Carousel for modular biological production units

Abstract

To provide: an automated carousel for use with a variety of biological production units supporting cell culture and / or tissue engineering systems in clinical and laboratory settings; and a method for improving ergonomics for users of automated carousel systems.SOLUTION: The invention provides an automated carousel 10 and a system configured for translationally moving a plurality of biological production units 16 in unison along a vertical frame while maintaining precise alignment of each of the biological production units relative to gravity, and simultaneously providing independent dynamic adjustment of axial orientation of each of the biological production units relative to gravity.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an upright carousel that provides translational movement of multiple biological production units along a defined vertical path while maintaining each individual unit stable against gravity, and further provides individual dynamic axial rotation of each independent unit. The carousel is automated and adaptable for use with a variety of modular biological production units designed for cell culture and / or tissue culture systems in a variety of clinical and laboratory settings. The carousel and associated systems and methods allow ergonomic and practical access to each of the biological production units. [Background technology]

[0002] Existing robotic engineering systems for automated cell culture and tissue engineering are complex, require significant laboratory space to operate, and represent a significant capital investment.

[0003] Facility design is often recognized as a critical component in successful GMP (Good Manufacturing Practice) biological production, but is not always implemented with a full understanding of the implications of the process. In the case of mammalian cell culture, there are recognized problems and risks that arise when moving to large-scale automated operations. The growing demand for cell culture production capacity in the biopharmaceutical industry has led to a gradual increase in the scale of automated operations.

[0004] There is an increasing demand for patient-specific treatments, such as autologous cell therapies. Autologous cell therapies require complex, multiple simultaneous processing events, which places significant demands on automation. Automated production units can only serve one patient in any given production cycle. Scaling massively parallel processing for multiple patients creates the need for space-efficient tissue expression and access to multiple production units within a production facility.

[0005] Therefore, it is desirable to develop methods for achieving maximized cell and / or tissue production within the constraints of existing production facilities. It is further desirable to develop methods for achieving maximized cell and / or tissue production within the constraints of existing production facilities that do not adversely affect the integrity of the cell and tissue culture systems. It is also desirable to improve the ergonomics for users of automated cell and tissue engineering systems.

[0006] The background discussion herein is included to explain the context of the invention described herein and is not an admission that any of the referenced material was published, known, or part of the common general knowledge as of the priority date of the claims. Summary of the Invention

[0007] Described herein is a more economical and space-efficient method for operating several biological production units in a floor space-demanding production facility while providing practical and ergonomic access to the cell and / or tissue culture systems within each of the biological production units.

[0008] Shown is an upright, automated carousel configured to support several biological production units that can move translationally in unison along the carousel's vertical path and stop at user-selected locations to access any one of the biological production units. During this translational movement, each individual unit remains stable with respect to gravity, i.e., properly horizontally oriented with respect to gravity. At the same time, the automated carousel further provides for individual dynamic adjustment of the axial rotation of any one or all of the units. The proper orientation of each of the units with respect to gravity is maintained during active translation of the unit and when the carousel is stationary. Similarly, individual dynamic adjustment of the axial orientation of any one or all of the units can be actuated during active translation of the unit or when the carousel is stationary.

[0009] Advantageously, operation of the automated carousel for user positioning does not adversely affect the cell and / or tissue culture / engineering processes being supported within any one of the biological production units.

[0010] Advantageously, the automated carousel is configured such that each of the biological production units supported on the carousel is independently operable and customized for the cell and / or tissue culture / engineering process supported within any one of the biological production units.

[0011] Advantageously, the biological production units supported on the carousel are well-connected such that the operational resources required for each biological production unit are optionally one central means for ease of use. Surprisingly, the connection to the central operational resource is maintained operationally during translational movement of the biological production units along the vertical curved path of the carousel, and during any individual adjustment of the axial rotation of any one of the units. This is particularly advantageous in that multiple biological production units can be provided on a single carousel, each with a customized cell and / or tissue culture / engineering process, optionally all sharing the same central operational resource and also the same translational capabilities for user positioning and separate capabilities for independent axial rotation.

[0012] The automated carousel of the present invention is advantageously configured to utilize vertical space for the distribution, operation, and uniform translation of multiple biological production units arranged in close spatial relationship along its curved vertical path. The translation is in a vertical plane and follows the curved shape of the carousel. The translation may be up to approximately 180 degrees clockwise or counterclockwise, at various speeds, and is user-controlled. The translation is designed with precision and controlled increments so that an operator (regardless of height) can position any one of the biological production units for ergonomic access, whether in a standing or seated position. The carousel is configured with a safety stop mechanism to stop movement at any time as desired or needed. The axial rotation of any one individual biological production unit may also be clockwise or counterclockwise to provide a rocking motion or for agitation.

[0013] The attachment of the biological production units to the carousel is reversible so that each unit can be inspected, removed, replaced, or repositioned to a different location on the carousel or to a different carousel. In embodiments, the biological production units are attached in a cantilevered orientation to facilitate access by users and maintain efficient use of floor space.

[0014] It is contemplated that different types of biological production units may be mounted on a single carousel, so long as their basic size, weight, and independent functional capabilities are comparable to other units mounted on the carousel, so as not to adversely affect the overall balance of the carousel, the uniform bidirectional translational movement along the carousel frame, the gravitational orientation of the biological production units mounted on the carousel, or the ability to independently and dynamically adjust the bidirectional axial orientation with respect to gravity of any one of the units. Additionally, each of the biological production units mounted on the carousel may support a different cell culture and / or tissue culture system customized for a particular need or a particular patient.

[0015] The automated carousel may be provided as a vertically arranged system within a vertical housing for centralized operation and provision of operating resources to each of the independently controlled biological production units that function to support the cell and / or tissue culture systems therein. The vertical housing serves as a support frame and mounting structure for maintaining the upright positioning of the carousel and its operation. The vertical housing is configured to allow for reversible mounting of the biological production units, their appropriate translational movement along the carousel shape, and easy user access. The vertical housing has a support base and retractable wheels for easy relocation. The vertical housing is configured for easy assembly and disassembly, centralized storage of required resources, and user safety.

[0016] User access, service access, and space efficiency are improved when supporting multiple biological production units on the automated carousel of the present invention. Furthermore, the carousel of the present invention can provide increased scalability by optimizing the height of the biological production facility. Multiple carousels can be aligned and used in series. Thus, multiple biological production units can be implemented in a production facility in a space-efficient yet operator-accessible manner.

[0017] The carousel is used in conjunction with one or more controllers, a controller communication interface, associated software, and a remote management device (e.g., a computer). The software is customizable for specific applications, menu-driven, and user-friendly. For example, the rotation of the biological production units mounted on the carousel may be defined by a user-set program for precise control of the movement and positioning of each biological production unit. The carousel can be operable from a central workstation or a remote management device. A convenient user-operated touchpad screen device may be used and connected to each of the biological production units operatively connected to the central computer.

[0018] According to an aspect of the present invention, there is provided an upright carousel for translating multiple biological production units in unison along a vertical elliptical orbit while stabilizing each individual biological load against gravity, and for providing for individual dynamic axial rotation of any one or all of the biological production units.

[0019] In an embodiment, the carousel is provided with a spacing adjustment means that adjusts the spacing of each biological production unit relative to adjacent biological production units so as to maximize the spatial density of the biological production units in selected zones of the carousel by closing the spacing and to enhance user access to biological production units in other selected zones by opening the spacing.

[0020] In embodiments, each of the biological production units is independently operable and is coupled to a central source of operating resources.

[0021] In embodiments, the biological load is sensitive to orientation with respect to gravity.

[0022] In an embodiment, the carousel comprises upright drive and support tracks vertically offset from one another and held together by a plurality of linkages, each of which is adapted to support a biological production unit during translational movement of the drive and support tracks along an elliptical orbit.

[0023] In embodiments, the biological production unit is supported in a cantilevered position for ease of user access once positioned.

[0024] In embodiments, the multiple cantilevered biological production units are translationally positioned in unison along an upright frame that includes two vertically offset tracks. In embodiments, the tracks are substantially oval. In embodiments, the tracks are oval closed loops.

[0025] In embodiments, the speed and direction of translation (clockwise or counterclockwise) is user controlled and adjustable.

[0026] In embodiments, the alignment of each cantilevered biological production unit is substantially maintained against gravity during translational movement of the unit or when the carousel is stationary.

[0027] In embodiments, the carousel provides dynamic adjustment of the axial orientation (bidirectional) of each independent cantilevered biological production unit with respect to gravity during translational movement of the unit or when stationary.

[0028] In embodiments, the precise positioning of each cantilevered biological production unit is user controlled for ergonomic access.

[0029] In an embodiment, the cantilevered biological production unit is a cantilevered biological production unit.

[0030] In embodiments, the cantilevered biological production unit operatively supports an automated cell culture and / or tissue engineering system.

[0031] In embodiments, each of the biological production units is independently operable to provide a customized cell culture and / or tissue engineering system, hi embodiments, the cell culture and / or tissue engineering system is for autologous cell therapy.

[0032] In aspects, the carousel reduces the overall space / storage footprint while improving employee safety and efficiency.

[0033] In embodiments, the carousel is part of a system further comprising a housing for supporting vertical movement of the carousel, and means for connecting each biological production unit in series to a central source of assistance and resources.

[0034] In an embodiment of the present invention is an automated carousel system for organizing, storing, and ergonomically accessing cell and / or tissue engineered systems enclosed in a biological production unit.

[0035] In embodiments, automated carousels and systems incorporating carousels significantly increase a facility's biological operation capacity by fully utilizing overhead space and reclaiming up to 70% of the floor space required by conventional biological culture systems.

[0036] According to one aspect of the present invention, there is provided an automated vertical track assembly for supporting a plurality of biological production units, the carousel comprising: (i) user-activated starting and stopping of translational movement of the biological production units in unison along a defined path of the vertical track while maintaining each of the biological production units properly oriented with respect to gravity; and (ii) configured to allow a user to start and stop the axial rotation of each individual biological production unit; During both (i) and (ii), each of the biological production units is independently operable to support a customized automated cell and tissue culture system therein; Each of the biological production units is interconnected to share a central source of operating resources.

[0037] According to an aspect of the present invention, a vertical carousel is provided comprising a plurality of biological production units substantially geometrically constrained to move translationally in unison in a vertical elliptical orbit while maintaining the proper orientation of each of the plurality of biological production units relative to gravity, and wherein any independent one or more of the plurality of biological production units are separately rotated axially.

[0038] According to another aspect of the present invention, a vertical carousel includes: a plurality of biological production units substantially geometrically constrained for translational movement along a vertical elliptical orbit in unison and for separate axial rotation of any one or more of the plurality of biological production units while maintaining a stable orientation of each of the plurality of biological production units with respect to gravity; - means for controlling the translational movement of the biological production unit for user positioning; means for actuating the axial rotation of any one or more of the plurality of biological production units.

[0039] According to one aspect of the present invention, an automated carousel comprises: a vertical track assembly comprising a drive track and a support track vertically offset from one another; - a plurality of translation assemblies connecting the drive track and the support track at spaced apart locations, each translation assembly supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected track while maintaining the proper orientation of each cantilevered biological production unit relative to gravity, and separately, (ii) axial rotation of each biological production unit.

[0040] According to one aspect of the present invention, there is provided a system for maximizing cell and / or tissue engineering production, the system comprising a plurality of automated carousels as described herein supported and arranged in series.

[0041] According to a further aspect of the present invention, there is provided a method for maximizing cell and / or tissue engineering production, the method comprising providing a series of automated carousel systems as described herein at a production facility.

[0042] According to a further aspect of the present invention, there is provided a translation assembly for a vertical carousel having a drive track and a vertically offset support track for supporting a biological production unit for translational movement and independent axial rotation, the translation assembly comprising: a first end defining a reversible coupling for receiving an input shaft of a biological production unit; a central hub, an outer hub shell supporting a drive carriage that cooperatively engages the drive track for translational movement thereon; a central hub comprising an inner hub including a separate mechanism configured for axial rotation of the biological production unit; a vertically downwardly extending resistance arm mounted via the inner hub, and a second end having at its vertically lowest point a pivotally connected support carriage cooperatively engaged for translational movement thereon, the vertically extending resistance arm preventing rotation of the inner hub and maintained in a vertical orientation by geometric constraints resulting from the fixed vertical offset of the drive track and support track during translational movement along the track.

[0043] According to one aspect of the present invention, there is provided an automated carousel system for distribution and ergonomic positioning of a plurality of biological production units, each of the units comprising an automated, individually operable cell and / or tissue culture system, the automated carousel system comprising: An automated carousel, comprising: a vertical track assembly comprising a drive track and a support track vertically offset therefrom; a plurality of translation assemblies connecting the drive track and the support track at spaced locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected tracks in unison, and separately, (ii) axial rotation of each biological production unit while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity; - means for independent biological control of each cell and / or tissue culture system within each of said biological production units; a vertical housing assembly supporting the carousel, the housing assembly comprising a central source of operating resources; - means for interconnecting a central source of operating resources to each successive biological production unit; and a computer connection.

[0044] According to one aspect of the present invention, a method for improving ergonomics for users of an automated carousel system comprising a plurality of independent culture systems each supported within a biological production unit comprises: and mounting a plurality of biological production units on an automated carousel, the automated carousel comprising: a vertical track assembly comprising a drive track and a support track vertically offset therefrom; a plurality of translating assemblies connecting the drive track and the support track at spaced locations, each of the plurality of translating assemblies supporting a cantilevered biological production unit, the plurality of translating assemblies configured to provide (i) translational movement along the connected tracks in unison, and separately, (ii) axial rotation of each biological production unit while maintaining proper orientation of each cantilevered biological production unit with respect to gravity; (i) and (ii) are user controlled for ergonomic access by the user to each biological production unit.

[0045] According to a further aspect of the present invention, a method for increasing biological production capacity utilizing cell and / or tissue culture systems in a production facility comprises: The invention includes supporting a plurality of biological production units, each housing a cell and / or tissue culture system, on an upright automated carousel, the carousel comprising a plurality of translation assemblies connecting a drive track and a support track at spaced apart locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to (i) provide translational movement along the connected track in unison, and separately, (ii) axial rotation of each biological production unit while maintaining proper orientation of each cantilevered biological production unit relative to gravity.

[0046] According to a further aspect of the present invention, there is provided an ergonomic, automated carousel for supporting an automated, individually operable biological system, the carousel comprising: a plurality of translation assemblies connecting the drive track and the support track at spaced locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected tracks in unison, and separately, (ii) axial rotation of each biological production unit while maintaining proper orientation of each cantilevered biological production unit with respect to gravity; and means for selecting to translate any one of the biological production units along the connected tracks to a particular position to accommodate a user for ergonomic testing by the user.

[0047] According to a further aspect of the present invention, a method for ergonomically positioning an automated selection cell culture and / or tissue engineering system for inspection by a user comprises: transmitting one or more translational movement operation commands to an upright carousel comprising a plurality of spaced apart cantilevered biological production units configured to include a cell and / or tissue culture system for translationally moving the plurality of cantilevered biological production units in unison via a remote management device, wherein the one or more translational movement operation commands include information regarding a location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications where a particular user is standing or sitting; The carousel includes a controller and a communication interface, the controller (i) receiving one or more rotational operation instructions from a remote management device via a communications interface; (ii) operating the carousel for translational movement of the plurality of cantilevered biological production units while maintaining the proper orientation with respect to gravity of each of the cantilevered biological production units during translational movement or when stationary; (iii) adjusting the axial orientation of any one or more of the plurality of cantilevered biological production units with respect to gravity while in translation or at rest; (iv) identifying a target biological production unit for ergonomic positioning for a particular user; (v) positioning the target biological production unit according to physical measurements of where the particular user is standing or sitting; (i) to (v) are configured to transmit the results of one or more of (i) to (v) to a remote management device via a communication interface; and receiving instructions from a remote management device via a communication interface of the carousel to operate the carousel for translational movement to ergonomically position the target biological production unit to a particular user's physical measurement specifications; ceasing the translational motion command when the target biological production unit is ergonomically positioned; and transmitting one or more results of the ergonomic positioning to a remote management device via a communication interface of the carousel.

[0048] In any of the above-described embodiments, one skilled in the art will recognize that the automated upright carousel can operatively support any desired number of biological production units, such as at least two biological production units, up to about six units, up to about eight units, up to about ten units, up to about twelve units, up to about fourteen units, up to about sixteen units, up to about eighteen units, or up to about twenty units or more.

[0049] The automated carousel allows ergonomic access to a specific individual cell and / or tissue culture system without disrupting ongoing biological processing in any of the other multiple individual cell and / or tissue culture systems. The carousel is generally height adjustable and easily configurable to a wide variety of user sizes, shapes, and weights. The ergonomic carousel is configured to alleviate existing muscular, skeletal, or neurological problems and / or prevent such problems in the first instance for laboratory personnel. In embodiments, the ergonomic carousel is suitable for vertical adjustment from a sitting to a standing configuration, or vice versa.

[0050] A1. An automated vertical track assembly for supporting a plurality of biological production units, the vertical track assembly comprising: (i) a user-operated start and stop of translational movement of the biological production units in unison along a defined path of the vertical track assembly while maintaining each of the biological production units properly oriented with respect to gravity; and (ii) configured to allow a user to start and stop the axial rotation of each individual biological production unit; During both (i) and (ii), each of the biological production units is independently operable to support a customized automated cell and tissue culture system therein; An automated vertical track assembly, each of said biological production units interconnected to share a central source of operating resources.

[0051] A2. A vertical carousel comprising a plurality of biological production units substantially geometrically constrained to move translationally in unison in a predetermined trajectory while maintaining the proper orientation of each of the plurality of biological production units relative to gravity, and wherein any independent one or more of the plurality of biological production units are independently rotated axially.

[0052] A3. A vertical carousel comprising a plurality of biological production units substantially geometrically constrained to move translationally in unison in a predetermined trajectory while maintaining a proper orientation of each of the plurality of biological production units relative to gravity, and the ability to separately adjust the spacing of each biological production unit relative to adjacent biological production units so as to maximize the spatial density of the biological production units in selected zones of the carousel by closing the spacing and to enhance user access to biological production units in other selected zones by opening the spacing.

[0053] A4. A vertical carousel, a plurality of biological production units substantially geometrically constrained for translational movement along a vertical elliptical orbit in unison and for separate axial rotation of any one or more of the plurality of biological production units while maintaining a stable orientation of each of the plurality of biological production units with respect to gravity; - means for controlling the translational movement of the biological production unit for user positioning; - means for actuating axial rotation of any one or more of the plurality of biological production units while in translational motion or when stationary.

[0054] 1. An automated carousel, a vertical track assembly comprising a drive track and a support track vertically offset from one another; a plurality of translating assemblies connecting the drive track and the support track at spaced apart locations, each translating assembly supporting a cantilevered biological production unit; The automated carousel, wherein the multiple translation assemblies are configured to provide (i) translational movement along the connected tracks in unison while maintaining proper orientation of each cantilevered biological production unit relative to gravity, and separately, (ii) axial rotation of each biological production unit.

[0055] 1a. The automated carousel of claim 1, wherein each of the plurality of translating assemblies is a horizontal hub assembly.

[0056] 1b. The horizontal hub assembly a first end defining a reversible coupling for receiving an input shaft of a cantilevered biological production unit; a central hub, an outer hub shell supporting a drive carriage cooperatively engaged with the drive track for translational movement thereon; a central hub comprising an inner hub including a separate mechanism configured for axial rotation of the biological production unit; 12. The automated carousel of claim 1a, comprising: a vertically downwardly extending resistance arm mounted via the inner hub; and a second end having at its vertically lowest point a pivotally connected support carriage cooperatively engaged with the support track for translational movement thereon, the vertically extending resistance arm preventing rotation of the inner hub and maintained in a vertical orientation by geometric constraints resulting from a fixed vertical offset of the drive track and support track during translational movement along the track.

[0057] 2. The automated carousel of claim 1b, wherein the reversible coupling is a laterally extending cantilever coupling.

[0058] 2a. The automated carousel of claim 1b, 2 or 2a, wherein during translational movement in the track curve, the outer hub shell and fixed drive carriage undergo rotation and reversal while the corresponding support carriage pivots from a vertical position to a horizontal position, with both the drive carriage and support carriage remaining cooperatively engaged with their respective tracks and the resistance arm remaining vertically downward.

[0059] 3. The automated carousel of any one of claims 1b, 2 or 2a, wherein a separate mechanism in the inner hub includes a motor-driven central shaft for engaging an input shaft of a biological production unit, and actuation of the motor actively rotates the central shaft at a controlled speed to cause axial rotation of the associated biological production unit.

[0060] 3a. The automated carousel of claim 3, wherein the axial rotation is intermittent or continuous.

[0061] 3b. The automated carousel of claim 3, wherein said axial rotation is bidirectional.

[0062] 4. An automated carousel as claimed in any one of claims 1b, 2, 2a or 3, wherein the drive carriage comprises a drive block assembly having one face thereof provided with a fixed, vertically disposed pair of outwardly projecting bearing members for gripping the drive track and for engaging a drive means adapted to move along a path of travel defined by the drive track.

[0063] 5. An automated carousel as claimed in any one of claims 1b, 2, 2a, 3 or 4, wherein the support carriage comprises a support block assembly having one face thereof provided with a fixed, vertically disposed pair of outwardly projecting bearing members for gripping the support track and for engaging a drive means adapted to move along a path of travel defined by the support track.

[0064] 5a. The automated carousel of claim 4 or 5, wherein the translational movement of the support carriage is synchronized with the translational movement of the drive carriage.

[0065] 6. The automated carousel of any one of claims 1b, 2, 2a, 3, 4, or 5, further comprising: a second end of the horizontal hub assembly comprising a port for entry of a connector for operating resources centrally provided to the biological production unit.

[0066] 7. The automated carousel of any one of claims 1b, 2, 2a, 3, 4, 5 or 6, wherein the port leads to a hollow shaft that extends through a central hub to a biological production unit.

[0067] 8. The automated carousel of claim 7, wherein the connector comprises a cable that encloses separate operating resources, the cable originating from a central source and connecting to each successive biological production unit on the carousel.

[0068] 9. The automated carousel of claim 8, wherein the operating resources are electrical supply lines, gas supply lines, and controller connections.

[0069] 10. An automated carousel according to any one of claims 1 to 9, wherein the translational movement along the connected tracks is clockwise or counterclockwise.

[0070] 11. The automated carousel of claim 10, wherein the translational movement along the connected tracks is approximately 180 degrees.

[0071] 12. The automated carousel of claim 11, wherein the speed of the translational movement is adjustable.

[0072] 13. The automated carousel of claim 12, further operatively connected to means for interrupting and / or stopping the translational movement.

[0073] 14. The automated carousel of any one of claims 1 to 13, wherein the cantilevered biological production unit is a biological production unit.

[0074] 15. The automated carousel of claim 14, wherein the biological production units support individually operationally controlled cell and / or tissue engineering systems.

[0075] 16. The cell and / or tissue engineering system includes: sterile reception / storage of tissue biopsies; automatic monitoring of the digestion process; digestion of biopsy tissue to obtain dissociated cells; 16. The automated carousel of claim 15, which performs one or more of the following: cell sorting and selection; safe waste collection; cell seeding on or within a growth substrate; cell scaffold propagation to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to enable specialization of cell activity; tissue formation; mechanical and / or biochemical stimulation to promote tissue maturation; harvesting of tissue engineered constructs / implants for reconstructive surgery; and storage and transport of cells and transplantable tissues.

[0076] 17. The automated carousel of any one of claims 1 to 16, wherein the drive track and the support track are substantially oval, circular, or elliptical.

[0077] 18. The automated carousel of claim 17, wherein the drive track and the support track are oval.

[0078] 19. The automated carousel of any one of claims 1 to 18, comprising up to 24 translating assemblies, each supporting a cantilevered biological production unit.

[0079] 19a. The automated carousel of any one of claims 1 to 19, further comprising means for adjusting the spacing of each biological production unit relative to adjacent biological production units so as to maximize the spatial density of the biological production units in selected zones of the carousel by closing the spacing and to enhance user access to biological production units in other selected zones by opening the spacing.

[0080] 19b. The automated carousel of any one of claims 1 to 19a, wherein the adjustment of the spacing can be during translational movement of the biological production unit or when stationary.

[0081] 20. An automated system for maximizing cell and / or tissue engineering production, the system comprising an automated carousel according to any one of claims 1 to 19 supported in a vertical housing and operatively connected to one or more controllers for user control of translational movement and precise ergonomic positioning of the biological production unit for inspection thereof.

[0082] 21. The system of claim 20, comprising a plurality of automated carousels arranged in series.

[0083] 21. An automated carousel system for distribution and ergonomic positioning of a plurality of biological production units, each of the units comprising an automated, individually operable cell and / or tissue culture system, the automated carousel system comprising: An automated carousel, comprising: a vertical track assembly comprising a drive track and a support track vertically offset therefrom; a plurality of translation assemblies connecting the drive track and the support track at spaced locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected track in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit; - means for independent biological control of each cell and / or tissue culture system within each of said biological production units; a vertical housing assembly supporting the carousel, the housing assembly comprising a central source of operating resources; - means for interconnecting a central source of operating resources to each successive biological production unit; An automated carousel system comprising an automated carousel comprising a computer connection.

[0084] 22. The automated carousel system of claim 21, wherein each biological production unit comprises a connected interface for communication by a user, the connected interface being connected to a computer.

[0085] 23. An automated carousel system as claimed in claim 21 or 22, wherein the upright frame comprises up to 24 translating assemblies.

[0086] 24. The automated carousel system of claim 21, wherein the vertical housing assembly comprises a base having retractable wheels.

[0087] 25. A method of maximizing cell and / or tissue engineering production, the method comprising providing, at a production facility, one or more automated carousel systems according to any one of claims 1 to 19.

[0088] 26. A method for improving ergonomics for users of an automated carousel system having multiple independent culture systems each supported within a biological production unit, comprising: and mounting a plurality of biological production units on an automated carousel, the automated carousel comprising: a vertical track assembly comprising a drive track and a support track vertically offset therefrom; a plurality of translating assemblies connecting the drive track and the support track at spaced locations, each of the plurality of translating assemblies supporting a cantilevered biological production unit, the plurality of translating assemblies configured to provide (i) translational movement along the connected track in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit; The method, wherein (i) and (ii) are user controlled for ergonomic access to each biological production unit by a user.

[0089] 27. A method for increasing biological production capacity utilizing cell and / or tissue culture systems in a production facility, comprising: A method comprising supporting a plurality of biological production units, each housing a cell and / or tissue culture system, on an upright automated carousel, the carousel comprising a plurality of translation assemblies connecting a drive track and a support track at spaced apart locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected track in unison while maintaining proper orientation of each cantilevered biological production unit relative to gravity, and separately, (ii) axial rotation of each biological production unit.

[0090] 28. An ergonomic automated carousel for supporting an automated, individually operable biological system, the carousel comprising: a plurality of translation assemblies connecting the drive track and the support track at spaced apart locations, each of the plurality of translation assemblies supporting a cantilevered biological production unit, the plurality of translation assemblies configured to provide (i) translational movement along the connected track in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit; and means for selecting to translate any one of the biological production units along the connected track to a specific position to accommodate a user for ergonomic testing by the user.

[0091] 29. A method for ergonomically positioning an automated selection cell culture and / or tissue engineering system for inspection by a user, comprising: transmitting one or more translational movement operation commands to an upright carousel comprising a plurality of spaced apart cantilevered biological production units configured to include a cell and / or tissue culture system for translationally moving the plurality of cantilevered biological production units in unison via a remote management device, wherein the one or more translational movement operation commands include information regarding a location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications where a particular user is standing or sitting; The carousel includes a controller and a communication interface, the controller (i) receiving one or more rotational operation instructions from a remote management device via a communications interface; (ii) operating the carousel for translational movement of the plurality of cantilevered biological production units while maintaining the proper orientation with respect to gravity of each of the cantilevered biological production units during translational movement or when stationary; (iii) adjusting the axial orientation with respect to gravity of any one or more of the plurality of cantilevered biological production units during translational movement or when stationary; (iv) identifying a target biological production unit for ergonomic positioning for a particular user; (v) positioning the target biological production unit according to physical measurements of where the particular user is standing or sitting; (i) to (v) are configured to transmit the results of one or more of (i) to (v) to a remote management device via a communication interface; and receiving instructions from a remote management device via a communication interface of the carousel to operate the carousel for translational movement to ergonomically position the target biological production unit to a particular user's physical measurement specifications; ceasing the translational motion command when the target biological production unit is ergonomically positioned; and transmitting one or more results of the ergonomic positioning to a remote management device via a communication interface of the carousel. [Brief explanation of the drawings]

[0092] The following description of exemplary embodiments described herein will be better understood when read in conjunction with the accompanying drawings. For purposes of illustrating the invention, the drawings presently show exemplary embodiments. It should be understood, however, that the invention is not limited to the precise arrangement and arrangement of the embodiments shown in the drawings. It should be noted that like reference numerals refer to like elements throughout the different embodiments as shown in the drawings and referenced in the description.

[0093] The present description will be more fully understood in view of the following drawings.

[0094] [Figure 1] 1 shows one non-limiting configuration of a carousel system comprising a carousel of the present invention supported on a vertical housing having a support base and supporting several vertically positioned biological production units, one of which is in an open configuration. [Figure 2]FIG. 2 is a side elevation view of the carousel system of FIG. 1, with the arrow indicating that the carousel has a vertical translational movement of approximately + / - 180°. [Figure 3] FIG. 2 is a side elevation view of the carousel system of FIG. 1, with arrows indicating the individual axial rotation of each independent biological production unit. [Figure 4] An isolated carousel track structure is shown supporting one representative biological production unit for simplicity. [Figure 5] A close-up view of the isolated carousel track structure and the mechanical connection to the biological production unit is shown. [Figure 6] The mechanical linkage of the carousel is shown in isolation with the central section disconnected to show the internal drive structure. [Figure 7] FIG. 1 shows a front right isometric perspective view of a carousel with a fully populated track assembly. [Figure 8] FIG. 1 is a front right side elevation view of a carousel system supported on a vertical housing with a support base. [Figure 9] A close-up of the cables used and connected to each of the biological production units that provide the required resources from a central source is shown. [Figure 10] Three different sizes of carousel are shown, shown to support 6, 8, or 10 biological production units. [Figure 11] 10 shows representative measurements that can be used to define the range of configurations of any particular biological production unit for ergonomic access by an operator. DETAILED DESCRIPTION OF THE INVENTION

[0095] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The publications and applications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Additionally, the materials, methods, and examples are illustrative only and are not intended to be limiting.

[0096] In case of conflict, the present specification, including definitions, will control.

[0097] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the subject matter of this specification belongs. As used herein, the following definitions are provided to facilitate the understanding of the present invention.

[0098] As used herein, the articles "a" and "an" preceding an element or component are intended to be open-ended regarding the number of instances (i.e., occurrences) of the element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of an element or component also includes the plural, unless a numerical value clearly implies a singular number.

[0099] As used herein, the term "invention" or "present invention" is an open-ended term and is not intended to refer to any single aspect of a particular invention, but rather encompasses all possible aspects described in the specification and claims.

[0100] As used herein, the terms "comprises," "comprising," "includes," "including," "having," and their conjugations and variations indicate "including but not limited to" and should be understood to be open-ended, e.g., meaning including but not limited to.

[0101] As used herein, the term "about" refers to a variation in a numerical quantity. In one embodiment, the term "about" means within 10% of the reported numerical value. In another embodiment, the term "about" means within 5% of the reported numerical value. In yet another embodiment, the term "about" means within 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% of the reported numerical value.

[0102] When a range of values ​​is listed, it is for convenience or brevity only and includes all possible subranges and individual numerical values ​​within and around the boundaries of that range. Any numerical value includes practically approximations unless otherwise specified, and integer values ​​do not exclude fractional values. Subrange values ​​and substantially approximations should be considered as specifically disclosed values.

[0103] It will be understood that any element defined as being included herein may be expressly excluded from the claimed invention as a proviso or negative limitation.

[0104] As may be used herein, the terms "close," "approximate," and "actually" indicate a respective relationship or measurement or number or amount or degree that does not adversely affect or have an effect on the referenced term or embodiment or operation or scope of the invention.

[0105] As may be used herein, any terms referring to geometric relationships, such as "vertical," "horizontal," "parallel," "opposite," "linear," "lateral," "perpendicular," and other angular relationships, also indicate approximate yet functional and / or practical respective relationships.

[0106] As used herein, "vertical" can be interchanged with "upright." As used herein, "substantially vertical" or "substantially upright" refers to an orientation in which the track assemblies and support tracks described herein are preferably perpendicular to (i.e., form a 90° angle with) the ground or floor of a warehouse, building, or production facility, but also includes embodiments in which the tracks are within about 0° to 60° from vertical. That is, in embodiments, substantially vertical allows the tracks to be tilted from vertical at angles of about 5°, about 10°, about 20°, about 30°, about 45°, etc.

[0107] As used herein, "translational movement" refers to the movement of an object from one location to another without a change in its orientation with respect to a fixed point, as opposed to rotation, in which the object rotates about an axis. For a carousel of the present invention, the carousel provides for translational movement of multiple biological production units along a substantially vertical, curved path of the carousel while maintaining each individual unit fixed (i.e., horizontal, stable) with respect to its orientation with respect to gravity. "Translational movement" can be bidirectional.

[0108] As used herein, "translate" or "translationally" refers to the movement of a load supported on a carousel structure of the present invention, where the carousel includes two tracks of the same size and shape, which may be oval, elliptical, spherical, orbital, capsule-shaped, etc. "Translate along the tracks" can be interchanged with "translate along the tracks," both of which refer to movement from one position to a second position along the oval path of an upright carousel, where translation does not invoke rotational reversal (of the supported units and contents therein) during movement / travel along such frame.

[0109] As used herein, "rotation" or "axial rotation" refers to the movement of an object rotating about its central axis. For each dynamic adjustment of the axial rotation of a biological production unit, this means that the biological production unit rotates about its axis. This can be bidirectional. This can also be referred to as "rocking movement" or "tilting."

[0110] As used herein, "user" is interchangeable with "operator."

[0111] As used herein, the terms "preferred," "preferably," "typical," "typically," or "optionally" do not limit the scope of the invention or its embodiments.

[0112] As may be used herein, the term "substantially" (or its synonyms) indicates, relative to the context, a measure or extent, amount or degree that encompasses most or most of the referenced entity, or at least a moderate or much greater, or a more effective or more important extent with respect to the referenced entity or relative to the referenced subject matter.

[0113] As used herein, the term "may" refers to options or effects that may be included, not included, and / or used, and / or implemented, and / or produced, but that constitute at least part of some embodiments or results of the invention, without limiting the scope of the invention.

[0114] The term "and / or," as used herein in the specification and claims, should be understood to mean "either or both" of the elements so conjoined, e.g., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements other than those specifically identified by the "and / or" clause may be optionally present, whether related or not to the elements specifically identified, unless expressly indicated to the contrary.

[0115] As used herein in the specification and claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" should be interpreted as inclusive, e.g., including at least one, but more than one, of a number or list of elements, and, optionally, including additional, unlisted items. Generally, as used herein, the term "or" should be interpreted as indicating exclusive alternatives (e.g., "one or the other, but not both") only when preceded by terms of exclusivity, e.g., "either," "one of," "only one of," or "exactly one of."

[0116] As used herein in the specification and claims, the phrase "at least one," in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each element specifically recited in the list of elements, and not excluding any combination of elements in the list of elements. This definition also allows for the optional presence of elements other than those specifically identified in the list of elements to which the phrase "at least one" refers, whether related to the specifically identified elements or not.

[0117] As used herein, "plurality" is understood to be any number greater than one. "Plurality" means "two or more."

[0118] The use of ordinal terms such as "first," "second," "third," etc. in the claims to modify claim elements does not, in itself, imply any priority, precedence, or order of one claim element relative to another claim element or the chronological order in which method actions are performed, but is used solely as a label to distinguish one claim element having a particular name from another element having the same name (but for the purposes of the use of ordinal terms).

[0119] It should also be understood that, unless expressly stated to the contrary, in any method claimed herein including two or more steps or actions, the order of the method steps or actions is not necessarily limited to the order in which the method steps or actions are recited.

[0120] As used herein, a "unit" is a biological unit or biological production unit. A unit is generally meant to define a biological structure used to support cell and tissue culture systems therein.

[0121] As used herein, "cantilever unit" or "cantilevered biological production unit" refer to the same part and are therefore interchangeable.

[0122] As used herein, a "biological production unit" includes an independently operable automated cell culture and / or tissue engineering platform / system that includes components for one or more multifunctional operations of cell culture, cell seeding, cell digestion, cell growth, cell differentiation, cell expansion, tissue culture, and tissue growth.

[0123] The biological production unit may house and support an automated, portable, operational, multifunctional cell culture and / or tissue engineering system that performs / provides one or more of the following: sterile receipt / storage of tissue biopsies; automated monitoring of the digestion process; digestion of biopsy tissue to obtain unassociated cells; cell sorting and selection including safe waste collection; cell seeding on a growth substrate or within a scaffold to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineered scaffold or matrix; cell differentiation to enable specialization of cell activity; mechanical and / or biochemical stimulation to promote tissue maturation; harvesting tissue engineered constructs / implants for reconstructive surgery; and storage and transportation of transplantable tissues.

[0124] In some embodiments, this may be a tissue engineering cassette containing one or more interconnected bioreactors that provide precise control at each stage. From cell source isolation and cell expansion to cell collection, cell washing, and final implant formation, the system selectively combines critical processes to meet the unique challenges of different autologous and allogeneic clinical applications of cell and tissue therapies. Embedded sensors provide real-time biofeedback and enable automatic adjustment of the bioprocessing to accommodate natural variations in cell source behavior. The entire bioprocessing is contained within a disposable cassette to maximize patient and operator safety and streamline logistics. Suitable, non-limiting biological production units are described in US Pat. Nos. 8,492,140, ​​9,701,932, 9,534,195, 9,499,780, and 9,783,768 (the contents of each of these U.S. patents are incorporated by reference in their entirety).

[0125] As used herein, an "automated cell culture system" is an automated system that includes several operatively linked biological production units and processors.

[0126] As used herein, the terms "supported," "mounted," "connected," "joined," "coupled," "coupled," and "secured" may be used interchangeably with respect to the engagement of components of the carousel and of systems and methods incorporating the present invention. Additionally, any of these terms may be used in conjunction with the term "reversibly."

[0127] A general, non-limiting summary of the invention and its implementations is presented below. The summary outlines exemplary implementations of embodiments / aspects of the invention and provides a constructive basis for variations and / or alternative and / or divergent aspects / embodiments, some of which are described below.

[0128] An effective and economical automation strategy is to employ the use of process-specific bioreactors that can be controlled under automated sequencing. Such bioreactors may be configured within disposable, sterile cartridges or cassettes for robustness and operator convenience. Furthermore, the cassettes and associated control equipment required for automated sequencing implementation may be contained within an environmentally controlled enclosure (biological production unit) to achieve the following (non-limiting) operating conditions: 1. Mechanical and electrical control interface of dedicated cassette 2. Temperature control of environmental conditions for biological manipulation of cells 3. Gas control of environmental conditions for biological manipulation of cells 4. Separately controlled environment for refrigerated storage of reagents 5. Monitoring of critical processing parameters 6. Electronic storage of processed data consistent with data retention policies

[0129] To address the objectives of space-efficient organization and ergonomic access of multiple biological production units, an automated carousel has been developed and is described herein. The carousel is an upright carousel including a substantially vertical track assembly that supports and provides translational movement of multiple biological production units, either in unison or separately along a curved vertical track assembly, for precise user positioning. The carousel preferably translates the supported biological production units simultaneously (i.e., in unison) approximately ±180° vertically, clockwise or counterclockwise, along the curved vertical track assembly while maintaining precise alignment / orientation of each of the biological production units with respect to gravity. This ensures that any of the cell culture and / or tissue engineering systems supported within each of the biological production units are not adversely affected by changing the orientation of gravity applied thereto during changes in the vertical position of the biological production units. The carousel also includes means for individually and dynamically adjusting the axial rotation of any of the biological production units. Surprisingly, the translational and / or axial movement of the individual biological production units supporting the independently operable biological systems therein does not impair the interconnection of the units to a central source of operational resources. The carousel can also translate the supported biological production units separately. That is, rather than each unit moving in unison, a single unit can move while the remaining units remain stationary in a "grouped" or "gathered" orientation, for example, along the top or back of the carousel. If necessary, the next unit in the track can be translated separately from the remaining units, allowing work or inspection to be performed on that unit.

[0130] The carousel is configured within a housing that is powered by connection to a power source and is operatively connectable to a computer (e.g., via a remote device, a touchpad screen, or via a handheld device) for operational control.

[0131] The carousel of the present invention can be adapted for use with a variety of automated cell and tissue culture systems.

[0132] FIG. 1 illustrates one non-limiting embodiment of the present invention, showing the configuration of an automated carousel system 1 that enables the efficient integration of multiple independent cell production processes within an efficient spatial envelope. Carousel system 1 comprises an upright carousel 10 supported within the framework of a vertical housing assembly 12, which serves as a support frame and mounting structure for carousel 10. Vertical housing assembly 12 is mounted on a base 14. Vertical housing assembly 12 provides multiple functions, including mechanical support, central delivery of auxiliary and resources (e.g., power, gas, data, etc.), and workflow management. Carousel system 1 is illustrated as a "stand-alone" structure that requires no additional support and can be sized to a variety of sizes, not just the corresponding size of a carousel, as desired, limited only by the vertical space of a particular industrial biological setting.

[0133] Carousel system 1 illustrates the scale-up of biological production units, supporting eight biological production units 16 on its common framework. The carousel system's carousel 10 is shown configured substantially vertically to support eight individual, operationally independent biological production units 16 in an oval arrangement that follows the curved shape of the vertical carousel track frame (not shown) in a spatially close manner. One of the biological production units 16 is shown in an open configuration. The biological production units 16 are mounted on the carousel in a configuration for easy user access. In FIG. 1, this is shown in a cantilevered position that allows space for the user to easily access the cell and tissue culture systems therein when the unit is open. The biological production units 16 are translated along the carousel track frame, either in unison or separately, while maintaining their substantially uniform spacing and proper orientation relative to gravity. Because space is a key influencer of efficiency in Good Manufacturing Practice (GMP) facilities, the automated carousel system is configured to be compact by not only utilizing unused vertical space within the biological facility but also by centralizing and accommodating operational resources within the housing assembly 12. This allows the specific operational resource connections linking each of the biological production units in series to be neatly stored and merged into a central source of operational resources within a manifold-style cable system (see Figure 9). This configuration allows resources to be provided to each biological production unit when the carousel is stationary or during translation and / or individual axial rotation of any biological production unit.

[0134] FIG. 2 shows that the carousel 10 can rotate a total of ±180 degrees during translational movement (indicated by the arrows) along the carousel frame, allowing all biological production units 16 to be moved to any position relative to a preferred access point for the operator. Movement can be either clockwise or counterclockwise. Movement is precisely controlled incrementally, directional, and for a selected desired speed. Translational movement of the biological production units along the carousel track is optionally constrained to approximately ±180 degrees to eliminate any tendency to compromise the integrity of the cables (not shown) that supply resources (e.g., power, data, gas, etc.) to each of the individual biological production units in series from a central location within the vertical housing assembly.

[0135] Unlike traditional carousel designs for inventory management, mounting of the biological production units is important not only for efficient use of space but also to ensure that cell and tissue culture processing within each biological production unit is not adversely affected during translation of the biological production units along the carousel's vertical, curved path. Mounting also provides a further mechanism for additional dynamic control of the axial orientation of individual biological production units. Figure 3 shows that each biological production unit 16 can be independently and dynamically adjusted with respect to gravity and its axial orientation (arrow) through a defined range of angles (also referred to as "tilt" or "rock"). Dynamic axial rotational adjustment of any one of the biological production units can be performed during simultaneous translation of the biological production units along the carousel or when the carousel is stationary.

[0136] FIG. 4 shows the structure of a carousel 10 of the present invention, supporting a single cantilevered biological production unit 16 for simplicity. The carousel 10 is oriented upright (vertically) and includes a track assembly 18 having a drive track 20 and a support track 22, which are spaced apart, substantially parallel to one another, and mechanically secured to a rigid support frame (not shown). The carousel 10 may be oriented substantially vertically, with the drive track 20 and the support track 22 vertically related, e.g., at an angle of approximately 0° to 60° relative to fully vertical (perpendicular to the ground or floor). Each of the drive track 20 and the support track 22 is shown to be oval (closed loop) in shape, oriented such that the long path of the loop extends vertically and the track curves are located at the top and bottom of the track. The drive track is positioned forward of the support track for coupling with biological production units requiring user access. The support track is spaced vertically downward relative to the drive track. This vertical offset is fixed.

[0137] A translator assembly 24 is shown, serving as a mechanical link connecting the drive track 20 and the support track 22, providing simultaneous translational movement along the connected tracks. The translator assembly is configured to couple with the biological production units 16 at one end adjacent the drive track 20. The biological production units 16 are shown individually attached to the translator assembly 24 in a cantilevered position via a single cantilevered fixed reversible coupling (not shown). The translator assembly allows for cantilevered positioning of the biological production units. The single attachment point for each cantilevered biological production unit enhances service access to each of the biological production units, further improving overall space efficiency. The cantilevered fixed reversible coupling allows for coupling and uncoupling so that any given biological production unit can be removed / detached from the carousel arm assembly and replaced or repositioned in another position on the carousel. While one translator assembly is shown, it will be understood by those skilled in the art that multiple translator assemblies may be attached in any desired spacing relationship, each connecting the drive track to a support track supporting a cantilevered biological production unit.

[0138] Operationally, an automated carousel must exhibit geometric stability by ensuring that each production unit remains precisely aligned with respect to the gravity vector throughout the automated carousel's positioning / rotation. Systems in which orientation is not critical use gravity as a mechanism for alignment, with the center of gravity lower than the object's pivot point. However, such systems inadequately compensate for changes in the center of mass, which affect the position of the gravity vector relative to the object undergoing movement. The automated carousel described herein specifically orients the biological production unit with respect to the gravity vector, such that secondary movements within the biological production unit that affect the center of mass do not affect its orientation with respect to gravity. Furthermore, the resulting stability of the biological production unit(s) allows for movement of internal components with respect to the gravity vector to accomplish specific biological or fluidic events. For certain production unit operations requiring axial rotation apart from translational movement around the automated carousel's oval track, additional linkages are implemented to independently control the orientation of the production unit (as shown in Figure 3).

[0139] FIG. 5 shows in more detail the structure of the translation assembly 24, which is configured for synchronous translational movement along the tracks while supporting the biological production unit 16 in a cantilevered orientation. The translation assembly 24 includes a horizontal hub assembly 28 having a first end 30 with a laterally extending cantilevered fixed reversible coupling (not shown) for receiving the shaft of the biological production unit 16. The horizontal hub assembly 28 also includes a central hub 32 having a rigid extension 33 for supporting a drive carriage 36 that cooperatively engages the drive track 20 and its associated drive means (e.g., a drive belt or drive linkage, not shown). The horizontal hub assembly has a second end 38 to which is fixedly mounted a vertically downwardly extending resistance arm 40 via the inner hub. The resistance arm 40 extends downwardly parallel to both tracks, to which a support carriage 42 is fixed at its lowermost end via a pivotal mounting. The support carriage 42 cooperatively engages the support track 22 and its associated drive means (e.g., a drive belt or drive linkage, not shown). The drive carriage and support carriage move synchronously around the oval track such that the geometric constraints resulting from the fixed vertical offset of the drive track 20 and support track 22 ensure that the resistance arm 40 is always maintained in a vertical orientation.

[0140] The use of a translating assembly to support a biological production unit allows for repositioning of the biological production unit to a location convenient for operator access to the cell and / or tissue culture system supported therein. While only one biological production unit is shown, multiple translating assemblies may be configured to each support a cantilevered biological production unit and move along the track. The relative positions of each translating assembly may be constrained by interconnecting links. Furthermore, it is feasible to provide adjustable spacing for the positions of the biological production units, such that the spacing is exaggerated where unrestricted operator access is required, such as the rear aspect of a carousel, and reduced where operator access is not required.

[0141] In addition to providing consistent vertical axial orientation of the biological production unit during translation along the track, the provision of two mechanically and operatively linked carriages also provides the mechanical rigidity needed to resist any bending moments imparted on the drive rack by the cantilevered biological production unit.

[0142] It will be understood by those skilled in the art that the distance between the drive track and the support track can vary, and this may be due in part to the size of the translation assembly that provides the connection between the two tracks, the size and weight of the biological production unit, and the engineering forces required for proper cantilever mounting of multiple units. Although the biological production units are cantilevered using cantilever mounting, it will be understood that other mountings with other orientations may be used. Furthermore, where only one biological production unit is shown cantilevered on each translation assembly, it will be understood that smaller biological production units may be used, and thus two or more biological production units may be mounted in either a serial or cantilevered position adjacent each translation assembly.

[0143] It is also understood that the shape and size of the drive track and support track should be substantially identical for proper translational movement along the carousel track and orientation relative to gravity. While the frame tracks are shown to be substantially oval, the shape can vary, limited only by the ability to space the biological production units supported on the carousel and provide approximately ±180 degrees of rotational bidirectional movement. Thus, the tracks may be substantially oval, substantially elliptical, or substantially capsule-like. The carousel can be designed to any vertical height (e.g., size), limited only by the facility in which it will be used. The two tracks that make up the carousel frame can be of any desired thickness and made of suitable materials capable of withstanding the stress cycles and dynamic loading conditions during its use. Suitable materials include typically used engineering materials, such as, but not limited to, metals and metal alloys (e.g., composed of high-grade stainless steel, steel alloys, iron, copper, aluminum, and combinations thereof).

[0144] FIG. 6 shows the translation assembly 24 with a portion of the central hub 32 detached and separated. The translation assembly 24 shows a central section that is a horizontal hub assembly 28. A first end 30 of the horizontal hub assembly has a cantilevered fixed reversible coupling 26 for mounting a biological production unit. The central hub 32 has an outer hub shell 34 having one side fixed via a rigid extension to a drive carriage 36 that cooperatively engages a drive track for translational movement thereon. An inner hub 44 is held via bearings within the outer hub shell 34. The inner hub 44 is constrained from rotation within the outer hub shell via a resistance arm 40 fixedly attached to the inner hub and from projecting vertically downward to connect with a support carriage 42 via a pivot connection and configured to cooperatively engage the support track 22 and its associated drive means (not shown). As the outer hub shell 34 undergoes rotational reversals while traveling the oval path of the primary track, the inner hub is constrained to maintain a consistent orientation with respect to gravity by constraining the attached resistance arms to remain vertical. This constraint on the resistance arm orientation occurs through the cooperative positioning of the drive carriage and support carriage, such that the drive carriage is always positioned vertically above the secondary carriage as the carriages travel around the track.

[0145] The coupling 26 supporting the cantilevered biological production unit mechanically engages a motor-driven central shaft 54 ​​within the via-bearing inner hub 44. The motor-driven central shaft is either constrained from rotation within the inner hub 44 or actively rotated at a controlled speed by a motor drive and gearbox mounted on the inner hub that drives the axial rotation of the central shaft. Through controlled orientation of the inner hub with respect to gravity and controlled orientation of the central shaft with respect to the inner hub, selective axial rotation of the central shaft and therefore of the biological production unit with respect to gravity is possible.

[0146] The drive carriage 36 is a drive block assembly 56 having one face 58 thereof secured to a pair of vertically disposed outwardly projecting bearing members 60 for engaging the primary track 20 and its associated drive means adapted for translational movement along a path of travel defined by the primary track.

[0147] The support carriage 42 is a support block assembly 62 having one face 64 to which a pair of vertically disposed outwardly projecting bearing members 66 are fixed for gripping the support track for movement along a path of travel defined by the support track. The support carriage actively translates along the support track in a synchronized manner with the drive carriage while maintaining a fixed vertical offset depending on the length of the lever arm.

[0148] Although two bearing pairs are shown on each of the primary and support carriages (i.e., 60 and 66, respectively), it will be understood by those skilled in the art that additional sets may be incorporated for additional gripping of either the primary or support tracks.

[0149] During operation, translation assembly 24 and similar translation assemblies present on the track move in unison through the physical connection of the primary carriage to the primary drive belt and motor assembly and the secondary drive belt connecting the secondary carriage. This movement is a gliding movement with minimal friction due to the bearing interface between the carriage and the track. Furthermore, the carriage supports significant lateral and bending loads. This load-bearing capability and the use of two carriages offset through the translation assembly allows significant cantilever loads to be resisted, thereby ensuring stable translation of the biological production unit from position to position.

[0150] The biological production unit 16 is rigidly mounted to the translation assembly 24 via a cantilevered fixed reversible coupling 26 that cooperates with a motor-driven central shaft 54 ​​held within an inner central hub 44. The inner central hub maintains a consistent orientation relative to the gravity vector at all times. The motor-driven assembly positions the central shaft 54 ​​axially relative to the inner central hub. When the motor-driven coupling 46 is quiescent, the biological production unit (and thus the cell and / or tissue culture system contained therein) maintains a given orientation relative to the gravity vector. Through activation of the motor-driven coupling 46, the axial position of the central shaft 54 ​​can be changed in either direction, thereby dynamically changing the position of the cell and / or tissue culture system relative to the gravity vector axially. This change in the axial orientation of the biological production unit can be intermittent to support specific biological activities occurring within a cassette mounted within the biological production unit, or it can be continuous (e.g., rocking or tilting) of a bioreactor within a cassette housed within the biological production unit.

[0151] FIG. 7 shows a fully populated carousel, illustrating the positioning of the translation assembly components relative to different positions of the biological production unit on the carousel, both in the long path section and the track bend. It is clear that the resistance arm 40 is held in its vertical position regardless of the position of the biological production unit along the track. During translation along the track bend, the outer hub shell 34 and drive carriage 36 undergo a rotational reversal while the support carriage pivots to undergo a reversal. The drive carriage and associated support carriage move cooperatively from position "A" (vertical) to position "B" (horizontal, with the outer hub shell undergoing a rotational reversal) to position "C" (vertical, with the rotational reversal completed). Throughout this arrangement, the resistance arm 40 is held in a vertical orientation by the linkage mechanism.

[0152] In the production of patient-specific therapies, a need exists to enable independent operation of each biological production unit because the initialization, processing, and completion of each patient-specific production activity typically do not align with other concurrent production requirements. Thus, each biological production unit is independently controlled with respect to the biological processing conditions occurring within it. This requires the delivery of common resources to each biological production unit, with the consumption of such resources being internally controlled within each production unit.

[0153] The rotational movement of multiple biological production units presents unique challenges to resource delivery and management. To minimize the complexity of resource distribution, a rotation limit of approximately ±180 degrees for the automated carousel is preferred. Due to this rotational constraint, a robust and functionally reliable cabling strategy has been developed for the transport of auxiliary equipment and resources (e.g., power, supply gas, and data).

[0154] Figure 8 illustrates the complexity of a representative fully populated carousel operatively supported on a vertical housing assembly 12 that supports a central operating resource for delivery. As shown in Figure 9, each biological production unit is operatively attached via a cable (70) inserted through a port connection 50 that extends and connects to a centrally located source within the vertical housing assembly 12. The cable 70 from the central source connects to the first biological production unit and onward to each successive biological production unit. This interconnected cabling strategy eliminates the complexity of establishing separate cables for resources for every biological production unit to the centrally located source.

[0155] Safety precautions are operational requirements for automated carousels to protect both the operator and the continued viability of ongoing biological processing within each biological production unit. Moving parts are either contained or have uninterrupted surfaces relative to other moving / fixed parts to prevent pinch points. In cases where these conditions are not possible, other methods to avoid injury are required. The housing assembly shown in Figure 8 is further configured with a protective cover 72 to help isolate and therefore protect the user from the resource distribution network and other parts.

[0156] A safety clutch is also provided to allow automatic interruption of carousel movement in the event of a higher than normal torque being generated by the drive system of the automated carousel. Clutch slippage during high torque protects users from pinch hazards that may be created by the biological production units rotating along the track path and prevents the transfer of potentially damaging torque to other components within the automated carousel in the event of a malfunction.

[0157] Servicing and cleaning of the automated carousel is required for operation within a GMP facility. Temporary relocation of the automated carousel is potentially advantageous in maintaining a clean production space. Wheels 74 present beneath the base 14 are configured to deploy when portability is required. When stationary, the wheels 74 are retracted within the base to ensure stable placement of the base 14 relative to the underlying floor structure.

[0158] Figure 10 shows a typical configuration / size of a carousel supporting six to ten biological production units. A fully populated "housed" carousel is also shown in series, demonstrating a greatly increased production capacity of a biological facility for cell and / or tissue culture engineering. Carousels can be configured / sized to accommodate any number of biological production units. The height of a carousel is typically determined by the overhead clearance within the building in which it will be installed. Generally, carousels are configured to have a maximum height compatible with the building structure to maximize the number of biological production units supported on a given carousel. For example, a carousel can be two or more stories tall, fitting within a two- to three-story (or higher) building to maximize the use of vertical space within the biological facility. In such embodiments, scaffolding and / or platforms can be added to the carousel to add structural integrity and provide additional work areas for scientists to stand and monitor biological production. Carousels can also span or physically incorporate walkways or platforms that allow technicians to access the carousel at different heights, allowing for multiple access points for multiple users. Additional laboratory equipment can also be housed on the platform as needed to provide multiple work areas. Carousels can also be used to allow the movement of biological production units from one environmental class to another. For example, a carousel can span a sufficient height such that the bottom section has a first cleanroom classification (e.g., a regulated cleanroom environment), and then allow the translation of the biological production unit to an upper section with a different cleanroom classification (e.g., an unregulated cleanroom environment) to allow different production unit interactions to occur under different environmental conditions. Additional classifications can also be envisioned.

[0159] The spacing between biological production units is adjustable and selected to provide spacing appropriate for the size of the biological production units. This allows for customization of a given carousel for the specific type of biological production unit supported thereon. It should be noted that while the drawings show all biological production units as being similar in type, it is within the scope of the present invention to simultaneously display various types of biological production units on a given carousel. It is further provided that carousels and carousel systems may be further configured with the distinct ability to adjust the spacing of each biological production unit relative to adjacent biological production units, such that closing the spacing maximizes the spatial density of biological production units in selected zones of the carousel, and opening the spacing increases user access to biological production units in other selected zones. In one non-limiting example, once a desired biological production unit is selected and properly positioned for the user, adjacent biological production units may be further translationally repositioned "away" from the selected biological production unit to provide more space for the user.

[0160] To accommodate different user access requirements, the biological production units may be precisely positioned by the user for a selected user, and an interface for the user to effectively communicate with each biological production unit on the carousel is provided and adjustable.

[0161] Figure 11 shows representative measurements that can be used to define the range of placements of any particular production unit to provide ergonomic access by the operator. Thus, using the automated carousel of the present invention not only increases biological production, but also provides easy and comfortable access for users to any one of the biological production units, whether for inspection, replacement, removal, or repositioning. A user may position any of the biological production units at a vertical ergonomic level while standing or sitting.

[0162] As described herein, the biological production units 16 are suitably configured to move together or separately to allow easy access to the vertical position of any single unit. In embodiments, one or more additional stationary units can be attached to the carousel as workflow units. These workflow units can be utilized for specific functions by retrieving cassettes from the currently translated unit in the carousel series and translating them to the stationary unit for additional processing. The stationary workflow units can also be utilized as resources when temporary operational support is needed to address the malfunction event of a single biological production unit. This temporary role can support unit repair or unit replacement.

[0163] In further embodiments, a secondary processing module can also be included in the carousel described herein. This secondary processing module can be engaged when the biological production unit 16 reaches a specific position in its translation. For example, the secondary processing module can be a bioisolator for creating a controlled environment around a specific production unit for specific cassette processing requirements or other technical functions. This bioisolator can allow an operator to intervene in the operation of the unit in a way that would not be possible if the unit were open to the general public (e.g., external contamination, or either highly specialized or potentially toxic cells or viruses used in the unit).

[0164] The above illustrates that the automated device of the present invention achieves further significant improvements in automated cell and tissue culture applications. Complex, automated, modular biological culture systems can be improved by incorporating the device of the present invention, allowing for greater capacity to provide much-needed cells and tissues for patient treatment in the same space without compromising system integrity or system versatility. Operation of each biological production unit in terms of ready access is ergonomic and easily achievable by any user as needed.

[0165] While several embodiments of the present invention have been described and illustrated herein, those skilled in the art will readily envision a variety of other means and / or structures for carrying out the functions and / or for obtaining the results and / or one or more advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the specific application(s) for which the teachings of the present invention are used. Accordingly, the foregoing embodiments are presented by way of example only, and it should be understood that, within the scope of the appended claims and equivalents thereof, the invention may be practiced otherwise than as specifically described and claimed.

[0166] The description of various embodiments and / or examples of the present invention is presented for illustrative purposes, but is not intended to be exhaustive or limited to the disclosed embodiments and / or examples. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terms used herein were selected to best express the principles of the embodiments, practical applications or technical improvements to technology found in the market, or to enable those skilled in the art to understand the embodiments disclosed herein.

Claims

1. a vertical housing assembly attached to the base; a plurality of biological production units, each biological production unit supported on and separately movable along a carousel track, each biological production unit further comprising a cell culture system enclosed within the respective biological production unit; a translation assembly disposed within the vertical housing assembly, the translation assembly configured to support each biological production unit and move each biological production unit along the carousel track to a location for operator access to the cell culture system within the plurality of biological production units; The automated carousel is configured such that the translation assembly further provides a consistent vertical axial orientation of the plurality of biological production units when moving each biological production unit to the location for operator access, and the translation assembly provides adjustable spacing of the plurality of biological production units where unrestricted operator access is required and reduced spacing of the plurality of biological production units where operator access is not required.

2. The automated carousel of claim 1 , further comprising a plurality of translating assemblies for supporting the plurality of biological production units.

3. The automated carousel of claim 1 further comprising a location within the vertical housing assembly for supplying resources to each biological production unit.

4. The automated carousel of claim 3 , further comprising power cables, data cables, and gas cables connecting each biological production unit to the location for supplying resources.

5. 10. The automated carousel of claim 1, further comprising a motor-driven central shaft for engaging an input shaft of each biological production unit, wherein actuation of the motor-driven central shaft actively rotates the motor-driven central shaft at a controlled speed to cause the associated biological production unit to pivot.

6. 10. The automated carousel of claim 1, wherein each biological production unit is a cell and / or tissue engineering system configured to perform one or more of the following: sterile receipt / storage of tissue biopsies; automated monitoring of the digestion process; digestion of biopsy tissue to obtain dissociated cells; cell sorting and selection; safe waste collection; cell seeding on or within a growth substrate; scaffold propagation of cells to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to enable specialization of cell activity; tissue formation; mechanical and / or biochemical stimulation to promote tissue maturation; harvesting of tissue engineered constructs / implants for reconstructive surgery; and storage and transport of cells and transplantable tissues.

7. 1. An automated carousel system for distribution and ergonomic placement of a plurality of biological production units, each biological production unit comprising an individually operable automated cell culture system, the automated carousel system comprising: a) an automated carousel; and b) a controller; a) the automated carousel is a vertical housing assembly attached to the base and having locations for supplying resources to each biological production unit; a translation assembly disposed within the vertical housing assembly and configured to support each biological production unit and move each biological production unit to a location for operator access to a cell culture system within each biological production unit; a translation assembly that further provides a consistent vertical axial orientation of each biological production unit as it is moved to the location for operator access; an inner hub having a central shaft for engaging an input shaft of each biological production unit, the central shaft attached to an extending resistance arm, the inner hub configured to separately pivot each biological production unit; the translation assembly further supports each biological production unit; (i) translating each biological production unit separately while maintaining the cantilevered orientation of each biological production unit; (ii) pivoting each biological production unit; (iii) configured to provide adjustable spacing of each biological production unit where unrestricted operator access is required and reduced spacing of each biological production unit where operator access is not required; b) An automated carousel system, wherein the controller is for independent biological control of each cell culture system within each biological production unit.

8. 8. The automated carousel system of claim 7, further comprising power cables, data cables, and gas cables connecting each biological production unit to the location for supplying resources.

9. 8. The automated carousel system of claim 7, wherein each biological production unit comprises a connected interface for communication by a user, said connected interface being connected to a computer connection.

10. The automated carousel system of claim 7 further comprising a plurality of translating assemblies.

11. The automated carousel system of claim 10 further comprising up to 24 translating assemblies.

12. The automated carousel of claim 7 , wherein the translation assembly further provides a consistent vertical axial orientation of each biological production unit as it moves each biological production unit to the location for operator access.

13. 10. The automated carousel of claim 7, wherein each biological production unit is a cell and / or tissue engineering system configured to perform one or more of the following: sterile receipt / storage of tissue biopsies; automated monitoring of the digestion process; digestion of biopsy tissue to obtain dissociated cells; cell sorting and selection; safe waste collection; cell seeding on or within a growth substrate; scaffold propagation of cells to expand cell populations; cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to enable specialization of cell activity; tissue formation; mechanical and / or biochemical stimulation to promote tissue maturation; harvesting of tissue engineered constructs / implants for reconstructive surgery; and storage and transport of cells and transplantable tissues.

14. 1. A method for improving ergonomics for an operator of an automated carousel system, the automated carousel system comprising a plurality of independent cell and / or tissue engineering systems each supported within a biological production unit, the method comprising: mounting a plurality of biological production units on an automated carousel, the automated carousel comprising carousel tracks for separately moving each biological production unit along the carousel tracks; separately moving each biological production unit along the carousel track via a translation assembly to a location for operator access while maintaining a cantilevered orientation of each biological production unit; Including, The method, wherein the translation assembly is configured to provide adjustable spacing between each biological production unit where unrestricted operator access is required, and to provide reduced spacing between each biological production unit where operator access is not required.

15. 15. The method for improving ergonomics described in claim 14, further comprising sending one or more translational movement commands to the automated carousel to translate each biological production unit in unison, wherein the one or more translational movement commands include information regarding a location on the automated carousel of a target biological production unit for placement and information regarding physical measurement specifications of a particular operator who is standing or sitting.

16. 16. The method for improving ergonomics described in claim 15, further comprising identifying the target biological production unit for ergonomic placement for a specific operator and placing the target biological production unit according to the physical measurement specifications of the specific operator standing or sitting.

17. 17. The method for improving ergonomics described in claim 16, further comprising stopping the one or more translational movement commands when the target biological production unit is positioned at the location for operator access, and transmitting one or more results of the ergonomic positioning to a remote management device via a communication interface of the automated carousel.

18. 15. The method for improving ergonomics of claim 14, further comprising maintaining a consistent vertical axial orientation of each biological production unit when moving each biological production unit to the location for operator access.

19. 15. The method for improving ergonomics of claim 14, further comprising communicating operational instructions from a remote management device to a controller via a communication device.

20. 15. The method for improving ergonomics described in claim 14, further comprising limiting the translational movement of each biological production unit to approximately 180° to reduce the risk of compromising the integrity of cables supplying resources to each biological production unit from their positions within the automated carousel.

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