Flow-through removal device and system using such device
Flow-through systems for processing biological fluid are disclosed. The flow-through systems include a removal device in the flow path for removing unwanted compounds and agents. The removal device includes a removal media contained within a housing made of two separate portions sealed together. The housing is maintained in a substantially vertical disposition, thereby ensuring substantially uniform and complete exposure of the fluid to the media.
The present invention is directed to a flow-through device for removing selected compounds and/or components from a fluid such as, but not limited to, a biological fluid. The present invention is also directed to fluid processing systems using such flow-through devices.
BACKGROUND OF THE INVENTIONFlow-through devices for removing compounds or other components from a biological fluid are known. For example, flow-through removal devices have been used in medical processing sets where the biological fluid is filtered to remove undesired blood components, such as leukocytes. Flow-through devices have also been proposed for use where the biological fluid has been treated with a solvent or chemical agent as, for example in a pathogen inactivation process.
In many pathogen inactivation processes, a chemical agent is typically added to the biological fluid to either (1) directly inactivate present pathogens or (2) inactivate present pathogens in combination with other means, such as light. Regardless of the method used, after treatment, it is desirable to remove unreacted chemical agents or by-products of the inactivation process from the biological fluid prior to its transfusion to the patient.
One example of such a pathogen inactivation processing system is described in U.S. patent application Ser. No. 09/325,599, which is incorporated herein by reference in its entirety. In the system described therein, fluid from a source container that has been treated in a pathogen inactivation process (e.g., photoactivation with ultraviolet light and a psoralen compound) is passed through a removal device and collected in a receiving container. The removal device includes a sorbent selected to remove residual chemical agent and/or by-products of the inactivation process.
Flow-through devices may also be used in the filtration of blood products to remove, for example, leukocytes from a collected blood product. An example of a fluid processing system that includes a leukoreduction filter in a flow-through arrangement is described in U.S. Pat. No. 6,358,420. Flow-through devices may also be used to remove treating agents used in the treatment of blood or a blood fraction, which agent is desirably removed from the fluid prior to further use of the fluid.
In the above-described examples, the removal device includes a housing and a removal media inside the housing. Regardless of the removal for which the device is used (i.e., leukoreduction, or removal of inactivation compounds or other agents), complete and uniform exposure of the fluid to the removal medium is important. To obtain the greatest efficiency for the removal medium, it is desirous for the fluid to come in contact with as much of the removal medium as possible. For example, to ensure substantially complete removal of the inactivating agent in the pathogen inactivation example described above, it is desirable that the fluid contact the removal media as completely as possible, without bypassing any part of the removal media. Likewise in a leukoreduction device, complete exposure is important to ensure substantially complete removal of leukocytes, which if otherwise transfused, may cause an adverse reaction in the recipient.
To further ensure substantially complete and uniform exposure of the fluid to the media, it is important that the removal media be maintained in a substantially fixed orientation. For example, in a processing set that includes a hanging-type filter where the flow is “top to bottom,” very often, a natural twisting moment causes the filter to hang at an angle. As the weight below the filter changes (i.e., as the collection container fills), the moment increases and the angle changes. A device that tilts away from the central vertical axis may result in uneven distribution of the fluid across the removal media, resulting in incomplete exposure and removal of the undesired agents.
In addition to uniform and complete exposure of the fluid to the media, it is also important, to have substantial processing time consistency (i.e., reproducibility) from one device to the next.
It is also desirable that a device that meets the above performance requirements is also easy and economical to manufacture with a low rejection rate.
The above objectives are addressed by the present invention.
SUMMARY OF THE INVENTIONIn one aspect, the present invention is directed to a flow-through device for removing selected compounds from a liquid. The device includes a housing having a first portion and a second portion that are joined together. Each of the first and second portions include outer walls and inner walls, with a compound removing medium disposed between the walls of the portions. One of the first or second portions includes an inlet port on the outer wall and the other of the first or second portions includes an outlet port on the outer wall. The inner wall of the first or second portions includes a peripherally extending tongue while the inner wall of the other of the first or second portions includes a peripherally extending groove for receiving the tongue.
In another aspect, the present invention is directed to a flow-through device for removing selected compounds from a liquid that includes a housing. The housing includes first and second outer walls defining an interior chamber between the walls. A compound removing medium is disposed within the interior chamber. In a preferred embodiment, the housing includes an inlet port on one of the outer walls and an outlet port on the other of the outer walls, wherein the location of the outlet port is diametrically opposed to the location of the inlet port.
In another aspect, the present invention is directed to a flow-through system for removing selected compounds or components from a fluid. The system includes a source container, including a fluid outlet and a receiving container including a fluid inlet. The system includes a compound removal device disposed between the source and receiving containers. The device includes a housing having first and second outer walls and a compound removing medium between the walls. The housing further includes a fluid inlet on one of the outer walls and located between the center of the device and the receiving container, and a fluid outlet on the other outer wall and located between the center of the device and the source container on the other outer wall. The system further includes a first tube providing a flow path between the source container and the device inlet and a second tube providing a flow path between the device outlet and the receiving container inlet.
In another aspect, the present invention is directed to a flow-through device for removing selected compounds from a liquid. The device is comprised of a housing having a pair of side walls and a peripheral wall defining a chamber. A removal medium is located within the chamber, the medium having an end wall terminating interior to the peripheral wall of the housing. A liquid impermeable barrier is located in the area of the chamber substantially between the medium peripheral end surface and the peripheral end wall of the housing.
In another aspect, the present invention is directed to a flow-through processing system for removing selected compounds or components from a fluid. The flow-through system includes a source container including a fluid outlet and a receiving container including a fluid inlet. A compound removal device is located between the source container and the receiving container. The housing includes a first and second outer walls and a compound removing medium between the walls. The housing includes a fluid inlet on the first outer wall, the inlet being located between the center of the first housing wall and the receiving container and a fluid outlet on the second outer wall located between the second housing wall center and the source container. The system also includes a tubing providing a flow path between the source container outlet and housing inlet and tubing providing a flow path between the receiving container inlet and housing outlet. The length of the flow path between the source container and the inlet is greater than the length of the flow path between the device outlet and the receiving container.
BRIEF DESCRIPTION OF THE DRAWINGS
Turning now to the drawings,
In
Optionally, the system 10 may include additional containers. For example, in the embodiment shown in
One example of a pathogen inactivation compound is a psoralen compound, such as, but not limited to, 5′-(4-amino-2-oxa) butyl-4,5′,8-trimethyl psoralen as the pathogen inactivation compound. Examples of suitable psoralen compounds and methods of inactivating pathogens in biological fluid using psoralens are provided in U.S. Pat. Nos. 5,578,736 and 5,593,823, both of which are incorporated herein by reference.
Other examples of pathogen inactivating compounds include phthalocyanine derivatives, phenothiazine derivatives (including methylene blue or dimethyl-methylene blue); endogenous and exogenous photosensitizers such as alloxazines, isoalloxazines (including riboflavin), vitamin Ks, vitamin L, napththoquinones, naphthalenes, naphthols, pathogen inactivating compounds disclosed in U.S. Pat. Nos. 6,258,577, 6,268,120, and 6,277,337, which are incorporated herein by reference, or “Pen 110,” which is made by V.I. Technologies, Inc. (which is also known as the Inactine™ compound).
Examples of pathogen inactivation compounds that may be useful in red blood cell pathogen inactivation methods include the pathogen inactivation agents disclosed above and those disclosed in U.S. Pat. No. 6,093,725 and U.S. application Ser. No. 09/539,226 filed Mar. 30, 2000, which is directed to the use of compounds having nucleic acid affinity and containing a mustard group, or mustard group equivalent or mustard group intermediate. U.S. Pat. No. 6,093,775 and U.S. application Ser. No. 09/539,226 are incorporated herein by reference. A preferred compound for red blood cell pathogen inactivation is p-alanine, N-(acridin-9-yl), 2-[bis(2-chloroethyl)amino]ethyl ester.
Returning to
As further shown in
As shown in
An alternative flow-through system 10 is shown in
Regardless of the orientation of ports 30 and 32, a common aspect of both of the embodiments shown in
Turning now to
Housing 42 is preferably made of a hard plastic that can be injection molded. The material used for housing 42 should be suitable for sterilization by known forms of sterilization such as gamma or electron beam radiation. The material should also be amenable to preferred sealing operations such as, but not limited to, ultrasonic welding. Examples of suitable materials include polymethylmethacrylate (PMMA) and acrylonitrile butadiene styrene (ABS). As shown in
As shown in
As described in U.S. patent application Ser. No. 09/325,599, the removal media may be in the form of a disk made of, preferably, divinylbenzene styrene particulate that is finely ground and combined with a binding material, such as polyethylene or a blend thereof. This combination is sintered, resulting in disk 60 shown in
Of course, the removal media 60 described is not limited to the materials identified above. The medium can be made of any material, sorbent or otherwise, that can remove selected compounds or agents from the fluid. Examples of materials useful in the removal of compounds and agents are provided in U.S. Pat. No. 6,544,727 and U.S. Patent Application Publication Nos. US 2001/0018179 A1 and US 2001/0009756 A1, all of which are herein incorporated by reference. The medium can also be a filtration medium used to capture (other than by sorption) unwanted compounds or components. For example, the medium 60 may be used to capture leukocytes and remove them from the biological fluid.
As shown in
As shown and previously described, housing 42 of device 20 is preferably made of two portions 44 and 46 joined together with removal medium 60 (and one or more filter media 62 and 64) enclosed within housing 42. In a preferred embodiment, portions 44 and 46 are joined to each other at or near their outer peripheries. Proper alignment of housing portions 44 and 46 may be ensured by aligning alignment tab 57 with retaining member 58. (Alternative and optional alignment tabs 48 are also shown in
Preferably, portions 44 and 46 may be attached together by a mating tongue and groove arrangement.
During assembly of device 20, tongue 70 is inserted into groove 68. The area of the tongue and groove fitment is then preferably exposed to a sealing means. In a preferred embodiment, the sealing procedure may include an ultrasonic device for sonic welding and fusing of tongue 70 and groove 68. Other forms of welding or sealing, known to those of skill may also be used. The energy from the sonic weld melts the plastic parts of groove and tongue 68 and 70 and fuses them together, as shown in
As shown in
As best seen in
As further seen in
For additional assurance that liquid is not bypassing medium 60, the gap 90 remaining between medium 60 and housing 42 may be substantially filled with a liquid impermeable barrier. Shown in
Suitable sealants may include epoxies, RTVs, hot melts, polyurethane, EVA-based hot melts, silicones or other plastics, such as acrylic polymers. A preferred sealant is an EVA/wax hot melt available from Bostik Findley of Wauwatosa, Wisc. under the name Bostik H1714. The sealant may also be a gel that remains semi-solid after being injected. In any event, introducing sealant into gap 90, as shown in
Preventing liquid bypass of removal media 60 can also be accomplished by providing the disk of removal media 60 with a preformed sealing ring 93 or gasket around the perimeter of medium 60, as shown in
Ring 93 should have a thickness substantially equal to the gap 90 formed by housing portions 44 and 46 when the portions are brought together to form housing 42, as shown in
In a variant of the above-described embodiment, ring 93, or a suitable sealant or binding material may be formed first and placed in a sintering mold cavity. The removal media can then be sinter-formed inside the molded disk, resulting in a structure substantially similar to that shown in
In another alternative shown in
Still other alternatives include depositing or printing a hot-melt adhesive onto the perimeter of the medium disk 60, shrink-fitting a film around the perimeter of medium disk 60 or dipping the perimeter of the medium disk in a PVC plastisol.
In yet another alternative that does not require applying a sealant around to the disk 60 perimeter, the end surface 60c of the removal medium disk 60 may be treated to provide a liquid impermeable peripheral edge. In one embodiment, disk 60 perimeter may be exposed to a high temperature, such as, approximately 120° C. to create an impermeable skin around the perimeter. A skin can be formed by rotating the disk and exposing the peripheral edge of disk 60 to a hot air source or placing the disk in a hot-mold press to further form it after sintering. As shown in
Turning briefly back to
Housing portion 44 may also include a plurality of ribs 98. Ribs 98 may be raised surfaces that extend from inner surface 54 and provide strength and additional support for housing 44 during assembly. This may be particularly desirable when device 20 is joined by ultrasonic welding. Additionally, ribs 96 may prevent removal device 60 from adhering to the inner wall 54 of portion 44 (and possibly blocking inlet port 30). The plurality of ribs 98 may be spaced and arranged in any desirable configuration. For example, ribs 98 may be spaced from each other in parallel across the surface of inner wall 54. Other arrangements are also possible. In a preferred embodiment, ribs 98 are radially spaced extending from a point near the center 36 of device 20 (like spokes on a wheel), as shown in
As shown in
With reference to
As shown in
In one embodiment, such as the one shown in
For example, a flow through fluid processing system 10 where flow enters device 20 through an outlet that faces away from source container 12, may include a flow conduit to allow fluid entry. In this embodiment, the conduit diverts the flow in a direction that is approximately 180° turned from the direction of flow from container 12.
Thus, in the embodiment shown in
A similar arrangement is provided at outlet port 32. As shown in
In accordance with the present invention, it may be desired or even necessary to occasionally vent air from receiving container 14. Typically, this is achieved by “burping” air from receiving container 14 through a line in system 10. In many of the embodiments, this flow path is provided as bypass tube 38. In
Where bypass tube 38 is included, an additional branched flow conduit may also be provided as shown in FIG. 11. In one preferred embodiment, additional conduits may also be branched connectors 126 and 128. In a preferred embodiment, these branched conduits 126 and 128 are trifurcated conduits, such as, but not limited to, triple “Y” connectors of the type that will be known to those of skill in the art.
Thus, flow through the processing system 10 shown in
Once the fluid has passed through the device, where it contacts removing medium 60, it enters outlet 32. Flow exits the device 20 through port 32 and enters conduit 112 through port 114. As with fluid conduit 102, tube 122 is a “dummy line” that is sealed or flow therethrough is otherwise restricted. This prevents flow from entering the tube 122 and directs the flow through tube 118. Tube 118 communicates with conduit 128 and in particular port 128a. Port 128a communicates with tube 18 through which fluid is passed and collected in receiving container 14.
As shown in
Alternative fluid circuits are shown in
A further alternative embodiment is shown in
A further alternative embodiment is shown in
Turning now to
The tubing configurations described above assist in maintaining housing 42 in a substantially vertical orientation. As described above, this allows for substantially uniform and complete exposure of the biological fluid to the removal media 60.
Finally, shown in
As shown in
Additional means for retaining device 20 are shown in
Another important objective achieved by the present invention is the ability to ensure processing time consistency from one disposable set to the next. The challenge, of course, resides in the fact that there are inherent differences in the resistance to flow from removal medium disk to removal medium disk. Applicants have discovered that flow through the system can be substantially controlled and, thus, the influence of the resistance from disk 60, substantially diminished. In particular, and as discussed in more detail below, by adjusting the length of the flow path and the internal diameters of inlet tube 16 and outlet tube 18, it is possible to provide substantially consistent processing times from one set to the next.
For example, by lengthening the flow path of the system, namely the distance from source container 12 to collection container 14 (i.e., the “head height”), the force driving flow through the system may be increased. In addition, locating device 20 further from the source container 12 and closer to receiving container 14 (as generally depicted in
Thus, for example, the length of tube 16 may be approximately 1.5 to 8 times as long as tube 18. In one specific, non-limiting example, the length of tube 16 may be approximately 26 inches and the length of tube 18, approximately 3½ inches.
It has also been discovered that additional control over the flow rate can be achieved by adjusting the diameter of the flow path(s). For example, by narrowing the internal diameter of inlet tube 16 (as compared to the diameter found in standard sized tubings used in blood processing and the medical field, generally), together with the lengthening of the overall “head height,” as discussed above, the resulting flow rate is sufficient to substantially reduce the effect of the inherent resistance of the removal medium or disk. Thus, flow can be better controlled and remain relatively insensitive to the resistance provided by the disk.
For example, inlet tubing, disk and outlet tubing form a hydraulic circuit that can be described as resistances in series (R1 for inlet tubing, R2 for disk and R3 for outlet tubing and Rr describing additional resistances from connectors (such as Y-sites, diameter changes and other connections). Thus, total resistance in the fluid circuit is the sum of these individual resistances. The driver for the flow is head-height as described above.
It is known that disk manufacturing will generate variability in R2 resistance. If, R2 is the dominant resistor in the circuit, the variations in its magnitude will cause significant variations in flow rate and ultimately processing time. Thus, the impact of disk manufacturing variability can be minimized by making another component in the circuit, specifically inlet tubing R1, the dominant resistor. Since tubing ID and length manufacturing tolerances are controllable to a higher degree compared to disk manufacturing, inherent variations in R1 are expected to be significantly smaller in magnitude compared to R2 variances. Inlet tube resistance is primarily defined by the internal diameter of the tube and secondarily by the length for the laminar flow regime of interest (Reynolds number 100-1000). Thus, the internal diameter (of tube 16) is the primary parameter to be changed.
Selection of the inlet tubing compared to outlet tubing as the primary restrictor is also driven by relative tube length considerations. The rationale of having longer tube length on the inlet side of the processing set as compared to outlet side has been discussed above. By selecting R1 as the dominant resistor, added benefit from tube length is gained as well.
Thus, whereas standard tubing used in blood processing typically has an internal diameter of approximately 0.118 inches, to provide the benefits described above, the internal diameter of tube 16 must be less than the standard and, more preferably, substantially less than the above-identified diameter. In one preferred, non-limiting example, the internal diameter of the inlet tube 16 may be anywhere between 0.025 and 0.09 inches. Even more preferably, the internal diameter of the tubing may be approximately 0.057±0.03 inches.
Further improvement in the processing time and flow consistency can also be achieved by altering the internal diameter of outlet tubes that are in flow communication with outlet 30. In one embodiment, the internal diameter of the outlet tube 18 (and/or tube 118 in
The present invention has been described in the context of its preferred embodiments. It will be understood, however, that the present invention is not limited to the embodiments described, and that further improvements and modifications may be made without departing from the scope of the present invention which is set forth in the appended claims.
Claims
1-23. (canceled)
24. A flow-through fluid processing system for removing selected compounds from a fluid comprising:
- a source container including a fluid outlet;
- a receiving container including a fluid inlet;
- a compound removal device disposed between said source and receiving containers, said device comprising a housing having an interior chamber and a compound removing medium within said chamber, said housing including a fluid inlet on one side of said housing and nearer to said receiving container than to said source container and a fluid outlet on said housing and nearer to said receiving container than to said source container;
- a first tube providing a flow path between said source container outlet and said device inlet;
- a second tube providing a flow path between said device outlet and said receiving container inlet.
25. System of claim 24 wherein said inlet includes an opening that faces away from said source container.
26. System of claim 24 wherein said device outlet includes an opening that faces away from said receiving container.
27. System of claim 24 further comprising a retaining member adapted to receive said first tube.
28. System of claim 25 further comprising a retaining member adapted to receive said second tube.
29. System of claim 25 wherein said retaining member comprises a loop integral with said housing and substantially vertically aligned with said device inlet.
30. System of claim 24 wherein the flow of liquid through said device is in a direction 180° inverted relative to the flow-through said first tube.
31. System of claim 25 wherein said flow path from said source container to said device inlet port, comprises an approximately 180° turn.
32. System of claim 30 wherein said device comprises a connector having at least two openings wherein one of said openings is in flow communication with said inlet port of said device and the other of said openings is in flow communication with said first tube.
33. System of claim 32 wherein said device comprises a connector having two openings wherein one of said openings is in flow communication with said outlet port of said device and the other of said openings is in flow communication with said second tube.
34. System of claim 32 wherein said connector comprises one end that includes a bifurcated conduit wherein one branch of said conduit includes one of said openings and said other branch includes the other of said openings.
35. System of claim 34 wherein said connector comprises a second end with a port and a tube between said port and said receiving container.
36. The system of claim 35 wherein flow through said tube between said connector second end and said receiving container is restricted.
37. System of claim 32 wherein said connector comprises a U-shaped fluid flow conduit.
38. System of claim 24 comprising an upstream connector having an inlet in direct flow communication with said source container, and a plurality of outlets;
- a downstream connector including an outlet and a plurality of inlets,
- wherein said first tube provides a flow path between one of said upstream connector outlets and said device inlet; and
- said second tube provides a flow path between said device outlet and one of said downstream connector inlets.
39. System of claim 38 further comprising a tube defining a flow path, one end of which is connected to one of said upstream connector outlets and the other end connected to a downstream connector inlet, said tube including a valve in said flow path for selectively restricting flow therethrough.
40. System of claim 38 wherein said device inlet comprises a port facing away from said receiving container, said system further comprising a tube, one end of which is attached to said port facing said receiving container and other end of which is connected to one of said inlet ports of said downstream connector.
41. System of claim 39 wherein said tube comprises a permanently sealed flow path.
42. System of claim 38 comprising:
- a tube defining a flow path between one of said upstream connector outlets and said device inlet;
- a tube defining a flow path between one of said upstream connector outlets and one of said downstream connector inlets;
- a tube between one of said upstream connector outlets and said device outlet connector.
43. System of claim 42 wherein said upstream connector comprises a fluid conduit comprising an inlet and a trifurcated outlet.
44. System of claim 24 comprising a holder for supporting said removal device.
45. System of claim 38 wherein said holder comprises a sleeve for receiving the housing of said device.
46. System of claim 44 wherein said holder comprises two separate parts joined together to provide said sleeve.
47. System of claim 44 wherein said holder is attached to a pole support.
48-59. (canceled)
60. A flow-through fluid processing system for removing selected compounds or components from a fluid comprising:
- a source container including a fluid outlet;
- a receiving container including a fluid inlet;
- a compound removal device between said source container and receiving container, said device comprising a housing having first and second outer walls and a compound removing medium between said walls, said housing including a fluid inlet located between the center of said device and said receiving container and a fluid outlet located between said center and said source container;
- tubing providing a flow path between said source container outlet and said housing inlet;
- tubing providing a flow path between said housing outlet and said receiving container inlet;
- wherein the length of said flow path between said source container and said inlet is greater than the length of said flow path between said device outlet and said receiving container.
61. The flow-through fluid processing system of claim 60 wherein at least a portion of said tubing between said source container and said device inlet has an internal diameter that is smaller than the internal diameter of said tubing between said device outlet and said receiving container.
62. The flow-through fluid processing system of claim 61 wherein said tubing providing said flow path between said device outlet and said receiving container has an internal diameter of 0.08±0.003 inches.
63. The flow-through fluid processing system of claim 60 comprising a first connector in said flow path between said source container and said device inlet and said tubing defining said flow path between said source container and said device inlet comprises:
- a first tubing segment with a first end joined to said source container and said second end joined to said connector;
- a second tubing segment with a first end joined to said connector and said second end joined to said device inlet;
- said system further comprising a second connector in said flow path between said device outlet and said receiving container and a bypass tube having one end joined to said first connector and a second end joined to said second connector.
64. The flow-through fluid processing system of claim 63 wherein the internal diameter of said second tubing segment is smaller than the internal diameter of said bypass tube and said internal diameter of said first tubing segment is smaller than the internal diameter of said second tubing segment.
Type: Application
Filed: Nov 4, 2005
Publication Date: May 25, 2006
Inventors: Scott Ariagno (Mundelein, IL), Mihir Sheth (Gurnee, IL), Atif Yardimci (Northbrook, IL), David Pennington (Fox Lake, IL), Michael Prisco (Geneva, IL), Edwin Chim (Vernon Hills, IL)
Application Number: 11/267,391
International Classification: B01D 35/30 (20060101);