Centrifuge vessels with a center mound and an internal elongate tube suitable for live cell processing and associated systems and methods
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
B04B-007/08
B01L-003/00
B04B-013/00
출원번호
US-0372944
(2013-01-22)
등록번호
US-10022731
(2018-07-17)
국제출원번호
PCT/US2013/022512
(2013-01-22)
국제공개번호
WO2013/116041
(2013-08-08)
발명자
/ 주소
Monesmith, Tamara Tatroe
Caprihan, Arjun V.
Ryan, Christopher Thomas
Grant, Richard A.
Fitzpatrick, Ian S.
Leigh-Lancaster, Christopher John
출원인 / 주소
Argos Therapeutics, Inc.
대리인 / 주소
Myers Bigel, P.A.
인용정보
피인용 횟수 :
0인용 특허 :
13
초록▼
Centrifuge vessels suitable for live cell processing include a bowl with a cap, and a tube inside the bowl extending between the cap and a lower portion of the bowl. The bottom of the bowl can have a closed annular ring surrounding a center mound. The vessels can be particularly suitable for process
Centrifuge vessels suitable for live cell processing include a bowl with a cap, and a tube inside the bowl extending between the cap and a lower portion of the bowl. The bottom of the bowl can have a closed annular ring surrounding a center mound. The vessels can be particularly suitable for processing low volumes of live cells for vaccines or other therapies.
대표청구항▼
1. A centrifuge vessel, comprising: a bowl having a bottom portion and a top portion, the bottom portion having a downwardly extending outer wall that tapers inwardly from the top portion to merge into a closed bottom, the closed bottom having an internal annular concave surface surrounding a center
1. A centrifuge vessel, comprising: a bowl having a bottom portion and a top portion, the bottom portion having a downwardly extending outer wall that tapers inwardly from the top portion to merge into a closed bottom, the closed bottom having an internal annular concave surface surrounding a center mound;a cap configured to attach to the bowl to define an enclosed interior chamber, the cap comprising a plurality of spaced apart upwardly extending fluid ports, one residing proximate a center of the cap; andan elongate tube having a length with opposing top and bottom portions and an open flow channel extending therethrough, the tube held upright and encased inside the interior chamber with the bottom portion coupled to the center mound in the bottom of the bowl in a manner that allows fluid to flow into a bottom of the tube while coupled to the center mound, and wherein the top portion of the tube is attached to the cap and is in fluid communication with the fluid port proximate the center of the cap,wherein the center mound comprises at least one shoulder that provides a stop for the tube so that a bottom surface of the bottom portion of the tube engages the shoulder and resides proximate but a defined distance above the closed bottom of the bowl. 2. The vessel of claim 1, wherein the cap includes external tubing retainer brackets extending upwardly thereon, wherein the top portion of the bowl has an outer wall that provides a tubular body portion that is wider than the bottom portion, wherein the center mound has a width that is smaller than a width of the annular concave surface, wherein an upper end portion of the center mound extends into the bottom portion of the tube, and wherein the at least one shoulder is provided as first and second laterally spaced apart shoulders that reside on opposing sides of the center mound beneath the upper end portion of the center mound and abut the bottom of the tube. 3. The vessel of claim 2, further comprising a tube enclosure cap attached to the cap, wherein the tube enclosure cap is configured to enclose a plurality of tube tails with stacked loops of the tube tails with the loops stacked vertically above the cap and extending circumferentially adjacent an outer perimeter of the cap and about the tubing retainer brackets held inside the tube enclosure cap. 4. The vessel of claim 1, wherein the cap comprises an internal decanting surface with a concave shape that faces the bowl and resides proximate an outer perimeter portion of the cap adjacent at least one of the fluid ports. 5. The vessel of claim 1, wherein the cap comprises a ledge extending about a lower perimeter portion thereof, the ledge having a profile with a downwardly extending ridge portion that is integrally attached to a channel that extends about an upper end of the bowl. 6. The vessel of claim 1, wherein the at least one shoulder is provided as at least one planar shoulder. 7. A centrifuge vessel, comprising: a bowl having a bottom portion and a top portion, the bottom portion having a downwardly extending outer wall that tapers inwardly from the top portion to merge into a closed bottom, the closed bottom having an internal annular concave surface surrounding a center mound;a cap configured to attach to the bowl to define an enclosed interior chamber, the cap comprising a plurality of spaced apart upwardly extending fluid ports, one residing proximate a center of the cap; andan elongate tube having a length with opposing top and bottom portions and an open flow channel extending therethrough, the tube held upright and encased inside the interior chamber with the bottom portion coupled to the center mound in the bottom of the bowl in a manner that allows fluid to flow into a bottom of the tube while coupled to the center mound, and wherein the top portion of the tube is attached to the cap and is in fluid communication with the fluid port proximate the center of the cap,wherein the center mound comprises an upwardly projecting tang with a thickness dimension that is less than a width dimension and a height dimension that extends a distance into the bottom of the tube. 8. The vessel of claim 1, wherein the center mound defines a flow surface that tapers down to the closed bottom of the bowl from the at least one shoulder. 9. A centrifuge vessel, comprising: a bowl having a bottom portion and a top portion, the bottom portion having a downwardly extending outer wall that tapers inwardly from the top portion to merge into a closed bottom, the closed bottom having an internal annular concave surface surrounding a center mound;a cap configured to attach to the bowl to define an enclosed interior chamber, the cap comprising a plurality of spaced apart upwardly extending fluid ports, one residing proximate a center of the cap; andan elongate tube having a length with opposing top and bottom portions and an open flow channel extending therethrough, the tube held upright and encased inside the interior chamber with the bottom portion coupled to the center mound in the bottom of the bowl in a manner that allows fluid to flow into a bottom of the tube while coupled to the center mound, and wherein the top portion of the tube is attached to the cap and is in fluid communication with the fluid port proximate the center of the cap,wherein the center mound comprises first and second opposing shoulders, one residing on opposing sides of a center tang with a thickness dimension that is less than height and width dimensions thereof, wherein the shoulders have a thickness dimension that is the same as the center tang, and wherein the center mound comprises at least one flow clearance surface that tapers down across a width dimension of the center mound toward the closed bottom from the shoulders to allow fluid to be extracted from the vessel through the tube during use. 10. A processing system comprising the centrifuge vessel of claim 1 and a holder having a vessel cradle and a base, wherein the holder vessel cradle releasably engages the vessel so that the bottom of the bowl is held in the base with external orientation and/or locking members held in slots of the base, wherein the vessel cradle is attached to a shaker device that rotates the vessel through a defined sequence of movement, and wherein the defined sequence of movement has rotational motions that are less than 360 degrees to serially tilt the centrifuge vessel and orient the cap both below and above the bottom of the bowl. 11. The system of claim 10, further comprising a controller in communication with the shaker device that directs the shaker device to vibrate and/or shake the vessel and rotate to carry out the defined sequence of movement, then the controller directs the shaker to translate to a decant orientation where the holder and shaker device cooperate to hold the vessel tilted to be partially inverted. 12. The vessel of claim 1, further comprising live cells therein, wherein the cap has a perimeter portion with a circumferentially extending ledge that is ultrasonically welded to an upper end of the bowl to define a fluid-tight perimeter such that fluid can enter and/or exit only through the fluid ports, wherein the vessel defines a functionally closed sterile processing system with the live cells therein, and wherein the bowl comprises outwardly extending orientation and/or locking members that extend radially outward and are circumferentially spaced apart and terminate above an outer bottom surface of the bowl at a location where a diameter of the bowl increases from the bottom portion to a maximal width below the top portion of the bowl. 13. A method of processing live cells, comprising: providing the centrifuge vessel of claim 1, the vessel comprising live cells for processing; centrifuging the live cells in the vessel; capturing the live cells as a soft pellet in an annular shape in the bottom of the bowl; and then removing supernatant in the vessel through the tube and then through the fluid port of the cap. 14. The method of claim 13, further comprising attaching ends of flexible conduit to respective fluid ports on the cap so that the conduits have free tails, then wrapping the conduit tails in loops about brackets on the cap before the centrifuging step. 15. The method of claim 14, further comprising unwrapping the conduit tails and connecting the tails to target devices after the centrifuging step. 16. The method of claim 13, further comprising: mounting the vessel to an automated shaker;electronically directing the automated shaker to carry out a defined sequence of movement; andredistributing or re-suspending the live cells in the soft pellet in response to the directing step to thereby vibrate, shake and/or mix the cells using the automated shaker. 17. The method of claim 16, wherein the mounting is carried out using a mechanical holder that is attached to the shaker, the holder also having a vessel cradle that releaseably engages the vessel, the method further comprising electronically directing the shaker to stop at a position that causes the holder to tilt the vessel to a partially inverted position, then decanting fluid in the vessel through at least one fluid port into a respective flexible conduit. 18. A centrifuge vessel, comprising: a bowl having a bottom portion and a top portion, the bottom portion having a downwardly extending outer wall that merges into a closed bottom, the closed bottom having an annular surface surrounding a center mound, wherein the downwardly extending outer wall of the bottom portion tapers inwardly so that the bowl has a smaller width at the closed bottom than at the top portion;a cap attached to the bowl to define an enclosed interior chamber, the cap comprising a plurality of spaced apart upwardly extending fluid ports, one residing proximate a center of the cap; andan elongate internal tube having a length with opposing top and bottom portions and an open flow channel extending therethrough, the elongate internal tube held upright and encased inside the interior chamber with an upper end portion of the center mound extending into the bottom portion of the tube and the top portion of the elongate tube attached to the cap and in fluid communication with the fluid port proximate the center of the cap, wherein the upper end portion of the center mound is vertically oriented and planar with a width and height dimension greater than a thickness dimension, wherein the center mound has a shoulder which extends radially outward a distance beyond a width of the upper end portion, wherein the upper end portion of the center mound merges into a flow surface that extends across the width of center mound below the shoulder and tapers outwardly toward the outer wall in a downward direction to the closed bottom of the bowl with the bottom portion, and wherein the center mound and a bottom of the tube are cooperatively coupled to allow fluid to flow into the bottom of the tube while the tube is coupled to the center mound. 19. The vessel of claim 18, wherein the top portion of the bowl has a downwardly extending length with a constant width, wherein the cap includes upwardly extending external tubing retainer brackets on an outer perimeter portion of an upper surface of the cap, and wherein the cap comprises an internal decanting surface with a concave shape that faces the bowl and resides proximate an outer perimeter portion of the cap adjacent at least one of the fluid ports. 20. The vessel of claim 19, further comprising an upper tube enclosure cap attached to the cap of the vessel, wherein the tube enclosure cap encloses a plurality of tube tails with stacked loops of the tube tails extending about the tubing retainer brackets held inside the tube enclosure cap, and wherein the loops are stacked vertically above the cap and extend circumferentially adjacent an outer perimeter of the cap held by the tubing retainer brackets. 21. The vessel of claim 18, wherein the top portion of the bowl has an outer downwardly extending wall that merges into the outer downwardly extending wall of the bottom portion and that provides a tubular body portion, wherein the tubular body portion of the top portion of the bowl has a greater width than the bottom portion of the bowl and has a greater downwardly extending length than the bottom portion of the bowl, wherein the center mound has a width that is smaller than a width of the annular concave surface, and wherein the shoulder comprises first and second laterally spaced apart shoulders that reside on opposing sides of the center mound beneath the upper end portion of the center mound, abut a bottom surface of the bottom portion of the tube and hold the bottom of the tube a distance in a range of about 2 mm to about 3 mm above the closed bottom of the bowl.
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