Patent Application
20200200781
This invention relates to an upright carousel that provides translational movement of multiple biologic production units along a defined vertical path while maintaining each individual unit stable relative to gravity and further provides for separate dynamic axial rotation of each independent unit. The carousel is automated and adaptable for use with a variety of modular biologic production units designed for cell culture and/or tissue culture systems in various clinical and laboratory settings. The carousel and related systems and methods allow ergonomic and practical access to each of the biologic production units.
Existing engineered robotic systems for automated cell culture and tissue engineering processes are complex, require significant laboratory space for operation, and represent a substantial capital equipment investment.
Equipment design is frequently recognized as a key component in the success of GMP (Good Manufacturing Practice) biologics manufacturing, but is not always implemented with full appreciation of the processing implications. In the case of mammalian cell culture, there are recognized issues and risks that develop when transitioning to a large automated scale of operation. The developing demand for cell culture production capacity in the biopharmaceutical industry has led to a progressive increase in the scale of automated operation.
There is a growing demand for patient-specific treatments, such as for autologous cell therapy. Autologous cell therapy requires complex multiple concurrent processing events placing considerably more demands with respect to automation. Automated production units can only service one patient at any given production cycle. Scaling for large parallel processing for large numbers of patients generates the need for developing space-efficient organization and access to multiple production units within a production facility.
Accordingly, it is desirable to develop ways to achieve maximized cell and/or tissue production in existing production facility confines. Further, it is desirable to develop ways to achieve maximized cell and/or tissue production in existing production facility confines that does not detrimentally affect the integrity of the cell and tissue culture systems. It is also desired to improve ergonomics for users of automated cell and tissue engineering systems.
The discussion of the background herein is included to explain the context of the inventions described herein. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge as of the priority date of any of the claims.
Herein described is a more economical and space efficient manner to operate several biological production units in a production facility where floor space is in demand, while providing a practical and ergonomic access to the cell and/or tissue culture systems within each of the biological production units.
Set forth is an upright automated carousel configured to support several biological production units that can be translationally moved along the vertical path of the carousel in unison and stopped to a user selected position for access to any one of the biological production units. During this translational movement each individual unit remains stable relative to gravity, that is, remains properly orientated horizontal to gravity. Concurrently, the automated carousel further provides for individual dynamic adjustment of axial rotation of any one or all of the units. Proper orientation of each of the units relative to gravity is maintained during active translation of the units and when the carousel is stationary. Similarly, the individual dynamic adjustment of the axial orientation of any one or all of the units can be actuated during active translational movement of the units or when the carousel is stationary
Advantageously, the operation of the automated carousel for user positioning does not negatively affect the cell and/or tissue culture/engineering processes that are supported within any one of the biological production units.
Advantageously, the automated carousel is configured so that each of the biological production units supported on the carousel is independently operable and customized with respect to the cell and/or tissue culture/engineering processes that are supported within any one of the biological production units.
Advantageously, the biological production units supported on the carousel are so linked that the operational resources required for each of the biological production units are optionally one central means for ease of use. Surprisingly, the linkage to the central operational resources is operationally maintained during translational movement of the biological units along the vertical curved path of the carousel and during any individual adjustment of axial rotation of any one of the units. This is particularly advantageous for being able to provide multiple biological production units on a single carousel each with customized cell and/or tissue culture/engineering processes, yet optionally all share the same central operational resources and also share the same translational movement ability for user positioning and separate ability for independent axial rotation.
The automated carousel of the invention is advantageously configured to utilize vertical space for the distribution, operation and uniform translational movement of multiple biological production units arranged in a close spatial relationship along its curved vertical path. Translational movement is in a vertical plane and follows the curved shape of the carousel. Translational movement may be up to about 180 degrees clockwise or counterclockwise, of varying speeds and is user controlled. The translational movement is designed to be precise and in controlled increments such that an operator (no matter what height) can position any one of the biological units to a position for ergonomic access whether in a standing or a sitting position. The carousel is configured with a safety stop mechanism to stop movement at any time as desired or required. The axial rotation of any one individual biological production unit may also be clockwise or counterclockwise to provide a rocking motion or for agitation.
Attachment of the biological production units to the carousel is reversible such that each unit can be inspected, removed, replaced or repositioned to a different position on the carousel or to a different carousel. In an aspect, the biological production units are attached in a cantilevered orientation to allow easier access by a user and to maintain the efficient use of floor space.
It is contemplated that different types of biological production units may be mounted to one carousel so long as the basic size, weight and independent functioning capabilities are comparable to other units mounted on the carousel in order not to negatively affect the overall balance of the carousel, the uniform bi-directional translational movement along the carousel frame, the gravitational orientation of the biological production units mounted thereon, or the ability to independently dynamically adjust the bi-directional axial orientation relative to gravity of any one of the units. Further, each of the biological production units mounted on the carousel may support a different cell culture and/or tissue culture system therein customized for a specific need or a specific patient.
The automated carousel may be provided as a system disposed vertically within a vertical housing for central operation and central provision of operational resources to each of the independently controlled biological production units that function to support a cell and/or tissue culture system therein. The vertical housing serves as a support frame and attachment structure for the carousel to maintain an upright positioning of the carousel and for its operation. The vertical housing is configured to readily permit reversible attachment of the biological production units, their proper translational movement along the carousel shape, and for user access. The vertical housing has a supporting base and retractable wheels for ease of relocation. The vertical housing is configured for ease of assembly and disassembly, for centrally storing required resources and for user safety.
User access, service access and space efficiency is improved when supporting multiple biological production units on an automated carousel of the invention. Furthermore, the carousel of the invention can provide increased expandability, by taking full advantage of the height of a biological production facility. Several carousels can be arranged and used in series. Therefore numerous biological production units can be run in a production facility in a space efficient yet operator accessible manner.
The carousel is used in conjunction with one or more controllers, controller communications interface, associated software and remote management device (e.g. computer). Software is customizable for specific applications, is menu-driven and user-friendly. For example, rotation of the biological production units attached to the carousel may be defined by user set programs for precise control of movement and positioning of each biological production unit. The carousel can be operable from a central workstation or remote management device. A convenient user actuated touch pad screen device may be used and connected to each of the biological production units operationally connected to a central computer.
According to an aspect of the invention, is an upright carousel for translating a plurality of biological units in unison along a vertical elliptical orbit while maintaining each individual biological load stable relative to gravity, and providing for individual dynamic axial rotation of any one or all of the biological units.
In aspects, the carousel comprises a spacing adjustment means to adjust the spacing of each biological unit relative to adjacent biological units so as to maximize the spatial density of biological units in selected zones of the carousel by close spacing and enhance user access to biological units in other selected zones by open spacing.
In aspects, each of the biological units are independently operable and linked to a central source of operational resources.
In aspects, the biological loads are sensitive to orientation relative to gravity.
In aspects, the carousel comprises an upright drive track and a support track vertically offset from one another and held together by a plurality of linkage mechanisms, each of the linkage mechanisms adapted to support a biological unit during translational movement along the elliptical orbit of the drive track and support track.
In aspects, the biological units are supported in a cantilevered position for ease of user access once positioned.
In aspects, the plurality of cantilevered biological units are translationally positioned in unison along an upright frame comprising two vertically offset tracks. In aspects, the tracks are substantially oval. In aspects oval closed loops.
In aspects, the speed and direction of translation (clockwise or counter-clockwise) is user controlled and adjustable.
In aspects, alignment of each cantilevered biological unit is substantially maintained relative to gravity during translational movement of the units or when the carousel is stationary.
In aspects, the carousel provides dynamic adjustment of axial orientation (bi-directional) relative to gravity of each independent cantilevered biological unit during translational movement of the units or when stationary.
In aspects, precise positioning of each cantilevered biological unit is user controlled for ergonomic access.
In aspects, the cantilevered biological unit is a cantilevered biological production unit.
In aspects, the cantilevered biological production unit operationally supports an automated cell culture and/or tissue engineering system.
In aspects, each of the biological production units are independently operable to provide a customized cell culture and/or tissue engineering systems. In aspects, the cell culture and/or tissue engineering systems are for autologous cell therapies.
In aspects, the carousel reduces overall space/storage footprints while increasing employee safety and efficiency.
In aspects, the carousel is part of a system that further comprises a housing for vertical operational support of the carousel and means for connection of each biological production unit in succession to a central source of auxiliaries and resources.
In aspects of the invention is an automated carousel system for organizing, storing, and ergonomically accessing cell and/or tissue engineering systems enclosed in a biological production unit.
In aspects, the automated carousel and systems incorporating the carousel greatly increases facility biological operational capacity by fully utilizing overhead space to recover up to 70% of the floor space required by conventional biological culturing systems.
According to an aspect of the invention is an automated vertical track assembly for supporting a plurality of biological units, wherein the carousel is configured for:
(i) user operated start and stop of translational movement of the biological units in unison along a defined path of the vertical track while maintaining each of the biological units properly oriented with respect to gravity; and
(ii) user operated start and stop of axial rotation of individual biological units;
wherein during both (i) and (iii) each of the biological units is independently operable support a customized automated cell and tissue culture system therein; and
wherein each of said biological units is interlinked to share a central source of operational resources.
According to an aspect of the invention is a vertical carousel comprising a plurality of biological units substantially geometrically constrained to translationally move in unison in a vertical elliptical orbit while maintaining the proper orientation of each of the plurality of biological units with respect to gravity, and separately axially rotating any independent one or more of the plurality of biological units.
According to another aspect of the invention is a vertical carousel comprising:
a plurality of biological units substantially geometrically constrained for translational movement along a vertical elliptical orbit in unison while maintaining a stable orientation of each of the plurality of biological units with respect to gravity, and for separate axial rotation of any one or more of the plurality of biological units;
means to control the translational movement of the biological units for user positioning; and
means to actuate the axial rotation of the any one or more of the plurality of biological units.
According to an aspect of the invention is an automated carousel comprising:
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 positions, each translation assembly supporting a cantilevered biological unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological unit with respect to gravity, and separately, (ii) axial rotation of each biological unit.
According to an aspect of the invention is 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.
According to a further aspect of the invention is a method for maximizing cell and/or tissue engineering production, the method comprising providing a series of the automated carousel system as described herein in a production facility.
According to a further aspect of the invention is a translation assembly for a vertical carousel having a drive track and vertically off set support track, for supporting a biological 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 unit;
a central hub comprising:
a second end having a vertically downward extending resistance arm mounted via the inner hub and at its vertically lowest point a pivotally connected support carriage cooperatively engaged with the support track for translational movement thereon, wherein the vertically extending resistance arm prevents rotation of the inner hub and is maintained in a vertical orientation by geometrical constraint arising from the fixed vertical offset of the drive track and support track during translational movement along the tracks.
According to an aspect of the invention is an automated carousel system for the distribution and ergonomic positioning of multiple 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 apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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 operational resources;
means for interconnecting the central source of operational resources to each successive biological production unit; and
computer connection.
According to an aspect of the invention is a method for improving ergonomics for users of an automated carousel system that comprises a plurality of independent culture systems each supported within a biological production unit, the method comprising:
mounting a plurality of biological production units on 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 apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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;
wherein (i) and (ii) is user controlled for ergonomic access to each biological production unit by a user.
According to a further aspect of the invention is a method for increasing biological production capacity utilizing cell and/or tissue culture systems in a production facility, the 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 positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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.
According to a further aspect of the invention is an ergonomic automated carousel for supporting automated individually operable biological systems, the carousel comprising:
a plurality of translation assemblies connecting a drive track and a support track at spaced apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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 to select translationally move any one of the biological production units along the connected track to a specific position to accommodate a user for ergonomic inspection by said user.
According to a further aspect of the invention is a method for ergonomically positioning an automated selected cell culture and/or tissue engineering system for inspection by a user, the method comprising:
sending one or more translational movement operating instructions to an upright carousel comprising a plurality of spaced apart cantilevered biological production units configured to contain the cell and/or tissue culture system for translationally moving the plurality of cantilevered biological production units in unison via a remote management device, the one or more translational movement instructions comprising information about the location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications of a specific user standing or seated,
the carousel comprising a controller and a communication interface, the controller being configured to:
(i) receive the one or more rotation operating instructions from a remote management device via the communication interface,
(ii) operate the carousel for translational movement of the plurality of cantilevered biological production units, while maintaining proper orientation relative to gravity of each of the cantilevered biological production units during translational movement or when stationary,
(iii) adjust axial orientation relative to gravity of any one or more of the plurality of cantilevered biological production units during translational movement or when stationary,
(iv) identify the target biological production unit for ergonomic positioning for the specific user,
(v) position the target biological production unit according to the physical measurements of the specific user standing or seated, and
send one or more results of (i)-(v) to the remote management device via the communication interface,
receive instructions from the remote management device via the communication interface of the carousel to operate the carousel for translational movement to ergonomically position the target biological production unit to the physical measurement specifications of the specific user,
stopping the translational movement operating instructions when the target biological production unit is ergonomically positioned, and
sending one or more results of the ergonomic positioning to the remote management device via the communication interface of the carousel.
In any of the aforementioned aspects, one of skill in the art recognizes that the automated upright carousel can operationally 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 10 units, up to about 12 units, up to about 14 units, up to about 16 units, up to about 18 units or up to about 20 units or more.
The automated carousel enables ergonomic access to a specific independent cell and/or tissue culture system without disturbance of the biological processes underway in any of the other independent multiple 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 nervous system issues and/or configured to prevent such issues in the first instance for laboratory personnel. In embodiments, the ergonomic carousel is suitable for vertical adjustment for a sitting configuration to a standing configuration or vice-versa.
(i) user operated start and stop of translational movement of the biological units in unison along a defined path of the vertical track assembly while maintaining each of the biological units properly oriented with respect to gravity; and
(ii) user operated start and stop of axial rotation of individual biological units;
wherein during both (i) and (iii) each of the biological units is independently operable to support a customized automated cell and tissue culture system therein; and
wherein each of said biological units is interlinked to share a central source of operational resources.
a plurality of biological units substantially geometrically constrained for translational movement along a vertical elliptical orbit in unison while maintaining a stable orientation of each of the plurality of biological units with respect to gravity, and for separate axial rotation of any one or more of the plurality of biological units;
means to control the translational movement of the biological units for user positioning; and
means to actuate the axial rotation of the any one or more of the plurality of biological units during translational movement or when stationary.
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 positions, each translation assembly supporting a cantilevered biological unit,
wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological unit with respect to gravity, and separately, (ii) axial rotation of each biological unit.
a first end defining a reversible coupling for receiving an input shaft of the cantilevered biological unit;
a central hub comprising:
a second end having a vertically downward extending resistance arm mounted via the inner hub and at its vertically lowest point a pivotally connected support carriage cooperatively engaged with the support track for translational movement thereon, wherein the vertically extending resistance arm prevents rotation of the inner hub and is maintained in a vertical orientation by geometrical constraint arising from the fixed vertical offset of the drive track and support track during translational movement along the tracks.
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 apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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 operational resources;
means for interconnecting the central source of operational resources to each successive biological production unit; and
computer connection.
mounting a plurality of biological production units on 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 apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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;
wherein (i) and (ii) is user controlled for ergonomic access to each biological production unit by a user.
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 positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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.
a plurality of translation assemblies connecting a drive track and a support track at spaced apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks 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 to select translationally move any one of the biological production units along the connected track to a specific position to accommodate a user for ergonomic inspection by said user.
sending one or more translational movement operating instructions to an upright carousel comprising a plurality of spaced apart cantilevered biological production units configured to contain the cell and/or tissue culture system for translationally moving the plurality of cantilevered biological production units in unison via a remote management device, the one or more translational movement instructions comprising information about the location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications of a specific user standing or seated,
the carousel comprising a controller and a communication interface, the controller being configured to:
(i) receive the one or more rotation operating instructions from a remote management device via the communication interface,
(ii) operate the carousel for translational movement of the plurality of cantilevered biological production units, while maintaining proper orientation relative to gravity of each of the cantilevered biological production units during translational movement or when stationary,
(iii) adjust axial orientation relative to gravity of any one or more of the plurality of cantilevered biological production units during translational movement or when stationary,
(iv) identify the target biological production unit for ergonomic positioning for the specific user,
(v) position the target biological production unit according to the physical measurements of the specific user standing or seated, and
send one or more results of (i)-(v) to the remote management device via the communication interface,
receive instructions from the remote management device via the communication interface of the carousel to operate the carousel for translational movement to ergonomically position the target biological production unit to the physical measurement specifications of the specific user,
stopping the translational movement operating instructions when the target biological production unit is ergonomically positioned, and
sending one or more results of the ergonomic positioning to the remote management device via the communication interface of the carousel.
The following description of typical aspects described herein will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings aspects which are presently typical. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the aspects shown in the drawings. It is noted that like reference numerals refer to like elements across different embodiments as shown in the drawings and referred to in the description.
The description herein will be more fully understood in view of the following drawings:
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 is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.
In the case of conflict, the present specification, including definitions, will control.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the subject matter herein belongs. As used herein, the following definitions are supplied in order to facilitate the understanding of the present invention.
As used herein, the articles “a” and “an” preceding an element or component are intended to be non-restrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore, “a” or “an” should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
As used herein, the terms “invention” or “present invention” are non-limiting terms and not intended to refer to any single aspect of the particular invention but encompass all possible aspects as described in the specification and the claims.
As used herein the terms ‘comprises’, ‘comprising’, ‘includes’, ‘including’, ‘having’ and their inflections and conjugates denote ‘including but not limited to’ and are to be understood to be open-ended, e.g., to mean including but not limited to.
As used herein, the term “about” refers to variation in the numerical quantity. In one aspect, the term “about” means within 10% of the reported numerical value. In another aspect, the term “about” means within 5% of the reported numerical value. Yet, in another aspect, the term “about” means within 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% of the reported numerical value.
Should a range of values be recited, it is merely for convenience or brevity and includes all the possible sub-ranges as well as individual numerical values within and about the boundary of that range. Any numeric value, unless otherwise specified, includes also practical close values and integral values do not exclude fractional values. Sub-range values and practically close values should be considered as specifically disclosed values.
It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation.
As may be used herein the terms ‘close’, ‘approximate’ and ‘practically’ denote a respective relation or measure or amount or quantity or degree that has no adverse consequence or effect relative to the referenced term or embodiment or operation or the scope of the invention.
As may be used herein any terms referring to geometrical relationships such as ‘vertical’, ‘horizontal’, ‘parallel’, ‘opposite’, ‘straight’, “lateral”, “parallel”, “perpendicular” and other angular relationships denote also approximate yet functional and/or practical, respective relationships.
As used herein “vertical” can be interchanged with “upright”. As used herein “substantially vertical” or “substantially upright” is used to refer to an orientation where the track assemblies and support tracks described herein are suitably perpendicular (i.e., form a 90° angle relative to) to the ground or a floor of a warehouse, building, or production facility, but also includes embodiments where the tracks are within about 0°-60° from perpendicular. That is in embodiments, substantially vertical allows for the tracks to be tilted from perpendicular at an angle of about 5°, 10°, about 20°, about 30°, about 45°, etc.
As used herein “translational movement” refers to the movement of an object from one place to another without a change in its orientation relative to a fixed point, as opposed to rotation, in which the object is turning about an axis. With respect to the carousel of the invention, the carousel provides translational movement of multiple biologic 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 to gravity. “Translational movement” can be bi-directional.
As used herein, “translates” or “translational” refers to the movement of a load supported on the carousel structure of the invention where the carousel comprises two tracks of the same size and shape that are oval, elliptical, spherical, orbital, capsule-shaped and the like. “Translate along the tracks” can be interchanged with “translation along the tracks” both meaning the movement from one position to a second position along the oval path of the upright carousel, wherein the translation does not invoke rotational inversion (of a supported unit and contents therein) during movement/travel along such frame.
As used herein, “rotation” or ‘axial rotation” refers to movement of an object turning about its central axis. With respect to individual dynamic adjustment of axial rotation of a biological production unit, this means that the biological production unit rotates about its axis. This can be bi-directional. This can also be referred to as “rocking motion” or “tilt”.
As used herein, a “user” is interchangeable with an “operator”.
As may be used herein, the terms ‘preferred’, ‘preferably’, ‘typical’, ‘typically’ or ‘optionally’ do not limit the scope of the invention or embodiments thereof.
As may be used herein the term ‘substantially’ (or synonyms thereof) denote with respect to the context a measure or extent or amount or degree that encompass a large part or most of a referenced entity, or an extent at least moderately or much greater or larger or more effective or more important relative to a referenced entity or with respect to the referenced subject matter.
As used herein the term ‘may’ denotes an option or an effect which is either or not included and/or used and/or implemented and/or occurs, yet the option constitutes at least a part of some embodiments of the invention or consequence thereof, without limiting the scope of the invention.
The phrase “and/or,” as used herein in the specification and in the 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 may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary.
As used herein in the specification and in the 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” shall be interpreted as being inclusive, e.g., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (e.g. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of” “only one of” or “exactly one of.”
As used herein in the specification and in the 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 and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.
As used herein “a plurality” is understood to be any number greater than one. “Plurality” means “two or more”.
Use of ordinal terms such as “first,” “second,” “third,” etc., in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements.
It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.
As used herein, “unit” is a biological unit or biological production unit. Unit is meant to generically define a biological structure used for supporting cell and tissue culture systems therein.
As used herein “ cantilevered unit” or “cantilevered biological production unit” are interchangeable as they refer to the same part.
As used herein, “biological production unit” comprises an independently operable automated cell culture and/or tissue engineering platform/system comprising components for multifunctional operation of one or more of cell culture, cell seeding, cell digestion, cell growth, cell differentiation, cell expansion, tissue culture and tissue growth.
The biological production unit may house and support an automated, portable, operationally multifunctional cell culture and/or tissue engineering system that performs/provides one or more of the following: sterile reception/storage of tissue biopsy; automated monitoring of digestion process; digestion of biopsy tissue to yield disassociated cells; cell sorting and selection, including safe waste collection; cell seeding on or within a proliferation substrate or scaffold proliferation 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 allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of implantable tissue.
In aspects this may be a tissue engineering cassette comprising one or more interlinked bioreactors that provide precise control at each stage. From cell source isolation and cell expansion through to cell collection, cell washing and final implant formation, the present system selectively combines key processes to meet the unique challenges of different autologous and allogeneic clinical applications of cell and tissue therapy. Embedded sensors provide real-time biofeedback and enable automatic adjustment in bioprocessing to accommodate natural variations in cell source behaviour. The entire bioprocess is contained within a disposable cassette to ensure maximum patient and operator safety and to streamline logistics. Suitable non limiting biological production units are described in U.S. 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 is incorporated by reference in their entireties).
As used herein “automated cell culture system” is an automated system that comprises several operatively linked biological production units and processors.
As used herein “supported”, “attached”, “connected”, “joined”, “coupled”, “linked”, and “secured” may be interchangeably used with respect to the engagement of components of the carousel and components of systems and methods incorporating the invention. Further, any of these terms may be used with the term “reversibly”.
A general non-limiting overview of the invention and practising the invention is presented below. The overview outlines exemplary practice of embodiments/aspects of the invention, providing a constructive basis for variant and/or alternative and/or divergent aspects/embodiments, some of which are subsequently described.
An effective and economical automation strategy is to adopt the use of process-specific bioreactors that can be controlled under automated sequences. Such bioreactors may be configured within a disposable, pre-sterilized cartridge or cassette for handling robustness and operator simplicity. Furthermore, the cassette and the related control instrumentation required for implementation of the automated sequences may be contained in an environmentally controlled enclosure (a biological production unit) to achieve the following (non-limiting) operational conditions:
To address the objective of space-efficient organization and ergonomic access of multiple biological production units, an automated carousel was developed and described herein. The carousel is an upright carousel comprising a substantially vertical track assembly that supports and provides translational movement of a plurality of biological production units in unison or separately along the curved vertical track assembly for precise user positioning. The carousel suitably translates the supported biological production units simultaneously (i.e. in unison) along the curved vertical track assembly about ±180° vertical, in a clockwise or counter-clockwise direction, while maintaining a precise alignment/orientation of each of the biological production units relative to gravity. This ensures that any of the cell culture and/or tissue engineering systems supported within each of the biological production units is not negatively affected by changing the orientation of gravitational forces exerted thereon during the changing of the vertical positioning of the biological production units. The carousel also comprises a means for individually dynamically adjusting the axial rotation of any of the biological production units. Surprisingly, the translational and/or axial movement of individual biological production units supporting independently operable biological systems therein, does not compromise 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 moving in unison, a single unit can move, while the remaining units remain stationary (or substantially stationary), for example along a top or back of a carousel in a “bunched-up” or “collected” orientation. As desired, the next unit in line in the track can be separately translated out from the remaining units, allowing for work or inspection to be conducted on that unit.
The carousel is configured within a housing powered by connection with a power source and operatively connectable with a computer for operational control (e.g. remote device, via touchpad screen, via hand held device).
The carousel of the invention can be incorporated for use with a variety of automated cell and tissue culture systems.
The carousel system 1 shows the scale up of biological production units supporting eight biological production units 16 on its common framework. The carousel 10 of the carousel system is shown to be substantially vertically configured to support eight individual and 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 to the carousel in a configuration for easy user access. In
Unlike conventional carousel designs for inventory management, mounting of the biological production units is important not only for efficient use of space but also for ensuring that the cell and tissue culture processes within each biological production unit is not negatively affected during translation of biological units along the vertical curved path of the carousel. The mounting also provides a further mechanism for additional dynamic control of the axial orientation of each individual biological production unit.
A translation assembly 24 is shown that acts as the mechanical linkage connecting the drive track 20 and the support track 22 providing simultaneous translational movement along the connected tracks. The translation assembly is configured to couple with a biological production unit 16 at one end that is adjacent the drive track 20. The biological production unit 16 is shown to be individually mounted to the translation assembly 24 in a cantilevered position via a single cantilevered fixed reversible coupling (not shown). The translation assembly enables a cantilevered positioning of the biological production unit. The single attachment point for each cantilevered biological production unit enhances service access to each of the biological production units and further improves overall space efficiency. The cantilevered fixed reversible coupling allows for coupling and uncoupling such that any given biological production unit can be removed/detached from the arm assembly of the carousel and replaced or relocated to another position on the carousel. While one translation assembly is shown, is understood by one of skill in the art, that multiple translation assemblies are mounted in a desired spaced relationship linking the drive track to the support track each supporting a cantilevered biological production unit.
Operationally, the automated carousel must offer geometric stability by means of ensuring each production unit remains precisely aligned relative to the gravity vector throughout positional adjustment/rotation of the automated carousel. Systems where orientation is not critical employ the use of gravity as a mechanism for alignment, where the center of mass is lower than the pivot point of the object. However, such systems inadequately compensate for changes in the center of mass, which influences the position of the gravity vector relative to the object undergoing movement. The automated carousel described herein specifically orients the biological production unit relative to the gravity vector such that secondary operations within the biological production unit that influence the center of mass do not affect orientation relative to gravity. Furthermore, the resulting stability of the biological production unit(s) enables the movement of internal components relative to the gravity vector to achieve specific biological or fluidic events. In the case of specific production unit operations where a axial rotation is required, separate from the translation movement about the oval track of the automated carousel, an additional linkage is implemented for independent control of the orientation of the production unit (as shown in
The use of a translation assembly to support the biological production unit enables the repositioning of the biological production unit to a location that is convenient for operator access to the cell and/or tissue culture system supported therein. While only one biological production unit is shown, a plurality of translation assemblies may be configured to travel along the tracks with each supporting a cantilevered biological production unit. The relative position of each translation assembly may be constrained by interconnecting linkages. Furthermore, it is feasible to provide adjustable spacing for the positions of the biological production units whereby spacing is exaggerated for locations where unconstrained operator access is required and reduced in locations where no operator access is required, such as the rear aspect of the carousel.
In addition to providing consistent vertical axis orientation of the biological production unit during translation along the tracks, the provision of the two mechanically and operationally linked carriages also provides the mechanical rigidity that is required to resist any bending moment imparted on the drive rack by the cantilevered biological production unit.
It is understood by one of skill in the art that the distance between the drive track and the support track may vary and this in part may be due to the size of the translation assembly providing linkage between the two tracks, the size and weight of the biological production units and the engineering forces required for adequate cantilevered mounting of multiple units. While the biological production units are shown cantilevered using a cantilevered mount, it is understood that other mounts with other orientations may be used. Furthermore, where only one biological production unit is shown to be cantilevered at each translation assembly, it is understood that smaller biological units may be used and thus more than one biological unit may be mounted in a cantilevered position, either in series or adjacent to each translation assembly.
It is also understood that the shape and size of the drive track and the support track should be substantively the same for proper translational movement along the carousel tracks and orientation with respect to gravity. While the tracks of the frame are shown to be substantially oval in shape, the shape can vary and is limited only by the ability to space apart the biological production units that are supported on the carousel and the ability to provide about ±180 degrees of rotational bidirectional movement. Therefore, the tracks can be substantially oval, substantially elliptical, substantially circular or substantially capsule-shaped. The carousel can be designed to be of any vertical height (e.g. size) limited by only the facility in which it will be used. The two tracks that make up the frame of the carousel can be may of any desired thickness and made of suitable materials that can withstand stress cycles and dynamic loading conditions during its use. Suitable materials comprise typically used engineering materials such as but not limited to metals and metal alloys (e.g. comprising high grade stainless steel, steel alloys, iron, copper, aluminum and combinations thereof).
The coupling 26 supporting the cantilevered biological production unit mechanically engages with a motor driven central shaft 54 within the inner hub 44 of the via bearings. The motor driven central shaft is either constrained from rotating within the inner hub 44 or actively rotated at a controlled speed by the motor drive and gearbox mounted on the inner hub that drives the axial rotational of the central shaft. Through the controlled orientation of the inner hub relative to gravity and the controlled orientation of the central shaft relative to the inner hub, it is possible to selectively axially rotate the central shaft and hence the biological production unit relative to gravity.
The drive carriage 36 is a drive block assembly 56 with one face thereof 58 having affixed vertically arranged pairs of outwardly projecting bearing members 60 for gripping the primary track 20 and engaging its associated drive means adapted translational movement along the course of travel defined by the primary track.
The support carriage 42 is a support block assembly 62 with one face thereof 64 having affixed vertically arranged pairs of outwardly projecting bearing members 66 for gripping the support track for moving along the course of travel defined by the support track. The support carriage actively translationally moves along the support track in a synchronous manner with the drive carriage while retaining the fixed vertical offset according to the length of the lever arm.
Although two pairs of bearings are shown on each of the primary carriage and support carriage (i.e. 60 and 66, respectively), it is understood by one of skill in the art that additional sets may be incorporated for additional gripping of either the primary track or the support track.
In operation, the translation assembly 24 and similar translation assemblies present on the tracks are moved in unison through physical connection of the primary carriage to a primary drive belt and motor assembly and a secondary drive belt linking the secondary carriages. The motion is a gliding motion with minimal friction based on the bearing interface between the carriages and the tracks. Furthermore, the carriages support significant lateral and bending loads. This load carrying capability and the use of two carriages offset via the translation assembly enables significant cantilever loads to be resisted thereby ensuring stable translation of the biological product units from position to position.
The biological production unit 16 is rigidly mounted to the translation assembly 24 via the cantilevered fixed reversible coupling 26 that cooperates with the motor driven central shaft 54 retained within the inner central hub 44. The inner central hub always maintains a consistent orientation relative to the gravity vector. The motor drive assembly positions the axial rotation of the central shaft 54 relative to the inner central hub. When the motor driven linkage 46 is dormant, the biological production unit (thus the cell and/or tissue culture system contained therein) will maintain a given orientation relative to the gravity vector. Through the activation of motor driven linkage 46, the axial position of central shaft 54 may be changed in either direction, thereby dynamically axially changing the position of the cell and/or tissue culture system relative to the gravity vector. This changing of the axial orientation of the biological production unit may be intermittent to aid a specific biological activity occurring within a cassette mounted within a biological production unit or may be continuous (e.g. rocking or tilting) of a bioreactor within the cassette housed in the biological production unit.
In the production of patient-specific treatments, the necessity exists to enable independent operation of each biological production unit as the initialization, processing and completion of each patient specific production activity will not typically align with any other concurrent production requirements. Therefore, each biological production unit is independently controlled with respect to the biological processing conditions occurring therein. This necessitates the delivery of common resources to each biological production unit, where the consumption of such resources is controlled internally within each production unit.
The rotational movement of the plurality of biological production units presents a unique challenge for resource delivery and management. To minimize resource distribution complexity, a limit of about ±180 degrees rotation for the automated carousel is suitable. With this constraint on rotation, a robust and functionally reliable cabling strategy was developed for the conveyance of auxiliaries and resources (e.g. electrical power, supply gases and data).
Safety precautions are an operational requirement for the automated carousel in order to protect both the operator and the ongoing viability of the biological processes underway within each biological production unit. Moving parts are either contained or have an uninterrupted surface relative to other moving/stationary parts to prevent pinch points. In the event these conditions are not possible, alternate methods for avoiding injury are required. The housing assembly shown in
A safety clutch is also provided to allow automatic interruption of movement of the carousel in the event higher than normal torque is encountered by the drive system of the automated carousel. The clutch slip at high torques protects the user from pinch hazards that can be created by the biological production units rotating along the track orbit and also avoids potentially damaging torques being transferred to other components within the automated carousel in the event of a malfunction.
Service and cleaning of the automated carousel is required for operation within GMP facilities. The temporary relocation of the automated carousel is potentially advantageous in maintaining a clean production space. Wheels 74 present underneath 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.
The spacing between the biological production units is adjustable and is selected to provide adequate spacing for the size of the biological production unit. This allows customization of a given carousel for the particular type of biological production unit to be supported thereto. It should also be noted that although the figures illustrate all of the 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 the carousel and carousel systems may further be configured to have the separate ability to adjust the spacing of each biological unit relative to adjacent biological units so as to maximize the spatial density of biological units in selected zones of the carousel by close spacing and enhance user access to biological units in other selected zones by open spacing. In one non-limiting example, once a desired biological production unit is selected and properly positioned for a user, adjacent biological production units may be further translationally repositioned “away” from the selected biological production unit to provide more room for a user.
To accommodate different user access requirements, the biological production units may be precisely positioned for a selected user, by the user. An interface for the user to communicate effectively to each biological production unit on the carousel is provided and is adjustable.
As described herein, suitably the biological production units 16 are configured to move in unison or separately, so as to enable vertical positioning of any single unit for easy access. In embodiments, one or more additional stationary units can be mounted to the carousel as workflow units. These workflow units can be utilized for specific functions by removing a cassette from a unit currently translating in the carousel series, and transferring it to the stationary unit for additional processing. The stationary workflow units can also be utilized as a resource in the event temporary operational support is required to address a single biological production unit malfunction event. This temporary role can support unit repair or unit replacement.
In further embodiments, a secondary processing module can also be included in the carousels described herein. This secondary processing module can be engaged when a biological production unit 16 reaches a specific position in the translation. For example, the secondary processing module can be a bio-isolator to generate a controlled environment around a particular production unit for specific cassette handling requirements or other technical functions. This bio-isolator could allow an operator to intervene in the operation of a unit in ways not possible should the unit open into the general space (e.g., either external contamination, or a highly specialized or potentially toxic cell or virus being used in the units).
The foregoing illustrates the automated device of the invention achieves a further significant improvement to automated cell and tissue culture applications. Complex and automated modular biologic culture systems can be improved with the incorporation of the device of the invention allowing for a greater ability to provide much needed cells and tissues for patient treatment in the same space challenged facilities without compromise of the integrity of the system, or the versatility of the system. Operation of each biological production unit in terms of access at any time is ergonomic and easily achievable by any user as desired.
While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the 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 meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed.
The descriptions of the various embodiments and/or examples of the present invention have been presented for purposes of illustration but are not intended to be exhaustive or limited to the embodiments and/or examples disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.
The present application claims benefit of U.S. Provisional Application No. 62/783,529, filed Dec. 21, 2018, the disclosure of which is incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62783529 | Dec 2018 | US |
