Microarray manufacturing apparatus

Abstract

A microarray manufacturing apparatus according to an embodiment of the present invention comprises a microarray tip manufacturing apparatus and a microarray base manufacturing apparatus. The tip manufacturing apparatus includes: a dispensing unit that dispenses a tip composition including an active ingredient into an engraved portion of a supplied mold; and a first filling unit that simultaneously performs filling, in which even fine structures in the engraved portion of the mold are filled with the tip composition dispensed into the engraved portion of the mold, and drying of the filled composition. The base manufacturing apparatus includes: a dispensing unit that receives the mold, in which the tip composition has been filled and dried, and dispenses a base composition onto the tip composition filled and dried inside the engraved portion of the mold; and a second filling unit that simultaneously performs filling and drying of the base composition dispensed into the engraved portion of the mold.

Description

Microarray manufacturing device

[0001] The present invention relates to a microarray manufacturing apparatus.

[0002] Research on microarrays as a means of drug delivery is ongoing. Research on the structure of microarrays that enables better delivery of substances of interest, not limited to specific pharmaceutical active ingredients, through a user's skin is also being conducted by various research groups. As one example, we will refer to the disclosures of U.S. Patent No. 10,828,478 B2 and U.S. Patent No. 11,724,079 B2 (Title of Invention: MICRONEEDLES AND METHODS OF MANUFACTURE THEREOF), which are the results of research by the research group at Georgia Tech, USA, to which Prausnitz et al. The microarray disclosed in the two U.S. patents comprises a base substrate having a microneedle side and a side opposite thereto. Additionally, the microarray comprises a primary funnel portion extending from the microneedle side of the base substrate and one or more microneedles extending from the primary funnel portion. Here, one or more microneedles comprise a substance of interest and a matrix material, and the substance of interest is contained more in one or more microneedles than in the main funnel layer. For example, the main funnel layer may contain 0 to 20% of the substance of interest contained in one or more microneedles. Additionally, the two U.S. patents disclose a method for manufacturing a microarray. In the method for manufacturing a microarray illustrated in the flowchart of FIG. 25 of the U.S. patents, a mold is used that includes an upper surface, a lower surface, and an opening formed on the upper surface. Additionally, the mold includes a first cavity adjacent to the upper surface opening and a second cavity below the first cavity. The first cavity defines the main funnel layer, and the second cavity defines one or more microneedles.After preparing a mold of such a structure, a first material in which the substance of interest is dissolved or dispersed is filled into the second cavity. After the second cavity is filled with the first material, a drying process is performed to remove at least a portion of the first material, thereby forming the tip portion of the microneedle in the second cavity. Subsequently, a second material in which the matrix material is dissolved or dispersed is filled into the portion of the first cavity and the second cavity that is not filled with the dried first material. After that, a drying process is performed to remove at least a portion of the second material, thereby forming the main funnel layer of the microneedle and the remaining portion of one or more microneedles excluding the tip. The inventor(s) have recognized that the aforementioned U.S. patents of Prausnitz et al. disclose a structure and manufacturing method that reduces the waste of pharmaceutical active ingredients by concentrating the pharmaceutical active ingredients in the tip portion of a microarray, and the results of the research of the present invention are based at least partially on such prior art.

[0003] Next, another method for manufacturing a microarray that allows a pharmaceutical active ingredient to be concentrated in the tip portion of the microarray will be described with reference to FIGS. 1 and 2. The method for manufacturing a microarray is disclosed in Korean Registered Patent No. 10-2382088 (Title of Invention: Method for Manufacturing Microneedles) owned by the applicant of the present invention, and FIGS. 1 and 2 are included in the said Korean Registered Patent.

[0004] FIG. 1 illustrates the filling and drying of an advanced part composition for a mold (100), and FIG. 2 illustrates the filling and drying of a base part composition for a mold (100). After the filling and drying of the advanced part composition shown in FIG. 1, the filling and drying of the base part composition shown in FIG. 2 were performed to manufacture a microarray.

[0005] The provision of a raw material (120) comprising an advanced part composition and a base part composition may be performed by dispensing one or more droplets in a dot shape only to the recessed part (110) of the mold (100) (in the case of the advanced part composition), or by dispensing it entirely over the upper surface of the mold (100) where the recessed part (110) is formed (in the case of the base part composition). In the step of pressurizing the raw material (120) dispensed to the recessed part (110) in the pressurizing chamber (30), the raw material (120) is pressurized using the internal pressure of the pressurizing chamber (30) to fill the raw material (120) into the microstructure (111) of the recessed part (110). When the pressure chamber (30) is shielded, air is injected through the inlet (31) of the pressure chamber (30) to increase the pressure of the pressure chamber (30). Then, the raw material (120) is subjected to pressure by the gas pressure inside the pressure chamber (30), causing the microbubbles contained in the raw material (120) to naturally detach from the raw material (120) and be removed, and the raw material (120) is filled into the microstructure (111) within the engraved portion (110). At this time, air discharge through the outlet (32) of the pressure chamber (30) is carried out simultaneously to cause an air circulation phenomenon within the pressure chamber (30), thereby allowing the drying of the raw material (120) to be performed simultaneously.

[0006] The inventor(s) have developed a microarray manufacturing apparatus capable of implementing the manufacturing methods of the two prior art described above.

[0007] In the process, the inventor(s) discovered the following technical difficulties.

[0008] First, when carrying out a manufacturing method in which a base composition is filled and dried into a mold following the filling and drying of a tip composition, the amount of the tip composition containing a pharmaceutical active ingredient is very small compared to the amount of the base composition. In the mass production process of microarrays, it is difficult to dispense small amounts of tip compositions into a large number of molds and then transfer them all at once to a chamber for filling and drying. This is because the amount of moisture contained in the dispensed tip composition is small, causing it to dry quickly. If drying occurs while waiting to be transferred to the chamber for filling, the tip composition is not filled into the microstructure of the mold, and a microarray of the desired shape cannot be obtained.

[0009] Second, when producing microarrays for medical purposes, the quantitative injection of the leading edge composition containing pharmaceutical active ingredients is very important. If the exact amount of active ingredient is not injected into the mold, it is difficult to achieve the intended pharmaceutical effect. Even if the dispensing amount is primarily controlled in the equipment dispensing the composition into the mold, it is necessary to accurately determine the actual amount of composition injected into the mold at other stages of the manufacturing process, and if a mold is found to have been dispensed less or more than the intended amount, it is necessary to promptly determine it as defective and remove it from the manufacturing process.

[0010] Third, if the dispensing and individual filling processes for individual molds performed for the advanced part composition are also performed for the base part composition, the productivity of the microarray may decrease. In the dispensing and filling processes of the base part composition, which contains little to no expensive pharmaceutical active ingredients and is dispensed in relatively large quantities, a means to increase the productivity of the microarray is required.

[0011] The present invention aims to provide a microarray manufacturing apparatus that solves the aforementioned technical problem.

[0012] More specifically, the present invention aims to provide a microarray manufacturing apparatus that allows a small amount of an advanced component composition to be dispensed into a mold cavity during a mass production process of a microarray, and then transferred to a chamber for filling before the composition is naturally dried, thereby ensuring that the advanced component composition is well filled into the microstructure of the mold.

[0013] In addition, the present invention aims to provide a microarray manufacturing apparatus capable of determining whether the exact amount of a composition as intended, particularly the amount of a leading part composition containing a pharmaceutical active ingredient, has been introduced into the mold during a mass production process of a microarray, and removing molds that have not been introduced from the manufacturing process.

[0014] In addition, the present invention aims to provide a microarray manufacturing apparatus capable of increasing the productivity of a microarray in a base composition dispensing and filling process in which a relatively large amount of expensive pharmaceutical active ingredients are dispensed, and which contains none or almost none of the expensive pharmaceutical active ingredients.

[0015] A microarray manufacturing apparatus according to one embodiment of the present invention includes a microarray tip manufacturing apparatus and a base manufacturing apparatus. The tip manufacturing apparatus includes a dispensing unit that dispenses a tip composition containing an active ingredient into the recessed portion of a supplied mold, and a first filling unit in which filling and drying of the filled composition are performed simultaneously so that the tip composition dispensed into the recessed portion of the mold fills up to the microstructure of the recessed portion of the mold. The base manufacturing apparatus includes a dispensing unit that receives a mold in which the tip composition has been filled and dried, and dispenses a base composition onto the tip composition that has been filled into the recessed portion of the mold and dried, and a second filling unit in which filling and drying of the base composition dispensed into the recessed portion of the mold are performed simultaneously.

[0016] The first filling section comprises a first chamber, and the second filling section comprises a second chamber separate from the first chamber. The first filling section is configured such that a relatively small number of molds are processed in the first chamber compared to the second chamber, so that filling and drying are performed before the natural drying of the top section composition, which is in a relatively small amount compared to the base section composition. The second filling section is configured such that a relatively large number of molds, into which the base section composition is dispensed, are processed in the second chamber compared to the first chamber while loaded on a loading means.

[0017] The first filling section may include a seating section that receives and places a mold in which the advanced part composition has been dispensed, and a contact section that forms a closed chamber space upon contact with the seating section. Relative movement is performed so that the distance between the seating section and the contact section is narrowed, and when they come into contact with each other, a first chamber is formed and a filling and drying process is performed.

[0018] The above relative movement is performed by a cylinder device, and a seating portion is installed at the piston end of the cylinder device, and the seating portion can form the first chamber by moving by the cylinder device and coming into contact with a contact portion having a supply port and an exhaust port formed therein.

[0019] The above-described advanced part manufacturing device may further include an inspection unit for inspecting whether the amount of the dispensed advanced part composition is appropriate. The inspection unit includes weight sensing means positioned before and after the dispensing unit, and can inspect whether the dispensed amount of the advanced part composition is appropriate by comparing the value obtained by subtracting the weight value detected at the front end of the dispensing unit from the weight value detected at the rear end of the dispensing unit with a reference value.

[0020] Meanwhile, a device for manufacturing the tip portion of a microarray also falls within the scope of the present invention. The device for manufacturing the tip portion of the microarray comprises a dispensing unit that dispenses a tip portion composition containing an active ingredient into the recessed portion of a supplied mold, and a first filling unit in which filling and drying of the filled composition are performed simultaneously so that the tip portion composition dispensed into the recessed portion of the mold fills up to the microstructure of the recessed portion of the mold. The first filling unit is configured so that the mold is processed in a first chamber so that filling and drying are performed before the natural drying of the tip portion composition. The first filling unit comprises a seating unit that receives and places the mold in which the tip portion composition has been dispensed, and a contact unit that forms a closed chamber space upon contact with the seating unit. Relative movement is performed so that the distance between the seating unit and the contact unit is narrowed, and when they come into contact with each other, a first chamber is formed and the filling and drying process is performed.

[0021] Here, the relative movement is performed by a cylinder device, a seating portion is installed at the piston end of the cylinder device, and the seating portion is moved by the cylinder device to come into contact with a contact portion having a supply port and an exhaust port formed therein, thereby forming the first chamber.

[0022] In addition, additional configurations may be further included in the microarray manufacturing apparatus according to the present invention.

[0023] According to the present invention, a microarray manufacturing apparatus may be provided that, in a mass production process of a microarray, after dispensing a small amount of an advanced component composition into a mold cavity, transfers the composition to a chamber for filling before it naturally dries, thereby ensuring that the advanced component composition is well filled into the microstructure of the mold.

[0024] In addition, according to the present invention, a microarray manufacturing apparatus may be provided capable of determining whether the exact amount of a composition as intended, particularly the amount of a leading portion composition containing a pharmaceutical active ingredient, has been introduced into a mold during a mass production process of a microarray, and removing molds that have not been introduced from the manufacturing process.

[0025] In addition, according to the present invention, a microarray manufacturing apparatus can be provided that can increase the productivity of a microarray in a base composition dispensing and filling process in which a relatively large amount of expensive pharmaceutical active ingredients are dispensed, and which does not contain any or almost any expensive pharmaceutical active ingredients.

[0026] FIGS. 1 and FIGS. 2 are drawings illustrating a conventional method for manufacturing a microarray.

[0027] FIG. 3 is a drawing illustrating the overall structure of a microarray manufacturing apparatus according to one embodiment of the present invention.

[0028] FIG. 4 is a plan view illustrating the structure of the mold supply section and the tip composition dispensing section of a microarray manufacturing apparatus according to one embodiment of the present invention.

[0029] Figure 5 is a photograph showing a robot arm positioned on the top of the conveyor of the mold supply unit in an actual microarray manufacturing device according to one embodiment of the present invention.

[0030] FIG. 6 is a photograph showing a robot arm picking up a mold from a conveyor of a mold supply unit in an actual microarray manufacturing device according to one embodiment of the present invention and placing the mold down on a weight detection unit.

[0031] FIG. 7 is a photograph taken of a robot arm placing a mold on one of the mounting portions of a rotatable dispensing arm of a dispensing unit in an actual microarray manufacturing device according to one embodiment of the present invention.

[0032] FIG. 8 is a photograph taken of a dispenser dispensing an advanced component composition to a mold that has been moved to a dispensing position below the dispenser by rotating the dispensing unit in an actual microarray manufacturing device according to one embodiment of the present invention.

[0033] FIG. 9 is a plan view illustrating a filling section, an inspection section, and a tray loading section of a microarray manufacturing device according to one embodiment of the present invention.

[0034] FIG. 10 is a drawing illustrating the structure of a filling part for filling a leading part composition of a microarray manufacturing apparatus according to one embodiment of the present invention.

[0035] FIG. 11 is a drawing illustrating a state in which a chamber for filling an advanced part composition is formed by the expansion operation of a cylinder device supplied with a mold in a microarray manufacturing device according to one embodiment of the present invention.

[0036] FIG. 12 is a photograph taken just before a robot arm loads a mold into the central filling section among the three filling sections for the advanced part composition in an actual microarray manufacturing device according to one embodiment of the present invention.

[0037] FIG. 13 is a photograph taken of a chamber formed by expanding a cylinder after a mold is loaded onto a jig of the central filling part for the advanced part composition in an actual microarray manufacturing apparatus according to one embodiment of the present invention.

[0038] FIG. 14 is a plan view illustrating a base forming device of a microarray manufacturing device according to one embodiment of the present invention.

[0039] FIGS. 15 and 16 are photographs of a large chamber for filling a base composition provided in an actual microarray manufacturing apparatus according to one embodiment of the present invention.

[0040] Hereinafter, embodiments and examples of the present invention will be described in detail with reference to the attached drawings so that those skilled in the art can easily implement the present invention. However, the present invention may be embodied in various forms and is not limited to the embodiments and examples described herein.

[0041] Throughout this specification, when a part is described as “comprising” a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components.

[0042] The present invention is to be explained in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0043]

[0044] Overall configuration of the equipment

[0045] FIG. 3 is a drawing illustrating the overall structure of a microarray manufacturing apparatus according to one embodiment of the present invention.

[0046] In FIG. 3, numbers 1 to 6 are assigned and indicated for each functional part of the entire device. The functional part indicated by 1 is a bowl feeder, which is a mold supply unit. A mold is fed into a bowl-shaped input section, and the fed mold is supplied to a conveyor. The functional part indicated by 2 is an advanced part composition dispensing unit. Here, the weight of the mold is detected, and the advanced part composition is dispensed into the recessed part of the mold. The functional part indicated by 3 is a filling and inspection unit. In this functional part, the weight of the mold after the advanced part composition has been dispensed is detected, filled, and vision inspection is performed. The inspected mold is loaded onto a tray. The functional part indicated by 4 is a tray input unit. This functional part, namely the tray input unit, is a unit that feeds a tray loaded with a plurality of molds filled with the advanced part composition and dried into a base forming device. The functional part indicated by 5 is a base forming unit. In this functional section, a base composition is dispensed onto the dried tip composition of each mold in a tray loaded with a plurality of molds that have been filled with and dried with a tip composition, and an inspection is performed. The functional section indicated by 6 is the tray loading section. In this functional section, trays for which the dispensing and inspection of the base composition have been completed are loaded.

[0047] A microarray manufacturing device according to one embodiment of the present invention can be broadly divided into a microarray tip manufacturing device and a microarray base manufacturing device. In FIG. 3, the functional parts indicated by 1 to 3 correspond to the microarray tip manufacturing device, and the functional parts indicated by 4 to 6 correspond to the microarray base manufacturing device.

[0048]

[0049] Mold supply section and advanced section composition dispensing section (1+2)

[0050] The mold supply unit and the tip composition dispensing unit are functional units indicated as 1 and 2, respectively, in the overall structural drawing of FIG. 3. FIG. 4 is a plan view illustrating the structure of the mold supply unit and the tip composition dispensing unit of a microarray manufacturing apparatus according to one embodiment of the present invention.

[0051] In FIG. 4, a bowl is indicated by reference numeral 11. This bowl (11) is a container in the shape of a bowl with an open top surface and side walls formed except for a portion. A straight conveyor (12) is connected to the portion of the bowl (11) where the side walls are not formed. The bottom surface of the bowl (11) rotates in one direction, and in the embodiment shown in FIG. 4, counterclockwise, to transfer the mold poured into the bowl (11) to the conveyor (12).

[0052] Molds can be aligned on the conveyor (12) by the operation of the bowl (11) described above. Although the molds have an upper and lower distinction, they are arranged randomly on the conveyor (12). In order to perform dispensing toward the engraved portion of the mold, the engraved portion of the mold must be arranged so that it faces the dispenser from below. Accordingly, a measure can be taken to ensure that molds are aligned only in the forward direction on the conveyor (12) by detecting a reverse-arranged mold with the engraved portion facing downward using a visual inspection device (not shown), removing it from the conveyor (12), and supplying the removed mold back to the bowl (11) manually or automatically. Molds that are sequentially transported by the conveyor (12) in a state where only forward-arranged molds are aligned on the conveyor (12) in the manner described above can be grasped by a robot arm (13) and transported to a weight detection unit (14).

[0053] FIG. 5 is a photograph showing a robot arm (13) positioned on the top of a conveyor (12) of a mold supply unit in an actual microarray manufacturing device according to one embodiment of the present invention.

[0054] FIG. 6 is a photograph showing a robot arm (13) picking up a mold from a conveyor (12) of a mold supply unit in an actual microarray manufacturing device according to one embodiment of the present invention and placing the mold on a weight detection unit (14).

[0055] A mold that has been weighed and transported from a conveyor (12) to a weight detection unit (14) in a manner clearly understood with reference to FIGS. 6 and 7 can be supplied from the weight detection unit (14) to a dispensing device by the robot arm (13) or a separate robot arm (15).

[0056] FIG. 7 is a photograph taken of a robot arm (15) placing a mold on a mounting portion of a rotatable dispensing arm (16) in an actual microarray manufacturing device according to an embodiment of the present invention. Referring to FIG. 7, the method of transferring the mold from the weight detection unit (14) to the dispensing device can be clearly understood. Subsequently, the mold mounted on the dispensing arm (16) can be moved sequentially to a dispensing position by the rotation of the dispensing arm (16).

[0057] FIG. 8 is a photograph taken of a dispensing arm (16) rotating and moving to a dispensing position below the dispenser (17) in an actual microarray manufacturing device according to one embodiment of the present invention, in which the dispenser (17) dispenses an advanced composition.

[0058] From the photographs in FIGS. 6 to 8, an embodiment can be observed in which a robot arm (15) receives molds one by one from a conveyor (12) and a dispensing arm (16) also provides molds one by one, but it should be understood that the scope of the present invention is not limited to such an embodiment. The present invention may be implemented in such a manner that a suitable number of molds are received at once by the robot arm (15) and a plurality of molds are placed on a single mold seating portion of the dispensing arm (16). In this case, a suitable number of molds may be provided to a mold supply unit while stored in a single mold carrier, and the robot arm (15) may receive the carrier containing the plurality of molds from the mold supply unit and place it on the seating portion of the dispensing arm (16). Additionally, a plurality of dispensers (17) may simultaneously perform dispensing on these molds.

[0059] An adnate composition comprising a pharmaceutical active ingredient and a biodegradable polymer material as a matrix material can be dispensed by dotting one or more drops onto the recessed portion of a mold. The amount of the adnate composition dispensed onto a single recessed portion of a mold corresponding to a single microneedle shape is a very small amount, approximately a few mg.

[0060]

[0061] Filling, inspection and tray loading section (3)

[0062] The filling, inspection, and tray loading sections are functional sections indicated by 3 in the overall structural drawing of FIG. 3. FIG. 9 is a plan view illustrating the filling section, inspection section, and tray loading section of a microarray manufacturing device according to an embodiment of the present invention.

[0063] In the previous functional unit, the mold on which the advanced component composition is dispensed is transferred by the robot arm (21) to the weight detection unit (22) to detect its weight. In the microarray manufacturing device according to one embodiment of the present invention, the weight detection unit is implemented to include a total of two units. The first weight detection unit (14) detects the weight of the empty mold or mold carrier before dispensing. The second weight detection unit (22) detects the weight of the mold or mold carrier after dispensing. By subtracting the weight detected by the first weight detection unit (14) from the weight value detected by the second weight detection unit (22), the weight of the dispensed advanced component composition can be detected. Meanwhile, it is also possible to detect the weight of the dispensed advanced component composition using only one weight detection unit without departing from the scope of the present invention. If it is determined that the weight deviation of the mold or mold carrier before dispensing can be maintained below a predetermined value, the weight of the mold before dispensing can be fixed to a specific value, and the weight of the mold or mold carrier after dispensing can be detected to detect the weight of the dispensed tip composition.

[0064] If the weight detection result of the tip composition indicates that the desired amount has been dispensed, the dispensed mold is transferred to the filling section (23) by the robot arm (21). If the weight detection result of the tip composition indicates that the desired amount has not been dispensed, the dispensed mold can be transferred to a collection container by the robot arm (21) and disposed of.

[0065] As described above, the amount of the tip composition applied to one indentation of the mold corresponding to a single microneedle shape is approximately a few milligrams. This small amount of composition can be dried within a few seconds after application. If drying occurs while waiting to be transferred to the filling section (23), the tip composition will not be filled to the microstructure of the mold, and a microarray of the desired shape may not be obtained. Therefore, in the microarray manufacturing apparatus according to one embodiment of the present invention, it is preferable that individual molds in which the dispensing of the tip composition is completed are not transferred to the filling section (23) together with other molds, but are individually fed into the filling section (23) immediately after dispensing is completed.

[0066] Here, the word 'immediately' refers to a time interval during which drying of the advanced component composition does not occur in the mold in which the advanced component composition is dispensed. Additionally, the word 'individually' does not mean that the molds in which the advanced component composition is dispensed must be transferred to the filling section (23) and filled one by one. It should be understood that, without departing from the scope of the present invention, it is also possible to transfer multiple molds in pairs to the filling section (23) before drying of the advanced component composition occurs in the mold in which the advanced component composition is dispensed. When an appropriate number of molds are supplied to the mold supply section while stored in a single mold carrier and dispensed simultaneously as a single unit, filling may also be performed on a carrier unit rather than on a mold-by-mold basis.

[0067] As described above, molds that have been individually filled in the filling section (23) can be transferred to the vision inspection section (24) by a transfer robot. In the vision inspection section (24), the filled appearance of the individual mold is inspected using a means capable of detecting vision information, such as a camera. The good product judgment vision appearance is that the composition of the leading edge is discharged and filled only into the recessed part of the mold. If the composition exists in a state where it has spread out on the flat part around the recessed part, a defect judgment is made. Molds judged to be good are filled into an empty tray (26) that is fed by the transfer robot (25). The empty tray (26) filled with molds judged to be good is transferred to a discharge position for the next process. Afterward, the empty tray (26) is supplied to a position where molds judged to be good can be transferred. As described above, when an appropriate number of molds are supplied and dispensed and filled while stored in a carrier, it is possible to implement the process in a form where multiple carriers are stored in the tray (26).

[0068] FIG. 10 is a drawing illustrating a filling section (23) of a microarray manufacturing device according to one embodiment of the present invention.

[0069] The filling section (23) of the embodiment illustrated in FIG. 10 includes a cylinder device (42) with a jig (41) attached to its end, on which a mold from which the tip composition has been dispensed can be seated. The left illustration of FIG. 10 illustrates a state in which the cylinder device (42) is waiting because it has not received a mold from which the tip composition has been dispensed. The middle illustration of FIG. 10 illustrates a state in which a mold from which the tip composition has been dispensed is provided to the jig (41) of the cylinder device (42), but before the filling process is executed. The right illustration of FIG. 10 illustrates a state in which the cylinder device (42) has been extended to a chamber forming position to allow the mold to enter the filling process.

[0070] FIG. 11 is a drawing illustrating a state in which a chamber for filling is formed by the expansion operation of a cylinder device supplied with a mold in a microarray manufacturing device according to one embodiment of the present invention.

[0071] The jig (41) of the expanded cylinder comes into contact with a member (45) having an air supply port (43) and an exhaust port (44) formed therein. A space is formed between the jig (41) and the member (45), and this space defines the volume of the filling chamber. To form the chamber space, a groove may be formed in the member (45) having the air supply port (43) and the exhaust port (44). It is also possible to form a concave space on the jig (41) itself without such a groove, and for the member having the air supply port (43) and the exhaust port (44) to form only the upper surface of the chamber space.

[0072] In the embodiment illustrated in FIG. 11, the jig (41) of the cylinder device (42), which is raised and has a mold seated thereon, comes into contact with a concave groove in which an air supply port and an exhaust port are formed, thereby forming a chamber. It is preferable that a sealing O-ring (46) be formed on the jig side or the member side of the contact surface between the jig (41) and the member (45). In the embodiment illustrated in FIG. 11, a supply valve (47) and an exhaust valve (48) are respectively installed in the air supply port (43) and the exhaust port (44) to allow for the adjustment of the air supply pressure and / or speed and the exhaust pressure and / or speed.

[0073] FIG. 12 is a photograph taken just before the robot arm (21) loads the mold into the central filling part (23) among the three filling parts in an actual microarray manufacturing device according to one embodiment of the present invention.

[0074] FIG. 13 is a photograph taken of a chamber formed by expanding a piston, which is a component of a cylinder device (42), more specifically a cylinder device (42), after a mold is loaded onto a jig of a central filling part (23) in an actual microarray manufacturing device according to one embodiment of the present invention.

[0075] With reference to FIGS. 12 and 13, the function and operation method of the filling part of a microarray manufacturing device according to one embodiment of the present invention, more specifically the filling part of a microarray cutting part manufacturing device, will be more clearly understood.

[0076] In the process of filling the composition discharged into the recessed portion of a mold in a chamber, the composition is pressurized using the internal pressure of the chamber to fill the composition into the microstructure of the recessed portion of the mold. When the chamber is sealed and air is injected through the chamber's air supply port to increase the internal pressure of the chamber, the composition is subjected to pressure by the gas pressure inside the chamber; as a result, microbubbles contained in the composition naturally detach from the composition and are removed, allowing the composition to be filled into the microstructure within the recessed portion of the mold. At this time, air is simultaneously discharged through the chamber's exhaust port to induce an air circulation phenomenon within the chamber, thereby enabling simultaneous drying of the composition. That is, in the filling section of the microarray manufacturing device according to one embodiment of the present invention, pressurization and drying are performed simultaneously within the filling chamber for the composition discharged into the mold, particularly the advanced portion composition, and this simultaneous pressurized drying is performed for individual molds.

[0077] In the above embodiment, it is described that a pressurization process is performed to increase the pressure inside the chamber during the filling process within the chamber of a microarray manufacturing apparatus according to one embodiment of the present invention, but the scope of the present invention is not limited thereto. At the time of filing the present invention, the art knew that not only filling by pressurization but also filling by depressurization and filling at atmospheric pressure were all methods for producing microarrays. That is, as long as a mold in which a composition is dispensed is introduced into the chamber regardless of pressure conditions, filling of the composition into the indented portion of the mold is performed inside the chamber, and drying of the composition is performed inside the chamber simultaneously with such filling, all such methods fall within the scope of the present invention. This applies commonly to the aforementioned leading portion composition filling process and the subsequent base portion composition filling process.

[0078]

[0079] Microarray base manufacturing device (4+5+6)

[0080] FIG. 14 is a plan view illustrating a base forming device of a microarray manufacturing device according to one embodiment of the present invention.

[0081] A tray (27) loaded with a mold that has been filled and judged to be good quality and has been dispensed with an advanced composition is loaded onto the conveyor (51) of the base forming unit. The conveyor (51) of the base forming unit extends in a straight line from the tray loading position to the tray discharge position.

[0082] The tray (27) is moved by the conveyor (51) to a dispensing position, that is, a position below the base dispensing unit (52), and then stops. The dispensers included in the dispensing unit (52) are provided in multiple numbers. In the embodiment illustrated in FIG. 14, a total of five dispensers can simultaneously perform dispensing on the molds contained in the tray. While the top-part composition containing the pharmaceutical active ingredient is in a trace amount (in the order of a few mg), the amount of the base-part composition is in the order of approximately several hundred mg, which is a relatively large amount. Therefore, to increase production efficiency, it is desirable to perform dispensing using multiple dispensers at once. The dispensing unit (52) can be moved along the x, y, and z axes by the mobile robot (53).

[0083] The weight of the base composition dispensed by the dispenser can be checked by the weight detection unit (54). Although a method of measuring the weight of the base composition actually dispensed onto the mold loaded on the tray could be used, in this embodiment, a method other than the method of inspecting the mold on which the base composition is dispensed after being filled and dried with the top-grade composition is used. The dispenser moves onto the mold located in the test mold loading unit (55) of FIG. 14 to perform dispensing, and the dispensing mold is transferred to the weight detection unit (54) to detect the weight of the base composition dispensed by the dispenser. If the detected weight is determined to be within the appropriate range, the dispensing unit (52) performs dispensing of the base composition onto the mold loaded on the tray (27). This method of checking the dispensing amount contributes to increasing production efficiency.

[0084] When the discharge of the base composition for the molds loaded on the tray (27) in the manner described above is completed, the conveyor (51) operates again to move the tray (27) to the inspection position and then stops.

[0085] In the vision inspection unit (56) provided at the above inspection location, the filled appearance of individual molds is inspected using a means capable of detecting vision information, such as a camera. The vision appearance for a good product judgment is that the advanced part composition is discharged and filled only into the recessed part of the mold. If the composition exists in a state where it has spread out on the flat part around the recessed part, a defect judgment may be made. The vision inspection unit (56) can inspect the discharge appearance of individual molds loaded on the tray while moving on the upper part of the tray by a separate transfer robot (57).

[0086] A total of 70 molds, for example, in a 10*7 array can be loaded in the tray (27). Among the total of 70 molds loaded in one tray, a defect determination can be made for three molds at the following coordinates, for example: First defective mold: (2, 6), Second defective mold: (5, 3), Third defective mold: (8, 5). The location and tray information of these defective molds are stored separately so that when the entire process is completed, the molds determined to be defective are removed and only the good molds are provided for the packaging stage for product manufacturing.

[0087] In a different embodiment, a marker that can be mounted on the same unit as the vision inspection machine (56) can mark a defective mold. The marker can be, for example, a laser engraver or an ink indicator. For a mold judged defective by the vision inspection machine, the laser engraver can engrave a predetermined mark or the ink indicator can apply ink of a predetermined color, thereby allowing the defective mold to be visually distinguished from other good molds.

[0088] When the inspection and marking processes described above are completed, the conveyor (51) operates to transport the tray (27) to the discharge position. The discharged trays (27) can be collected in units of several or dozens and then transported all at once to a chamber for filling and drying. As described above, since the amount of the base composition is much larger in units of hundreds of mg compared to the top composition in units of several mg, natural drying may not occur for a period of time sufficient to complete the dispensing and inspection processes for several or dozens of base compositions per tray. As a result, the aforementioned collective filling and drying process can proceed in the base composition manufacturing process, and this acts as a factor that can increase the productivity of the base composition manufacturing process. When dozens of trays are transported to a large chamber and the filling and drying of the base composition into the mold engraving are completed, the final commercialization stage can proceed. The configuration of the chamber provided to the base manufacturing device among the microarray manufacturing devices according to one embodiment of the present invention can be understood by referring to FIGS. 15 and 16. From the photograph in FIG. 15, pipe devices for providing or releasing pressure inside the chamber of the base manufacturing device and for generating air circulation inside the chamber can be seen. From the photograph in FIG. 16, the interior of the chamber when the chamber of the base manufacturing device is opened can be seen. As can be seen from FIG. 16, trays filled with a plurality of molds in which the base composition is dispensed can be loaded into a rectangular structure inside the chamber. With the trays loaded, the chamber can be closed and the collective filling and drying process described above can proceed. Meanwhile, a load lock for an automated process may be placed before and after the filling section for the base of the microarray manufacturing device according to one embodiment of the present invention.More specifically, in a load lock positioned in front of a large chamber, which is the filling section of a base manufacturing device, after a tray is inserted for the filling process, the load lock is closed and set to a pressure equal to that of the large chamber, and then the door facing the large chamber is opened to connect the load lock with the large chamber. In a load lock positioned behind the large chamber, after a tray that has completed the filling process is transferred from the large chamber to the load lock, the load lock is closed and set to atmospheric pressure, and then the outer door is opened so that the tray that has completed the filling process can be removed for the next process, such as packaging. Any modified embodiment in which a load lock is positioned before and after a chamber where a process is performed in an internal chamber environment where atmospheric pressure and a pressure difference exist should be understood to fall within the scope of the present invention.

[0089]

[0090] As described in detail above, in a microarray manufacturing apparatus according to one embodiment of the present invention, the tip manufacturing apparatus and the base manufacturing apparatus are provided separately. Due to this configuration, when manufacturing the tip, which contains an expensive drug as an active ingredient and is dispensed in a relatively very small amount compared to the base, the molds can be processed individually to ensure quantitative injection of the tip composition and the formation of an accurate micro-needle shape, and when forming the base that serves as the basis for the tip, simultaneous mass processing can be performed to improve productivity.

[0091] In addition, in a microarray manufacturing device according to one embodiment of the present invention, the filling section of the tip manufacturing device and the filling section of the base manufacturing device are formed separately. Due to this configuration, when manufacturing the tip, the molds are processed individually, allowing the micro-needle shape to be accurately formed by the filling section before a relatively very small amount of the tip composition dries. On the other hand, when manufacturing the base, the molds are loaded in large quantities on a loading means and processed collectively in a large chamber, thereby improving productivity.

[0092] Furthermore, in a microarray manufacturing apparatus according to one embodiment of the present invention, a chamber is formed by relative movement in the filling section of the tip manufacturing apparatus, and the formation of the chamber is released by performing this movement in reverse. That is, a small chamber is formed by causing relative movement after an individual mold, from which the tip composition has been discharged, is placed in the seating section, thereby allowing the filling and drying processes to proceed rapidly. Consequently, even if the amount of the tip composition is very small, the filling process can be completed before drying, and the fine needle shape of the tip can be accurately formed. Additionally, by performing the relative movement in reverse, the chamber can be opened, allowing the mold with the tip formed to be easily removed from the chamber.

[0093]

[0094] Although the present disclosure has been described above with specific details such as specific components, limited embodiments, and drawings, this is provided only to aid in a more comprehensive understanding of the present disclosure and is not limited to the above embodiments, and a person skilled in the art to which the present disclosure belongs may make various modifications and variations from this description.

[0095] Accordingly, the concept of the present disclosure should not be limited to the embodiments described above, and should be interpreted as falling within the scope of the concept of the present disclosure, including the claims set forth below as well as all equivalent or equivalent variations thereof.

Claims

1. A microarray manufacturing apparatus comprising a leading edge manufacturing apparatus and a base manufacturing apparatus for a microarray, and The above-described advanced part manufacturing device comprises a dispensing unit that dispenses an advanced part composition containing an active ingredient into the recessed portion of a supplied mold, and It includes a first filling section in which filling and drying of the filled composition are performed simultaneously so that the advanced part composition dispensed into the intaglio portion of the mold fills up to the microstructure of the intaglio portion of the mold, and The above-described base manufacturing device comprises a dispensing unit that receives a mold in which the tip composition has been filled and dried, and dispenses the base composition onto the tip composition that has been filled and dried within the mold's intaglio portion; It includes a second filling section that simultaneously performs filling and drying of the base composition dispensed into the intaglio portion of the mold, and The first filling unit comprises a first chamber, and the second filling unit comprises a second chamber separate from the first chamber; the first filling unit is configured such that a relatively small number of molds are processed in the first chamber compared to the second chamber so that filling and drying are performed before natural drying of the tip composition, which is in a relatively small amount compared to the base composition; and the second filling unit is configured such that a relatively large number of molds, into which the base composition is dispensed, are processed in the second chamber while loaded on a loading means. Microarray manufacturing device.

2. In Paragraph 1, The first filling part includes a seating part that receives and seats a mold in which the advanced part composition has been dispensed, and a contact part that forms a closed chamber space upon contact with the seating part. A microarray manufacturing apparatus in which relative movement is performed so that the distance between the above-mentioned seating portion and the above-mentioned contact portion is narrowed, and when they come into contact with each other, a first chamber is formed and a filling and drying process is performed.

3. In Paragraph 2, The above relative movement is performed by a cylinder device, a seating portion is installed at the piston end of the cylinder device, and the seating portion is moved by the cylinder device to come into contact with a contact portion having a supply port and an exhaust port formed, thereby forming the first chamber. Microarray manufacturing device.

4. In Paragraph 3, The above-described advanced part manufacturing device further includes an inspection unit that checks whether the amount of the dispensed advanced part composition is appropriate, and The inspection unit includes weight sensing means positioned before and after the dispensing unit, and inspects whether the dispensed amount of the advanced part composition is appropriate by comparing the value obtained by subtracting the weight value detected at the front of the dispensing unit from the weight value detected at the rear of the dispensing unit with a reference value. Microarray manufacturing device.

5. It is a device for manufacturing the advanced part of a microarray, and The above-described advanced part manufacturing device comprises a dispensing unit that dispenses an advanced part composition containing an active ingredient into the recessed portion of a supplied mold, and It includes a first filling section in which filling and drying of the filled composition are performed simultaneously so that the advanced part composition dispensed into the intaglio portion of the mold fills up to the microstructure of the intaglio portion of the mold, and The above-mentioned first filling part is configured so that the mold is processed in the first chamber so that filling and drying are performed before the natural drying of the advanced part composition, and The above-mentioned first filling part is, A seating portion that receives and seats the mold in which the advanced component composition has been dispensed, and It includes a contact portion that forms a closed chamber space upon contact with the above-mentioned seating portion, and Relative movement is performed so that the distance between the above-mentioned seating portion and the above-mentioned contact portion is narrowed, and when they come into contact with each other, a first chamber is formed and a filling and drying process is performed. Microarray advanced manufacturing device.

6. In Paragraph 5, The above relative movement is performed by a cylinder device, and A seating portion is installed at the piston end of the cylinder device, and the seating portion is moved by the cylinder device to come into contact with a contact portion having a supply port and an exhaust port formed, thereby forming the first chamber. Microarray advanced manufacturing device.

Images