Automated orbital incubator oscillator compartment

Abstract

The invention relates to a kit for holding and transporting at least one cell culture flask, which is arranged in at least one cell culture flask holder (2, 12), as well as to a method and to the use thereof. The invention relates to an orbital incubator oscillator comprising a kit (7) of the invention, and to cell culture flask holders (2, 12) compatible with such a kit.

Description

Technical Field

[0001] The present invention relates to the field of cell culture platforms, and in particular to an automated cell culture platform comprising a shaker incubator and a device for handling laboratory appliances in the automated cell culture platform. In particular, the present invention relates to an automated incubator shaker compartment for an automated culture platform. Background Art

[0002] Cell culture refers to laboratory methods that enable eukaryotic or prokaryotic cells to grow under physiological conditions. Cell culture is a method used to study, for example, tissue growth and maturation, viral biology and vaccine development, the role of genes in disease and health, and the production of biopharmaceuticals using large-scale hybrid cell lines. The experimental applications of cultured cells are as diverse as the types of cells that can be grown in vitro. A specific example of a cell culture method is cell passaging (or subculturing), which involves removing the culture medium and transferring the cells from the previous culture medium to fresh growth medium. This procedure enables the cell line or cell strain to propagate further.

[0003] Cell culture methods require the use of specialized laboratory equipment and precise multi-step cell manipulation. Manual procedures are difficult to pass GMP (Good Manufacturing Practice) and GLP (Good Laboratory Practice) and should not generally be used in biotech or pharmaceutical companies. Therefore, some processes / steps of cell culture are automated. An example of an automated cell passaging platform is the microwell plate (MTP) culture format, as described by the University of Luxembourg (Automated Cell Culture Maintenance and High-Throughput / High-Content Screening Platform;

[0004] https: / / wwwen.uni.lu / lcsb / research / translational_neuroscience / automation_platform). This is an example of a high-throughput / high-content platform used to maintain induced pluripotent stem cells in culture, differentiate these cells into neurons, and simultaneously perform chemical genetic screens or viral vector-based genetic screens.

[0005] The example of the device for cell culture is an oscillating incubator (or oscillator incubator), which is a laboratory device that allows cell culture to be cultivated and oscillated. A typical incubator oscillator at least includes a chamber equipped with a door, an oscillating tray equipped with a motor, and a device for oscillation control, as well as a device for temperature control. The loading and unloading of the oscillating tray is usually carried out manually, and includes opening the door. In order to further reduce the manual operation of the oscillating laboratory equipment, the process can be automated so that the door of the incubator is automatically opened and closed, and a manipulator placed outside the incubator can perform the loading and unloading of the oscillating tray. The automated process is usually compatible with a type of laboratory equipment, which is usually a microplate (MTP). In this example, the loading and unloading of the oscillating tray must be carried out when the door is open, and the manipulator imitates the manual action of manipulation, such as the manual action of manipulating the MTP. The cell culture in the incubator needs to maintain the temperature, humidity and composition of the specified gas environment in the incubator. If the incubator is opened during cultivation, the temperature, humidity and composition of the gas environment in the incubator and therefore the culture may change, and negatively affect the cell.

[0006] Furthermore, typically, the shaking incubator may be provided with a universal tray which may be equipped with: fixtures for labware, such as for conical flasks; test tube holders; microplates; or other custom holders fixed to the tray. In another example, such a tray may be equipped with pins so that the flasks are fixed in place by these pins. In another example, such a tray may be equipped with an adhesive strip, wherein the labware is placed directly on the adhesive strip without any other support. Such solutions are mostly incompatible with loading and unloading of the shaking tray performed with an automated manipulator.

[0007] It is an object of the present invention to reduce the manual handling of shaking cultures and to provide improved devices and methods for automated cultivation and handling of cell cultures contained in suitable laboratory appliances for cell cultivation.

[0008] Document CN 112940917 discloses a robot for manipulating culture bottles. These culture bottles are in the shape of culture dishes and are moved individually by a robot into a frame mounted on a device that can rotate and shake.

[0009] Document JP 2009284810 describes an incubator equipped with a lock and a heated conveyor for transporting containers containing culture samples kept growing in a static environment. A robot is able to move the containers in and out of the heated chamber while preventing changes in the culture conditions. Summary of the invention

[0010] The above documents do not respond to the manipulation of suspension cells cultured in individual conical flasks or tubes mounted on flask holders or tube holders adapted for orbital motion within an orbital shaker incubator.

[0011] The present invention is based on the selection of the favorable laboratory equipment for keeping cell culture, preferably, the laboratory equipment is used for using in the cell passage method of suspension cell culture.Especially, conical flask or bioreactor tube are suitable laboratory equipment for keeping suspension cell culture.The particularity of suspension culture is to need stirring, to avoid cell sedimentation to the bottom of flask.Although adherent cell culture can be maintained in a flat and static flask with a large surface area (to promote cell adhesion), suspension culture needs stirring, otherwise cells will be deposited to the bottom of flask, which greatly affects cell acquisition of nutrition and oxygen, and eventually causes cell death.Therefore, special flask (for example, including oscillator flask and rotator flask) is used to stir culture medium and keep cell suspension.The common point of these flasks is to have a circular footprint, thereby allowing the orbital motion of the oscillator to produce eddy current motion.

[0012] The present invention is based on the provision of specific laboratory equipment for maintaining cells cultured therein (e.g. Figure 1 Flask (1) as shown; or Fig. 9 The flask has a circular footprint and is designed for suspension cell culture. Cell suspension culture simply multiplies single cells at a higher rate in a liquid culture medium. The liquid culture medium is continuously stirred on an orbital shaker. Scientists use this culture method to study the growth and development of cells. The present invention is based on providing an automation kit (7) for holding and transporting cell culture laboratory equipment (e.g., flasks, bioreactor tubes), which automation kit (7) is suitable for an orbital culture shaker compartment and includes a culture shaker tray (3), a three-axis motorized platform (4), a sliding door (5) and a transfer shuttle (6) ( Figure 7 The invention relates to an orbital shaking incubator having an interior space in which a plurality of baskets for suspension cell culture labware (e.g., flasks, bioreactor tubes) can be arranged on an shaking tray. The orbital shaking incubator has a chamber designed to be arranged with a set of holders for holding and transporting cell culture labware (e.g., flasks, bioreactor tubes). The invention is particularly suitable for use in automated cell passaging platforms.

[0013] The present invention allows, via a cell culture labware holder removably connected to a shaking tray, the manipulation of labware containing suspension cell cultures individually and independently of one another in an orbital shaker incubator. The present invention is designed for suspension cultures. Cell suspension or suspension culture is a type of cell culture in which cells are grown in a stirred growth medium, thereby forming a suspension.

[0014] In the case of multiple cultures being cultured in parallel in an orbital shaker incubator, one of the flask holders is removed from the incubator via the kit of the present invention with limited impact on the environment of the cultures in other labware. Although the temperature changes slightly when the automated sliding door of the kit is opened, this small temperature change has little or no impact on the cultures in other labware. The kit of the present invention facilitates loading and unloading of the shaking tray, thereby improving the ergonomic handling of the cultures.

[0015] In one embodiment, a kit is provided for holding and transporting at least one cell culture flask, wherein the kit is designed to be disposed in an orbital incubator shaker chamber, and the kit comprises:

[0016] - a flask holder designed to receive at least one cell culture flask having a circular footprint and suitable for suspension cell culture,

[0017] - an incubator shaker tray designed to be mounted inside an orbital incubator shaker chamber, the incubator shaker tray comprising at least one guide element arranged for holding each cell culture flask holder,

[0018] - an orbital incubator shaker tray for receiving the flask holders and imparting orbital motion to the flask holders,

[0019] a three-axis motorized platform designed to be mounted on the inside of the top wall of the orbital incubator shaker chamber, comprising an X-axis, a Y-axis and a Z-axis, and three linear motors for driving the three axes and a device for grabbing a cell culture flask holder,

[0020] - a sliding door designed to be mounted in a side wall of the orbital incubator shaker chamber, the sliding door comprising a door panel and at least one motor for driving the movement of the door,

[0021] - A transfer shuttle designed to be mounted on the outside of the side wall of the orbital incubator shaker chamber, the transfer shuttle comprising a sliding frame, a track, at least two conveyor belts arranged on the sliding frame, a cell culture flask holder plate and a motor for driving the sliding movement of the plate on the track.

[0022] In another embodiment, a kit for holding and transporting at least one suspension cell culture flask according to the present invention is provided, wherein the cell culture flask is a 125 ml Erlenmeyer flask or a bioreactor tube having a circular footprint.

[0023] In another embodiment, a kit according to the present invention is provided, wherein the device for grasping a cell culture flask holder is attached to the Z-axis of the three-axis motorized platform, and the device for grasping the cell culture flask holder comprises a parallel gripper having an adjustable gripping force and equipped with claws and fingers for detachable connection with the flask holder.

[0024] In another embodiment, a kit according to the present invention is provided, wherein a motor for driving door movement of a sliding door comprises a stepper motor for driving sliding movement of a door panel and a stepper motor for driving pressing movement of the door panel.

[0025] In another embodiment, a kit according to the present invention is provided, wherein the sliding door further comprises a precision sensor for detecting a sliding movement of the door panel and a precision sensor for detecting a pressing movement of the door panel.

[0026] In another embodiment, a kit according to the present invention is provided, wherein the sliding door further comprises a temperature probe, a heating mat, a heating tape and a controller, and wherein the temperature probe controls the heating mat and the heating tape via the controller.

[0027] In another embodiment, a kit according to the present invention is provided, wherein the sliding door further comprises a silicone o-ring mounted between the door frame and the door panel.

[0028] In another embodiment, a kit according to the present invention is provided, wherein the transfer shuttle also includes an amplified precision sensor for detecting the origin position of the transfer shuttle, a sensor for detecting the loading position of the cell culture flask holder, and a sensor for detecting the unloading position of the cell culture flask holder.

[0029] In another embodiment, a set according to the present invention is provided, which also includes a cell culture flask holder, and the cell culture flask holder includes a base, two handles arranged perpendicular to the base and opposite to each other, a locking device for holding the cell culture flask, and a thermally conductive pad arranged on the base of the holder.

[0030] In another embodiment, a set according to the present invention is provided, wherein the cell culture flask holder further comprises at least two magnets, which are arranged on the outside of the base of the cell culture flask holder and provide attachment means to an incubator shaker, which incubator shaker comprises a permanent electromagnet.

[0031] In another embodiment, a kit according to the invention is provided, wherein the locking device of the cell culture flask holder comprises a clamping device arranged on the base of the cell culture flask holder and a safety latch.

[0032] In another embodiment, a set according to the invention is provided, wherein the locking device of the cell culture flask holder comprises four blades, each blade being provided with a toothed jaw and being arranged on the base of the cell culture flask holder.

[0033] In another embodiment, there is provided a use of a kit according to the invention for holding and transporting at least one cell culture flask arranged in at least one cell culture flask holder compatible with the kit.

[0034] In another embodiment, an incubator shaker is provided, the incubator shaker comprising a kit according to the present invention.

[0035] In another embodiment, an automated cell passaging platform is provided, which includes a liquid handling system, at least one robot, at least one automated storage system (hotel), an automated refrigerated incubator, an automated microplate centrifuge with an automated loader, a cell counting device and at least one orbital shaker incubator, and optionally an automated orbital shaker incubator, characterized in that at least one orbital shaker incubator is designed to be arranged together with a kit for holding and transporting at least one cell culture flask according to the present invention.

[0036] The above documents (CN 112940917 and JP 2009284810) do not respond to the manipulation of suspension cells cultured in individual conical flasks or tubes mounted on a flask holder or tube holder adapted for orbital motion within an orbital shaker incubator. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1An example of a flask basket for a 125 ml conical flask is shown; pictures A, D, and E are shown as drawings; pictures B and C are shown as photographs. The flask basket (2) for a 125 ml conical flask (1) includes a base (2.1), two handles (one handle-2.2), a heat conductive pad (2.3), a toothed elastic member having a horseshoe shape (2.4), a safety latch (2.5), a latch magnet (2.6), a latch protrusion (2.7), an anti-magnetic pad (2.8), and an RFID tag or a QR code (2.9).

[0038] Figure 2 An example of an incubator shaker tray (3) is shown. Picture A shows a lower plate (3.1) with eighty permanent electromagnets (3.4). Picture B shows the assembled lower plate (3.1) and upper plate (3.2) (tray lock 3.3 not shown). The upper plate (3.2) has eighty centering pins (3.5) and forty RFID antenna holes (3.6). Picture C shows an incubator shaker tray (3) with forty flask holders (2) for 125 ml conical flasks (1) and arranged in an 8×5 array.

[0039] Figure 3 An example of a three-axis motorized platform (4) is shown, which includes an X-axis (4.1), a Y-axis (4.2), a Z-axis (4.3), a linear motor (4.4) (not visible) for driving the X-axis (4.1), a linear motor (4.5) (not visible) for driving the Y-axis (4.2), a linear motor (4.6) (not visible) for driving the Z-axis (4.3), and a parallel gripper (4.7) with claws (4.8) and fingers (4.9).

[0040] Figure 4 An example of a sliding door (5) is shown. Picture A shows an example of a sliding door (5), which includes a door frame (5.1) and a door panel (5.2), a door channel (5.3), a stepper motor (5.4) driving a sliding movement and a stepper motor (5.5) driving a pressing movement, a precision sensor for sliding movement (5.6) and a precision sensor for pressing movement (5.7), a temperature probe (5.8) (not visible), a heating pad (5.9) (not visible), an o-ring (5.10) (not visible; in Figure 4 D or Figure 6 Figures B to D show the three parts of the door panel (5.2), namely the front panel (5.2.1) ( Figure 4 B shows an external view of the open sliding door), the main body (5.2.2) ( Figure 4 C shows the central part of the open sliding door) and the pressing plate (5.2.3) ( Figure 4 D).

[0041] Figure 5 An example of a transfer shuttle (6) is shown, which includes a sliding frame (6.1) with two upper rails (6.2) and two lower rails (6.2), a stepper motor (6.3) driving the sliding movement, a gear (6.4) (not visible), a flask holder plate (6.5), a flask holder plate (6.5) with two centering pins (6.6) (not visible), an amplified precision sensor (6.7) for detecting the origin position of the transfer shuttle, a sensor (6.8) for detecting the loading position of the flask holder and a sensor (6.9) for detecting the unloading position of the flask holder, a laser detector (6.10), a conveyor belt (6.11) (not visible; in FIG. Figure 6 A), double extension plate (6.12), and ball screw (6.13) (not visible).

[0042] Figure 6 An example of a transfer shuttle (6) is shown that is designed to be mounted outside the side wall of an orbital incubator shaker chamber, below a sliding door (5). Picture A shows the conveyor belt (6.11) of the transfer shuttle (6), and picture C shows the o-ring (5.10) of the sliding door (5).

[0043] Figure 7 An example of a kit (7) for holding and transporting cell culture flasks designed to be mounted in an orbital incubator shaker chamber (chamber indicated as a shaded outline) is shown, the kit (7) comprising an incubator shaker tray (3), a three-axis motorized stage (4), a sliding door (5) and a transfer shuttle (6).

[0044] Figure 8 An example of an arrangement of a culture shaker (8) comprising a kit (7) of the present invention within an automated cell passaging platform is shown, wherein the automated orbital shaker culture is integrated with a liquid handling system (9) through a hole / window drilled in the wall of a rear cabinet (not shown) and connected to the liquid handling system (9) via a transfer shuttle (6) (Image A). Image B shows a sliding door (5) and a transfer shuttle (6) for transporting flask holders to the liquid handling system (9) as seen on the outside of the side wall of the culture shaker.

[0045] Fig. 9An example of a flask basket (12) for 50 ml bioreactor tubes (11) with locking devices (10) for four bioreactor tubes is shown. Figures A and B are shown as drawings. The flask basket (12) for 50 ml bioreactor tubes includes four gate knives (10.1), eight toothed jaws (10.2), four track-and-pivots (10.3) (pivots not visible), plungers (10.4), plunger holders (10.5), eccentric clamps (10.6), control latches (10.7), and RFID tags or QR codes (2.9) (not shown).

[0046] List of reference numerals:

[0047] 1. Flask (e.g., 125 ml conical flask); 1.1. Lid (e.g., 125 ml conical flask lid); 2. Flask basket; 2.1. Base of flask basket; 2.2. Handle of flask basket; 2.3. Thermal pad for flask basket; 2.4-2.7. Locking device for conical flask; 2.4. Horseshoe-shaped toothed elastic member of flask basket; 2.5. Safety latch; 2.6. Latch magnet; 2.7. Latch protrusion; 2.8. Anti-magnetic pad; 2.9. RFID tag or QR code; 3. Incubator tray; 3.1. Lower plate; 3.2. Upper plate; 3.3. Tray lock; 3.4. Permanent electromagnet; 3.5. Centering pin; 3.6. RFID antenna hole; 4. Three-axis electric platform; 4.1. X-axis; 4.2. Y-axis; 4.3. Z-axis; 4.4. Linear motor for X-axis (4.1); 4.5. Linear motor for Y-axis (4.2); 4.6. Linear motor for Z-axis (4.3); 4.7. Parallel gripper; 4.8. Claws of parallel gripper; 4.9. Fingers of parallel gripper; 5. Sliding door; 5.1. Door frame; 5.2. Door panel; 5.2.1. Front panel of door panel; 5.2.2. Main body of door panel; 5.2.3. Pressing plate of door panel; 5.3. Door channel; 5.4. Stepping motor for driving sliding motion; 5.5. Stepping motor for driving pressing motion; 5.6. Precision sensor for sliding motion sensor; 5.7. precision sensor for pressing movement; 5.8. temperature probe; 5.9. heating pad; 5.10. o-ring; 5.11. heating belt; 6. transfer shuttle; 6.1. sliding frame; 6.2. upper and lower rails; 6.3. stepper motor driving sliding movement; 6.4. gear; 6.5. flask holder plate; 6.6. two centering pins of the flask holder plate; 6.7. amplified precision sensor for detecting the origin position of the transfer shuttle; 6.8. sensor for detecting the loading position of the flask holder; 6.9. sensor for detecting the unloading position of the flask holder; 6.10. presence of laser detector; 6.11. conveyor belt; 6.12. double extension plate ;6.13. Ball screw; 7. Kit for holding and transporting at least one cell culture flask; 8. Culture incubator shaker comprising the kit of the present invention; 9. Liquid handling system; 10.1-10.7. Locking device for four bioreactor tubes; 10.1. Gate knife; 10.2. Toothed claw; 10.3. Track-and-pivot; 10.4. Plunger; 10.5. Plunger holder; 10.6. Eccentric clamp; 10.7. Control latch; 10.8. Side heat conductor; 10.9. Bottom heat conductor; 10.10. Anti-magnetic pad; 11. Bioreactor tube; 11.1. Bioreactor tube cover (e.g., filter cover); 12. Flask basket for bioreactor tube. DETAILED DESCRIPTION

[0048] The term "orbital shaking incubator" or "orbital shaker incubator" or "orbital incubator shaker" (these terms can be used interchangeably) refers to a laboratory device that combines the incubation function with the orbital shaking function. A typical orbital incubator shaker comprises at least a chamber (preferably, the chamber is made of stainless steel or painted stainless steel), a door (here a main door) including a door glass and a door frame, a tray, a motor for making the tray perform an oscillating motion, a device for oscillation control (e.g., speed, frequency), a device for heating / cooling, and a device for temperature (heating / cooling) control. In addition, the incubator shaker may include a device for regulating humidity and a device for humidity control, a device for regulating CO 2 Horizontal device and for CO 2 The invention relates to a kind of oscillator for the invention. The oscillator can be used for various applications in the fields of biology, chemistry, biochemistry, pharmacology, etc., including but not limited to any type in cell culture (including bacterial culture, tissue culture and yeast culture), protein expression, solubility research or general mixing. According to laboratory settings and specified uses, the scope of oscillator incubator can be from compact desktop system to large capacity, stackable system on the floor, etc., with various devices for temperature control and a device for oscillation speed control. The application is developed around track incubator oscillator, and the track incubator oscillator has a tray, which is used to receive flask holder and pass orbital motion to flask holder, and the track oscillating motion has a slow speed (25rpm to 500rpm).

[0049] The term "flask" or "oscillator flask" refers to a specific type of flask for suspension culture that is suitable for orbital oscillators. What these flasks have in common is a circular footprint in which an orbital (or circular) motion increases the surface area at the top of the liquid to maximize gas exchange between the liquid and the air. An oscillator flask can be an Erlenmeyer flask, also known as a conical flask or titration flask, characterized by a flat bottom, a conical body, and a cylindrical neck. Another example of an oscillator flask can be a French flask, which has a baffle at the bottom to maximize oxygen transfer to the culture medium during oscillation. Another example of an oscillator flask can be a bioreactor tube, which can be conical at the bottom and allow a smaller working volume of 1 ml to 15 ml.

[0050] The term "suspension cell culture" refers to the process in which cells grow under controlled conditions outside their natural environment. Cell suspension or suspension culture is a type of cell culture in which cells are grown in a stirred growth medium to form a suspension. Cells cultured in the laboratory can be classified into three different types: primary cells, transformed cells, and self-renewing cells. Common manipulations performed on cultured cells include medium replacement, cell passage, and cell transfection. "Passage" (also referred to as subculture or cell splitting) involves transferring a small amount of cells to a new container. If cells divide regularly, cells can be cultured for longer periods of time because this avoids the aging associated with long high cell densities.

[0051] Cell passaging can be performed using an automated cell passaging platform. Exemplary automated cell passaging platforms may include:

[0052] - Liquid handling systems (such as Hamilton's VANTAGE 2.0 Liquid Handling System),

[0053] - at least one robot (such as Precise's PF400 Extended),

[0054] - at least one automated storage system (such as Liconic's LPX740),

[0055] - Automated refrigerated incubators (such as Liconic's STX44-HCBT),

[0056] - optionally, an automated cryogenic freezer (such as Liconic's STX88-DFMISA),

[0057] - an automated microplate centrifuge with automated loader (such as Agilent),

[0058] - a cell counting device (such as the Rxn2-785 Raman spectrometer from Kaiser / Endress & Hauser), and

[0059] - At least one (up to four) orbital shaker incubator (such as Kühner's ISF1-ZC Peltier).

[0060] Flask holder

[0061] The present invention is based on the selection of favorable laboratory equipment for maintaining cell culture, preferably, the laboratory equipment is used for use in the cell passage method of seed strain culture. In particular, conical flasks are suitable laboratory equipment for maintaining cell culture. Preferably, the conical flask of 125ml specification provides enough volume of cell culture for required cell culture application (20ml). However, conical flasks are considered to be high laboratory equipment, such as higher than microplates. The size of conical flasks is incompatible with known automated laboratory equipment. However, compared with the form of deep well plates, conical flasks limit the risk of cross contamination. Preferably, conical flasks are sterile, baffled and threaded flasks with 0.2μm PTFE (polytetrafluoroethylene) vent caps (i.e., filter caps) for increasing ventilation, and conical flasks can provide the best growth of selected cell lines. Another suitable piece of labware for holding cell cultures is a bioreactor tube that is sterile and is a threaded tube with a 0.2 μm PTFE vent cap (ie, filter cap).

[0062] In one embodiment, a holder for a flask is provided, such as a 125 ml conical flask (1). In this article, the flask holder is referred to as a basket. The terms "(oscillator) flask holder" and "(oscillator) flask basket" can be used interchangeably. In particular, the laboratory equipment of cell culture can be a flask, and the laboratory equipment holder (basket) of cell culture is a flask holder (basket). Since the flask holder is arranged in an orbital oscillator incubator, the flask holder can be referred to as an oscillator flask holder in this article.

[0063] In one embodiment, the flask holds a CHO-M (Chinese Hamster Ovary) seed cell line (Selexis).

[0064] In one embodiment, a flask holder is provided, the side dimensions of which can be a width of 87.26 ± 0.07 mm and a length of 85.64 ± 0.08 mm. The use of the flask holder of this size is compatible with other automated laboratory equipments known to be compatible with MTP laboratory equipment, such as the MTP platform of a VANTAGE 2.0 liquid handling system (Hamilton). Therefore, the flask holder described herein is matched with the size defined by the Society for Biomolecular Screening (SBS) for standard plates.

[0065] In one embodiment, a flask holder (2) is provided, which comprises at least a base (2.1), two handles (2.2), a heat conductive pad (2.3), a locking device (such as a combination of 2.4, 2.5, 2.6, 2.7). The flask holder (2) may also include an anti-magnetic pad (2.8) and an identification device (2.9).

[0066] Possible elements of a flask holder can be described as follows.

[0067] -Base(2.1)

[0068] In one embodiment, the flask holder has a base that supports other elements of the holder, such as two handles (2.2), a heat conductive pad (2.3), a toothed elastic member with a horseshoe shape (2.4), a safety latch (2.5), a latch magnet (2.6), a latch protrusion (2.7), an anti-magnetic pad (2.8), and an RFID tag or QR code (2.9). In one embodiment, the base can be as Figure 1 As shown in AE.

[0069] In one embodiment, preferably, the base is made of PEEK polymer (polyetheretherketone polymer). Typically, PEEK polymer is used to prevent corrosion inside the incubator shaker compartment.

[0070] -Handle (2.2)

[0071] In one embodiment, one or two handles are arranged on the base of the flask holder. Preferably, two handles are arranged on the base of the flask holder so that the handles are perpendicular to the base and the handles are opposite to each other.

[0072] In one embodiment, the handle is rectangularly shaped, preferably hollow, wherein at least one edge is shaped to provide a gripping edge compatible with a gripping device, such as a gripping device of a three-axis electric platform or a four-axis collaborative robot. In another embodiment, the handle is rectangularly shaped, preferably hollow, wherein at least one edge is convex to provide a gripping edge compatible with a gripping device, such as a gripping device of a three-axis electric platform or a four-axis collaborative robot. The shape of the handle enables gripping by a gripping device (such as a gripping device of a three-axis electric platform (4.7) or a gripping device of a four-axis collaborative robot), which may be referred to herein as a gripping handle.

[0073] The handle may be attached to the base by any attachment means, such as screws.

[0074] In one embodiment, the handle is preferably made of hard anodized aluminum alloy. Typically, hard anodized aluminum alloys are used to prevent corrosion inside the incubator shaker compartment.

[0075] In one embodiment, the two handles may be Figure 1 The arrangement shown in AE.

[0076] In one embodiment, the handle height can be modified to accommodate labware of varying heights and still allow grasping.

[0077] -Thermal pad (2.3)

[0078] In one embodiment, the thermally conductive pad is mounted within a hollow cylindrical opening on the base of the flask holder, and the thermally conductive pad is disposed below the bottom of the flask.

[0079] In one embodiment, the thermal pad (2.3) can be as follows Figure 1 As shown in E. Fig. 9 A and Fig. 9 Another embodiment is shown in B.

[0080] The thermally conductive pad is arranged to provide direct heating to a flask placed in the flask holder.

[0081] A thermally conductive pad is an example of a way to provide heat to a flask placed in a flask holder.

[0082] The thermal pad is made of a heat-conducting material that conducts heat, preferably, the thermal pad is made of a material with high thermal conductivity such as metal. When the material is placed on a heated surface, heat transfer occurs, so that the material is conducive to heat exchange with, for example, a flask.

[0083] In one embodiment, preferably, the thermal pad is made of hard anodized aluminum alloy.

[0084] exist Figure 1 In the example shown at E, the thermal pad 2.3 is placed on the base of the flask holder and is designed to contact the bottom flat surface of the flask. Heat is transferred from the tray to the flask via the thermal pad 2.3.

[0085] In another embodiment, the thermally conductive pad (10.9) extends on the side of the flask. Fig. 9 In the example shown at A of , four side heat conductors (10.8) are connected to the bottom pad (10.9), and the four side heat conductors (10.8) provide heat along the sides of the flask. It should be noted that the side heat conductors (10.8) can be used for a basket with one conical flask, or for a basket with four tubular flasks, such as Fig. 9 shown.

[0086] - Locking device (for flasks, the locking device is a combination of 2.4, 2.5, 2.6, 2.7; or for bioreactor tubes, the locking device is a combination of 10.1, 10.2, 10.3, 10.4, 10.5, 10.6, 10.7)

[0087] In one embodiment, the locking means is arranged on the base of the flask holder.

[0088] In an alternative embodiment, the locking device is suitable for a conical flask and may include at least one of a toothed clamping device (such as 2.4) with a latching protrusion (such as 2.7) and a latch (such as a safety latch (2.5)) with a latching magnet (such as 2.6). The function of the locking device is to hold the flask to prevent rotational and vertical displacement. Figure 1 As shown, a locking device for an Erlenmeyer flask is arranged on the base of the flask holder.

[0089] In another alternative embodiment, the locking device is suitable for bioreactor tube flasks and comprises four gate knives (10.1) each holding a toothed jaw (10.2) and arranged on the base of the holder of the cell culture flask.

[0090] In another embodiment, the locking device is suitable for a bioreactor vial and can be a combination of four gate knives (10.1), eight toothed claws (10.2), four track-and-pivots (10.3) (pivots not visible), a plunger (10.4), a plunger retainer (10.5), an eccentric clamp (10.6), and a control latch (10.7).

[0091] The function of the locking device is to hold up to four bioreactor tubes against rotational and vertical displacement. Fig. 9 As shown, a locking device for a bioreactor tube is arranged on the base of the flask holder.

[0092] ○ Locking device for conical flasks

[0093] In one embodiment, the locking device for the conical flask is arranged on the base of the holder and is perpendicular to the bottom of the base. The locking device is arranged on the base portion of the holder that is not attached to the handle. The locking device can be attached to the base by any attachment means (such as a pivot).

[0094] ○ Clamping device (2.4)

[0095] In one embodiment, a clamping device (or element) for the bottom of the flask is mounted in the hollow opening of the base of the flask holder and is arranged to hold the bottom of the flask. The function of the clamping element is to hold the flask to prevent rotational and vertical displacement. The clamping element can be attached to the base by any attachment means, such as a pivot.

[0096] In one embodiment, the flask is a conical flask, and the clamping element is an annular toothed elastic member having a horseshoe shape. The function of the element is to hold the conical flask to prevent rotational displacement and vertical displacement. When the clamping element is arranged around the bottom of the conical flask, the annular elastic member is arranged to contact (to lock) at least 60% of the cylindrical bottom of the conical flask. The annular elastic member has an additional toothed protrusion on the edge portion, and the protrusion helps to maintain the position of the conical flask. In one example, the toothed elastic member (2.4) having a horseshoe shape for holding the conical flask can be as shown in Figure 1 As shown in BD.

[0097] The additional protrusions that the annular elastic member has at one or both ends of the elastic member are referred to herein as latching protrusions (2.7). In one embodiment, the toothed clamping device has at least one latching protrusion, preferably at least two latching protrusions.

[0098] The latching protrusion is designed to latch the safety latch (2.5). The latching protrusion helps to clamp the flask. In one example, the latching protrusion (2.7) of the latching safety latch (2.5) can be as follows Figure 1 As shown in C.

[0099] ○ Safety latch (2.5)

[0100] In one embodiment, the locking device is exemplified by a latch further comprising at least one magnet inserted into the latch and at least one countermagnet arranged on the base of the holder. The at least one inserted magnet can be glued to the latch, and the at least one countermagnet can be glued to the base of the holder. The at least one inserted magnet can be a permanent magnet. In one embodiment, at least two permanent magnets can be used and the at least two permanent magnets can be inserted into the latch. In one embodiment, at least two countermagnets can be used and the at least two countermagnets can be arranged on the base of the flask holder so that the magnets are perpendicular to the base. In another exemplary embodiment, as Figure 1 As shown in C, two permanent magnets inserted into the latch and two counter magnets arranged on the base can be used. In one embodiment, the magnet pair is collectively referred to as a latch magnet (2.6). It is understood that, as Figure 1 As shown in FIG. 1B , when the safety latch is in the closed position, at least one insertion magnet in the latch and at least one counter-magnet arranged on the base are attached to each other by magnetic attraction. Thus, the set of the insertion magnet on the latch and the counter-magnet on the base provides an additional latching device that secures the toothed clamping device in the closed position, such as Figure 1 As shown in B.

[0101] In this context, the latch may be referred to as a safety latch (2.5). In this context, at least one magnet inserted into the latch and at least one counter-magnet arranged on the base of the retainer are referred to as latch magnets (2.6) ( Figure 1 DE).

[0102] In an embodiment, the security latch is made of hard anodized aluminum alloy.

[0103] In one embodiment, the clamping device is lifted away from the base of the holder, thereby placing the flask on the base of the holder. Next, the clamping device is lowered and placed around the bottom of the flask. Finally, the safety latch is lifted so that at least one insertion magnet in the latch and at least one counter-magnet arranged on the base can attach to each other, and the safety latch is then secured by the latch protrusion of the clamping device. In one example, as Figure 1 As shown in B, when the clamping device and the safety latch are in the closed position, the latching protrusion (2.7) of the clamping device (2.4) can latch on the safety latch (2.5).

[0104] ○ Locking device for bioreactor tube flask (10)

[0105] In one embodiment, the locking device for the bioreactor tube (11) is arranged on the base of the holder and is perpendicular to the bottom of the base. The locking device can be attached to the base by any attachment means, such as screws.

[0106] In one embodiment, a locking device for up to four bioreactor tubes (11) may include four gate knives (10.1), eight toothed claws (10.2), four track-and-pivots (10.3) (pivots not visible), a plunger (10.4), a plunger retainer (10.5), an eccentric clamp (10.6), and a control latch (10.7).

[0107] In one embodiment, a locking device for a bioreactor tube (11) comprises four gate knives (10.1) held by toothed jaws (10.2). The four gate knives are driven by four track-and-pivots (10.3) located in a plunger (10.4). The up and down movement of the plunger (10.4) is driven by an eccentric clamp (10.6). The assembly (10) is connected to a control latch (10.7).

[0108] It will be appreciated that up to four bioreactor tubes may be mounted into one flask holder.

[0109] It is understood that, although the exemplary alternative locking device for conical flasks and the exemplary alternative locking device for bioreactor tubes are used, this does not affect the technical specifications and functions of other elements of the flask holder. Similarly, the exemplary alternative locking device used in the flask holder does not affect the handling method of the flask holder.

[0110] In this context, a flask holder with a locking device for a bioreactor tube is referred to as a flask basket (12) for a bioreactor tube.

[0111] - Anti-magnetic pads (2.8 and 10.10)

[0112] In one embodiment, at least one anti-magnet, at least two anti-magnets, at least three anti-magnets, at least four anti-magnets are arranged on the outside of the base of the flask holder. Preferably, four anti-magnets are arranged on the outside of the base of the flask holder. In one embodiment, the anti-magnets are glued to the outside of the base of the flask holder.

[0113] In one embodiment, Figure 1 E and Fig. 9 As shown in A, the anti-magnet is shaped as a magnetic pad (2.8 and 10.10).

[0114] In an embodiment, the diamagnetic pad is made of magnetizable stainless steel (ferrite or martensite). Typically, stainless steel is used to prevent corrosion inside the incubator shaker compartment.

[0115] At least two conical positioning guide elements present on the oscillator tray and at least two magnets present on the oscillator tray ensure the horizontal position of the flask holder on the oscillator tray, and the at least two magnets can be attached to at least two anti-magnetic pads arranged on the outside of the base of the flask holder by magnetic attraction.

[0116] The horizontal position of the flask holders on the flask holder plate of the transfer shuttle is ensured by the presence of up to four conical positioning guide elements on the flask holder plate.

[0117] The function of these anti-magnetic pads is to further maintain the vertical position of the flask holder.

[0118] - Identification device (2.9)

[0119] In one embodiment, the flask holder is provided with an identification device, such as RFID (radio frequency identification) or a two-dimensional barcode (eg, QR code) to enable culture information tracking (cell line ID, passage number, passage date, etc.).

[0120] In one embodiment, the flask holder has an RFID tag or a QR code (2.9). In one embodiment, the RFID tag or QR code (2.9) can be arranged on the outside of the handle, opposite to the gripping side, such as Figure 1 The QR code in the E is shown (alternatively, the RFID tag can be located under the base of the flask holder).

[0121] The RFID is acquired through a reader / writer that communicates with the incubator shaker's PLC (Programmable Logic Controller). The PLC then uses this RFID information to create a database to track the baskets during use, which can be used as a safety net in the event of a failure in scheduling software, such as Hamilton's.

[0122] In one embodiment, the flask holder is sized to accommodate any flask.

[0123] In one embodiment, the flask to be placed in the holder is a conical flask, wherein the capacity of the flask can be selected from about 25ml to 4000ml, such as 25ml, 50ml, 125ml, 250ml, 500ml, 1000ml, 2000ml or 4000ml. In one embodiment, the flask is a conical flask, wherein the bottom diameter of the flask can be selected from about 4cm to 20cm, such as 4.1cm, 5.1cm, 6.7cm, 8.2cm, 10.1cm, 12.9cm, 16cm or 20.6cm. In one embodiment, the flask is a conical flask, wherein the height of the flask can be selected from about 6cm to 36cm, such as 6.1cm, 7.8cm, 11.4cm, 13.2cm, 17.6cm, 21.6cm, 26.8cm or 36.0cm.

[0124] In one embodiment, the flask is a 125 ml Erlenmeyer flask.

[0125] In one embodiment, the flask is a 125 mL Erlenmeyer flask (Thomson Optimum Growth TM 125 ml flask; No. 931110).

[0126] In one embodiment, the flask to be placed in the holder is a bioreactor tube, wherein the capacity of the bioreactor tube can be selected from about 15ml to 600ml, such as 15ml, 50ml, 450ml or 600ml. In one embodiment, the bioreactor tube can have a conical or rounded bottom. In one embodiment, the flask is a bioreactor tube, wherein the size can be selected from 17.1×120mm, 30×115mm, 96×145mm and 98×183mm.

[0127] In one embodiment, the flask is a bioreactor tube (TPP Bioreactor 15), which may be conical at the bottom and allow a smaller working volume of 1 ml to 15 ml.

[0128] In one embodiment, the flask has a closure cap (1.1, 11.1), which has a top, and the closure cap is adjacent to the sidewall of the flask along the circumferential periphery of the neck of the flask. The closure cap is detachably connected to the flask. In a preferred embodiment of the present invention, by configuring the closure cap as a threaded closure, a good seal of the inner space of the flask for the surrounding environment and a stable fixing of the closure cap and the flask are achieved. The closure cap can be a threaded cap (1.1, 11.1), and the threaded cap can be a filter cap. The advantage of this cap is that the ventilation increased is provided while maintaining the aseptic conditions for cell culture.

[0129] Incubator Shaker Trays

[0130] In one embodiment, an incubator tray (3) is provided for supporting at least one flask holder (2, 12) as described herein. The incubator tray (3) is suitable for use inside an orbital shaker incubator and may be referred to herein as an incubator shaker tray.

[0131] In one embodiment, Figure 2 As shown in Figure C, the incubator tray can accommodate up to 40 flask holders, such as 40 flask holders arranged in an 8×5 array for 125 ml conical flasks. The function of the incubator tray is to hold the flask holders in a stable position while the orbital shaker incubator is running.

[0132] In one embodiment, the shaker tray is preferably made of anodized hard anodized aluminum alloy. This prevents the tray from corroding inside the incubator shaker compartment.

[0133] In one embodiment, an incubator tray (3) is provided, which comprises a lower plate (3.1), an upper plate (3.2) and a tray lock (3.3).

[0134] Possible elements of an incubator tray can be described as follows.

[0135] -Lower plate (3.1)

[0136] In one embodiment, the lower plate (3.1) is arranged below the upper plate (3.2), and the lower plate (3.1) is attached to the upper plate (3.2) by any attachment means, preferably, by screws.

[0137] In one embodiment, preferably, the lower plate is made of hard anodized aluminum alloy.

[0138] In one embodiment, the thickness of the lower plate is between about 3 mm and about 5 mm, preferably, the thickness is about 4 mm.

[0139] In one embodiment, the lower plate (3.1) has up to eighty electromagnets arranged on the top of the lower plate. The electromagnets can be screwed on the top of the lower plate. In one embodiment, permanent electromagnets (3.4) can be used.

[0140] The permanent electromagnet (3.4) is guided into the upper plate (3.2) through a hole. When the coil is activated, the magnetic field of the permanent electromagnet is suppressed. The permanent electromagnet is divided into eight sections inside the tray, each section is controlled by a solid-state relay. The relays are controlled by a microcontroller (such as an Arduino controller) through a controller means such as an I2C bus, and the microcontroller communicates with a programmable logic controller (PLC) (such as a programmable logic controller from Festo) through a ME3 / ME4 control card (such as a control card from Coppley control).

[0141] In one embodiment, the lower board (3.1) has up to forty RFID readers arranged on the top of the lower board. The RFID readers communicate with a microcontroller (such as an Arduino microcontroller) via the I2C protocol. The RFID readers may include a built-in antenna.

[0142] In one embodiment, the lower plate is Figure 1 In one embodiment, the lower plate assembled with the upper plate is as shown in A. Figure 1 As shown in B.

[0143] - Upper board (3.2)

[0144] In one embodiment, the upper plate (3.2) is arranged above the lower plate (3.1), and the upper plate (3.2) is attached to the lower plate (3.1) by any attachment means, preferably by screws, and is held together at a distance by spacers. In one embodiment, the distance between the lower plate (3.1) and the upper plate (3.2) arranged above is between about 10 mm and about 11 mm, preferably about 10.5 mm.

[0145] In one embodiment, preferably, the upper plate is made of hard anodized aluminum alloy.

[0146] In one embodiment, the thickness of the upper plate is between about 3 mm and about 5 mm, preferably, the thickness is about 3 mm.

[0147] In one embodiment, the upper plate has at least one guide element arranged at the top of the upper plate. In one embodiment, the upper plate has up to eighty guide elements arranged at the top of the upper plate. The guide elements can be attached to the top of the upper plate by any attachment means, preferably, by screws. In this document, the guide elements are referred to as centering guide elements or positioning guide elements. The guide elements can be arranged so that two guide elements are arranged for each flask basket position. The centering guide elements can have a conical shape. The centering guide element can be exemplified by a pin, such as a centering pin (3.5).

[0148] In one embodiment, the flask holder is placed between two guide elements present on the incubator tray, which provide a horizontal position for the flask holder.

[0149] In one embodiment, the upper plate (3.2) has up to forty holes for RFID reader antennas, referred to herein as RFID antenna holes (3.6).

[0150] It is understood that the counter-magnets on the flask holder (2.8) and the electromagnets (3.4) on the tray coincide with each other through the guiding function of the guiding elements, such as the centering pins (3.5), arranged on the upper plate (3.2).

[0151] -Tray lock (3.3)

[0152] In one embodiment, a tray lock (3.3) is arranged on the rail tray holder.

[0153] In one embodiment, the pallet lock (3.3) provides precise positioning of the pallet in two ways. First, by milling two half-moons on the pallet, which correspond to two cylindrical clamps on the back side of the pallet. Second, on the front side of the pallet, by an eccentric handle that locks the pallet in a fixed and precise position.

[0154] In one embodiment, the tray lock (3.3) is compatible with the automation described herein.

[0155] Three-axis electric platform

[0156] In one embodiment, a three-axis motorized platform (4) is provided, which is designed to be mounted on the inner side of the top wall (top plate) of the orbital incubator shaker chamber. The three-axis motorized platform is attached to the orbital incubator shaker chamber by any attachment means, preferably, by stainless steel threaded pins and non-thermally conductive PEEK nuts.

[0157] It will be appreciated that the three-axis motorized platform can be a compact system (with double extensions) that allows for increased operating height of the gripping system. This compact (low height) three-axis motorized platform allows for handling and transporting tall flask holders, such as those for conical flasks or bioreactor tubes. In one embodiment, the three-axis motorized platform has a payload capacity of 0.8 kg.

[0158] In one embodiment, a three-axis motorized platform (4) is provided, the three-axis motorized platform (4) comprising an X-axis (4.1), a Y-axis (4.2), a Z-axis (4.3), and at least one motor for driving each axis. In one embodiment, the motor for driving the X-axis, the Y-axis, or the Z-axis (4.3) is a linear motor. In one embodiment, at least one encoder is provided, the encoder providing feedback for closed-loop control of at least one motor driving each axis.

[0159] In one embodiment, a three-axis motorized platform (4) is provided, such as Figure 3 As shown, the three-axis electric platform (4) includes an X-axis (4.1), a Y-axis (4.2), a Z-axis (4.3), a linear motor (4.4) for driving the X-axis (4.1), a linear motor (4.5) for driving the Y-axis (4.2), a linear motor (4.6) for driving the Z-axis (4.3), and a device (4.7) for grasping a flask holder.

[0160] Possible elements of a three-axis motorized stage can be described as follows.

[0161] -X axis (4.1)

[0162] In one embodiment, the X-axis has a travel range of about 685 mm. Preferably, the three-axis motorized platform has one X-axis.

[0163] In one embodiment, the X-axis (4.1) is connected to a linear motor (4.4).

[0164] -Y axis (4.2)

[0165] In one embodiment, the Y axis has a travel range of about 375 mm. Preferably, the three-axis motorized stage has one Y axis.

[0166] -Z axis (4.3)

[0167] In one embodiment, the Z axis has a travel range of about 175 mm. Preferably, the three-axis motorized stage has one Z axis.

[0168] - Linear motor (4.4) for driving the X-axis (4.1)

[0169] In one embodiment, the X-axis (4.1) is connected to a linear motor (4.4) such that the linear motor drives the X-axis. In one embodiment, the linear motor driving the X-axis is selected from linear motors known in the art, such as a TM6 linear motor (Technotion).

[0170] In one embodiment, an LA11 absolute encoder (RLS) is provided which provides feedback for closed loop control of the linear motor (4.4) via the ME3 card.

[0171] - Linear motor (4.5) for driving the Y-axis (4.2)

[0172] In one embodiment, the Y axis (4.1) is connected to a linear motor (4.5) such that the linear motor drives the Y axis. In one embodiment, the linear motor driving the Y axis is selected from linear motors known in the art, such as a TM6 linear motor (Technotion).

[0173] In one embodiment, an LA11 absolute encoder (RLS) is provided which provides feedback for closed loop control of the linear motor (4.5) via the ME3 card.

[0174] - Linear motor (4.6) for driving the Z axis (4.3)

[0175] In one embodiment, the Z axis (4.3) is connected to a linear motor (4.6) such that the linear motor drives the Z axis. In one embodiment, the linear motor driving the Z axis is selected from linear motors known in the art, such as TM3 linear motors (Technotion). The Z axis provides extension motion.

[0176] In one embodiment, an LA11 absolute encoder (RLS) is provided which provides feedback for closed loop control of the linear motor (4.6) via the ME3 card.

[0177] In one embodiment, the linear motor can be placed in a box (such as Figure 3 shown).

[0178] - Device for gripping flask holder

[0179] In one embodiment, a device for grabbing a flask holder is provided. The device for grabbing a flask holder is attached to the Z axis (4.3) by any attachment means, such as being attached to the Z axis (4.3) by a screw. The function of these grabbing devices is to allow grabbing the flask holder for transportation. The function of the grabbing devices is to allow a detachable connection with the flask holder. Therefore, the grabbing device must be compatible with the handle of the flask holder.

[0180] In one embodiment, the example of a device for gripping a flask holder is a parallel gripper (4.7) having an adjustable gripping force and equipped with a claw (4.8) and a finger (4.9) for detachably connecting to the flask holder. In one embodiment, the parallel gripper is selected from parallel grippers known in the art, such as an electric EHPS parallel gripper (Festo).

[0181] In an embodiment, the parallel gripper is made of hard anodized aluminum alloy.

[0182] In an embodiment, the jaws of the parallel gripper are made of stainless steel.

[0183] In an embodiment, the fingers of the parallel gripper are made of hard anodized aluminum alloy.

[0184] In an embodiment, the parallel grippers are controlled by a PLC by communicating via an IO-Link interface.

[0185] Sliding Doors

[0186] In one embodiment, a sliding door (5) is provided, which is designed to be installed in the side wall of the orbital incubator oscillator chamber. The sliding door (5) is designed to be installed in a chamfered rectangular hole, which is drilled on the side wall of the orbital incubator oscillator chamber. Preferably, the sliding door (5) is designed to be installed on the left side wall of the orbital incubator oscillator chamber. In one embodiment, the sliding door is automated. In one embodiment, the sliding door is attached to the orbital incubator oscillator chamber by any attachment method, preferably, by screws. In one embodiment, the sliding door includes a door frame (5.1) and a door panel (5.2), and when the door panel is opened, the sliding door forms a door channel (5.3).

[0187] In another further embodiment, the door panel (5.2) comprises three parts, namely the front panel (5.2.1) ( Figure 4 B), subject (5.2.2) ( Figure 4 C) and the pressure plate (5.2.3) ( Figure 4 D).

[0188] In one embodiment, a sliding door (5) is provided, the sliding door (5) comprising a door frame (5.1) and a door panel (5.2) and at least one motor for driving the door movement. In one embodiment, a sliding door (5) is provided, the sliding door (5) comprising a door frame (5.1) and a door panel (5.2), a stepping motor (5.4) for driving the sliding movement and a stepping motor (5.5) for driving the pressing movement. The sliding door may further comprise at least one sensor for the door movement.

[0189] The sliding door may also include a heating device, for example, including a temperature probe (5.8), a heating pad (5.9), a heating belt (5.11) and a controller. Figure 4 As shown, the sliding door may also include a precision sensor (5.6) for sliding motion and a precision sensor (5.7) for pressing motion, a temperature probe (5.8), a heating pad (5.9), an O-ring (5.10) and a heating belt (5.11).

[0190] Possible elements of a sliding door can be described as follows.

[0191] -Door frame (5.1)

[0192] -Door panel (5.2)

[0193] The door panels of the door slide to open and close. When the door panels are open, the door forms a doorway (5.3). The doorway is the space through which items move when the door is open.

[0194] The door panel (5.2) comprises three parts, namely the front panel (5.2.1) ( Figure 4 B), subject (5.2.2) ( Figure 4 C) and the pressure plate (5.2.3) ( Figure 4 D). In another embodiment, the front plate (5.2.1) is arranged with a stepper motor (5.4) for driving the sliding movement and a stepper motor (5.5) for driving the pressing movement. In one embodiment, the main body (5.2.2) is arranged between the front plate (5.2.1) and the pressing plate (5.2.3). In one embodiment, the pressing plate (5.2.3) is arranged with a temperature probe (5.8) and a heating pad (5.9), preferably, the temperature probe and the heating pad are embedded in the pressing plate. In one embodiment, when the door is closed, the pressing plate (5.2.3) contacts the O-ring (5.10). The sliding door applies pressure to the O-ring.

[0195] - Two stepper motors: a stepper motor (5.4) for driving the sliding movement and a stepper motor (5.5) for driving the pressing movement

[0196] In one embodiment, the sliding door comprises at least one motor for driving the door movement, such as a stepper motor (5.4) for driving the sliding movement and a stepper motor (5.5) for driving the pressing movement. In one embodiment, the stepper motor is selected from stepper motors known in the art, such as NEMA-23. In one embodiment, the stepper motor is controlled by means of a controller such as an ME4 control card.

[0197] In one embodiment, a stepper motor drives the sliding motion (5.4) via a simple rack and pinion. In one embodiment, a stepper motor driving the sliding motion is located on the right side of the door, such as on the right side on the front plate (5.2.1).

[0198] In one embodiment, a stepper motor drives the pressing motion (5.5) via a motor gearbox, two toothed wheels and four satellite wheels. The four satellite wheels drive four lead screws, which control the pressing motion. Two sliding ball bearings guide the entire mechanism.

[0199] In one embodiment, one stepper motor driving the sliding movement is located on the left side of the door, such as on the left side on the front plate (5.2.1).

[0200] - Two sensors: a precision sensor for sliding movement (5.6) and a precision sensor for pressing movement (5.7)

[0201] In one embodiment, the sliding door comprises at least one sensor for door movement, such as a sensor for sliding movement (5.6) and a sensor for pressing movement (5.7). In one embodiment, the sensor is a precision sensor. In one embodiment, the precision sensor is selected from sensors known in the art, such as precision sensor switches (Baumer). In one embodiment, the sensor is controlled by means of a controller such as an ME4 control card, which is controlled by a PLC.

[0202] In one embodiment, a precision sensor is dedicated to detecting the sliding movement when the door is open (not detected when the door is closed). The precision sensor is located on the door frame (5.1). In this article, the precision sensor is called the precision sensor for homing of the sliding movement (5.6).

[0203] In one embodiment, a precision sensor is dedicated to detecting the pressing movement. The precision sensor is located on the sliding door panel (5.2). In this article, the precision sensor is called a precision sensor (5.7) for homing the pressing movement when the door is not pressed (such as an open door).

[0204] -Temperature probe (5.8)

[0205] In one embodiment, the temperature probe is selected from temperature probes known in the art, such as a Pt1000 probe (5.8). The temperature probe used is suitable for precision temperature sensing. In one embodiment, at least one temperature probe is used. The temperature probe is located on the door, such as embedded in the press plate (5.2.3).

[0206] In one embodiment, the temperature probe is connected to a microcontroller (such as an Arduino controller) that controls the heating pad (5.9) and / or the heating belt (5.11). The microcontroller can transmit the temperature value of the door to the PLC for temperature monitoring.

[0207] -Heating pad (5.9)

[0208] In one embodiment, the heating pad is selected from heating pads known in the art, such as polyimide encapsulated heating pads (5.9). In one embodiment, at least one heating pad is used. In one embodiment, a polyimide encapsulated heating pad is embedded in the door, such as embedded in the press plate (5.2.3). The heating pad is used to achieve temperature control of the door and prevent condensation on the door surface.

[0209] -O-ring (5.10)

[0210] In one embodiment, the o-ring is selected from o-rings known in the art, such as silicone o-rings (5.10). The o-ring can be called a profile ring. In one embodiment, at least one o-ring is used. In one embodiment, a silicone o-ring is installed between the door frame (5.1) and the pressing plate (5.2.3) of the door panel (5.2). The o-ring is used to ensure airtightness.

[0211] -Heating belt (5.11)

[0212] In one embodiment, the door frame (5.1) is arranged with at least one heating strip (5.11) which is located around an opening forming the door passage (5.3).

[0213] In one embodiment, the heating tape is selected from heating tapes known in the art, such as polyimide encapsulated heating tapes. In one embodiment, at least one heating tape is used. The heating tape is used to achieve temperature control of the channel and prevent condensation on the channel surface.

[0214] Transport Shuttle

[0215] In one embodiment, a transfer shuttle (6) is provided, which is designed to be mounted on the outside of the side wall of the orbital incubator shaker chamber. Preferably, the transfer shuttle (6) is designed to be mounted on the left side wall of the orbital incubator shaker chamber. In one embodiment, the transfer shuttle is automated.

[0216] In one embodiment, the transfer shuttle is attached to the orbital incubator shaker chamber by any attachment means, preferably, by screws.

[0217] For example, Figure 6 A to Figure 6 The transfer shuttle (6) shown in FIG. 1 is designed to be mounted on the outside of the side wall of the orbital incubator shaker chamber, below the sliding door (5), as shown in FIG. Figure 6 This allows the flask holder plate (6.5) to move through the sliding door channel (5.3) formed when the sliding door plate (5.2) is opened.

[0218] In one embodiment, the automated transfer shuttle (6) may include at least a sliding frame (such as 6.1), a track (such as 6.2), at least two conveyor belts (such as 6.11) arranged on the sliding frame, a cell culture flask holder plate (such as 6.5) and a motor (such as 6.3) for driving the sliding movement of the plate on the track.

[0219] In one embodiment, the automated shuttle (6) may include at least a sliding frame (6.1) and a track (6.2), a stepper motor (6.3) driving the sliding motion, a ball screw (6.13), a flask holder plate (6.5), a conveyor belt (6.11), and a flask holder plate (6.5) with two guide elements (6.6). Figure 5 or Figure 6 As shown, the automated transfer shuttle (6) may also include a gear (6.4), an amplified precision sensor (6.7) for detecting the origin position of the transfer shuttle, a sensor (6.8) for detecting the loading position of the flask holder and a sensor (6.9) for detecting the unloading position of the flask holder, and a laser detector (6.10).

[0220] Possible elements of the transfer shuttle (6) can be described as follows.

[0221] - Sliding frame (6.1) and track (6.2) and motor (6.3) to drive the sliding movement

[0222] In one embodiment, at least one frame is used. In one embodiment, the frame is made of stainless steel.

[0223] In one embodiment, the sliding frame (6.1) holds at least two rails. In another exemplary embodiment, the sliding frame (6.1) holds four rails, namely two upper rails (6.2) and two lower rails (6.2). The upper plate can slide on the upper rails. The sliding frame slides on the shuttle base via the lower rails.

[0224] In one embodiment, the motor driving the sliding movement is a stepper motor (6.3).

[0225] The sliding is controlled by a stepper motor (6.3) through a ball screw (6.13) ( Figure 5 )(first movement). In one embodiment, the stepper motor is selected from stepper motors known in the art, such as NEMA-23. In one embodiment, a stainless steel frame slides on the track, wherein the sliding movement is controlled by the NEMA-23 stepper motor via a ball screw (6.13) (first movement). In one embodiment, a stepper motor driving the sliding movement is located below the track.

[0226] In one embodiment, the stepper motor is controlled by means of a controller such as an ME4 control card which is controlled by a PLC.

[0227] -Gear(6.4)

[0228] In one embodiment, the gear (6.4) is attached to the sliding frame (6.1) via a gear holder, which is screwed onto the sliding frame (6.1). In one embodiment, the gear (6.4) drives the double extension (second movement) of the upper plate (6.12) via a rack.

[0229] -Flask holder plate (6.5)

[0230] In one embodiment, at least one flask holder plate is used. The flask holder plate slides on the track (6.2). The sliding movement of the flask holder plate (6.5) on the track (6.2) is driven by at least two conveyor belts (6.11) arranged on the sliding frame (6.1) (third movement). In another embodiment, the sliding movement of the flask holder plate (6.5) on the track (6.2) is driven by at least four conveyor belts (6.11) arranged on the sliding frame (6.1) (third movement). In one embodiment, one side of the conveyor belt is glued to the sliding frame and the other side is screwed to the flask holder. A tensioner is installed on one side. The pulley installed on the double extension plate (6.12) reverses the direction of movement. Preferably, the conveyor belt is made of polyimide film. Generally, the use of polyimide film provides greater mechanical strength (no stretching), and because polyimide film is thinner than other common materials used for conveyor belts, polyimide film allows a more compact conveyor belt while maintaining the strength of the conveyor belt.

[0231] In one embodiment, the flask holder plate (6.5) includes at least two guide elements, which are attached to the top of the flask holder plate by any attachment method, preferably, attached to the top of the flask holder plate by screws. In this article, the guide element is called a centering guide element or a positioning guide element. Preferably, four centering guide elements are arranged for the flask holder. The guide element can have a conical shape. The centering guide element can be taken as an example of a pin, such as a centering pin (6.6). In one example, the flask holder is placed between at least two or at least four guide elements (such as pins) present on the flask holder plate, which provides a horizontal position for the flask holder.

[0232] - Position sensors / detectors, including an amplified precision sensor (6.7) for detecting the origin position of the transfer shuttle, a precision sensor (6.8) for detecting the loading position of the flask holder, a precision sensor (6.9) for detecting the unloading position of the flask holder

[0233] In one embodiment, the transfer shuttle includes at least one sensor for detecting the origin position of the transfer shuttle such as the origin position, and / or the loading position of the flask holder, and / or the unloading position of the flask holder, so preferably, in this article, the sensor is called a position sensor / detector. In one embodiment, the sensor is selected from an amplified precision sensor or a precision sensor.

[0234] ○ Amplified precision sensor for detecting the origin position of the shuttle (6.7)

[0235] In one embodiment, the sensor (6.7) for detecting the origin position of the transfer shuttle can be an amplified precision sensor. In one embodiment, the amplified precision sensor is selected from sensors known in the art, such as precision sensor switches (Baumer). In one embodiment, the sensor is controlled by a controller means such as an ME4 control card, which is controlled by a PLC.

[0236] In one embodiment, preferably, at least one amplified precision sensor is dedicated to detecting the origin position of the transfer shuttle. The amplified precision sensor is located at the frame of the shuttle and detects the position of the sliding frame. In this article, the amplified precision sensor is referred to as a precision sensor (6.7) for detecting the origin position of the transfer shuttle. The origin position is as follows: Figure 5 or Figure 6 As shown, the origin position represents an idle state, which is defined as a non-extended state in which the flask holder plate is located outside the incubator compartment.

[0237] ○ Precision sensor for detecting the loading position of the flask holder (6.8) / Precision sensor for detecting the unloading position of the flask holder (6.9)

[0238] In one embodiment, the sensor (6.8) for detecting the loading position of the flask holder / the sensor (6.9) for detecting the unloading position of the flask holder can be a precision sensor. In one embodiment, the precision sensor is selected from sensors known in the art, such as precision sensor switches (Metrol). In one embodiment, the sensor is controlled by means of a controller such as an ME4 control card, which is controlled by a PLC.

[0239] In one embodiment, preferably, at least one precision sensor is dedicated to detecting the loading position of the flask holder, i.e., the position when the flask holder is placed on the flask holder plate inside the incubator shaker compartment. In one embodiment, preferably, at least another precision sensor is dedicated to detecting the unloading position of the flask holder, i.e., the position when the flask holder is removed from the flask holder plate outside the incubator shaker compartment. In this document, these two sensors are referred to as a sensor (6.8) for detecting the loading position of the flask holder and a sensor (6.9) for detecting the unloading position of the flask holder. The two sensors for detecting the loading position / unloading position of the flask holder are located on opposite sides of the double extension plate (6.12). The loading position indicates the state when the transfer shuttle is extended, wherein the flask holder plate is located in the incubator shaker compartment. The unloading position corresponds to Figure 5 or Figure 6 The origin position is shown and is defined as the non-extended state, where the flask holder plate is located outside of the incubator shaker compartment.

[0240] ○ Laser presence detector (6.10)

[0241] The laser detector allows to detect the presence or absence of the flask holder (basket), so preferably, in this document, the laser detector is called a presence laser detector. In one embodiment, the presence laser detector is selected from presence laser detectors known in the art.

[0242] Preferably, the presence laser detector used is suitable for measuring distances, such as the distance between a basket on a shuttle inside the incubator and a basket outside the incubator. If a flask holder is present, the presence laser detector allows identification of whether the flask holder can be grabbed inside / outside the incubator. In one embodiment, at least one presence laser detector is used. The presence laser detector can be located on an external end of the transfer shuttle. The presence laser detector can be directly controlled by a controller such as a PLC via an IO-Link interface for communication.

[0243] Automated Incubator Shaker Compartment

[0244] In one embodiment, a component assembly is provided, the component assembly comprising:

[0245] - Incubator shaker tray (3),

[0246] - Three-axis electric platform (4),

[0247] - sliding doors (5), and

[0248] -Transportation shuttle (6),

[0249] The component assembly is designed to be arranged in the orbital incubator oscillator chamber. The component assembly is essential for holding and then transporting at least one cell culture flask arranged in at least one cell culture flask holder, and is therefore referred to as a set in this article, or alternatively, as a device. In one embodiment, the incubator oscillator tray is used to hold at least one cell culture flask holder. In one embodiment, the function of the three-axis electric platform is to first hold, and then simultaneously hold and transfer a cell culture flask holder. In one embodiment, the function of the sliding door is to allow a cell culture flask holder to be transferred to the inside / outside of the orbital incubator oscillator chamber. In one embodiment, the function of the transfer shuttle is to first hold, and then simultaneously hold and transfer a cell culture flask holder.

[0250] In one embodiment, a system is provided, the system comprising:

[0251] - Incubator shaker tray (3),

[0252] - Three-axis electric platform (4),

[0253] - sliding doors (5), and

[0254] -Transportation shuttle (6),

[0255] This system is for use with orbital incubator shaker chambers.

[0256] In one embodiment, the incubator shaker tray (3), three-axis motorized platform (4), sliding door (5), or transfer shuttle (6) described herein can be used individually and can be assembled with any other compatible device.

[0257] In one embodiment, a kit (7) is provided for holding and transporting at least one cell culture flask, the kit being adapted for use in an incubator shaker compartment and comprising:

[0258] - Incubator shaker tray (3),

[0259] - Three-axis electric platform (4),

[0260] - sliding doors (5), and

[0261] -Transportation shuttle (6),

[0262] Therein, the at least one cell culture flask is arranged in at least one cell culture flask holder (2, 12) that is compatible with the set (7).

[0263] In one embodiment, the kit is an automated kit.In one embodiment, the kit (7) for holding and transporting cell culture flasks, adapted for use in an incubator shaker compartment, may be referred to as an automated incubator shaker compartment.

[0264] In one embodiment, the kit (7) is designed to be mounted to an orbital incubator shaker chamber such that:

[0265] - The incubator shaker tray (3) is designed to be mounted inside an orbital incubator shaker chamber,

[0266] - a three-axis motorized platform (4) designed to be mounted on the inside of the top wall of the orbital incubator shaker chamber,

[0267] - the sliding door (5) is designed to fit into a chamfered rectangular hole in the side wall of the orbital incubator shaker chamber,

[0268] - The transfer shuttle (6) is designed to be mounted outside the side wall of the orbital incubator shaker chamber.

[0269] The above exemplary design for the set (7) of orbital incubator shaker chambers is as follows Figure 7 shown.

[0270] In one embodiment, the components of the kit (7) of the present invention include:

[0271] - Incubator shaker tray (3),

[0272] - Three-axis electric platform (4),

[0273] - sliding doors (5), and

[0274] -Transportation shuttle (6),

[0275] The components of the set (7) have at least one feature or any combination of features as described herein.

[0276] In one embodiment, at least one cell culture flask holder (2, 12) compatible with the set (7) has at least one feature or any combination of features as described herein.

[0277] In one embodiment, the kit of the present invention is suitable for installation on any incubator shaker, particularly an incubator shaker having a size selected from a length (L) of about 1288 mm, a depth (D) of between about 859 mm and 917 mm, and a height (H) of about 771 mm.

[0278] In one embodiment, the set of the present invention is mounted to an incubator shaker having a chamber having dimensions selected from 1288×859×771 mm (L×D×H) or 1288×917×771 mm (L×D×H) or 1288×887×771 mm (L×D×H) or 1288×859×771 mm (L×D×H), preferably, the dimensions are 1288×859×771 mm (L×D×H).

[0279] Incubator shaker with automated incubator shaker compartment

[0280] In one embodiment, an incubator shaker is provided that includes a kit, apparatus, system, or component assembly as described herein.

[0281] In one embodiment, there is provided an incubator shaker (8) comprising a kit (7) for holding and transporting at least one cell culture flask, the kit comprising:

[0282] - Incubator shaker tray (3),

[0283] - Three-axis electric platform (4),

[0284] - sliding doors (5), and

[0285] -Transportation shuttle (6),

[0286] Therein, at least one cell culture flask is arranged in at least one cell culture flask holder (2, 12) which is compatible with the set (7).

[0287] In one embodiment, the set in the incubator shaker is an automated set. In one embodiment, the set in the incubator shaker can be referred to as an automated incubator shaker compartment.

[0288] In one embodiment, an incubator shaker (8) is provided, the incubator shaker (8) comprising a kit (7), wherein the kit is designed to be mounted to an orbital incubator shaker chamber such that:

[0289] - The incubator shaker tray (3) is designed to be mounted inside an orbital incubator shaker chamber,

[0290] - a three-axis motorized platform (4) designed to be mounted on the inside of the top wall of the orbital incubator shaker chamber,

[0291] - the sliding door (5) is designed to fit into a chamfered rectangular hole in the side wall of the orbital incubator shaker chamber,

[0292] - The transfer shuttle (6) is designed to be mounted outside the side wall of the orbital incubator shaker chamber.

[0293] In one embodiment, the sliding door (5) is designed to fit within a chamfered rectangular hole drilled into the side wall of the orbital incubator shaker chamber.

[0294] In one embodiment, an incubator shaker (8) is provided, the incubator shaker (8) comprising a set (7), wherein the components of the set (7) of the present invention include:

[0295] - Incubator shaker tray (3),

[0296] - Three-axis electric platform (4),

[0297] - sliding doors (5), and

[0298] -Transportation shuttle (6),

[0299] The components of the set (7) have at least one feature or any combination of features as described herein.

[0300] In one embodiment, at least one cell culture flask holder (2, 12) compatible with an incubator shaker (8) comprising the set (7) has at least one feature or any combination of features as described herein.

[0301] In one embodiment, the incubator shaker comprising the set of the present invention can be any incubator shaker, in particular an incubator shaker having a size selected from a length (L) of about 1288 mm, a depth (D) between about 859 mm and 917 mm, and a height (H) of about 771 mm.

[0302] In one embodiment, the incubator oscillator comprising the set of the present invention has the following chamber, the size of which is selected from 1288×859×771mm (L×D×H) or 1288×917×771mm (L×D×H) or 1288×887×771mm (L×D×H) or 1288×859×771mm (L×D×H), preferably, the size is 1288×859×771mm (L×D×H).

[0303] In one embodiment, a culture shaker comprising a kit of the invention is provided, wherein the culture shaker is part of an automated cell culture platform, such as an automated passaging platform.

[0304] An exemplary arrangement of an incubator shaker (8) comprising the kit (7) of the present invention is as follows Figure 8 Shown is an exemplary arrangement with an automated cell passaging platform.

[0305] In one embodiment, the chamber of the liquid handling system (9) has a hole that follows the contour of the automated sliding door (5) of the incubator shaker (8), and the incubator shaker (8) is designed so that the flask holders (2, 12) can be transferred to the liquid handling system (9) on a transfer shuttle (6).

[0306] In one embodiment, there is provided a use of a culture shaker comprising the kit of the present invention for cell culture, in particular for cell passaging.

[0307] In one embodiment, a method of culturing cells is provided, the method comprising using an incubator shaker comprising the kit of the present invention.

[0308] Automated Programs for Automated Incubator Shakers

[0309] It will be appreciated that the flask holders (2, 12) may be placed in or removed from the incubator shaker (8) through the main front door of the incubator shaker (8).

[0310] The non-automated steps for handling / loading the flask holder (2, 12) may include the following steps:

[0311] a) Clear the keeper position (unlock the safety latch),

[0312] b) placing the flask in the flask holder,

[0313] c) Lock the safety latch,

[0314] d) Open the incubator shaker through the main front door,

[0315] e) loading the holder on the incubator tray; positioning the holder on the tray by two pins and locking the basket on the tray by magnetic attraction,

[0316] f)RFID detection and verification,

[0317] g) Close the incubator shaker through the main front door.

[0318] It will be appreciated that the flask holder (2, 12) may be placed in or removed from the incubator shaker (8) through the sliding door (5) of the incubator shaker (8).

[0319] The automated steps for transporting the flask holder (2, 12) may include:

[0320] a) The three-axis platform is at the origin position,

[0321] b) The X / Y axis platform moves to the top of the holder pick-up position,

[0322] c) The Z-axis stage moves to the holder pick-up position,

[0323] d) gripping the holder by opening the fingers of the gripper,

[0324] e) deactivating the electromagnet of the retainer,

[0325] f) Move the pick-up holder via the Z-axis stage,

[0326] g) The X / Y axis platform moves to the position above the shuttle,

[0327] h) opening the sliding door and extending the shuttle towards the shaker incubator compartment (loading position),

[0328] i) Load the holder onto the shuttle by moving the Z-axis stage,

[0329] j) Return the shuttle to the origin position and close the sliding door to the origin position,

[0330] k) The X / Y / Z axis platform returns to the origin position.

[0331] In case of parallel cultivation of multiple cultures in an orbital shaker incubator, the automated procedure for transporting a flask holder via the kit of the invention allows limiting negative changes to the environment of the cultures in other laboratory equipment.

[0332] In one embodiment, a method for holding at least one cell culture flask disposed in at least one cell culture flask holder is provided, the method using a kit as described herein.

[0333] In one embodiment, a method for holding and transporting at least one cell culture flask disposed in at least one cell culture flask holder is provided, the method using a kit as described herein.

[0334] Automated cell passaging platform including an incubator shaker with an automated incubator shaker compartment

[0335] In one embodiment, an automated cell passaging platform is provided, comprising a liquid handling system, at least one robot, at least one automated storage system, an automated refrigerated incubator, an automated microplate centrifuge with an automated loader, a cell counting device, and at least one shaker incubator, and optionally an automated orbital shaker incubator, characterized in that:

[0336] At least one orbital shaker incubator is designed to be installed with a kit as described herein for holding and transporting at least one cell culture flask.

[0337] In one embodiment, there is provided an automated cell passaging platform as described herein, characterized in that the automated cell passaging platform comprises at least two orbital shaker incubators, and

[0338] The at least two orbital shaker incubators are designed to be installed with the kit for holding and transporting cell culture flasks described herein.

[0339] It is understood that the capacity of the automated cell passaging platform is up to 80 cell culture flasks, such as conical flasks, i.e. up to 40 cell culture flasks in each orbital shaker incubator. It is understood that the capacity of the automated cell passaging platform is up to 320 bioreactor tubes, i.e. up to 160 bioreactor tubes in each orbital shaker incubator.

[0340] In one embodiment, the chamber of the liquid handling system (9) has a hole that follows the contour of the automated sliding door (5) of the incubator shaker (8), and at least one incubator shaker (8) is designed so that the flask holders (2, 12) can be transferred to the liquid handling system (9) on a transfer shuttle (6).

[0341] In one embodiment, there is provided the use of an automated cell passaging platform comprising at least one incubator shaker for cell passaging, the incubator shaker having an automated incubator shaker compartment as described herein.

[0342] In one embodiment, a method of cell culture is provided, the method comprising using an automated cell passaging platform comprising at least one incubator shaker having an automated incubator shaker compartment as described herein.

[0343] The entire contents of the references cited herein are incorporated herein by reference. The scope of the present invention is not limited by the specific embodiments and drawings described herein, which are intended to be used only to illustrate various aspects of the present invention, and functionally equivalent methods and components are also within the scope of the present invention. The examples used to illustrate the present invention are not intended to limit the scope of the present invention in any way.

Claims

1. A kit for holding and transporting at least one cell culture flask, wherein: The kit is designed to be placed in an orbital incubator shaker chamber and includes: - a flask holder designed to receive the at least one cell culture flask having a circular footprint and suitable for suspension cell culture, - an incubator shaker tray designed to be mounted inside the orbital incubator shaker chamber, the incubator shaker tray comprising at least one guide element arranged for holding each cell culture flask holder, - an orbital incubator shaker tray for receiving the flask holders and imparting orbital motion to the flask holders, - a three-axis motorized platform designed to be mounted on the inner side of the top wall of the orbital incubator shaker chamber, the three-axis motorized platform comprising an X-axis, a Y-axis and a Z-axis, and three linear motors for driving the three axes and a device for grabbing the cell culture flask holder, - a sliding door designed to be mounted in a side wall of the orbital incubator shaker chamber, the sliding door comprising a door panel and at least one motor for driving the movement of the door, - A transfer shuttle designed to be mounted on the outside of the side wall of the orbital incubator shaker chamber, the transfer shuttle comprising a sliding frame, a track, at least two conveyor belts arranged on the sliding frame, a cell culture flask holder plate and a motor for driving the sliding movement of the plate on the track.

2. The kit for holding and transporting at least one cell culture flask according to claim 1, wherein: The cell culture flasks were 125 ml Erlenmeyer flasks or bioreactor tubes.

3. The set according to claim 1 or 2, wherein: The device for grasping the cell culture flask holder is attached to the Z-axis of the three-axis motorized platform, and the device for grasping the cell culture flask holder includes a parallel gripper having an adjustable gripping force and equipped with claws and fingers for detachable connection with the flask holder.

4. A set according to claim 1, 2 or 3, wherein: The motor for driving the door movement of the sliding door includes a stepping motor for driving the sliding movement of the door panel and a stepping motor for driving the pressing movement of the door panel.

5. The set according to any one of claims 1 to 4, wherein: The sliding door further includes a precision sensor for detecting a sliding motion of the door panel and a precision sensor for detecting a pressing motion of the door panel.

6. The set according to any one of claims 1 to 4, wherein: The sliding door further comprises a temperature probe, a heating pad, a heating belt and a controller, and wherein the temperature probe controls the heating pad and the heating belt through the controller.

7. The set according to any one of claims 1 to 6, wherein: The sliding door also includes a silicone o-ring installed between the door frame and the door panel.

8. The set according to any one of claims 1 to 7, wherein: The transfer shuttle also includes an amplified precision sensor for detecting the origin position of the transfer shuttle, a sensor for detecting the loading position of the cell culture flask holder, and a sensor for detecting the unloading position of the cell culture flask holder.

9. The set according to any one of claims 1 to 8, wherein: The flask holder includes a bottom heat conductor at the base of the holder, one side of the heat conductor being designed to contact the orbital incubator shaker tray and the other side of the heat conductor being designed to contact the flask.

10. The set according to claim 9, wherein: The bottom heat conductor includes four side heat conductors at the four corners of the basket that provide heat to the sides of the flask.

11. The set according to any one of claims 1 to 10, further comprising a cell culture flask holder, wherein the cell culture flask holder comprises a base, two handles arranged perpendicular to the base and opposite to each other, a locking device for holding a cell culture flask, and a thermally conductive pad arranged on the base of the holder.

12. The set according to claim 11, wherein: The cell culture flask holder further comprises at least two magnets arranged on the outside of the base of the cell culture flask holder, the at least two magnets providing an attachment means to an incubator shaker comprising a permanent electromagnet.

13. The set according to claim 11, wherein: The locking device of the cell culture flask holder comprises a clamping device and a safety latch arranged on the base of the cell culture flask holder.

14. The kit according to claim 11, wherein: The locking device of the cell culture flask holder comprises four blades, each of which is provided with a toothed jaw and is arranged on the base of the cell culture flask holder.

15. Use of a kit according to any one of claims 1 to 14 for holding and transporting at least one cell culture flask, the at least one cell culture flask being arranged in at least one cell culture flask holder compatible with the kit.

16. An incubator shaker comprising the kit according to claim 1.

17. An automated cell passaging platform comprising a liquid handling system, at least one robot, at least one automated storage system, an automated refrigerated incubator, an automated microplate centrifuge with an automated loader, a cell counting device, and at least one shaker incubator, and optionally an automated orbital shaker incubator, It is characterized in that At least one of the orbital shaker incubators is designed to be arranged together with a set according to claim 1 for holding and transporting at least one cell culture flask.

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