U.S. patent application number 11/379309 was filed with the patent office on 2006-08-10 for container or bag mixing apparatuses and/or methods.
This patent application is currently assigned to Gambro, Inc.. Invention is credited to Dennis J. HLAVINKA, Michael A. Martinez.
Application Number | 20060176767 11/379309 |
Document ID | / |
Family ID | 29270692 |
Filed Date | 2006-08-10 |
United States Patent
Application |
20060176767 |
Kind Code |
A1 |
HLAVINKA; Dennis J. ; et
al. |
August 10, 2006 |
CONTAINER OR BAG MIXING APPARATUSES AND/OR METHODS
Abstract
A mixing system, apparatus and/or method. Pathogen reduction of
and/or mixing storage solutions into blood or blood components are
useful purposes for these. Squeezing or clapping devices may be
used to activate the mixing process, as may rotational devices or
laterally movable, rotational and/or orbital devices. Constriction
elements may also be used to create useful vortex mixing actions.
Photoradiation may be provided while the components continue to be
mixed together for pathogen reduction of blood or blood
components.
Inventors: |
HLAVINKA; Dennis J.;
(Arvada, CO) ; Martinez; Michael A.; (Golden,
CO) |
Correspondence
Address: |
GAMBRO, INC;PATENT DEPARTMENT
10810 W COLLINS AVE
LAKEWOOD
CO
80215
US
|
Assignee: |
Gambro, Inc.
Lakewood
CO
|
Family ID: |
29270692 |
Appl. No.: |
11/379309 |
Filed: |
April 19, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10425281 |
Apr 28, 2003 |
|
|
|
11379309 |
Apr 19, 2006 |
|
|
|
60375734 |
Apr 26, 2002 |
|
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|
Current U.S.
Class: |
366/197 |
Current CPC
Class: |
B01F 5/0688 20130101;
A61L 2/08 20130101; A61M 1/025 20130101; A61L 2/10 20130101; A61L
2202/22 20130101; A61M 1/0277 20140204; B01F 11/0065 20130101; B01F
5/0683 20130101; B01F 5/0682 20130101; B01F 13/001 20130101; A61L
2/0088 20130101; A61M 1/3683 20140204; A61L 2/0011 20130101; B01F
9/0014 20130101; B01F 13/0001 20130101; A61L 2/084 20130101 |
Class at
Publication: |
366/197 |
International
Class: |
B01F 13/00 20060101
B01F013/00 |
Claims
1. A mixing system for use in mixing a fluid contained in a fluid
container, the system comprising: a rotational support structure
which is substantially vertical; an irradiation source for
irradiating the fluid contained in the fluid container; a holding
device disposed in operable relationship with the support
structure; whereby the holding device is adapted to hold the fluid
container; and whereby when the fluid container is disposed in the
rotational support structure; whereby the rotational support
structure may be rotated to thereby rotate the fluid container, and
thereby mix the fluid contained therein.
2. The mixing system according to claim 1 wherein the irradiation
source irradiates the fluid while the rotational support structure
is rotated to mix the fluid contained in the container.
3. A mixing system according to claim 1 in which the mixing system
further includes: a roller housing; and at least one roller
mechanism disposed in said roller housing; whereby the rotational
support structure is adapted to be disposed in operable rotational
engagement with the at least one roller mechanism such that at
least one roller mechanism imparts a rotational movement to the
rotational support structure.
4. A mixing system according to claim 3 in which the mixing system
further includes: a motor disposed in operable relationship with
the at least one roller mechanism; whereby the motor is adapted to
impart a rotational movement to the rotational support
structure.
5. A mixing system according to claim 4 in which the mixing system
further includes: a motor; and a motor connection assembly disposed
in operable relationship with the motor; and whereby the motor
connection assembly is disposed on operable rotational drive
relationship with the rotational support structure.
6. A mixing system according to claim 1 which further comprises a
constriction element disposed in operative relationship with the
fluid container.
7. A mixing system according to claim 1 wherein the irradiation
source further comprises LEDs.
8. A mixing system according to claim 1 wherein the irradiation
source further comprises fluorescent bulbs.
9. A mixing system according to claim 1 wherein the irradiation
source emits light in the visible region.
10. A mixing system according to claim 1 wherein the irradiation
source emits light in the ultraviolet region.
11. A mixing system according to claim 1 which the fluid to be
mixed includes a blood product.
12. A mixing system for use in mixing a fluid contained in a fluid
container, the system comprising: a lateral support structure; a
double sided movable squeezing element operably disposed relative
to said lateral support structure; wherein the moveable squeezing
element is a rotatable squeezing or clapping assembly connected via
a pivot assembly to the lateral support structure in a relative
central position and preferably has one or two flappers; an
irradiation source; and whereby said fluid container contains a
fluid to be mixed; and whereby the double sided movable squeezing
element is adapted to move so as to squeeze the fluid container
against said lateral support structure to thereby mix the fluid
contained in the fluid container.
13. A mixing system for use in mixing a fluid, the system
comprising: a lateral support structure; an irradiation source; a
holding device disposed in operable relationship with the lateral
support structure; whereby the holding device is adapted to hold a
fluid container; whereby the fluid container contains a fluid to be
mixed; and whereby when a fluid container is disposed in said
lateral support structure, said lateral support structure may be
moved in lateral or longitudinal rotations in at least two
dimensions to thereby move the fluid container, and thereby mix the
fluid contained therein; and whereby the irradiation source
irradiates the fluid in the fluid container while the fluid
container is being mixed.
14. A mixing system according to claim 13 in which the lateral
support structure is laterally moveable to laterally move the fluid
container.
15. A mixing system according to claim 13 in which the lateral
support structure is rotationally moveable to rotationally move the
fluid container
16. A mixing system according to claim 15 in which the rotational
movement is about a transverse axis.
17. A mixing system according to claim 15 in which the rotational
movement is about a longitudinal axis.
18. A mixing system according to claim 13 in which the lateral
support structure is circularly moveable to circularly move the
fluid container
19. A mixing system according to claim 13 in which the lateral
support structure is elliptically moveable to elliptically move the
fluid container
20. A mixing system according to claim 13 in which the fluid to be
mixed includes a blood product.
Description
PRIORITY CLAIM
[0001] This application is a Divisional of U.S. regular application
Ser. No. 10/425,281, filed Apr. 28, 2003 claiming priority from
U.S. Provisional application 60/375,734, filed Apr. 26, 2002.
FIELD OF THE INVENTION
[0002] This invention is generally related to apparatuses and/or
methods for mixing the contents of various containers or bags while
the contents are being irradiated. Of particular note is the use of
these apparatuses and methods in a pathogen reduction
procedure.
BACKGROUND
[0003] Contamination of human blood and blood components with
pathogens such as human immunovirus (HIV), hepatitis and/or
bacteria create a serious risk for patients who receive blood or
blood components via blood transfusions.
[0004] To help combat the problem of pathogenic contamination in
blood and/or blood components, one method of reducing pathogens in
blood and biologically useful fluids may be to use radiation to
substantially destroy any pathogens contained in the fluid.
Radiation may be used to inactivate pathogens contained in blood
and blood components by generating mutagenic alterations in their
genetic material. Above a minimum dose of radiation, the pathogens
lose their capacity to reproduce. Radiation damages the nucleic
acids of the pathogens by creating intrastrand nicks and inducing
nucleotide photodimerization, both of which disrupt nucleic acid
replication. Through such mechanisms, irradiating blood and blood
components with either visible or ultraviolet (UV) light can be an
effective means for reducing undesirable pathogens within blood and
other biologically useful fluids.
[0005] Unfortunately, the energy of short wavelength UV light may
also damage the blood and blood components that are the desired
end-products of the irradiation process. Thus, an inherent problem
in the application of UV-irradiation techniques is controlling the
irradiation of the fluid so as to ensure sufficient radiation
exposure to reduce undesirable pathogens within a fluid while at
the same time minimizing or eliminating damage to the biologically
useful fluids. One way to avoid substantial damage to the
biologically useful fluid by UV light is to design an apparatus
which will effectively mix the fluid in such as way so as not to
over-expose the fluid to the radiation.
[0006] Blood and blood components can also be decontaminated using
pathogen reducing agents or photosensitizers which, when activated,
also reduce pathogens contained in the blood or other biologically
useful fluids but does not destroy the biological activity of the
blood or blood component product.
[0007] Pathogen reduction agents, which may be used with this
invention, include the class of photosensitizers known in the art
to be useful for reducing pathogens. A "photosensitizer" as defined
here is any compound which absorbs radiation of one or more defined
wavelengths and subsequently transfers the absorbed energy to an
energy acceptor. Thus, such photosensitizers may be activated by
the application of electromagnetic spectra (e.g., UV and visible
light) to then reduce certain pathogens with which they may
interact.
[0008] Various photosensitizers have been proposed for use as blood
or blood component additives to inactivate pathogens in body
fluids. Examples of non-endogenous photosensitizers that have been
proposed for use as blood or blood component additives include
porphyrins, psoralens, acridines, toluidines, flavins (acriflavin
hydrochloride), phenothiazine derivatives, coumarins, quinolines,
quinones, anthroquinones and dyes such as neutral red and methylene
blue.
[0009] Other categories of photosensitizers are endogenous pathogen
reduction agents, such as 7,8,10-trimethylisoalloxazine
(lumiflavin), 7,8-dimethylalloxazine (lumichrome),
isoalloxazine-adenine dinucleotide (flavin adenine dinucleotide
[FAD]), alloxazine mononucleotide (flavin mononucleotide [FMN] and
riboflavin-5-phosphate), vitamin K and vitamin L and their
metabolites and precursors, napththoquinones, naphthalenes and
naphthols as well as their derivatives. One preferred example of an
endogenous photosensitizer contemplated for use with this invention
is an alloxazine such as 7,8-dimethyl-10-ribityl isoalloxazine,
commonly known as riboflavin. An advantage of using endogenous
photosensitizers to reduce blood contaminants is that endogenous
photosensitizers are not inherently toxic to the blood cells and if
photoactivated do not yield toxic photoproducts after exposure to
radiation. Therefore, a removal or purification step is not
required after the decontamination process, and the treated product
can then be stored in the same solution used in the pathogen
reduction process, transfused into a patient, or returned directly
to the donor.
[0010] One method of decontaminating blood or blood components
using a photosensitizer includes mixing an effective amount of a
photosensitizer with the fluid to be decontaminated in a batch-wise
way; then exposing the fluid to an amount of photoradiation at an
appropriate wavelength sufficient to activate the photosensitizer
and allow the activated agent to interfere with the pathogens
contained within the fluid such that the pathogens contained in the
fluid are reduced. The wavelength of light used will depend on the
photosensitizing agent selected as well as the type of blood
components being pathogen reduced. The light source or sources may
provide light in the visible range, the ultraviolet range, or a
mixture of light in both the visible and the ultraviolet range
[0011] Decontamination or pathogen reduction systems may be
designed as stand-alone units as described above, or may be
incorporated into existing apparatuses known to the art for
separating or treating blood to be withdrawn from or administered
to a patient. For example, such blood-handling apparatuses include
the COBE Spectra.TM. or TRIMA.RTM. apheresis systems, available
from Gambro BCT Inc., Lakewood, Colo., as well as apheresis systems
of other manufactures. The decontamination system may be inserted
before the collected blood is separated into components.
Alternatively, the decontamination system may be inserted
downstream of the point where the blood is separated and/or
collected, or at any point after separation of blood constituents.
It may even be inserted just prior to reinfusion of the blood
product back into the patient. It is further understood that
discrete irradiation sources could be placed upstream from the
collection points of each separated blood component, such as red
blood cells, platelets, and plasma. The use of three separate blood
decontamination systems, one for each separated blood component,
may be preferred to placement of a single blood decontamination
system upstream of the blood separation vessel of an apheresis
system because the lower flow rates in the separated component
lines may allow for greater ease of irradiation.
[0012] In other embodiments, decontamination systems for use in
and/or with the present invention may be used to process previously
collected and/or stored blood products, whole blood or components,
in a batch-wise way, as discussed above, and in further detail
below. In some photosensitizer methods, the blood product to be
decontaminated is flowed through an entry port into a
photopermeable bag or other container. The term "photopermeable"
means that the material of the container is adequately transparent
to photoradiation.
[0013] Polymeric bags and like containers, flexible or otherwise,
which are commonly used to collect and store blood and blood
components, are useful as the photopenneable containers referred to
above.
[0014] After the pathogen reduction process, the pathogen reduced
fluid may then be flowed out of the photopermeable container into a
storage container through an exit port, or may be stored in the
same photopermeable container used in the photoinactivation process
until transfused into a patient.
[0015] One problem with the use of light alone or light in
combination with a photosensitizer to reduce pathogens in blood or
blood products, is that during the pathogen reduction process, a
portion of the fluid to be pathogen reduced may become trapped
within dead spaces or opaque portions of the bag or container.
Fluid trapped in these dead spaces or opaque portions may not be
reached by light and may therefore still contain pathogens which
will re-infect the fluid which was previously pathogen reduced.
[0016] Another problem in pathogen reducing fluid using light
results from the laminar nature of fluid flow in a container. In
either a flow-through or a batch wise system, a parabolic velocity
profile exists for the fluid contained in either the fluid-flow
channel or a self contained bag. Upon agitation or application of a
force, the fluid at the center of the flow channel or bag is
traveling at a maximum velocity, while the fluid close to the walls
at the bag-fluid interface remains nearly stationary. Because of
this flow profile, upon irradiation of blood or blood components,
the exposure time of the blood is the shortest for the blood
traveling at maximum velocity at the center of the container, and
increases for successive portions of the flow profile moving
outwardly from the center. Therefore, not all of the blood in a bag
is irradiated at the same intensity and for the same length of
time. In addition to the velocity profile, blood tends to spread in
a thin film along the surface of the bag due to surface tension and
the tendency of blood to cling to the bag's surface. In the absence
of vigorous agitation, the blood located along the walls of the
container would have an extremely long residence time. Thus, the
blood or blood component nearest the walls (closest to the
irradiation source) runs the risk of being overexposed to radiation
which may significantly damage the blood or blood components, while
the fluid in the middle of the container runs the risk of being
under irradiated, thus any pathogens contained in this region would
receive little or no radiation, and would be likely to
re-contaminate the fluid with still viable pathogens.
[0017] In view of the above background, it can be seen that there
is a need for a method and apparatus for pathogen reducing a fluid
that ensures adequate exposure of all of the fluid to radiation
while simultaneously minimizing the damage to the blood or blood
components.
SUMMARY OF THE INVENTION
[0018] The present invention relates to methods, systems and
apparatuses for mixing various fluid (or other substance) elements.
More particularly, the present invention applies desirably to the
preparation including mixing of a blood or blood component product
in a pathogen reduction procedure. In one embodiment, the apparatus
comprises a support structure for hanging a flexible polymeric
container or bag therein or thereon and a moveable "clapper"
structure which alternately squeezes the bag and releases the bag
to mix the contents thereof. A clamp-like structure may also be
provided to create one or more constrictions in the bag to provide
mixing vortices within the bag to enhance the exposure of the bag
contents to or adjacent the internal surface of the bag and thus
also to any photoradiation impinging thereon. Photoinactivation is
thus enhanced particularly for relatively opaque fluids (such as
RBCs). A photosensitizer may be added to the blood or blood
component to be pathogen inactivated and then thoroughly mixed
therein. Then, also or alternatively the mixing effect could be
sustained during illumination of the product therein.
[0019] Another embodiment involves a rotating structure in which a
flexible bag may be disposed such that when rotated, the contents
of the bag are continually rotated up and alternately pulled down
by gravity. Rotating embodiments may also have light illumination
and/or clamp-like structures constricting portions of the bag to
create vortices which enhance mixing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 is a schematic isometric view of one embodiment of a
mixing system according to the present invention.
[0021] FIG. 2 is another isometric view of an embodiment of a
mixing system according to the present invention.
[0022] FIG. 3 shows an isometric view of a flexible container and a
mixing assembly according to one embodiment of the present
invention.
[0023] FIG. 4 shows a substantially elevational view of a flexible
container and a mixing assembly according to the embodiment of FIG.
3.
[0024] FIG. 5 illustrates an extracorporeal tubing and bag assembly
which may be used with and/or in a system of the present
invention.
[0025] FIG. 6 shows a partial cross-sectional view of a bag and
clamp assembly.
[0026] FIG. 7 shows a partial cross-sectional view of a bag and
clamp assembly as in FIG. 6.
[0027] FIG. 8 shows another partial cross-sectional view of a bag
and clamp assembly as in FIG. 6.
[0028] FIG. 9 shows an elevational schematic view of a flexible
container and clamp assembly.
[0029] FIG. 10 shows an isometric view of an alternative mixing
assembly.
[0030] FIG. 11 shows a plan view of the alternative embodiment of a
mixing structure according to FIG. 10.
[0031] FIG. 12 shows an elevational view of another embodiment of a
mixing structure and clamp.
[0032] FIG. 13 shows a partially cut away isometric view of a
mixing structure with a flexible container.
[0033] FIG. 14 shows an elevational view of an alternative
embodiment mixing structure somewhat like that in FIGS. 12-13.
[0034] FIG. 15 shows an isometric view of an alternative embodiment
of a mixing structure according to the present invention.
[0035] FIG. 16 shows a side elevational view of the alternative
embodiment of FIG. 15.
[0036] FIG. 17 shows another side elevational view of the
embodiment of FIG. 15.
[0037] FIG. 18 shows a rear isometric view of the embodiment of
FIG. 15.
[0038] FIG. 19 is a plan view of a frame for use with the
embodiments of FIGS. 15-18.
[0039] FIG. 20 is an isometric view of an alternative embodiment of
the present invention.
[0040] FIG. 21 is a top plan view of the embodiment of FIG. 20.
[0041] FIG. 22 is an isometric view of another alternative
embodiment of the present invention.
[0042] FIG. 23 is an isometric view of a part of the embodiment of
FIG. 22.
[0043] FIG. 24 shows a partial cross-sectional view including fluid
vortices created within a bag used in an embodiment like that shown
in FIG. 22 upon application of a force causing the fluid to flow in
the general direction of the lateral pointing arrows.
[0044] FIG. 25 shows a partial cross-sectional view including fluid
vortices created within a bag used in an embodiment like that shown
in FIG. 22 upon rotation in the direction of the arrows.
[0045] FIG. 26 shows a plan view of an alternative bag for
containing fluid to be mixed according to the present
invention.
[0046] FIG. 27 shows a plan view of an alternative bag for
containing fluid to be mixed according to the present
invention.
DETAILED DESCRIPTION
[0047] FIG. 1 shows a blood or blood component mixing system 20 for
mixing blood components in accordance with the present invention.
Whole blood is withdrawn from a donor/patient (not shown) and may
be treated in whole blood form by the present invention, or it may
be provided to an apheresis system or other type of blood component
separation device (not shown) often of a centrifugal type, where
the blood may be separated into one or more of various component
types and at least one of these blood component types can then be
removed/collected as a product from the separation device. The
blood or blood component products (e.g., platelets, plasma, white
blood cells, or red blood cells) may then be pathogen reduced
either continuously in a flow-through manner within or adjacent the
apheresis machine (not shown) or in a separate batchwise step.
Ultimately, the pathogen reduced blood components may then be
stored for later transfusion into a patient.
[0048] The system 20 shown generally in FIG. 1 includes a mixing
device 22 (shown schematically here) which has a support structure
generally designated 23 disposed on a base 21. A moveable
"clapping" member 24 is disposed in operative relation to support
23, and as shown here, has a pivotable relationship therewith as
depicted in FIG. 1 by the connection through pins 25 (see pins 25a
and 25b). As shown in FIGS. 2-4, moveable member 24 has openings or
slots disposed therein. Such openings or slots may be used to allow
radiation to penetrate the bag 35 (see FIG. 3) which may be
contained therein, or may be used to allow heat generated during
the irradiation process to escape so as not to damage the blood or
blood product being irradiated. Support structure 23 also may have,
as shown, one or more devices for holding a container therein such
as the two holding members 26 which may be, as shown here,
protrusions or hooks on which a bag may be hung (see below). Also
shown schematically are two clamp-like constriction elements 27,
the use of which for creating mixing vortices will be described
further below.
[0049] An exemplar device 22 is shown in more detail in FIGS. 2-4.
One additional detail reflected herein is a motor 28 connected to
movable member 24 via a linkage connection 29. Motor 28 provides
the motive force to move the movable member 24 as will be described
further below. FIG. 3 also shows a flexible container or bag 35
disposed in/on device 22 as supported by hanging members 26.
[0050] FIG. 5 is but one example of a preconnected extracorporeal
tubing circuit 30 which may be used to obtain a blood product
according to known (or to be developed) methods. In general, a
blood removal/inlet tubing sub-assembly 31 provides a needle 32 to
interface a donor (not shown) with the remainder of the tubing
circuit 30. A platelet collection tubing and bag assembly 40, a
plasma collection tubing and bag assembly 42, and a red blood cell
collection tubing and bag assembly 44 may also be connected within
circuit 30. As will be appreciated, this is but one example of an
extracorporeal tubing circuit 30 and further various blood
component assemblies (more or less than shown) are or may be
pre-interconnected to combinatively yield a closed, pre-sterilized
disposable assembly suitable for a one time use. Any of these bags
35 may then be used in system 20, as well as any of the other
systems described herein below.
[0051] Most portions of the tubing assemblies 30, 40, 42 and 44
including bags 35 may be made from flexible polymeric or plastic
components including, for example, polyolefin or polyvinyl chloride
(PVC) tubing lines and bags 35, that preferably permit visual
observation and monitoring of blood/blood components therewithin
during use, as well as for irradiation purposes. All tubing lines
and bags may be preconnected before sterilization of the entire
disposable assembly to assure that maximum sterility of the system
is maintained. Thus, bag 35 may be pre-connected and/or
post-connectable with the extracorporeal tubing circuit 30 as
described relative to FIG. 5 above, or may be used separately, as a
stand alone apparatus, neither alternative departing from the
spirit and scope of the invention. Note further that alternative
resilient or even rigid containers may also be used in some
embodiments of the present invention.
[0052] In any case, FIGS. 3 and 4 show any of the FIG. 5 flexible
polymeric containers or bags 35 disposed in a mixing structure 22
of a system 20 in accordance with the present invention. The
container or bag 35 may be made of a flexible polymeric type film
which is sealed or welded around its outer border zones during
manufacture to form pre-formed seals or welds (see weld 36 denoting
the circumference of container or bag 35). The seals or welds 36
create a fluid tight, sealed interior space or main body
compartment (not separately shown in FIGS. 3-4). Ports or openings
37 allow fluid ingress and/or egress into and/or out of the
container or bag 35. As shown in FIGS. 3-4, two ports 37 may be
located on the same side of the container or bag 35. Such a
container or bag 35 could contain one, two or more ports as is
generally known. Known types of ports may be used in this
invention, including one or more ports having a frangible-type
closure mechanism (not shown).
[0053] As shown in FIG. 3, the container or bag 35 may have a hole
or holes 38 punched in for example, the upper or lower edges of the
pre-formed factory seal 36 to mount the container or bag 35 in a
hanging position as will be described further. Alternatively, the
bag may not have holes punched in the preformed factory seal (see
FIG. 4) and then may be hung in various other fashions, as for
example, using clamps (not shown). The container or bag 35 may be
hung before, during or after the process of combining the blood
component with any additive solutions, if used, into the bag 35.
The pre-formed factory seal 36 or any of the other pre-formed seals
may also be made wide enough so that a label describing the
contents of the bag 35 may preferably be placed on the area over
the seal (not shown). The bag 35 may also have a connection to a
sample bulb via a port (not separately shown) to allow for fluid
removal and sample testing or the like. A port which allows for the
connection of a spike receptor (not shown) or to enable the sterile
docking of a further bag or tube for the addition of a
photosensitizer or blood component may also be added to container
or bag 35. A spike connector (not shown) may also preferably
include a sterile barrier filter as is known in the art.
[0054] In one embodiment, and as introduced above and further
described below, an external constriction element or clamp assembly
27 on or otherwise associated with (or dissociated from) device 22
may be a clamp, a clip, or anything of the like which may be
removably connected to the container and thus divides a single
container into multiple removable sub-compartments by a restricted
flow area (though preferably still allowing flow therethrough) and
limits fluid communication between each of the separate
sub-compartments. More constriction elements than specifically
shown in the figures may be used to create more than the two
general sub-compartments shown in a single container as well.
Alternatively, pre-formed seals or welds (not shown) may be made in
container 35 to create one or more sub-compartments with
constricted flow areas, yet permitting flow between compartments.
Bags containing sub-compartments made with pre-formed seals or
welds may be used alone or in combination with clamp assembly 27.
United States Patent Application US2002/0138066, published Sep. 26,
2002 and herein incorporated by reference in its entirety to the
amount not inconsistent, discloses containers having multiple
pre-formed subcompartments made with seals or welds which may be
used with the present invention.
[0055] FIGS. 1-3 show isometric views of clamp assemblies 27 (not
shown with container or bag 35 in FIGS. 1 and 2, but shown
therewith in FIG. 3) according to the present invention. Each clamp
assembly 27 preferably includes at least one bar 271 (see FIG. 1),
and as shown, preferably a second bar 272. As will be described,
these bars 271, 272 assist in creating a narrowed fluid passage in
container 35 between the sub-compartments formed by the clamp
assemblies 27.
[0056] FIG. 6 shows a partially broken away cross-sectional view of
a clamp assembly 27 (shown in dashed lines) creating separate
sub-compartments 50 and 51 in a flexible container or bag 35. The
clamp assembly 27 creates a temporary, preferably removable
constriction 55 along all or part of the width of the bag to create
the two distinct sub-compartments 50 and 51. The clamp assembly 27
may, in one embodiment, be easily removed from the container or bag
35 (as described below) to create a single bag with only one
internal compartment. This may be achieved by simply loosening
and/or removing the bar(s) 271, 272 on/from the device 22. Once the
bars 271, 272 are loosened or removed, the bag 35 may be removed
from the structure 22 by removing the bag 35 from the hooks 26 (if
applicable). In an alternate embodiment, clamp assembly 27 may not
need to be removable or loosenable from device 22. Clamp assembly
27 may be permanently affixed to device 22, and bag 35 may be slid
in and out of the clamp assembly 27.
[0057] One method of using the above-described embodiments is as
follows, described in relation to the embodiment of FIGS. 1-4 as
shown by FIGS. 6, 7 and 8. Although not specifically described, the
method may also be used generally with the alternative embodiments
described below. Initially, blood or blood components to be
pathogen reduced are disposed in bag 35. Any other components which
may be desirable for the pathogen reduction procedure such as a
photosensitizer may be further disposed in bag 35, or may be
prepackaged in a satellite bag assembly (not shown). Any number of
other solutions containing other necessary components for pathogen
reduction or other purposes such as storage of blood or separated
blood components may be added to bag 35 through port 37 at any
desirable time. Note, the additional components may be in a dry
solid or a liquid form.
[0058] In one use of the invention, solutions for the pathogen
reduction and/or storage of blood and/or blood components may be
preliminarily mixed together or may be simultaneously mixed with
the blood product to be pathogen reduced. After combination of the
fluids either before or after addition to the blood or blood
component product to be pathogen reduced, the blood or blood
component to be pathogen reduced and the solution which may contain
a photosensitizer are mechanically mixed together using a mixing
structure 22 according to the present invention. The mixture may be
exposed to a light source while continuing the mixing process.
[0059] FIG. 6 shows the creation of multiple vortices within a
flexible polymeric bag similar to the type described in FIGS. 3, 4
and 5, when disposed in operative relationship with a clamping
device, such as device 27. Because of the flexible nature of the
bag 35, clamp 27 causes a partial constriction which may be located
approximately halfway up the length of the bag and as shown in
FIGS. 1-4 each clamp 27 may extend inwardly from the sides of the
container/bag 35. As shown in FIGS. 6, 7 and 8, the created
narrowed or constricted portion 55 in the sides of the container 35
acts as follows. In the first instance, gravity pulls the fluid
down from the upper compartment 50, through the constriction 55 and
then into the lower compartment 51. This is shown generally in
FIGS. 6 and 7. Flow vortex action is shown by the flow arrows 56,
which help reach and "scrub" the interior surfaces 54 of the bag
35. Such mixing action helps to replace the fluid located along the
fluid-bag surface interface 54 with fluid from the interior of the
bag. Such turn over of fluid helps to prevent overexposure of the
fluid nearest the bag surface 54 (and nearest to the irradiation
system) to radiation, and helps bring fluid from the interior of
the bag 35 to the surface to be irradiated. Although such
"scrubbing" action is described in relation to fluid vortices
generated by the mixing process, random flow mixing will also work
to facilitate fluid turn over. Then, in the second instance, as
shown by FIG. 8 and upon the application of a force or pressure to
the bag, such as by squeezing of the lower bag portion 51 by the
moveable member 24, the fluid within the container 35 may be forced
to move to the upper portion 50 from the lower portion 51 of the
container 35 through the narrowed portion 55 created by the
clamp(s) 27. Moveable member 24 is shown in FIG. 7 in a relative
open position relative to a back wall 231 (see FIG. 1) of a device
22, whereas moveable member 24 is shown moved in FIG. 8 to a
relative closed position adjacent wall 231 between which the bag 35
has been squeezed thereby providing the force that moved the fluid
up from the lower compartment 51 to the upper compartment 50. This
force also caused the flow vortices 57 which scrub the upper inner
walls 54 of bag 35. This movement creates vortices within the fluid
as shown in FIG. 8 which helps to further mix the fluid. Although a
force application and resultant vortices shown in FIG. 8 are shown
as being directed towards the upper portion of bag 35 respectively,
the force application and resultant vortices could be directed to
either the upper portion or the lower portion of the bag 35 or
both, depending upon the squeezing or relaxing of the device 22. In
a relatively substantially vertically disposed system 20, the fluid
within the bag 35 may be repeatedly forced to flow to the upper
portion 50 of the container by action of device 22 and then allowed
to be pulled to the lower portion by gravity to ensure thorough
mixing of the blood or blood component product and a
photosensitizer (if added) as well as ensuring thorough mixing of
the component product to expose the entire product to light during
illumination (light rays 65 are shown in FIG. 6). Thus, a
substantially vertically disposed device 22 may have an advantage
in using gravity for a substantial part of fluid movement, and only
a bottom compartment squeezing element may be used.
[0060] Such turn over of fluid by mixing provides an advantage
especially to pathogen reduction of relatively opaque substances
such as RBC component products. With such products, light is not
readily able to penetrate very deeply into the component product
(e.g. not far past the bag film). Thus, the layer of blood product
immediately adjacent the inner bag wall is irradiated, but should
then be "turned over" or removed therefrom and replaced with a new
layer of blood product which may then be irradiated. Mixing as
described herein serves to "scrub" these bag wall layers of product
away in desirable fashion. Moreover, such action may be made very
aggressive during irradiation and help to shorten the pathogen
reduction process.
[0061] Bag 35 is shown in FIGS. 3 and 4 and more particularly in
FIG. 9 as constricted by clamps 27 only partially across the width
thereof as limited by the lateral extensions of clamps 27. This may
provide an advantage because it may provide additional lateral
flows and mixing vortices as shown by arrows 58 in FIG. 9. Even so,
and although thus far only partial constrictions have been shown
and described extending from the outer border zones of the bag 35,
it ought to be noted that such a bag could be divided more fully
into two (or multiple) sub-compartments by placing one (or more)
complete cross bar clamp assemblies over the bag at a desired
location similar to the clamp assemblies shown in FIGS. 3 and 4,
except that they might cover the entire width of the bag 35.
Moreover, such a closure assembly could be an external removable
openable assembly, an internal openable assembly, a clamp, a clip,
or anything of the like which would entirely or partially divide
the single container/bag into multiple sub-compartments though
continuing to provide merely limited or constricted communication
between the fluid contents contained within each separate
sub-compartment such that flow is still viable therethrough as
shown in FIGS. 6, 7 and 8. It is further noted that a number of
alternative bag embodiments having one or more partial seals or
welds, or other bag shapes such as those shown below in FIGS. 26
and 27 (see the hourglass shape therein) could be used as any bag
including all of the bags or containers described herein.
Otherwise, other mechanical closure (not shown) assemblies or
resilient or even rigid containers with built in or external
removable assemblies or other structural equivalents such as a
clamp, a clip, a tongue and groove seal, a vise, a clasp, a grip,
or a fastener may be used to create a narrowed portion within a
container. These may be connected to device 22, 72, 92, 400, 500 or
not, as may be desired.
[0062] Note, a primary embodiment using a squeezing device such as
this could also make use of light sources (not directly shown as
yet but see FIGS. 10 and 11) to shine on the bag, or multiple bags
simultaneously (see the light rays 65 represented schematically in
FIG. 6). Such an embodiment with a substantially vertically
arranged squeezing or "clapping" mechanism is shown in FIGS. 10 and
11. Such a system 20a is shown having capacity for two bags though
only one bag 35 is shown. In this embodiment two full length bars
(not shown in FIG. 10) which stretch across the entire width of the
two bags could be used one each on the front and back sides of the
bags to create the clamping assembly 27 and associated mixing
described in detail above. Here, however, at least one set of light
sources 60 are shown which can be used to irradiate the bag(s) 35
and the contents thereof while mixing the contents using the
motions and vortices described above. The contents may be fully
exposed to photoradiation, and if a photosensitizer is used, such
mixing would ensure proper exposure of the photoactivatable agent
(e.g., riboflavin or psoralens) to the photoradiation, as well as
to ensure fluid turn over. Note, though only one set of lights 60
are shown in FIGS. 10 and 11, another could be established on the
opposing side of the bag(s) 35. Light radiation arrows 65 are shown
in FIG. 6. A reflective surface to reflect the light throughout the
chamber could also be used. The dashed line schematic light rays in
FIG. 6 are intended to reflect these options (separate light
sources or reflective surfaces). In any event, it may be preferred
that light be made to impinge upon the bag(s) 35 from both sides
(e.g. UV light, if used, may need to be provided from both sides).
Note also that it may be advantageous for all or most of the
physical elements touching or near bag(s) 35, e.g., the clapper
structure 24 (see FIG. 11) and the back wall 231, to be transparent
to light radiation, and may thus be made of a transparent
polycarbonate, plexiglass, quartz glass or other sturdy
substantially transparent material to allow light transmissivity
therethrough. This may be advantageous in any or all embodiments
described herein.
[0063] An alternative mixing structure may include a rotatable
device or wheel in which a bag may be disposed. Shown in FIGS. 12
and 13 is a wheel 400 of a system generally designated 200. Wheel
400 has a cutout or aperture 401 defined therein in which a bag
such as bag 35 (FIGS. 3-5) may be disposed. The cutout 401 where
the bag 35 may be disposed, may be substantially transmissive to
radiation. It is also contemplated that the cutout 401 may not be a
cutout at all, but may be an indentation or well in the wheel 400
for holding the bag 35 to be irradiated. If this is the case, 401
may be made of material which is transparent to radiation, and may
thus be made of a transparent polycarbonate, plexiglass, quartz
glass or other sturdy substantially transparent material to allow
light transmissivity therethrough. It is also contemplated that the
indentation or well 401 may be made of material which is not
transparent to radiation. The bag 35 may be clamped or otherwise
held in place at four corners and/or along the sides at one or more
locations with any of numerous alternative devices (not
specifically shown). However, at least one bar or clamp device 470
is preferably used to provide the narrowed flow constrictions
described above for the enhancement of mixing.
[0064] Preferably, as shown in FIG. 13, a bag 35 is disposed in the
wheel 400 and constrained between two cross bar clamping members
471, 472 to squeeze or narrow the dimension therebetween for
mixing. These may be disposed to divide the chamber of the
container into approximate half or other sized portions. Then the
wheel 400 is preferably disposed in an operably rotatable manner in
a device (not shown) which will provide the rotating force to
rotate the wheel 400 about its central axis 480 (FIG. 13). In one
embodiment, the rotation will be .+-.360 continuous degrees with
light shining at the bag from both sides of the bag/wheel. In one
embodiment, the wheel may be rotated in an alternating fashion in
one direction for a period of time, and then the wheel could be
reversed to rotate in the other direction for a period of time.
Gravity is used to first pull the contents of the bag 35 down into
the lower portion of the bag 35, and as the bag is rotated and
turned or flipped over, gravity pulls the contents down into what
was the upper portion, now inverted and disposed under the previous
lower portion (FIG. 6). Upon continued rotation, the bag is
re-inverted so that the original upper portion is once again
disposed above the original lower portion and gravity pulls the
contents again down into this lower portion (FIG. 6). As shown in
FIG. 6, upon each inversion, the flow of contents passes through a
constriction 55 between clamping members 471, 472 et al. and
creates mixing as depicted. Such mixing again provides for
scrubbing the inner bag surface to ensure removal of already
irradiated material therefrom and ensures that new material not yet
irradiated is deposited there so that the newly deposited material
may be exposed to light.
[0065] Another version 200a of a wheel 410 is shown in FIG. 14 in
which multiple (here, four (4)) bags 35 are shown disposed thereon
for rotation with the wheel 410. Clips or clamps 471, 472 are also
shown for holding the bags and/or providing the flow constrictions
for mixing as described throughout. Rollers 499 are shown
schematically as one alternative for providing the motion necessary
to rotate wheel 410 (or 400, see FIGS. 12, 13). Thus, such rollers
could be disposed in a device (not shown but not unlike that shown
in FIGS. 10, 11) and be mechanized to roll in a direction similar
to that shown in FIG. 14 to provide a rotational motion to the
wheel 410 designated by the arrow 411 in FIG. 14, and thus the
wheel and bag(s) may be rotated and the contents thereof mixed
while also being exposed to photoradiation. Note, though not shown
in these rotating wheel embodiments, light sources may be used to
shine light on one or the other, or in some embodiments, both sides
of a rotating bag for photoactivation of photosensitizer chemicals
in the bag, if used. Such lights may be disposed in banks on either
side of the respective bag. These banks may thus be stationary
relative to the rotating/moving bag (see FIG. 10) and/or wheel
device such as wheel 400 (or 410, inter alia), or the light banks
may be made to rotate with the bag. As an example of this please
see the further alternative wheel embodiment as shown in the
embodiments of FIGS. 15-18.
[0066] In the embodiment of FIGS. 15-18, a system 2000 is shown
with a device 500 which includes a base 501, a support arm 503 and
a rotatable member 504 which here includes front and back light
banks 505, 506 which are thus rotatable. A motor 508 with a chain
link style gear driving mechanism 509 is also show in FIGS. 15-18
(particularly FIG. 18). A frame 510 which is adapted to hold a bag
35 (as shown in FIG. 19, see below) is shown as disposed in device
500 in FIGS. 15, 17 and 18 (FIG. 16 shows device 500 without frame
510). Thus, when a bag 35 is disposed in a frame (see FIG. 19), and
frame 510 is disposed in device 500, the motor 508 can be activated
to turn the gear assembly 509 which in turn rotates the rotatable
member 504 with light banks 505, 506 and frame 510. A mixing action
of contents in bag 35 like that shown and described relative to
FIG. 6 then occurs.
[0067] As shown in more detail in FIG. 19, a bag 35 (shown in
dashed lines), held in place by clips/clamps/hooks 511, may also be
crossed by a crossbar clamping assembly 570 which includes a cross
bar member 572 which provides a flow constriction for mixing like
that shown in FIG. 6. It should be noted that constriction element
570 extends the entire length of the bag, however, constriction
element 570 may also extend partially across the bag such as the
constriction elements shown in FIGS. 3 and 13. A corresponding bar
571 is shown in FIGS. 15, 17, and 18 on the opposing side of the
frame 510.
[0068] Thus, when rotated and illuminated, a pathogen reduction
process can be achieved. In this embodiment, the irradiation source
is shown as being LEDs (light emitting diodes). One advantage in
using LEDs is their ability to be located in close proximity to the
bag containing fluid to be pathogen reduced without emitting much
heat, which could damage the blood or blood component being
irradiated. LEDs are also useful in this invention because they
emit light in very narrow bandwidths. Light in a narrow spectrum
may be beneficial to the blood product being irradiated because all
non-useful wavelengths of light which might damage the blood or
blood components are eliminated.
[0069] Fluorescent bulbs may also be used as the irradiation source
(see FIGS. 10 and 22). Visible or ultraviolet light may be used,
depending on the type of blood or blood product to be pathogen
reduced as well as the type of photosensitizer to be used, if
any.
[0070] Note, in the rotatable examples, more resilient or even
rigid containers may be used. Constriction elements which are built
in or completely removable may also be used in these
embodiments.
[0071] Further embodiments may include other than the substantially
vertical embodiments described heretofore (which take advantage of
gravity as a flow forcing element therein). For example,
substantially horizontal-mixing structures may also be used. A
first such embodiment is shown in FIGS. 20, 21. The system 70 of
FIGS. 20, 21 includes a mixing device 72 which may include a base
frame 71, to and/or in which may be a screen-like support 73 on
which a bag 35 may be disposed (note, metal or transparent plastics
may be used). A rotatable squeezing or clapping assembly 74 may
then be disposed in operative relationship therewith. Assembly 74
is connected via a pivot assembly 75 to the frame 71 assembly in
relative central position and preferably has one or two flappers 76
which may be moved down onto and squeeze the bag 35 when this is
disposed therein. A motor 78 may be used to impart the back and
forth rotational movement, through motor connection 79, to the
rotatable assembly 74. Back and forth rotation hereof is generally
shown by the arrows 69 (FIG. 20.) A constriction or clamp member 77
may also be used herewith. Indeed, constriction member 77 may be a
part of the rotation connection assembly, as for example, an axle
which may lay across the bag 35, again in a substantially central
location. A corresponding upraised portion or member (not directly
shown) may be disposed on the underside of bag 35 as perhaps a
portion of or a member connected to the support structure 73. A
further alternative in this or any of the embodiments in this
specification, is to use a separate clamping assembly (not
separately shown), not directly attached to the device 72. In any
case, it may be preferred (though not necessary) to have a
constriction device in order to provide the mixing action shown and
described relative to FIG. 6 above.
[0072] Note, as introduced above this system 70 can be disposed
substantially horizontally, so long as there is access to lights if
so desired, and in an embodiment these could be shining from both
top and bottom sides (although one side or the other may also be
operable). Even so, it could also be disposed vertically or in
numerous other dispositions in three-dimensional space.
[0073] A further usually substantially horizontally disposed
embodiment is shown in FIGS. 22, 23, 24 and 25 (although this also
could be disposed in any number of other dispositions in 3D space).
In the primary embodiment shown in FIG. 22, the system 90 is shown
which includes an irradiation unit 91 in which is disposed a mixing
device 92. Device 92 includes a moveable tray or frame 93 with a
screen or other support 94. As shown in more detail in FIG. 23, the
movable tray 93 may be connected by a pivot assembly 95 to a motor
98 which may provide the movement for mixing the contents of the
bag 35 which may be disposed thereon (see FIGS. 24 and 25,
described below). In one embodiment, a clamp device 97 (see FIGS.
24-25) may be also included to provide flow-mixing vortices as
shown and described both above and below.
[0074] As shown in FIG. 24, the moveable tray 93 may be moveable
back and forth in a lateral or longitudinal type of motion or both.
This is shown by the lateral arrows 101. This can then create the
fluid flow vortices identified by the flow arrows 102 inside bag
35.
[0075] Similarly, as shown in FIG. 25 the tray may also be rotated
slightly to cause fluid motion in the bag 35. This rotation is
shown by arrows 103 and the fluid flow vortices created thereby are
shown by arrows 104 in the bag 35. Note, the tray 93 may rotate in
either or both lateral or longitudinal rotations (e.g., rotations
about lateral or longitudinal axes). Lateral rotations are shown by
arrows 105 (FIG. 23.) The movements such as the back and forth
lateral or longitudinal movements (as shown in FIG. 24) may be
combined with rotations in other directions (as in the lateral
and/or longitudinal rotations as shown in FIG. 25), and may be in
either ordered or random combinations. Thus wobbles and/or
nutations (as from wobbulators or nutators, as known) may be
further alternatives included here as well. Still further rotations
may be circular or elliptical or other orbital movements, as
depicted generally by the arrows 107 in FIG. 23. Such orbital
motions may be used in lieu of or in addition to those previously
described. Churning, undulating, oscillating, gyrating, shaking
and/or stirring are but a few of a host of other motions which may
be performed here within one, two or three dimensions, alone or in
combination to provide mixing according to this invention.
[0076] FIG. 26 shows another embodiment of a flexible container
which may be used in/with the present invention (squeezing or
rotation, or mere movement) wherein the flow constriction assembly
is a part of the bag/container 350. The container 350 may be made
of polymeric type film material extruded in a tube-like shape. The
main body compartment of container 350 has two partial seals or
welds 370 which at about half way up the length of the main body
compartment extend inwardly from the sides of the container 350.
The partial seals or welds 370 divide the main body portion into
two partial sub-compartments 351, 352 respectively. Although shown
as extending inwards from the sides of container 350, one or more
partial seals or welds 370 may extend from any of the four sides of
the bag 350 without departing from the spirit and scope of the
invention. These partial seals or welds 370 are intended to provide
vortices 58 in the fluid during the mixing process.
[0077] FIG. 27 shows a plan view of another alternative embodiment
of a further polymeric container 3500 which may be used in/with the
present invention. This container 3500 may be made of a polymeric
type film such as PVC or polyolefin (flexible or not). The
container may be sealed or welded around its outer border zones
during manufacture. The seals or welds create a fluid tight, sealed
interior space. The container is configured in a substantial figure
eight or hourglass shape as shown (and as introduced above). The
container 3500 has an upper expanded interior or sub-compartment
portion 3510, and a lower expanded interior portion or
sub-compartment 3520. The upper expanded sub-compartment 3510 and
the lower expanded sub-compartment 3520 are connected to each other
in a fluidly communicative relationship by narrowed portion 3555
defined by the indented sides of the container. Both the upper
expanded sub-compartment 3510 and the lower expanded
sub-compartment 3520 may also be further sub-divided into multiple
sub-compartments (not shown) without departing from the spirit and
scope of the invention. As shown in FIG. 27 a constriction 3700 is
formed by the figure eight or hourglass shape in such a fashion so
as to divide bag 3500 into two separately contained fluid-tight or
fluidly separated sub-compartments 3510, 3520. Sub-compartment 3510
is located above sub-compartment 3520.
[0078] As shown in FIG. 27, the figure eight or hourglass
configuration may aid in mixing the solution within the bag 3500.
The fluid in the bag may be mixed in a substantially vertical
manner or a substantially horizontal manner and/or any angle
therebetween (although a vertical disposition will have gravity
assistance). A force imparted to the bag at a particular location
creates the movement of fluid within the bag. As the fluid is
forced to move through the narrowed portions 3555 of the
hourglass/figure eight shape, vortices 58a are created within the
fluid which helps to further mix the fluid. A clamp (not shown)
such as those described herein may also be used to create narrowed
portions within the bag. A seal or weld like a clamp structure
could also be used to further separate any portion into two smaller
sub-compartments and may thus also assist in creating further
vortices within the fluid. The narrowed portion or portions create
vortices within the fluid as the fluid is forced to flow through
the narrowed portions as described throughout.
[0079] FIG. 27 shows the bag 3500 in the figure eight or hourglass
configuration being mixed by clapping or rotation in either a
substantially vertical and/or a substantially horizontal manner. If
rotated, the bag may be rotated about its centerpoint (not shown)
between about 150.degree. and about 360.degree. in a continuous
fashion. A force (from the rotation itself and/or due to the force
of gravity when in a vertically disposed embodiment) may be
imparted to the bag by virtue of the rotation of the bag to create
the initial movement of fluid within the bag. As the fluid is
forced to move around the figure eight or hourglass shape, vortices
are created within the fluid which helps to further mix the fluid.
The bag may be rotated in a continuous manner, or may be agitated
in varying degrees from between about 0.degree. to about
360.degree. without departing from the spirit and scope of the
invention. The bag may also be rotated either singly or in a
repetitive manner.
[0080] The examples of the above-described systems, methods, and
apparatuses and bags are for illustrative purposes only. Because of
variations which will become apparent to those skilled in the art,
the present invention is not meant to be limited to the particular
embodiments described above. Any such variations and other
modifications or alterations are included within the scope and
intent of the invention.
* * * * *