Single-use manifold and sensors for automated, aseptic transfer of solutions in bioprocessing applications

• US 20060118472A1
• Filed: 12/05/2005
• Published: 06/08/2006
• Est. Priority Date: 06/14/2002
• Status: Active Grant

• Current Assignee: Parker Intangibles LLC (Parker-Hannifin Corporation)
• Original Assignee: Parker-Hannifin Corporation
• Inventors: Uhen, David, Schick, Karl G.
• Granted Patent: US 9,283,521 B2
• Time in Patent Office: Days
• US Class Current: 210/198.200
• CPC Class Codes: B01D 15/10 characterised by constructional or operational features
• CPC Class Codes: B01D 15/14 relating to the introduction of the feed to the apparatus
• CPC Class Codes: B01D 15/247 Fraction collectors
• CPC Class Codes: B01D 2311/06 Specific process operations in the permeate stream
• CPC Class Codes: B01D 2311/2649 Filtration
• CPC Class Codes: B01D 2313/50 Specific extra tanks
• CPC Class Codes: B01D 2313/501 Permeate storage tanks
• CPC Class Codes: B01D 2313/58 Parts of membrane modules specifically adapted for single use
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 61/20 Accessories; Auxiliary operations
• CPC Class Codes: B01D 61/22 Controlling or regulating
• CPC Class Codes: G01N 2030/8813 biological materials
• CPC Class Codes: G01N 27/10 Investigation or analysis specially adapted for controlling or monitoring operations or for signalling

Abstract

Presteralized manifolds are provided which are designed for sterile packaging and single-use approaches. Disposable tubing and flexible-wall containers are assembled via aseptic connectors. These manifolds interact with valves and pumping equipment which can be operated by a controller which provides automated and accurate delivery of biotechnology fluid. The manifold also being used in conjunction with one or more conductivity sensors used to measure the conductivity of the biotechnology fluid. Such sensors interact with the controller or are connected to a separate user interface. The combination of disposable tubing, flexible-wall containers, aseptic connectors, manifold, controller, and conductivity sensors provides an aseptic environment while avoiding or reducing cleaning and quality assurance procedures.

Claims

1. A manifold system for biotechnology uses, comprising:

a manifold unit which is pre-sterilized and disposable so as to be adapted for single-time usage, including;

(a) at least one length of tubing having at least one inlet end portion, at least one outlet end portion, an outside surface, and an inside surface which is sterilized for passage of a biotechnology fluid therethrough,

(b) at least one single-use bag having a primary access port;

(c) an aseptic connector means for operatively connecting said length of tubing with said primary access port of the single-use bag; and

(d) one or more pre-sterilized and disposable conductivity sensors adapted for single-time usage.

2. The manifold system in accordance with claim 1, further including a plurality of pinch valves, at least one of which is remotely operable in response to a signal remote from said pinch valve, each said pinch valve engages said outside surface of the length of tubing at a discrete location therealong, each said pinch valve independently selectively allowing or stopping flow of the biotechnology fluid through said inside surface of the length of tubing at said discrete location for that pinch valve.

3. The manifold system in accordance with claim 1, wherein said disposable conductivity sensor is comprised of:

(a) a conduit for directing biotechnology fluid therethrough, said conduit being connectable to at least one said length of tubing;

(b) a sensing portion, said sensing portion being arranged for sensing the conductivity of the biotechnology fluid; and

(c) a memory component, said memory component being capable of storing data.

4. The manifold system in accordance with claim 2, further including a user interface unit, and wherein said disposable conductivity sensors are electrically connected to said user interface unit.

5. The manifold system in accordance with claim 4, wherein said user interface unit includes control logic that dictates or controls, at least in part, the external operations on said manifold system.

6. The manifold system in accordance with claim 5 further comprising a pump unit that engages said exterior surface of at least one length of tubing, said pump unit, at least in part, being controlled by the user interface unit, whereby the user interface unit performs an exterior operation on the manifold system by engaging or stopping the pumping unit.

7. The manifold system in accordance with claim 5 further comprising one or more pinch valves, at least one of which is remotely operable, wherein said user interface unit controls operation of said pinch valve, said user interface unit having control logic which controls or dictates the timing of opening and closing of said remotely operable pinch valve, whereby the user interface unit performs an exterior operation.

8. The manifold system in accordance with claim 5, wherein said user interface unit controls the external operation of the manifold system in response to the conductivity of the biotechnology fluid passing through said conductivity sensor.

9. The manifold system in accordance with claim 5, wherein said user interface unit measures the conductivity of the biotechnology fluid passing through the conduit by driving a current through the sensing portion of the conductivity sensor.

10. The manifold system in accordance with claim 1, further including a disposable pressure sensor positioned along said tubing such that the biotechnology fluid flows therethrough at a location upstream of said outlet end portion.

11. The manifold system in accordance with claim 1, wherein said system is for automated preparative chromatography, wherein:

(a) said tubing is in at least two sections including a chromatography feed section and a chromatographed fluid section,

(b) said chromatography feed section has an outlet and a plurality of serially arranged inlet passageways having one of said aseptic connector means for operable connection with said single-use bag, and

(c) said chromatographed fluid section has an inlet and said outlet end portion of the tubing which has a plurality of serially arranged outlet passageways having one of said aseptic connector means for operable connection with said single-use bag; and

further comprising a chromatography column between said chromatography feed section and said chromatographed fluid section.

12. The manifold system in accordance with claim 11, wherein at least one of the said disposable conductivity sensors is disposed downstream of the chromatography column.

13. The manifold system in accordance with claim 11, wherein at least one of the said disposable conductivity sensors is disposed upstream of the chromatography column.

14. The manifold system in accordance with claim 11, further including a user interface unit, and wherein said one or more disposable conductivity sensors are electrically connected to said user interface unit.

15. The manifold system in accordance with claim 14, wherein said user interface unit controls the external operation on the manifold system in response to the conductivity of the biotechnology fluid passing through said conductivity sensor.

16. The manifold system in accordance with claim 15 further comprising a pump unit that engages said exterior surface of at least one length of tubing, said pump unit, at least in part, being controlled by the user interface unit, whereby the user interface unit performs an exterior operation on the manifold system by engaging or stopping the pumping unit.

17. The manifold system in accordance with claim 15, further comprising one or more pinch valves, at least one of which is remotely operable, wherein said user interface unit controls operation of said pinch valve, said user interface unit having control logic which controls or dictates the timing of opening and closing of said remotely operable pinch valve, whereby the user interface unit performs an exterior operation.

18. The manifold system in accordance with claim 1, which said system is for tangential flow filtration, wherein

one said single use bag is a process solution bag and another single-use bag is a permeate collection bag;

said tubing is in at least two sections including a filtration flow-through section and a filtered fluid section, said filtration flow-through section includes said process solution bag;

said filtered fluid section includes said permeate collection bag utilizing said aseptic connector means for operatively connecting said length of tubing with said single-use bag,

and further comprising;

a disposable filter between said filtration flow-through section and said filtered fluid section, whereby fluid from said process solution bag is filtered through said disposable filter and is collected in said permeate collection bag.

19. The manifold system in accordance with claim 18, further including a user interface unit, and wherein said disposable conductivity sensors are electrically connected to said user interface unit, said user interface unit containing control logic that receives and interprets signals from the conductivity sensors.

20. The manifold system in accordance with claim 19, wherein one of said disposable conductivity sensors is positioned along a location downstream of said disposable filter, said conductivity sensor being connected to said user interface unit whereby the user interface unit monitors the conductivity of the fluid within said tubing.

21. The manifold system in accordance with claim 19, further comprising one or more pinch valves, at least one of which is remotely operable, wherein said user interface unit controls operation of said pinch valve, said user interface unit having control logic which controls or dictates the timing of opening and closing of said remotely operable pinch valve, whereby the user interface unit performs an exterior operation.

22. The manifold system in accordance with claim 19, wherein said user interface unit includes control logic which dictates or controls, at least in part, the external operations on-said manifold system.

23. A manifold system for biotechnology uses, wherein said system is for automated, aseptic fluid transfer, comprising:

A manifold unit which is pre-sterilized and disposable so as to be adapted for single-time usage, including;

(a) at least one length of tubing having at least one inlet end portion, at least one outlet end portion, an outside surface, and an inside surface which is sterilized for passage of a biotechnology fluid therethrough;

(b) a plurality of single-use bags, each having a primary access port;

(c) aseptic connector means for operatively connecting said length of tubing with said primary access port of at least one of said single-use bags;

(d) said outlet end portion of the tubing has a plurality of serially arranged outlet passageways having one of said aseptic connector means for operable connection with said single-use bag; and

(e) one or more pre-sterilized and disposable conductivity sensors adapted for single-time usage.

24. The manifold system in accordance with claim 23, further including a plurality of pinch valves, at least one of which is remotely operable in response to a signal remote from said pinch valve, each said pinch valve engages said outside surface of the length of tubing at a discrete location therealong, each said pinch valve independently selectively allowing or stopping flow of the biotechnology fluid through said inside surface of the length of tubing at said discrete location for that pinch valve.

25. The manifold system in accordance with claim 23, wherein said disposable conductivity sensor is comprised of:

(a) a conduit for directing biotechnology fluid therethrough, said conduit being connectable to at least one said length of tubing;

(b) a sensing portion, said sensing portion being arranged for sensing the conductivity of the biotechnology fluid; and

(c) a memory component, said memory component being capable of storing data.