected directly to obtain the experimental results. The results are shown in Table 2.

[0178] Table 2 Test results

[0179] It can be seen that the reaction uniformity of the 48-well plate is good, and the standard deviation of the yield is 1.5%, indicating that the blister plate and the sealing process have good reaction uniformity for high-throughput screening.

[0180] Furthermore, during the heating and oscillation process, when the reaction temperature reached 100° C., the blind hole did not rupture at the end of the reaction, and the seal was still effective.

[0181] Example 3 - Example 12

[0182] Examples 3 to 12 were all subjected to high-throughput screening with reference to Example 1, except that the conditions for blister molding of PP materials were different. For specific conditions, see Table 3.

[0183] Table 3 Conditions for PP material blister molding

[0184] The blister plate blister molding effects of Examples 3, 4, 6, 7, and 11 in the above table are good, and the blister plate blister molding effects of Examples 5, 8, 9, 10, and 12 are excellent. The blister plate in these examples can all be used for subsequent heat sealing.

[0185] Example 13 - Example 21

[0186] Examples 13-21 were all subjected to high-throughput screening with reference to Example 1, except that the PP material was blow molded. The specific conditions are shown in Table 4.

[0187] Table 4 Blow molding conditions of PP materials

[0188] The blister plate blow molding results of Examples 13, 16, 17, 18, and 19 in the above table are excellent, and the blister plate blow molding results of Examples 14, 15, 20, and 21 are good. The blister plates in these examples can all be used for subsequent heat sealing.

[0189] Example 22-Example 31

[0190] Examples 22-31 were all subjected to high-throughput screening with reference to Example 1, except that the heat-sealing process conditions were different. See Table 5 for details.

[0191] Table 5 Heat sealing conditions

[0192] The heat sealing effects of Examples 22, 23, 27, 28, 29, and 30 in the table above were excellent, and the heat sealing effects of Examples 24, 25, 26, and 31 were good. The blister plates in these examples showed no solution leakage after heat sealing and were suitable for subsequent reactions.

[0193] Example 32

[0194] Example 32 performs high-throughput screening with reference to Example 1, except that the PP material is injection molded.

[0195] First, PP resin pellets are heated to 170°C to melt, turning them into a flowable molten plastic. The molten plastic is then injected into the cavity of a mold. The mold is then cooled to room temperature and solidifies. Finally, the mold is opened to produce the blister plate described in Example 1.

[0196] Comparative Example 1

[0197] High-throughput screening was conducted using the same method as in Example 1. However, the difference was that the PP sheet was heated to 170°C during the blister forming process. During the heating process, the PP sheet temperature exceeded its melting point, resulting in poor thermoforming. Almost all areas were deformed, making it impossible to form a blister sheet suitable for subsequent heat sealing. See Figure 6 for details.

[0198] Comparative Example 2

[0199] High-throughput screening was performed using the same method as in Example 1. The difference was that the PP sheet thickness was 0.1 mm when forming the blister plate. The thin surface of the PP sheet during the blister forming process resulted in poor thermoforming. Some blind holes had poor strength and were easily flattened, making it impossible to form a blister plate suitable for subsequent heat sealing. See Figure 7 for details.

[0200] Comparative Example 3

[0201] High-throughput screening was performed with reference to Example 1. The difference was that when forming the blister hole plate, the thickness of the PP sheet was 1 mm. During the blister molding process, the PP sheet could not fit the mold to form a blister hole plate that could be used for subsequent heat sealing, resulting in poor thermoforming effect. In some areas, a complete and round blind hole structure was not formed. See Figure 8 for details.

[0202] Comparative Example 4

[0203] High-throughput screening was performed with reference to Example 1. The difference was that the heat sealing temperature was 230°C, the blister plate and the heat sealing film melted and broke, and directly adhered to the hot press head, resulting in a poor heat sealing effect and inability to be used for subsequent heating and oscillation. See Figure 9 for details.

[0204] Comparative Example 5

[0205] High-throughput screening was performed with reference to Example 1. The difference was that the heat sealing time was 5s, the liquid temperature in the blind hole was higher than 30°C (the surface temperature at the bottom of the blind hole reached 40-50°C), and the blind hole was bent and deformed as a whole (plastic tends to shrink and agglomerate when heated), resulting in poor heat sealing effect and inability to be used for subsequent heating and oscillation. See Figure 10 for details.

[0206] Comparative Example 6

[0207] High-throughput screening was performed with reference to Example 1, except that the heat sealing temperature was 160°C, some blind holes were not completely sealed, and liquid leakage occurred. The unsealed blind holes could not be used for subsequent heating and oscillation, as shown in FIG11 .

[0208] Comparative Example 7

[0209] High-throughput screening was performed with reference to Example 1, except that the heat sealing time was 0.3 s, some blind holes were not completely sealed, and liquid leakage occurred. The unsealed blind holes could not be used for subsequent heating and oscillation, as shown in FIG12 .

[0210] Comparative Example 8

[0211] High-throughput screening was performed with reference to Example 1, except that the PP film thickness during heat sealing was 0.2 mm, some blind holes were not completely sealed, and liquid leakage occurred. The unsealed blind holes could not be used for subsequent heating and oscillation, as shown in FIG13 .

[0212] Comparative Example 9

[0213] High-throughput screening was performed with reference to Example 1. The difference was that the thickness of the PP film during heat sealing was 0.02 mm. Due to the low thickness, the blister plate and the heat-sealing film were partially melted and cut by the hot press head, resulting in uneven distribution of surface material. This led to poor heat sealing effect and could not be used for subsequent heating and oscillation. See Figure 14 for details.

[0214] Comparative Example 10

[0215] High-throughput screening was performed with reference to Example 1, except that the equipment used for heat sealing did not have a boss, and no additional forced sealing method was used. Other heat sealing conditions were the same as in Example 1. When the reaction temperature was 100°C, some blind holes in the blister plate failed to seal. During the heating process, the solution in the blind holes with failed seals completely evaporated, and there were traces of solution leakage between the blind holes, see Figure 15.

[0216] Comparative Example 11

[0217] High-throughput screening was performed with reference to Example 1. The difference was that when forming the blister hole plate, the PP sheet was heated for 45 seconds. During the blister molding process, some areas of the PP sheet, especially the edge areas, were not softened enough to fit the mold to form a blister hole plate that could be used for subsequent heat sealing. This resulted in poor thermoforming effects and the failure to form a complete and rounded blind hole structure in some areas, as shown in Figure 16.

[0218] Comparative Example 12

[0219] High-throughput screening was performed using the same method as in Example 1. However, when forming the blister plate, the PP sheet was heated for 110 seconds. This significantly softened the surface of the PP sheet, resulting in poor thermoforming and the collapse of some blind hole structures, making it impossible to form a blister plate suitable for subsequent heat sealing. See Figure 17 for details.

[0220] Comparative Example 13

[0221] High-throughput screening was conducted using the same method as in Example 1. However, the difference was that the PP sheet was heated to 120°C during the blister forming process. The PP sheet surface barely softened during the blister forming process, making it difficult to adhere to the mold and form a blister plate suitable for subsequent heat sealing. This resulted in poor thermoforming and the failure to form a complete, rounded blind hole structure. See Figure 18 for details.

[0222] Referring to FIG. 19 , an embodiment of the present disclosure provides a hole plate heat sealing device 100, which includes a bracket configured to house various components and ensure the stability of the hole plate heat sealing device 100. Specifically, the bracket includes an aluminum profile frame 112, a top fixing plate 111, and a bottom fixing plate 113. The top fixing plate 111 and the bottom fixing plate 113 are respectively located on both sides of the aluminum profile frame 112, that is, the top fixing plate 111 and the bottom fixing plate 113 are arranged opposite to each other, and the top fixing plate 111 and the bottom fixing plate 113 are respectively connected to the aluminum profile frame 112. The aluminum profile frame 112 can withstand the reaction force of the force-applying device and maintain the stability of the device.

[0223] The bracket further includes a telescopic device 120, a first connecting plate 116, and a second connecting plate 117. The first connecting plate 116 and the second connecting plate 117 are disposed vertically between the top fixing plate 111 and the bottom fixing plate 113. One side of the first connecting plate 116 is connected to one side of the second connecting plate 117 via a plurality of guide posts, and the other side of the second connecting plate 117 is connected to the bottom fixing plate 113 via a plurality of guide posts.

[0224] It should be noted that the telescopic device 120 can be a device capable of achieving telescopic movement, such as a cylinder, a hydraulic cylinder, and a telescopic rod. The embodiment of the present disclosure is described using a cylinder as an example.

[0225] Specifically, the cylinder body of the cylinder is arranged between the first connecting plate 116 and the top fixed plate 111, and is connected to the top fixed plate 111. The piston rod of the cylinder passes through the second connecting plate 117, and then the piston rod of the cylinder can move vertically up and down along the direction of the guide column.

[0226] The orifice plate heat sealing device 100 also includes a heating element 130, which is disposed between the second connecting plate 117 and the bottom fixing plate 113 and connected to the telescopic device 120. In this embodiment, the heating element 130 is connected to the piston rod of the cylinder. The piston rod then drives the heating element 130 to move vertically up and down along the guide column, aligning the hot pressing head 133 in the heating element 130 with the blind hole of the orifice plate to be sealed. Specifically, when the cylinder is pressurized, the heating element 130 moves downward, and when the cylinder is depressurized, the heating element 130 moves upward.

[0227] Optionally, referring to FIG. 20 , the heating element 130 in this embodiment includes a hot pressing head mounting plate 134 and 48 hot pressing heads 133 , each of the hot pressing heads 133 is an annular structure, and one end of each of the hot pressing heads 133 is connected to the hot pressing head mounting plate.

[0228] Specifically, the heat press head 133 is an annular structure that prevents direct heat exposure to liquids or solids within the orifice plate's blind holes. Specifically, the orifice plate and the upper heat-sealing film fuse together under heat. Since only the annular portion of the heat press head 133 is in direct thermal contact with the heat-sealing film, the reaction solution within the orifice plate's blind holes is not. Simultaneously, the heat-sealing time is extremely short, effectively sealing the orifice plate while maintaining the temperature of the liquid within the orifice plate's blind holes below 30°C. This heat-sealing effect is ideal for sealing heat-sensitive solids or liquids.

[0229] Referring to Figure 21 , the hot press head mounting plate 134 comprises a hot press head mounting plate body 135, 48 springs 132, and 48 bushings 131. One end of the hot press head mounting plate body 135 is connected to the piston rod of the cylinder, which in turn drives the heating element 130 up and down. The hot press head mounting plate body 135 positions and mounts the hot press head 133, bushings 131, springs 132, and other mechanical components. A heating rod is also installed within the body, configured to heat the hot press head 133 to the heat-sealing temperature.

[0230] Specifically, 48 cavities (not marked in the figure) are provided in the thermal compression head mounting plate body 135, and each cavity is configured to place a corresponding spring 132 and a sleeve 131, and the spring 132 is sleeved on the outside of the sleeve 131. One end of each sleeve 131 is connected to the thermal compression head mounting plate 134, and the other end is connected to a thermal compression head 133.

[0231] It should be noted that the 48 springs 132, thermal compression heads 133, sleeves 131 and cavities recorded in this embodiment are only examples of this embodiment. In the disclosed embodiment, the number of springs, thermal compression heads and sleeves can be limited according to actual needs. Specifically, they are set according to the number of blind holes in the orifice plate that need to be sealed. For example, an 8×6 arrangement of springs, thermal compression heads and sleeves can be set to adapt to an 8×6 arrangement of 48-orifice plate.

[0232] The purpose of setting the shaft sleeve 131 is to guide and lubricate the up and down movement of the hot pressing head 133, so as to prevent the movement of the hot pressing head 133 from deviating from the vertical direction. The shaft sleeve 131 can be made of brass or other materials.

[0233] The purpose of setting the spring 132 is to buffer and ensure the uniformity of heat sealing of the multi-channel orifice plate. The specific reasons are as follows: when the hot pressing head 133 moves downward and contacts the heat-sealing film, the upward thrust exerted by the heat-sealing film on the hot pressing head 133 (the reaction force of the thrust of the telescopic device 120) is converted into the elastic force of the spring 132 (the hot pressing head 133 presses the spring 132 upward, and the spring 132 contracts). This structural design has two advantages: 1) buffering. If the hot pressing head 133 moves directly downward and contacts the heat-sealing film, the orifice plate and the heat-sealing film may be directly cut off due to excessive thrust (the annular edge of the hot pressing head 133 1) The spring 132 can relieve the force and play a buffering role; 2) To ensure the uniformity of heat sealing of the multi-channel orifice plate, it is difficult to ensure that the annular bottom surfaces of multiple heat pressing heads 133 are in the same plane during installation. If the spring 132 structure is not used, during the heat sealing process, the annular bottom surfaces of some heat pressing heads 133 cannot make good contact with the heat sealing film. Preferably, after the spring 132 is installed, the spring 132 can be compressed to apply a thrust to those heat pressing heads 133 that cannot make good contact, thereby ensuring that all heat pressing heads 133 can effectively contact the heat sealing film, thereby achieving uniformity of heat sealing of the multi-channel orifice plate.

[0234] Optionally, when the spring 132 is in a natural state (not under force), its length is slightly longer than the length of the sleeve 131 . This structure is more conducive to the performance of the spring 132 .

[0235] Optionally, a slide rail 114 is provided on the bottom fixing plate 113 , and the slide rail 114 is configured to cooperate with the fixed mold sliding base plate 115 . That is, the fixed mold sliding base plate 115 is slidably connected to the bottom fixing plate 113 via the slide rail 114 .

[0236] Optionally, referring to FIG. 22 , the orifice plate heat sealing device 100 further includes a transfer plate 140 , which is connected to the fixed mold sliding base plate 115 . In the disclosed embodiment, the two are connected by a snap-fit ​​connection. The transfer plate 140 and the heating element 130 can selectively contact each other. Specifically, the side of the heat press head mounting plate 134 relatively close to the heat press head 133 can selectively contact the transfer plate 140. When the orifice plate is not required to be heat sealed, the two are separated and do not contact each other. When the orifice plate is required to be heat sealed, the heating element 130 moves downward, and the heat press head 133 on the heating element 130 contacts the film configured to heat seal the orifice plate. The side of the heat press head mounting plate 134 relatively close to the heat press head 133 also largely contacts the film, and partially contacts the area of ​​the transfer plate 140 that is not required to be heat sealed. Furthermore, if the film thickness is less than the distance between the heat press head mounting plate 134 and the transfer plate 140, the heat press head mounting plate 134 will not contact the film.

[0237] Specifically, referring to Figure 23, the transfer plate 140 includes an orifice plate transfer plate 141, a lower mold plate 142 and a film pressing frame 143, the lower mold plate 142 is connected to the bracket, and the film pressing frame 143 is in selective contact with the heating element; the orifice plate transfer plate 141 is connected to the lower mold plate 142. In this embodiment, the connection method between the two can be that a accommodating cavity configured to place the orifice plate transfer plate 141 is provided in the lower mold plate 142, and then the orifice plate transfer plate 141 is placed in the accommodating cavity.

[0238] Of course, the two can also be connected in other ways. For example, a protruding structure is provided on the lower mold plate 142, and a recessed structure is provided on the side of the orifice plate transfer plate 141 relatively close to the lower mold plate 142, and the protruding structure is snap-connected with the recessed structure.

[0239] The film pressing frame 143 is connected to the lower mold plate 142 so that the heat-sealing film is evenly covered on the multi-channel orifice plate and ensures that the heat-sealing film will not shift during the heat-sealing process. Specifically, mounting parts are provided along the four sides of one side of the lower mold plate 142, and the film pressing frame 143 is connected to the lower mold plate 142 through the mounting parts. For example, in this embodiment, mounting holes 144, such as magnet holes, are provided along the four sides of one side of the lower mold plate 142. The film pressing frame 143 is connected to the lower mold plate 142 by adsorption, such as magnet adsorption. Then, during heat sealing, the film pressing frame 143 can press the heat-sealing film so that the heat-sealing film is evenly covered on the multi-channel orifice plate and ensures that the heat-sealing film will not shift during the heat-sealing process. The other side of the lower mold plate 142 is clamped with the fixed mold sliding bottom plate 115.

[0240] Alternatively, protrusions may be provided along the four sides of one side of the lower mold plate 142 , and grooves may be provided at corresponding positions of the film pressing frame 143 , and the two may be snap-connected.

[0241] Optionally, referring to Figures 24 and 25 , the film pressing frame 143 is positioned a certain distance above the orifice plate transfer plate 141. This structure serves to limit the position of the hot pressing head 133 of the heating element 130. The operating principle is as follows: the downward pressure exerted by the hot pressing head 133 on the heat-sealing film depends on the limit distance. When the hot pressing head 133 stops moving downward, the pressure exerted on the heat-sealing film is equal to the elastic force of the internal spring 132 at that time. The elastic force of the spring 132 depends on the length of the compression of the spring 132, which in turn depends on the limit distance. Therefore, the limit distance can be used to adjust the pressure exerted by the hot pressing head 133. The limit distance can be adjusted for thermoplastic materials of different thicknesses and qualities.

[0242] It can be seen that the orifice plate heat sealing device 100 of the embodiment of the present disclosure is suitable for multi-channel orifice plate structures, that is, multiple orifice plate blind holes are densely distributed and the area available for heat sealing between the blind holes is small, which can ensure the high efficiency and uniformity of heat sealing of the multi-channel orifice plate.

[0243] On the other hand, the present disclosure also provides a high-throughput screening system (not shown), which includes the well plate heat sealing device. In the high-throughput screening system, other devices except the well plate heat sealing device can adopt existing technologies and are not specifically limited by the present disclosure.

[0244] Specifically, the use process of the orifice plate heat sealing device in this embodiment is as follows:

[0245] (1) Set the heat sealing temperature to the specified temperature. The heat sealing temperature refers to the temperature on the heating element in Figure 19, which is heated by the heating rod inside the heating element.

[0246] (2) Place the multi-channel orifice plate filled with liquid or solid on a transfer plate. For example, a commercially available multi-channel orifice plate made of PP can be used. The transfer plate should be used in conjunction with the multi-channel orifice plate. That is, the shape of the recessed portion of the transfer plate should be the same as the shape of the blind hole portion of the orifice plate.

[0247] (3) Place a heat-sealing film on top of the multi-channel orifice plate.

[0248] (4) Install the film pressing frame on the heat-sealing film and fix the pressing frame film and the orifice plate transfer plate by magnets, and gently flatten the film. This step can fix the position of the heat-sealing film and the orifice plate, ensuring that they are not misaligned during the subsequent heat-sealing process.

[0249] (5) Push the fixed mold sliding base along the slide rail to the limit position. The purpose of this step is to move the orifice plate and heat sealing film to the position just below the hot pressing head, that is, the limit position.

[0250] (6) The telescopic device is pressed down and maintained for the specified heating (hot pressing) time. The heating time here can be adjusted according to the hot pressing time required for actual heat sealing.

[0251] (7) After heat sealing, the telescopic device is lifted up, the fixed mold sliding bottom plate is pulled out along the slide rail, the film pressing frame is removed, and then the sealed orifice plate is taken out from the orifice plate transfer plate.

[0252] It should be noted that the heat sealing temperature and other factors can be adjusted according to the selected heat sealing material. In addition to PP materials, the heat sealing materials that can be selected include polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polyethylene terephthalate (PET), polyisocyanurate (PPO), polymethyl methacrylate (PMMA), polycarbonate (PC), nylon (PA), polyperfluoroethylene propylene (FEP), polychlorotrifluoroethylene (PCTFE) and composite materials (PCTFE and PVC composite double-layer materials) and almost all thermoplastics.

[0253] The foregoing description is merely a specific embodiment of the present disclosure and is not intended to limit the present disclosure. Those skilled in the art will readily appreciate that the present disclosure is susceptible to various modifications and variations. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present disclosure shall be included within the scope of protection of the present disclosure. Industrial Applicability

[0254] In summary, the disclosed embodiments provide a well plate sealing process, a high-throughput screening method, a well plate heat-sealing device, and a high-throughput screening system. These processes address the difficulties encountered in sealing small-volume, single-well wells in existing well plates, as well as the low temperature tolerance of existing sealing processes. These processes also address the limitations of reaction temperature and reaction solvents in well plate-based high-throughput screening methods, which prevent reactions from proceeding at temperatures above the boiling point of the solvent and the inability to achieve heating and oscillating reaction conditions.

Claims

1. A sealing process for an orifice plate, characterized in that: include: A film is covered on the blind hole of the orifice plate and then heat-sealed. The material forming the film is consistent with the material of the contact part of the orifice plate and the film. The heat-sealing conditions include: the heat-sealing temperature is 5-65°C higher than the melting point of the film material, and the heat-sealing time is 0.3-4.5s.

2. The sealing process of the orifice plate according to claim 1, characterized in that: The heat sealing temperature is 10-55°C higher than the melting point of the film material, preferably 10-50°C higher than the melting point of the film material. Optionally, the heat sealing time is 0.5-4s; more preferably 0.5-3s, further preferably 0.5-1s or 1-3s.

3. The sealing process of the orifice plate according to claim 1 or 2, characterized in that: The material forming the film is a thermoplastic material; Preferably, the thermoplastic material is selected from any one of polyolefin materials, polyester materials, polyamide materials and polyurethane materials, or a composite material of a combination of at least two of them; Preferably, the thermoplastic material is selected from any one of polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyethylene terephthalate, polybutylene terephthalate, polyarylate, polyisocyanate, polymethyl methacrylate, polycarbonate, nylon, polyperfluoroethylene propylene and polychlorotrifluoroethylene, or a composite material of a combination of at least two thereof.

4. The sealing process of the orifice plate according to any one of claims 1 to 3, characterized in that: The thickness of the film is 0.04-0.18 mm, preferably 0.04-0.15 mm, and more preferably 0.04-0.1 mm.

5. The sealing process of the orifice plate according to any one of claims 1 to 4, characterized in that: The film is a PP film, and the thickness of the PP film is 0.04-0.18 mm, preferably 0.04-0.15 mm, and more preferably 0.04-0.1 mm; the heat sealing temperature is 170-215° C., preferably 180-210° C.; the heat sealing time is 0.5-4.5 s, preferably 0.5-3 s, and more preferably 1-3 s.

6. The sealing process of the orifice plate according to any one of claims 1 to 4, characterized in that: The film is a FEP film, the thickness of the FEP film is 0.04-0.18 mm, preferably 0.04-0.15 mm, more preferably 0.04-0.1 mm; the heat sealing temperature is 250-350° C., preferably 280-300° C.; the heat sealing time is 0.3-4.5 s, preferably 0.5-3 s, more preferably 0.5-1 s.

7. A high-throughput screening method, characterized in that: The invention comprises the sealing process of the orifice plate according to any one of claims 1 to 6.

8. The high-throughput screening method according to claim 7, characterized in that: The orifice plate comprises a bubble cap orifice plate; Preferably, the cross-sectional shape of the blind hole of the bubble cap hole plate is one of a circular shape, a quasi-circular shape, an elliptical shape and a quasi-elliptical shape; more preferably, a circular shape; Preferably, the blind holes of the bubble cap hole plate are generally in a shape of a semi-spherical shape or a semi-ellipsoidal shape; preferably, the shape is a semi-spherical shape.

9. The high-throughput screening method according to claim 8, characterized in that: The process also includes: forming the thermoplastic material into the blister plate; Preferably, it comprises: performing a thermoforming process on the thermoplastic material to form the blister hole plate; Preferably, the molding process includes: any one of a blow molding process, a vacuum molding process or an injection molding process.

10. The high-throughput screening method according to claim 9, characterized in that: The step of forming the blister plate comprises: heating the thermoplastic material having a thickness of 0.15-0.8 mm to a temperature 5-30° C. lower than the melting point of the thermoplastic material, and then processing the thermoplastic material substrate into a mold shape by a blow molding process or a vacuum molding process to form the blister plate; Preferably, the temperature is 5-25°C below the melting point of the thermoplastic material, more preferably 5-20°C below the melting point of the thermoplastic material; or heating the thermoplastic material to a molten state, and then processing the base of the thermoplastic material into a mold shape by an injection molding process to form the blister hole plate with a thickness of 0.15-0.8 mm; Preferably, the thermoplastic material has a thickness of 0.2-0.6 mm.

11. The high-throughput screening method according to claim 9, characterized in that: The step of forming the blister plate comprises: heating the thermoplastic material with a thickness of 0.15-0.8 mm to a temperature 5-30° C. lower than the melting point of the thermoplastic material, and maintaining the temperature for 50-100 seconds, and then quickly sending the thermoplastic material to the top of the mold, and then forming the thermoplastic material by vacuum molding in a vacuum environment to form the blister plate; Preferably, the thickness of the thermoplastic material is 0.2-0.6 mm; Preferably, the temperature is 5-25°C below the melting point of the thermoplastic material, more preferably 5-20°C below the melting point of the thermoplastic material; Preferably, the heating temperature is maintained for 70-90 seconds.

12. The high-throughput screening method according to claim 9, characterized in that: The step of forming the bubble cap hole plate comprises: placing the thermoplastic material with a thickness of 0.15-0.8 mm on the top of the mold, heating it to 5-30° C. below the melting point of the thermoplastic material, and then blow molding the thermoplastic material under a certain pressure to form the bubble cap hole plate; Preferably, the thickness of the thermoplastic material is 0.2-0.6 mm; Preferably, the heating is performed to a temperature 5-25°C below the melting point of the thermoplastic material, more preferably 5-20°C below the melting point of the thermoplastic material.

13. The high-throughput screening method according to any one of claims 9 to 12, characterized in that: The thermoplastic material is selected from any one of polyolefin materials, polyester materials, polyamide materials and polyurethane materials, or a composite material of a combination of at least two of them; Preferably, the thermoplastic material is selected from any one of polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyethylene terephthalate, polybutylene terephthalate, polyarylate, polyisocyanate, polymethyl methacrylate, polycarbonate, nylon, polyperfluoroethylene propylene and polychlorotrifluoroethylene, or a composite material of a combination of at least two thereof.

14. The high-throughput screening method according to any one of claims 9 to 13, characterized in that: The thermoplastic material is a PP material, and the steps of the molding process include: heating the PP material to 130-165° C., maintaining the temperature for 50-100 seconds, and performing vacuum molding in a vacuum environment, wherein the thickness of the PP material is 0.15-0.8 mm; Preferably, the thickness of the PP material is 0.2-0.6 mm; Preferably, the heating temperature is 150-155°C; Preferably, the heating temperature is maintained for 70-90 seconds; Alternatively, the steps of the molding process include: heating the PP material to 130-165° C., and blow molding the PP material at a pressure of not less than 0.4 MPa, wherein the thickness of the PP material is 0.15-0.8 mm; Preferably, the thickness of the PP material is 0.2-0.6 mm; Preferably, the heating temperature is 140-150°C.

15. The high-throughput screening method according to any one of claims 9 to 13, characterized in that: The thermoplastic material is FEP material, and the molding process comprises: heating the FEP material to 220-260° C., maintaining the temperature for 50-100 seconds, and performing vacuum molding in a vacuum environment, wherein the thickness of the FEP material is 0.15-0.8 mm; Preferably, the thickness of the FEP material is 0.2-0.6 mm; Preferably, the heating temperature is 240-250°C; Preferably, the heating temperature is maintained for 70-90 seconds; Alternatively, the steps of the molding process include: heating the FEP material to 220-260° C., blow molding at a pressure of not less than 0.4 MPa, and the thickness of the FEP material is 0.15-0.8 mm; Preferably, the thickness of the FEP material is 0.2-0.6 mm; Preferably, the heating temperature is 240-250°C.

16. The high-throughput screening method according to any one of claims 9 to 15, characterized in that: include: After the bubble cap plate is formed, the reaction solution and / or solid is added into the blind hole of the bubble cap plate, and then sealed according to the sealing process of the plate, followed by heating and / or shaking, and then the reaction system is analyzed.

17. The high-throughput screening method according to claim 16, characterized in that: During the sealing process, a sealing ring is formed at the opening of each blind hole of the bubble cap hole plate; Preferably, the shape of the sealing ring is the same as the shape of the blind hole of the bubble cap hole plate; Preferably, a space for forming the sealing ring is provided between two adjacent blind holes; Preferably, the inner contour line of the sealing ring covers the outer contour line of the blind hole or is flush with the outer contour line of the blind hole.

18. The high-throughput screening method according to claim 16 or 17, characterized in that: The device for achieving heating and / or oscillation is provided with a boss, and when the heating temperature is higher than the boiling point of the solvent, the boss contacts the sealed bubble cap plate to perform secondary reinforcement sealing on the blind hole of the bubble cap plate. The diameter of the boss is between the outer diameter and the inner diameter of the sealing ring at the opening of the blind hole of the bubble cap well plate.

19. A perforated plate heat sealing device, characterized in that: It includes a support, a transfer plate and a heating element, wherein the transfer plate and the heating element are both connected to the support, and the transfer plate and the heating element can selectively contact; The heating element includes a hot pressing head mounting plate and at least one hot pressing head, each of the hot pressing heads is an annular structure, one end of each of the hot pressing heads is connected to the hot pressing head mounting plate, a side of the hot pressing head mounting plate relatively close to the hot pressing head can selectively contact the transfer plate, and the other side of the hot pressing head mounting plate is connected to the bracket.

20. The orifice plate heat sealing device according to claim 19, characterized in that: The thermal compression head mounting plate includes a thermal compression head mounting plate body, at least one spring and at least one sleeve. Each of the springs and each of the sleeves are arranged in the thermal compression head mounting plate body. One end of a sleeve is connected to the thermal compression head mounting plate body, and the other end is connected to a thermal compression head. A spring sleeve is arranged outside the sleeve.

21. The orifice plate heat sealing device according to claim 20, characterized in that: At least one cavity is provided on the main body of the thermal pressure head mounting plate, and one of the springs and one of the sleeves are both arranged in one of the cavity.

22. The orifice plate heat sealing device according to claim 20 or 21, characterized in that: The heating element also includes a heating rod configured to heat the thermal compression head, and the heating rod is arranged in the thermal compression head mounting plate body.

23. The orifice plate heat sealing device according to any one of claims 19 to 22, characterized in that: The transfer plate includes a hole plate transfer plate, a lower mold plate and a film pressing frame, the hole plate transfer plate is connected to the lower mold plate, and the film pressing frame is connected to the lower mold plate, so that the heat-sealing film is evenly covered on the multi-channel hole plate and ensures that the heat-sealing film will not shift during the heat sealing process; the lower mold plate is connected to the bracket, and the film pressing frame selectively contacts the hot pressing head mounting plate.

24. The orifice plate heat sealing device according to claim 23, characterized in that: The lower mold plate is provided with a receiving cavity configured to place the orifice plate transfer plate.

25. The orifice plate heat sealing device according to claim 23 or 24, characterized in that: Mounting parts are arranged around the lower mold plate, and the film pressing frame is connected to the lower mold plate through the mounting parts, so that the heat-sealing film is evenly covered on the multi-channel orifice plate and the heat-sealing film is not offset during the heat-sealing process.

26. The orifice plate heat sealing device according to any one of claims 19 to 25, characterized in that: The bracket includes a telescopic device, which is connected to the thermal pressure head mounting plate to push the heating element and the transfer plate to selectively contact each other.

27. The orifice plate heat sealing device according to any one of claims 19 to 26, characterized in that: The bracket includes a fixed mold sliding bottom plate and a bottom fixed plate, the fixed mold sliding bottom plate is connected to the transfer plate; the bottom fixed plate is provided with a slide rail, and the fixed mold sliding bottom plate is slidably connected to the bottom fixed plate through the slide rail.

28. A high throughput screening system, characterized in that It comprises the orifice plate heat sealing device as described in any one of claims 19-27.

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