Automated vial filling system
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- CELLTRIO INC
- Filing Date
- 2026-01-19
- Publication Date
- 2026-07-30
Smart Images
Figure KR2026001044_30072026_PF_FP_ABST
Abstract
Description
Automated vial filling system
[0001] This invention relates to an automated vial filling system.
[0002] In the manufacturing of biopharmaceuticals and cell therapies, the process of dispensing cultured cells into small vials for storage and distribution is essential. Particularly in pharmaceutical environments that must meet Good Manufacturing Practice (GMP) standards, the task of dispensing precise volumes of cell culture medium into multiple vials while maintaining sterile conditions is required.
[0003] Conventional vial filling processes have primarily relied on manual labor or simple automated equipment. In the case of manual work, dispensing accuracy varies depending on the operator's skill level, and there is a high possibility of errors due to increased fatigue during prolonged repetitive tasks. Furthermore, the constant risk of contamination associated with direct operator intervention makes it difficult to meet GMP standards.
[0004] In the case of simple automated equipment, dispensing operations rely on mechanical precision, but consumables such as pipette tips are manufactured as injection-molded parts, resulting in dimensional variations between units. These dimensional variations cause positional errors when pipette tips are mounted, which leads to inaccurate dispensing that deviates from the opening of the vial, potentially causing product loss and contamination. Particularly for small-diameter 1-milliliter vials, even a positional error of a few millimeters can lead directly to dispensing failure.
[0005] In addition, fine dust particles are continuously generated in the drive parts of automated equipment due to mechanical friction from motors, belts, guide rails, etc. These particles degrade the cleanliness of the cleanroom environment and, if mixed into products, cause quality defects and safety issues. Existing equipment had limitations in maintaining a GMP environment because it lacked structures to effectively isolate or discharge particle sources.
[0006] The technology forming the background of this invention is disclosed in Korean Registered Patent Publication No. 10-2373674.
[0007] The present invention aims to solve the problems of the aforementioned conventional technology by providing an automated vial filling system capable of dispensing at an accurate location by measuring the position of a pipette tip in real time using a vision system and correcting errors.
[0008] The present invention aims to solve the problems of the aforementioned conventional technology by providing an automated vial filling system that can maintain a clean environment compliant with GMP standards by effectively isolating and discharging particles generated during the operation of the equipment.
[0009] The present invention aims to solve the problems of the aforementioned conventional technology by providing a vial filling automation system that can improve work efficiency and minimize the risk of contamination by automating the opening, closing, and dispensing operations for multiple vials.
[0010] However, the technical problems that the embodiments of the present invention aim to solve are not limited to the technical problems described above, and other technical problems may exist.
[0011] As a technical means for achieving the above-mentioned technical problem, a vial filling automation system according to one embodiment of the present invention may include: a culture medium storage unit in which a conical tube containing a culture medium containing cultured cells is loaded; a dispensing unit equipped with a pipette tip that draws culture medium from the culture medium storage unit and dispenses it into vials; a vial loading unit in which a vial rack in which a plurality of vials are arranged is loaded; a transfer unit that changes the relative position between the dispensing unit, the culture medium storage unit, and the vial loading unit; and a vision measurement unit that measures the position of the pipette tip mounted on the dispensing unit, calculates the error between the measured position and a reference position, and controls the transfer unit to move the dispensing unit by correcting the error.
[0012] In addition, the vision measurement unit can capture the center position of the pipette tip using a camera module, extract the actual position coordinates of the pipette tip from the captured image, and calculate a horizontal error value by comparing the actual position coordinates with a preset reference position coordinate.
[0013] In addition, the transfer unit can be controlled using the error value so that the discharge position by the pipette tip is aligned with the center of the opening of the vial.
[0014] In addition, a vial filling automation system according to one embodiment of the present invention may include a tip supply unit configured to supply the pipette tips to a dispensing unit, wherein a tip rack on which the pipette tips are arranged is loaded.
[0015] In addition, a vial filling automation system according to one embodiment of the present invention may include a tip alignment unit that pre-aligns the position of the pipette tip mounted on the dispensing unit.
[0016] In addition, the tip alignment unit can first align the pipette tip within a reference position range after the dispensing unit has mounted the pipette tip from the tip supply unit and before the position measurement by the vision measuring unit.
[0017] In addition, a vial filling automation system according to one embodiment of the present invention may include a vial opening / closing unit configured to open or close the caps of the plurality of vials loaded in the vial loading unit.
[0018] In addition, the vial opening / closing unit can simultaneously open or close the caps of a reference number of vials arranged in a row among the plurality of vials arranged in the vial rack.
[0019] In addition, the dispensing unit and the vial opening / closing unit may each be equipped with a sealing housing that seals a working area and an exhaust unit that discharges particles generated inside the sealing housing to the outside.
[0020] In addition, the exhaust unit may be equipped with an exhaust fan installed at the bottom of the sealed housing to discharge the particles downward.
[0021] The means for solving the problem described above are merely exemplary and should not be interpreted as intended to limit the present invention. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and the detailed description of the invention.
[0022] According to the means for solving the problem of the present invention described above, it is possible to provide an automated vial filling system capable of dispensing at an accurate location by measuring the position of a pipette tip in real time using a vision system and correcting the error.
[0023] According to the means for solving the problem of the present invention described above, it is possible to provide a vial filling automation system that can maintain a clean environment compliant with GMP standards by effectively isolating and discharging particles generated during the operation of the equipment.
[0024] According to the means for solving the problem of the present invention described above, a vial filling automation system can be provided that can improve work efficiency and minimize the risk of contamination by automating the opening, closing, and dispensing operations for multiple vials.
[0025] According to the solution to the problem of the present invention described above, by measuring and correcting the positional error of the pipette tip in real time through vision, it is possible to accurately dispense the product to the center of the vial despite dimensional deviations of the injection molded product, thereby preventing product loss and contamination.
[0026] According to the solution to the problem of the present invention described above, through automatic opening, closing, and dispensing operations at the vial rack level, worker intervention is minimized and processing speed is improved, thereby simultaneously enhancing the productivity and safety of the manufacturing process for cell therapies and biopharmaceuticals.
[0027] However, the effects obtainable from this invention are not limited to those described above, and other effects may exist.
[0028] FIG. 1 is a schematic diagram of a vial filling automation system according to one embodiment of the present invention.
[0029] FIG. 2 is a conceptual diagram showing the operation flow of a vial filling automation system according to one embodiment of the present invention.
[0030] Figure 3 is a diagram illustrating a method for measuring pipette tip position error using a vision measuring unit.
[0031] Figure 4 is a diagram illustrating a position movement method for correcting an error calculated using a vision measurement unit.
[0032] Figures 5 and 6 are drawings showing a structure for maintaining a clean environment by removing particles generated from the equipment drive unit.
[0033] Embodiments of the present invention are described below with reference to the attached drawings to enable those skilled in the art to easily implement the invention. However, the present invention may be embodied in various different forms and is not limited to the embodiments described herein. Furthermore, in order to clearly explain the present invention in the drawings, parts unrelated to the explanation have been omitted, and similar parts throughout the specification are denoted by similar reference numerals.
[0034] Throughout this specification, when a part is described as being "connected" to another part, this includes not only cases where they are "directly connected," but also cases where they are "electrically connected" or "indirectly connected" with other elements interposed between them.
[0035] Throughout the entire specification, when a component is described as being located "on," "on top," "on top," "under," "on bottom," or "on bottom" of another component, this includes not only cases where the component is in contact with the other component but also cases where another component exists between the two components.
[0036] 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.
[0037] For reference, terms related to direction or position (front, rear, rear end, top, upward, downward, width direction, etc.) in the description of the embodiments of the present invention are described based on the arrangement state of each component shown in the drawings. For example, when viewed in FIG. 1, the front-back direction may be from 2 o'clock to 8 o'clock, the width direction may be from 4 o'clock to 10 o'clock, and the up-down direction (vertical direction) may be from 12 o'clock to 6 o'clock.
[0038] However, such direction setting may vary depending on the arrangement of the present invention. For example, if necessary, the present invention may be arranged so that the upward direction relative to FIG. 1 faces the horizontal direction (left and right direction), and as another example, the present invention may be arranged so that the upward direction relative to FIG. 1 faces the oblique inclination direction.
[0039] This invention relates to an automated vial filling system.
[0040] FIG. 1 is a schematic diagram of a vial filling automation system according to one embodiment of the present invention.
[0041] Referring to FIG. 1, a vial filling automation system (10) according to one embodiment of the present invention may include a culture medium storage unit (100), a dispensing unit (200), a vial loading unit (300), a transfer unit (400), a vision measuring unit (500), a tip supply unit (600), a tip alignment unit (700), and a vial opening and closing unit (800).
[0042] FIG. 2 is a conceptual diagram showing the operation flow of a vial filling automation system according to one embodiment of the present invention.
[0043] Referring to FIG. 2, the vial filling automation system (10) is a facility that automatically dispenses a culture medium containing cultured cells into multiple vials, and can be configured to satisfy the cleanliness and precision required in a Good Manufacturing Practice (GMP) environment.
[0044] In particular, the vial filling automation system (10) disclosed herein can dispense culture medium at an accurate location despite dimensional deviations of pipette tips by applying real-time position correction technology through a vision measuring unit (500), and can maintain a clean environment by effectively isolating and discharging particles generated from the driving unit through a sealed and exhaust structure.
[0045] Specifically, referring to FIG. 2, the vial filling automation system (10) can be controlled to sequentially perform a loading step, a vial decapping step, a vial filling step, a vial capping step, and an unloading step.
[0046] First, in the loading step, a conical tube (CT) containing culture medium and a vial rack containing multiple vials can be loaded into the culture medium storage unit (100) and the vial loading unit (300), respectively. For example, a standard number of vial racks (e.g., 3) can be loaded simultaneously, and each vial rack may contain multiple vials arranged in a matrix form. Next, in the vial opening step, a vial opening / closing unit (800) can simultaneously open the caps of multiple vials (e.g., 8) arranged in a row on the vial rack.
[0047] Next, a vial filling step may be performed, in which the dispensing unit (200) may first receive a pipette tip (1) from the tip supply unit (600) (Tip Get), and may draw culture from the conical tube of the culture storage unit (100) using the attached pipette tip (1). For example, culture corresponding to a preset standard volume (e.g., 4.0 ml) may be drawn in with one draw. The drawn culture may be dispensed into an open vial through the dispensing unit (200) which has been moved to the vial loading unit (300) by the transfer unit (400) (Liquid Dispense to Vial), and this drawing and dispensing operation may be repeated a standard number of times (e.g., 2 times) so that a total standard volume (e.g., 8.0 ml, 4.0 ml x 2 times) of culture may be filled into each vial.
[0048] After dispensing is completed, the pipette tip (1) can be ejected (TIP Ejecting). Subsequently, in the vial closing step, the vial opening / closing unit (800) can simultaneously close the caps of a row of vials filled with culture medium. The vial opening, vial filling, and vial closing steps correspond to a single row vial filling process and can be repeated a standard number of times (e.g., 12 times) until processing of the entire row of vials is completed. After the filling of the entire row is completed, an unloading step is performed so that the conical tube and the vial rack can be removed from the culture medium storage unit (100) and the vial loading unit (300), respectively.
[0049] Below, the structure, function, and operation of each sub-module constituting the vial filling automation system (10) will be described in detail.
[0050] The culture medium storage unit (100) may be a sub-module of a vial filling automation system (10) in which a conical tube (CT) containing culture medium containing cultured cells is loaded.
[0051] In this regard, in the description of the embodiments of the present invention, a conical tube (CT) is a container used in the fields of bio-experiments and pharmaceutical manufacturing for storing and centrifuging liquids such as cell culture media and reagents, and may have a conical shape in which the diameter gradually decreases toward the bottom.
[0052] These conical tubes can generally be made of transparent plastic materials such as polypropylene, and may be equipped with a screw-type cap at the top to allow for airtight storage. Although the capacity may vary, in one embodiment of the present invention, a conical tube with a standard capacity (e.g., 50 ml) may be used. The conical shape causes the precipitate to concentrate at the bottom of the tube during centrifugation and minimizes the amount of residue even when liquid is drawn using a pipette.
[0053] Specifically, the culture medium storage unit (100) is configured to stably load a conical tube containing a culture medium containing cultured cells, and may be referred to as a 'CT Holder'. The culture medium storage unit (100) may have a holder structure corresponding to the outer shape of the conical tube, and a plurality of pockets may be formed to accommodate a plurality of conical tubes simultaneously.
[0054] For example, the culture medium storage unit (100) may have a standard number of pockets (e.g., 3) to store 3 conical tubes simultaneously. Each pocket may be formed in a shape capable of accommodating the conical lower portion of the conical tube and may support the tube so that it can be maintained in a vertically stable position.
[0055] Additionally, the culture medium storage unit (100) may be positioned so as to be movable by the transfer unit (400), or, according to an embodiment of the present invention, may be positioned at a predetermined fixed location so that the dispensing unit (200) can access it. Furthermore, the upper part of the pocket of the culture medium storage unit (100) is open so that the pipette tip (1) of the dispensing unit (200) can enter the inside of the conical tube and suck up the culture medium.
[0056] The dispensing unit (200) may be a sub-module of a vial filling automation system (10) equipped with a pipette tip (1) for drawing culture from a culture storage unit (100) and dispensing it into a vial.
[0057] In this regard, in the description of the embodiment of the present invention, the pipette tip (1) is a disposable nozzle part that is detachably mounted to the dispensing unit (200) to suck in and discharge culture solution, and can generally be manufactured by injection molding of a plastic material such as polypropylene. The pipette tip (1) may include an upper mounting part and a lower discharge part, and the mounting part may have a conical or cylindrical shape that can be fitted into the nozzle of the dispensing unit (200) to maintain airtightness, and the discharge part may have a shape that gradually narrows toward the bottom to enable precise liquid discharge.
[0058] Meanwhile, the capacity of the pipette tip (1) may vary, but in one embodiment of the present invention, a pipette tip with a standard capacity (e.g., 5 ml) may be used. Due to the characteristics of the injection molding process, there may be dimensional variations between individual pipette tips (1), and in particular, the center position of the dispensing part may have a deviation of several millimeters relative to the standard position in the horizontal direction. Considering that such dimensional variations may cause positional errors during precise dispensing of small vials, the vial filling automation system (10) disclosed herein may provide a function to correct such positional errors through a vision measuring unit (500) described in detail below.
[0059] Specifically, the dispensing unit (200) is equipped with a pipette tip (1) and is configured to draw culture medium from the culture medium storage unit (100) and dispense it into a vial, and may be referred to as an 'ADP' or 'Air Displacement Pipette'. The dispensing unit (200) can operate by drawing in and dispensing liquid using changes in air pressure, and precise volume control may be possible.
[0060] In one embodiment, the dispensing unit (200) may include a nozzle to which a pipette tip (1) is mounted, a piston and a motor for regulating air pressure, and a control unit for controlling them. The dispensing unit (200) may be configured to be able to move up and down in the vertical direction (Z-axis), thereby allowing the pipette tip (1) to be inserted into the conical tube of the culture medium storage unit (100) or positioned at the vial opening of the vial loading unit (300).
[0061] Additionally, the dispensing unit (200) can draw in a pre-set standard volume (e.g., 4.0 ml) of culture solution once, dispense it into a vial, and then repeat the same operation to dispense a total standard volume (e.g., 8.0 ml). Furthermore, as described below, the dispensing unit (200) can be placed inside a sealed housing (210) to be protected from external contamination, and particles generated during operation can be discharged through the exhaust unit (220).
[0062] The vial loading section (300) may be a sub-module of a vial filling automation system (10) in which a vial rack with multiple vials arranged thereon is loaded.
[0063] In this regard, in the description of the embodiments of the present invention, a vial is a small container for storing and distributing liquid or freeze-dried products, such as pharmaceuticals, vaccines, and cell therapies, in small units, and can generally be made of glass or plastic. The vial may include a cylindrical body and an opening at the top, and the opening may be sealed with a septum made of rubber or silicone and a cap made of aluminum or plastic.
[0064] In one embodiment of the present invention, a vial of standard volume (e.g., 1 ml) may be used, and such a small-volume vial may require precise position control due to the small diameter of the opening. The diameter of the opening of the vial may generally range from several millimeters to several tens of millimeters, and liquid may be dispensed out of the vial if the position of the pipette tip (1) deviates by only a few millimeters. The vial may be supplied in a sterile state and may need to be handled in a GMP environment.
[0065] Specifically, the vial loading section (300) is configured to load a vial rack in which a plurality of vials are arranged, and may be referred to as ‘Vial & Rack’. The vial loading section (300) may have a platform structure capable of stably fixing and positioning the vial rack, and may be configured to be movable by a transfer section (400). The vial rack may have an arrangement according to Standard Bio System (SBS) specifications, and as an example, an SBS 96 Vial Rack in which 96 vials are arranged in 8 rows and 12 columns may be used. The vial rack may have holes formed in a matrix form in which each vial can be inserted while standing vertically, and each hole may have a diameter corresponding to the outer diameter of the vial to fix the vial.
[0066] Additionally, the vial loading section (300) may be configured to load multiple vial racks simultaneously, and, for example, a standard number of vial racks (e.g., 3) may be arranged side by side in the front-rear direction or the width direction. The vial racks loaded in the vial loading section (300) may be sequentially moved to the working positions of the vial opening / closing section (800) and the dispensing section (200) by the transfer section (400).
[0067] In addition, according to one embodiment of the present invention, the vial loading unit (300) may be equipped with a weight sensor at each vial location to check the dispensing completion status. In one embodiment, a small load cell or pressure sensor may be placed at the bottom of each hole of the vial rack, thereby allowing the weight of each vial to be measured in real time. The weight of the empty vial before dispensing is measured as a first reference weight, and the weight after dispensing is measured as a second reference weight, so that the weight increase amount (second reference weight - first reference weight) can be calculated. If the calculated weight increase amount is greater than or equal to the first reference weight increase amount corresponding to the target dispensing amount and less than or equal to the second reference weight increase amount (for example, in the range of 95% to 105% of the target dispensing amount, where the second reference weight increase amount is set to be greater than the first reference weight increase amount), it can be determined that the dispensing for the vial has been successfully completed.
[0068] Additionally, if the weight increase is less than the first standard weight increase (e.g., insufficient dispensing), the vial filling automation system (10) may perform additional dispensing or mark the vial as defective. Additionally, if the weight increase exceeds the second standard weight increase (e.g., excessive dispensing), the vial filling automation system (10) may generate a warning signal and process the vial as a rework target.
[0069] Through this weight sensor feedback, the dispensing quality for each vial can be verified in real time, and the occurrence of defective products can be minimized; furthermore, weight data is stored as a log to ensure process traceability and meet GMP documentation requirements.
[0070] The transfer unit (400) may be a sub-module of a vial filling automation system (10) configured to change the relative position between the dispensing unit (200), the culture medium storage unit (100), and the vial loading unit (300).
[0071] Specifically, the transfer unit (400) is configured to change the relative position between the dispensing unit (200), the culture medium storage unit (100), and the vial loading unit (300), and may be referred to as a 'Table Unit'. The transfer unit (400) can perform the function of moving the working position, and in one embodiment, it may be implemented as a table movement method that moves the culture medium storage unit (100) and the vial loading unit (300) in a horizontal direction.
[0072] As another example, the dispensing unit (200) may be implemented in a gantry manner that moves horizontally, but for convenience of explanation, the following description focuses on the table movement method, although it goes without saying that the type and operation method of the transfer unit (400) are not limited to this.
[0073] In particular, the transfer unit (400) may have a two-axis drive structure capable of moving a workpiece in the forward direction (X-axis) and the width direction (Y-axis) of the vial filling automation system (10), and each axis may be controlled independently. As an example, the transfer unit (400) may be equipped with a linear movement mechanism including a linear guide rail, a ball screw, a servo motor, etc.
[0074] First, in the culture medium suction step, the transfer unit (400) can position the culture medium storage unit (100) below the dispensing unit (200), thereby allowing the pipette tip (1) of the dispensing unit (200) to enter the inside of the conical tube and suck up the culture medium. Next, in the culture medium dispensing step, the transfer unit (400) can position the vial loading unit (300) below the dispensing unit (200), and at this time, fine adjustment can be performed so that the pipette tip (1) is accurately aligned with the center of the opening of the vial by reflecting the error value received from the vision measurement unit (500).
[0075] As another example, when multiple rows of vials are arranged in a vial rack, the transfer unit (400) can move the vial rack by a reference pitch in the forward / backward direction or width direction after filling of one row of vials is completed to position the next row of vials at the working position. Subsequently, this movement operation can be repeated until filling of the entire row is completed, thereby enabling automatic dispensing of the entire vial rack.
[0076] In addition, according to one embodiment of the present invention, the transfer unit (400) may be equipped with a position sensor or an encoder to determine the current position in real time and may move precisely to a target position according to a predetermined control command applied to the vial filling automation system (10).
[0077] Meanwhile, according to one embodiment of the present invention, the transfer unit (400) can optimize the movement path based on the arrangement information of the vial rack and the dispensing status of each vial. In one embodiment, when the vial rack has an arrangement of 8 rows and 12 columns, the transfer unit (400) can select either a method of moving sequentially in columns or a method of moving along a zigzag path. When the total amount of culture medium is greater than or equal to a first reference total amount and dispensing is required for all vials (e.g., an amount sufficient to fill all vials), the transfer unit (400) can move sequentially from the first column to the twelfth column by applying a method of moving sequentially in columns.
[0078] Additionally, if the total amount of culture medium is less than the first standard total amount and greater than or equal to the second standard total amount (for example, an amount that can only fill some vials, where the second standard total amount is set to be smaller than the first standard total amount), the transfer unit (400) can generate an optimized path that first visits vials with high priority (for example, a user-specified location or the center of the rack).
[0079] Additionally, before moving to each column, it can be checked whether all vials in that column are open, and if some vials fail to open, those vials can be skipped and the next vials can be moved. The transfer unit (400) can select a path that minimizes the travel distance and the number of moves, and to this end, a shortest path search algorithm or a heuristic algorithm can be applied. Through path optimization, the total operation time can be shortened and mechanical wear can be reduced.
[0080] The vision measurement unit (500) may be a sub-module of a vial filling automation system (10) for measuring the position of a pipette tip (1) mounted on a dispensing unit (200), calculating an error between the measured position of the pipette tip (1) and a preset reference position, and controlling the transfer unit (400) to move the dispensing unit (200) by correcting the calculated error.
[0081] Specifically, the vision measuring unit (500) disclosed herein is configured to measure the position of a pipette tip (1) mounted on a dispensing unit (200) and may include a camera. The vision measuring unit (500) may be positioned to capture the position of the pipette tip (1) after it is mounted from the tip supply unit (600) and before it is dispensed into a vial. In one embodiment, the vision measuring unit (500) may be positioned on the movement path of the dispensing unit (200) and may be positioned to capture images from below toward above while the pipette tip (1) is positioned so as to face downward. In other embodiments, a structure for capturing images from the side or from above may also be possible.
[0082] Additionally, the camera of the vision measurement unit (500) can capture an area including the end of the discharge portion of the pipette tip (1) and can extract the center position of the pipette tip (1) from the captured image. The vision measurement unit (500) can be equipped with a backlight or LED light so that the contour of the pipette tip (1) is clearly distinguishable, thereby improving the accuracy of image processing.
[0083] Additionally, the vision measurement unit (500) can analyze the captured image in real time to extract the actual position coordinates of the pipette tip (1), and calculate a horizontal error value by comparing it with a preset reference position coordinate, and the error value calculated in this way can be transmitted to the transfer unit (400) and used in the process of precise correction of the dispensing position.
[0084] Figure 3 is a diagram illustrating a method for measuring pipette tip position error using a vision measuring unit.
[0085] Referring to FIG. 3, the vision measurement unit (500) can capture the center position of the pipette tip (1) using a camera module, extract the actual position coordinates of the pipette tip (1) from the captured image, and calculate a horizontal error value by comparing the extracted actual position coordinates with a preset reference position coordinate.
[0086] In this regard, the function of calculating an error value through coordinate comparison of the vision measurement unit (500) is explained in more detail as follows. The vision measurement unit (500) applies image processing algorithms such as edge detection, binarization, and center point extraction to the captured image to obtain the center position of the dispensing part of the pipette tip (1) as a coordinate value (X) in the pixel coordinate system. actual , Y actual It can be extracted as ). Meanwhile, the system has reference position coordinates (X) when the pipette tip (1) is ideally aligned. ref , Y ref) may be pre-set and stored, and this can be determined through a calibration process.
[0087] In addition, the vision measurement unit (500) compares the actual position coordinates with the reference position coordinates to obtain an error value in the X-axis direction (ΔX = X actual - X ref ) and Y-axis direction error value (ΔY = Y actual - Y ref ) can be calculated. As illustrated in FIG. 3, if the center of the pipette tip (1) deviates horizontally from the reference position, the vision measuring unit (500) can quantitatively measure this deviation. For example, if the center of the pipette tip (1) deviates by +2mm in the X-axis direction and -1mm in the Y-axis direction relative to the reference position, the vision measuring unit (500) can calculate an error value of ΔX = +2mm and ΔY = -1mm. The calculated error value can be converted from pixel units to actual distance units (e.g., mm), which can be calculated using the resolution and magnification information of the camera.
[0088] Figure 4 is a diagram illustrating a position movement method for correcting an error calculated using a vision measurement unit.
[0089] Referring to FIG. 4, the transfer unit (400) can be controlled using an error value calculated by the vision measuring unit (500) so that the discharge position by the pipette tip (1) is aligned with the center of the opening of the vial.
[0090] In this regard, the position correction process using the error value calculated by the vision measurement unit (500) is explained in more detail as follows. The vision measurement unit (500) can transmit the calculated error value (ΔX, ΔY) to the control unit of the transfer unit (400), and the control unit can generate a movement command for the transfer unit (400) based on this. For example, if the pipette tip (1) deviates by +2mm in the X-axis direction relative to the reference position, the control unit can transmit a command to the transfer unit (400) to move the vial loading unit (300) by -2mm in the X-axis direction or to move the dispensing unit (200) by +2mm in the X-axis direction. Through this, the discharge position of the pipette tip (1) can be accurately aligned with the center of the opening of the vial.
[0091] As another example, if the pipette tip (1) has errors in both the X-axis and Y-axis directions, the transfer unit (400) can control the two axes simultaneously to perform a diagonal correction movement. The correction movement can be completed before the dispensing operation begins, and after the correction is completed, the dispensing unit (200) can discharge the culture medium into the vial. Through this position correction function, dispensing can be performed with constant accuracy for all vials despite individual dimensional deviations of the pipette tip (1), and the dispensing failure rate and the possibility of contamination can be minimized. In one embodiment, the correction accuracy can be controlled to within ±0.5 mm, which can secure a sufficient margin relative to the opening diameter of a 1 ml class small vial.
[0092] Additionally, according to one embodiment of the present invention, the vision measurement unit (500) may provide a function to improve measurement accuracy by optimizing shooting conditions. In one embodiment, the vision measurement unit (500) may analyze the brightness distribution of the image after performing an initial shot and may adjust the lighting brightness based on the analysis results. If the average brightness of the image is less than a first reference brightness (e.g., a dark image), the vision measurement unit (500) may increase the brightness of the lighting unit by a reference increase amount and then perform a re-shot.
[0093] Additionally, if the average brightness of the image exceeds a second reference brightness (e.g., an excessively bright image, where the second reference brightness is set to be greater than the first reference brightness), the vision measurement unit (500) can reduce the brightness of the lighting unit by a reference reduction amount. If the average brightness of the image is greater than or equal to the first reference brightness and less than or equal to the second reference brightness (e.g., an appropriate brightness range), the vision measurement unit (500) can maintain the current lighting conditions and proceed with position measurement.
[0094] In addition, the contrast of the image (the difference in brightness between the pipette tip area and the background) can be evaluated, and if the contrast is below the reference contrast, the brightness of the backlight can be increased or the exposure time of the camera can be adjusted. Through automatic optimization of lighting conditions, stable measurement performance can be maintained despite changes in the material, color, transparency, etc. of the pipette tip (1). The optimized lighting conditions are stored in the system and can be reused when using the same type of pipette tip (1).
[0095] The tip supply unit (600) may be a submodule of a vial filling automation system (10) configured to supply pipette tips (1) to a dispensing unit (200) and a tip rack in which pipette tips (1) are arranged.
[0096] Specifically, the tip supply unit (600) is configured to load a tip rack in which pipette tips (1) are arranged and to supply pipette tips (1) to the dispensing unit (200), and may be referred to as 'Tip & Rack'. The tip supply unit (600) may have a platform structure capable of stably fixing and positioning the tip rack, and may be configured to be placed in a fixed position or movable by a transfer unit (400). A plurality of pipette tips (1) may be inserted in the tip rack in a matrix form, and each pipette tip (1) may be received in an upright state with the mounting part facing upward and the dispensing part facing downward.
[0097] For example, the tip rack may have a structure capable of accommodating a total of 96 pipette tips (1) of a standard capacity (e.g., 5 ml) arranged in 8 rows and 12 columns. The dispensing unit (200) may move to the upper part of the tip supply unit (600), then descend to insert a nozzle into the mounting part of the pipette tip (1), and pick up the pipette tip (1) while rising. The tip supply unit (600) may be configured to load multiple tip racks, and when all the pipette tips (1) accommodated in one tip rack are exhausted, it may automatically switch to the next tip rack.
[0098] The tip alignment unit (700) may be a submodule of the vial filling automation system (10) configured to pre-align the position of the pipette tip (1) mounted on the dispensing unit (200).
[0099] Specifically, the tip alignment unit (700) can operate to first align the pipette tip (1) within a reference position range before the position measurement by the vision measurement unit (500) after the dispensing unit (200) has mounted the pipette tip (1) from the tip supply unit (600).
[0100] In this regard, according to one embodiment of the present invention, the tip alignment unit (700) is configured to pre-align the position of the pipette tip (1) mounted on the dispensing unit (200) and may be referred to as a 'Tip Aligner'. The tip alignment unit (700) can perform the function of first aligning the pipette tip (1) within a reference position range before precise position measurement and correction by the vision measurement unit (500) is performed. During the process of mounting from the tip supply unit (600), the pipette tip (1) may have an initial error in the horizontal direction of several millimeters due to deviations in the hole position of the tip rack, deviations in the mounting angle, etc., and if such initial error is excessive, it may deviate from the shooting field of view of the vision measurement unit (500) or interference with the vial may occur.
[0101] The tip alignment unit (700) can mechanically guide the pipette tip (1) to align it within a reference position range to prevent such problems. In one embodiment, the tip alignment unit (700) may have a funnel-shaped or conical guide structure that is open at the top and has a diameter that decreases toward the bottom, and when the dispensing unit (200) moves to the top of the tip alignment unit (700) and then descends, the pipette tip (1) can be aligned to the center while coming into contact with the inner wall of the guide structure.
[0102] In another embodiment, the tip alignment unit (700) may include a plurality of rollers or guide pins to align the pipette tip (1) by pushing it around the center. After the first alignment by the tip alignment unit (700) is completed, the dispensing unit (200) can move to the vision measurement unit (500) to receive precise position measurement. At this time, since the pipette tip (1) is already aligned within the reference position range, it can be stably positioned within the shooting field of view of the vision measurement unit (500), and furthermore, the error range that the vision measurement unit (500) needs to measure is reduced, so the correction accuracy can be improved.
[0103] Meanwhile, the tip alignment unit (700) can be positioned between the tip supply unit (600) and the vision measurement unit (500) on the movement path of the dispensing unit (200), thereby enabling a sequential process flow of ‘tip mounting’, ‘primary alignment’, ‘precision measurement’, ‘position correction’, and ‘dispensing’.
[0104] Additionally, according to one embodiment of the present invention, the tip alignment unit (700) can adjust the alignment level according to the initial error size of the pipette tip (1). In one embodiment, the tip alignment unit (700) may include an iris structure having a variable diameter or a plurality of elastic guide pins, and the alignment strength thereof may be controlled by pneumatic pressure, spring tension, or an electric actuator. When the dispensing unit (200) approaches the tip alignment unit (700), a preliminary sensor (e.g., a proximity sensor or a simple optical sensor) may first measure the approximate positional error of the pipette tip (1). If the measured initial error is greater than or equal to a first reference initial error (e.g., 5 mm or more), the tip alignment unit (700) may set the alignment strength to a first alignment level to provide a strong guiding action, which may be implemented by increasing the pressure of the guide pins or decreasing the diameter of the iris opening.
[0105] When the initial error is less than the first standard initial error and greater than the second standard initial error (for example, 2 mm or more and less than 5 mm, where the second standard initial error is set to be smaller than the first standard initial error), the tip alignment unit (700) can set the alignment strength to a second alignment level, where the second alignment level is set lower than the first alignment level to prevent damage to the pipette tip (1) due to excessive contact force.
[0106] When the initial error is less than the second reference initial error (e.g., less than 2 mm), the tip alignment unit (700) can set the alignment strength to a third alignment level, where the third alignment level is set lower than the second alignment level to provide only a soft guide action or skip the alignment step and move directly to the vision measurement unit (500). Through adaptive adjustment of the alignment level, optimal alignment performance and protection of the pipette tip (1) can be achieved simultaneously for various initial error ranges.
[0107] The vial opening / closing unit (800) may be a sub-module of the vial filling automation system (10) configured to open or close the caps of a plurality of vials loaded in the vial loading unit (300).
[0108] Specifically, the vial opening / closing unit (800) is configured to open or close the caps of a plurality of vials loaded in the vial loading unit (300) and may be referred to as a 'Vial (De)Capper'. The vial opening / closing unit (800) may include a mechanism for gripping the vial cap and rotating or moving it up and down to release or tighten the screw connection.
[0109] In one embodiment, the vial opening / closing unit (800) may be equipped with a plurality of grippers or chucks, and each gripper may individually grip the cap of the vial. The grippers may be opened or closed by pneumatic or electric means, and while gripping the cap, they may be rotated by a rotary motor to loosen or tighten the screw.
[0110] Additionally, the vial opening / closing unit (800) may be capable of vertical movement, descend to the top of the vial rack to grasp the cap, and after the opening / closing operation is completed, ascend to return to its original position. The vial opening / closing unit (800) may be placed inside a sealed housing (810) to be protected from external contamination, and particles generated during operation may be discharged through the exhaust unit (820). The vial opening / closing unit (800) has a structure capable of simultaneously opening and closing a row of vials in correspondence with the arrangement of the vial rack, thereby improving work efficiency.
[0111] In addition, according to one embodiment of the present invention, the vial opening / closing unit (800) may provide a function of simultaneously opening or closing the caps of a reference number of vials arranged in a row among a plurality of vials arranged in a vial rack.
[0112] Specifically, the synchronous opening and closing function of the vial opening / closing unit (800) is described more specifically as follows. The vial opening / closing unit (800) can simultaneously open or close the caps of a plurality of vials arranged in a row on a vial rack, and, for example, can simultaneously process a reference number of vials (e.g., 8 vials). To this end, the vial opening / closing unit (800) may be equipped with a plurality of grippers arranged at intervals corresponding to the row or column pitch of the vial rack. In one embodiment, when the vial rack has an 8-row, 12-column arrangement, the vial opening / closing unit (800) may have 8 grippers arranged in a row so as to simultaneously grip 8 vial caps corresponding to one column.
[0113] Additionally, each gripper can operate in synchronization, so that when descending, all grippers simultaneously grasp the cap, and when rotating, all grippers rotate in the same direction and angle to open or close the cap. For example, when opening the vial, the grippers can rotate counterclockwise by a reference angle (e.g., 180 degrees) to loosen the screw and rise to detach the cap. When closing the vial, the grippers can descend to place the cap into the vial opening, rotate clockwise by a reference angle to tighten the screw, and then rise to release the cap. The detached cap can be stored by the grippers or transferred to a separate cap storage area, and can be re-mounted on the vial after vial filling is completed.
[0114] Additionally, for processing the entire row of the vial rack, the vial opening / closing unit (800) can repeat the same opening / closing operation when the vial rack is moved to the next row by the transfer unit (400) after processing of the first row is completed. In the embodiment of the present invention, when an arrangement of 8 rows and 12 columns is applied, the vial opening / closing unit (800) can complete the opening / closing operation for a total of 96 vials by repeating the simultaneous opening / closing operation 8 vials at a time 12 times, thereby significantly reducing the work time compared to manual work.
[0115] Below, with reference to FIGS. 5 and FIGS. 6, a particle discharge structure for maintaining a clean environment of the vial filling automation system (10) will be described in detail.
[0116] Figures 5 and 6 are drawings showing a structure for maintaining a clean environment by removing particles generated from the equipment drive unit.
[0117] Specifically, FIG. 5 shows a detailed structure for maintaining a clean environment provided for the dispensing unit (200), and FIG. 6 shows a detailed structure for maintaining a clean environment provided for the vial opening / closing unit (800).
[0118] Referring to FIGS. 5 and 6, the dispensing unit (200) and the vial opening / closing unit (800) may each be equipped with a sealing housing (210, 810) that seals a working area and an exhaust unit (220, 820) that discharges particles generated inside the sealing housing (210, 810) to the outside.
[0119] Specifically, the sealed housing (210, 810) is a structure that isolates and seals a work area including a dispensing unit (200) and a vial opening / closing unit (800) from the external environment, thereby preventing contaminants such as particles, dust, and microorganisms from entering the work area or leaking out of the work area. The sealed housing (210, 810) can generally be made of materials such as stainless steel, aluminum, or transparent acrylic, and may be partially or entirely made of a transparent material so that the interior can be visually inspected. The sealed housing (210, 810) may form a closed space including the top, sides, and bottom, and may be equipped with a door or access panel that can be opened and closed as needed to enable maintenance and replacement of consumables.
[0120] According to one embodiment of the present invention, the interior of the sealed housing (210, 810) may be designed to maintain a cleanliness equivalent to that of a cleanroom environment, and, for example, an ISO Class 5 or Class 7 cleanliness standard may be applied. The sealed housing (210, 810) may be configured so that the internal pressure is maintained as positive or negative pressure relative to the outside, and this can be controlled by adjusting the airflow of the exhaust unit (220, 820).
[0121] Additionally, the exhaust unit (220, 820) is configured to discharge particles generated inside the sealed housing (210, 810) to the outside and may include a blower fan, a duct, a filter, etc. The exhaust unit (220, 820) is positioned at a specific location in the sealed housing (210, 810) to forcibly discharge internal air, thereby preventing particles from remaining in the work area or attaching to the product. In one embodiment, the exhaust unit (220, 820) may be installed at the bottom of the sealed housing (210, 810), thereby effectively collecting and discharging particles descending due to gravity.
[0122] For example, the exhaust unit (220, 820) may be equipped with a HEPA (High Efficiency Particulate Air) filter or an ULPA (Ultra Low Penetration Air) filter to capture particles in the discharged air, thereby maintaining the cleanliness of the external cleanroom environment. The airflow volume of the exhaust unit (220, 820) may be adjustable, and an optimal airflow may be formed according to working conditions. For example, during a dispensing operation, the airflow volume may be increased to immediately discharge generated particles, and during a standby state, the airflow volume may be reduced to save energy.
[0123] Additionally, according to one embodiment of the present invention, the exhaust unit (220, 820) can differentially adjust the exhaust airflow according to each stage of the vial filling process. In one embodiment, the system can identify the current work stage and apply an exhaust profile optimized for each stage. In the vial opening and closing stage, since the amount of particle generation is relatively large due to the opening and closing operation of the cap, the exhaust unit (820) can set the airflow to a first reference airflow. In the vial filling stage, since particles and droplets are generated due to the lifting operation of the dispensing unit (200) and liquid discharge, the exhaust unit (220) can set the airflow to a second reference airflow, where the second reference airflow can be set to be similar to or slightly lower than the first reference airflow.
[0124] In particular, at the moment when liquid discharge begins, the airflow volume can be instantaneously increased to a third standard airflow volume, where the third standard airflow volume can be set to be greater than the second standard airflow volume. Additionally, since particles are generated due to friction of the guide rail during the movement phase of the transfer unit (400), the exhaust unit (220) can set the airflow volume to a fourth standard airflow volume, where the fourth standard airflow volume can be set to be smaller than the second standard airflow volume.
[0125] Since particle generation is minimal during the standby phase, the exhaust unit (220, 820) can reduce the airflow to a fifth standard airflow, where the fifth standard airflow is set to be smaller than the fourth standard airflow to save energy and reduce noise. Additionally, a particle sensor can be provided inside the sealed housing (210, 810) to measure the particle concentration in real time, and if the measured particle concentration exceeds the standard particle concentration, the airflow can be automatically increased to restore cleanliness. Through differential exhaust control, energy efficiency can be improved while providing exhaust performance optimized for the characteristics of each work stage.
[0126] Specifically, referring to FIG. 5, the exhaust section (220) of the dispensing section (200) may be equipped with an exhaust fan (222) installed at the bottom of the sealed housing (210) to discharge particles generated from a dust source (221) downward.
[0127] To explain the exhaust structure on the side of the dispensing unit (200) in more detail, a dust source (221) may exist inside the sealed housing (210), which may mainly originate from mechanical drive parts such as a linear guide, ball screw, and motor that drive the lifting movement of the dispensing unit (200). Since the dispensing unit (200) performs a repetitive lifting motion in the vertical direction, fine metal or plastic particles may be continuously generated due to friction between the guide rail and the slider, friction between the ball screw and the nut, etc.
[0128] The exhaust fan (222) is positioned at the bottom of the sealed housing (210) to suck in and discharge these particles downward. In one embodiment, the exhaust fan (222) may be located directly below the dust source (221), thereby allowing the particles to be collected immediately upon generation. A laminar flow may be formed inside the sealed housing (210) from top to bottom, which allows the particles to rapidly descend due to gravity and airflow and enter the exhaust fan (222).
[0129] Additionally, the air discharged by the exhaust fan (222) can be introduced into a filter through a duct, and after particles are removed, it can be discharged to the outside or recirculated. The exhaust structure on the dispensing part (200) side can also collect liquid droplets (aerosol) that may be generated during the process of the pipette tip (1) sucking up and dispensing the culture medium, thereby maintaining a high level of cleanliness in the work area.
[0130] Likewise, referring to FIG. 6, the exhaust section (820) of the vial opening / closing section (800) may be equipped with an exhaust fan (822) installed at the bottom of the sealed housing (810) to discharge particles generated from a dust source (821) downward.
[0131] To explain the exhaust structure on the side of the vial opening / closing part (800) in more detail, dust source (821) may exist inside the sealed housing (810), and this may mainly occur in mechanical drive parts such as pneumatic cylinders, rotary motors, and guide mechanisms that drive the gripper opening / closing, rotational, and lifting movements of the vial opening / closing part (800).
[0132] In particular, particles may be generated during the process in which the vial opening / closing part (800) grips and rotates the cap due to contact with the cap surface, wear of the gripper pad, etc., and, for example, in the case of a plastic cap, fine plastic dust may be generated due to friction. The exhaust fan (822) is positioned at the bottom of the sealed housing (810) to suck these particles downward and discharge them.
[0133] In one embodiment, the working area of the vial opening / closing unit (800) may include an area where a vial rack is located, and the exhaust fan (822) may be located at the bottom of the vial rack to prevent particles generated during the vial opening / closing process from falling into the vial. Inside the sealed housing (810), a local strong suction airflow may be formed around the dust source (821) to quickly capture particles generated during the vial opening / closing operation, and this can be implemented by optimizing the shape and placement of the suction port of the exhaust fan (822).
[0134] The air discharged by the exhaust fan (822) can be discharged to the outside after passing through a filter to remove particles. The exhaust structure on the side of the vial opening / closing part (800) may include a control logic that automatically increases the discharge air volume at the time when the opening / closing operation occurs intensively, thereby enabling the most effective exhaust to be achieved at the moment when particle generation is at its maximum.
[0135] A method for operating a vial filling automation system according to one embodiment of the present invention may be implemented in the form of program instructions that can be executed through various computer means and recorded on a computer-readable medium. The computer-readable medium may include program instructions, data files, data structures, etc., either individually or in combination. The program instructions recorded on the medium may be those specifically designed and configured for the present invention, or may be those known and available to those skilled in the art of computer software. Examples of computer-readable recording media include magnetic media such as hard disks, floppy disks, and magnetic tapes; optical recording media such as CD-ROMs and DVDs; magneto-optical media such as floptical disks; and hardware devices specifically configured to store and execute program instructions, such as ROM, RAM, and flash memory. Examples of program instructions include machine code, such as that generated by a compiler, as well as high-level language code that can be executed by a computer using an interpreter, etc. The hardware devices described above may be configured to operate as one or more software modules to perform the operation of the present invention, and vice versa.
[0136] In addition, the method of operating the aforementioned vial filling automation system may also be implemented in the form of a computer program or application executed by a computer stored on a recording medium.
[0137] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical concept or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.
[0138] The scope of the present invention is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and the concept of equivalents thereof should be interpreted as being included within the scope of the present invention.
[0139] [Explanation of the symbol]
[0140] 10: Automated vial filling system
[0141] 100: Culture medium storage section
[0142] 200: Busy Housewife
[0143] 210: Sealed housing
[0144] 220: Exhaust section
[0145] 221: Dust source
[0146] 222: Exhaust fan
[0147] 300: Vial loading section
[0148] 400: Transfer unit
[0149] 500: Vision Measurement Unit
[0150] 600: Tip supply unit
[0151] 700: Tip alignment section
[0152] 800: Vial opening / closing part
[0153] 810: Sealed housing
[0154] 820: Exhaust section
[0155] 821: Dust source
[0156] 822: Exhaust fan
[0157] 1: Pipette tip
Claims
1. In a vial filling automation system, A culture medium storage unit in which a conical tube containing a culture medium containing cultured cells is loaded; A dispensing unit equipped with a pipette tip, which draws culture medium from the culture medium storage unit and dispenses it into a vial; A vial loading section in which a vial rack with multiple vials arranged thereon is loaded; A transfer unit that changes the relative position between the dispensing unit, the culture medium storage unit, and the vial loading unit; and A vision measuring unit that measures the position of a pipette tip mounted on the dispensing unit, calculates an error between the measured position and a reference position, and controls the transfer unit to move the dispensing unit by correcting the error, A vial filling automation system including 2. In Paragraph 1, The above vision measurement unit is, The method involves using a camera module to capture the center position of the pipette tip, extracting the actual position coordinates of the pipette tip from the captured image, and calculating a horizontal error value by comparing the actual position coordinates with a preset reference position coordinate. The above transfer unit is, A vial filling automation system that controls the discharge position by the pipette tip using the error value so that it is aligned with the center of the opening of the vial.
3. In Paragraph 1, A tip supply unit configured to supply the pipette tips to the dispensing unit, wherein a tip rack on which the pipette tips are arranged is loaded. A vial filling automation system that further includes 4. In Paragraph 3, Tip alignment unit for pre-aligning the position of the pipette tip mounted on the dispensing unit, A vial filling automation system that further includes 5. In Paragraph 4, The above tip alignment part is, A vial filling automation system characterized by the dispensing unit aligning the pipette tip within a reference position range after mounting the pipette tip from the tip supply unit and before position measurement by the vision measuring unit.
6. In Paragraph 1, A vial opening / closing unit configured to open or close the caps of the plurality of vials loaded in the above-mentioned vial loading unit, A vial filling automation system that further includes 7. In Paragraph 6, The above vial opening and closing part is, A vial filling automation system that simultaneously opens or closes the caps of a reference number of vials arranged in a row among the plurality of vials arranged in the above-mentioned vial rack.
8. In Paragraph 6, The above dispensing unit and the above vial opening / closing unit are each, A vial filling automation system comprising a sealed housing that seals a work area and an exhaust unit that discharges particles generated inside the sealed housing to the outside.
9. In Paragraph 8, The above exhaust section is, A vial filling automation system having a discharge fan installed at the bottom of the above-mentioned sealed housing to discharge the particles downward.