U.S. patent application number 17/838410 was filed with the patent office on 2022-09-29 for system and method for plasma purification prior to mononuclear cell collection.
The applicant listed for this patent is Fenwal, Inc.. Invention is credited to Lan T. Nguyen, Jonathan W. Prendergast, Katherine N. Radwanski.
Application Number | 20220305187 17/838410 |
Document ID | / |
Family ID | 1000006391268 |
Filed Date | 2022-09-29 |
United States Patent
Application |
20220305187 |
Kind Code |
A1 |
Radwanski; Katherine N. ; et
al. |
September 29, 2022 |
System And Method For Plasma Purification Prior To Mononuclear Cell
Collection
Abstract
A method of collecting mononuclear cells includes separating
whole blood into plasma and cellular components, purifying the
plasma through a plasma adsorption column to create purified
plasma, combining the cellular components with the purified plasma
to form a first mixture, and separating the first mixture into
mononuclear cells and at least one component. Alternatively, whole
blood may be flowed through an adsorption column to create purified
whole blood, with the purified whole blood then being separated
into mononuclear cells and at least one component.
Inventors: |
Radwanski; Katherine N.;
(Highland Park, IL) ; Nguyen; Lan T.; (Vernon
Hills, IL) ; Prendergast; Jonathan W.; (Palatine,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Fenwal, Inc. |
Lake Zurich |
IL |
US |
|
|
Family ID: |
1000006391268 |
Appl. No.: |
17/838410 |
Filed: |
June 13, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15390549 |
Dec 26, 2016 |
11383015 |
|
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17838410 |
|
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62277198 |
Jan 11, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 1/3472 20130101;
B04B 3/00 20130101; A61M 1/0209 20130101; A61M 1/3681 20130101;
A61M 2205/331 20130101; A61M 2202/0443 20130101; A61M 1/3679
20130101; A61M 1/262 20140204; A61M 2205/051 20130101; A61M 1/3693
20130101; A61M 1/3496 20130101 |
International
Class: |
A61M 1/36 20060101
A61M001/36; A61M 1/34 20060101 A61M001/34; A61M 1/26 20060101
A61M001/26; A61M 1/02 20060101 A61M001/02 |
Claims
1-11. (canceled)
12. A method of collecting mononuclear cells, comprising:
separating whole blood into plasma and cellular components;
purifying the plasma through a plasma adsorption column to create
purified plasma; combining the cellular components with the
purified plasma to form a first mixture; and separating the first
mixture into mononuclear cells and at least one component.
13. The method of claim 12, further comprising the step of
performing extracorporeal photopheresis on the mononuclear cells,
and wherein the purified plasma contains fewer proteins, lipids,
and/or bilirubin than does the plasma.
14. The method of claim 12, wherein the step of separating whole
blood into plasma and cellular components is performed by a
centrifugal separator.
15. The method of claim 12, wherein step of separating whole blood
into plasma and cellular components is performed by a spinning
membrane separator.
16. The method of claim 12, wherein the mononuclear cells comprise
at least one of lymphocytes, monocytes, and stem cells.
17. A method of collecting mononuclear cells, comprising: providing
an adsorption column through which whole blood is flowed to create
purified whole blood; and separating the purified whole blood into
mononuclear cells and at least one component.
18. The method of claim 17, wherein the purified whole blood is
separated by a centrifugal separator.
19. The method of claim 17, wherein the mononuclear cells comprise
at least one of lymphocytes, monocytes, and stem cells.
20. The method of claim 17, wherein the purified whole blood
contains fewer proteins, lipids, and/or bilirubin than does the
whole blood.
21. A blood separation system comprising: a processing kit
including an adsorption column, a first separation chamber, and a
second separation chamber; and a separation component including a
pump system and a controller, wherein the controller is configured
to control the pump system to convey whole blood into the first
separation chamber to separate the whole blood into plasma and
cellular components, convey the plasma through the adsorption
column to create purified plasma, combine the cellular components
with the purified plasma to form a first mixture, and convey the
first mixture into the second separation chamber to separate the
first mixture into mononuclear cells and at least one
component.
22. The blood separation system of claim 21, further comprising a
photopheresis device configured to perform extracorporeal
photopheresis on the mononuclear cells, wherein the purified plasma
contains fewer proteins, lipids, and/or bilirubin than does the
plasma.
23. The blood separation system of claim 21, wherein the first
separation chamber is defined by a centrifugal separation
container.
24. The blood separation system of claim 21, wherein the first
separation chamber is defined by a spinning membrane separator.
25. The blood separation system of claim 21, wherein the
mononuclear cells comprise at least one of lymphocytes, monocytes,
and stem cells.
26. A blood separation system comprising: a processing kit
including an adsorption column and a blood processing container;
and a separation component including a pump system and a
controller, wherein the controller is configured to control the
pump system to convey whole blood through the adsorption column to
create purified whole blood, and convey the purified whole blood
into the blood processing container to separate the purified whole
blood into mononuclear cells and at least one component.
27. The blood separation system of claim 26, wherein the blood
processing container comprises a centrifugal separation
container.
28. The blood separation system of claim 26, wherein the
mononuclear cells comprise at least one of lymphocytes, monocytes,
and stem cells.
29. The blood separation system of claim 26, wherein the purified
whole blood contains fewer proteins, lipids, and/or bilirubin than
does the whole blood.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent App. No. 62/277,198 filed Jan. 11, 2016, which is expressly
incorporated herein by reference in its entirety.
FIELD OF THE DISCLOSURE
[0002] The present disclosure is directed to fluid treatment
systems and methods. More particularly, the present disclosure
relates to systems and methods for separating blood into its
constituents and subsequently treating and/or collecting the
constituents.
BACKGROUND
[0003] A variety of available blood processing systems allows for
the collection and processing of particular blood components,
rather than whole blood, from donors or patients. In the case of a
blood donor, whole blood is drawn from the donor, a desired blood
constituent separated and collected, and the remaining blood
components returned to the donor. By removing only particular
constituents rather than whole blood, it takes the donor's body a
shorter time period to recover to normal blood levels, thereby
increasing the frequency with which the donor may donate blood. It
is beneficial to increase in this manner the overall supply of
blood constituents made available for health care, such as red
blood cells (RBCs), leukocytes, mononuclear cells (MNCs), plasma,
and/or platelets, etc. In the case of a patient, whole blood is
similarly drawn from the patient, a particular blood constituent
first separated and then collected and/or treated, and the
remaining blood components returned to the patient. The collected
and/or treated blood constituent may be saved for future use,
returned to the patient, and/or discarded and replaced with a
suitable replacement.
[0004] The separation of blood components from whole blood
typically takes place prior to the collection or treatment of the
separated blood component and may be achieved through a spinning
membrane or centrifugation, in which whole blood is passed through
a centrifuge or membrane after it is withdrawn from the patient. To
avoid contamination and possible infection of the patient, the
blood is preferably contained within a sealed, sterile fluid flow
system during the entire separation process. Typical blood
processing systems thus may include a permanent, reusable hardware
assembly containing the hardware (drive system, pumps, valve
actuators, programmable controller, and the like) that pumps the
blood, and a disposable, sealed and sterile fluid circuit that is
mounted in cooperation on the hardware. In the case of separation
via centrifugation, the hardware assembly includes a centrifuge
that may engage and spin a separation chamber of the disposable
fluid circuit during a blood separation step. The blood, however,
may make actual contact only with the fluid circuit, which assembly
may be used only once and then discarded. In the case of separation
via a spinning membrane, a disposable single-use spinning membrane
may be used in cooperation with the hardware assembly and
disposable fluid circuit.
[0005] In the case of separation via centrifugation, as the whole
blood is spun by the centrifuge, the heavier (greater specific
gravity) components, such as red blood cells, move radially
outwardly away from the center of rotation toward the outer or
"high-G"wall of the separation chamber of the fluid circuit. The
lighter (lower specific gravity) components, such as plasma,
migrate toward the inner or "low-G" wall of the separation chamber.
Various ones of these components can be selectively removed from
the whole blood by forming appropriately located channeling seals
and outlet ports in the separation chamber of the fluid
circuit.
[0006] In the case of separation via a spinning membrane, whole
blood may be spun within a disposable spinning membrane, rather
than within a separation chamber of a fluid circuit. Larger
molecules, such as red blood cells, may be retained within one side
of the membrane, while the smaller molecules, such as plasma, may
escape through the pores of the membrane to the other side of the
membrane. Various ones of these components can be selectively
removed from the whole blood by forming appropriately located
outlet ports in the housing of the membrane column. Various types
of membranes with different pore sizes may be used, depending on
the components to be separated.
[0007] In the case of MNC collection, which includes the collection
of lymphocytes, monocytes, and/or stem cells, MNCs can be removed
from the whole blood of a patient, collected, and/or subjected to
various therapies. Collected and treated MNCs may then be returned
to the patient for the treatment of various blood diseases by,
e.g., eliminating immunogenicity in cells, inactivating or killing
selected cells, inactivating viruses or bacteria, reconstituting
the immune system, and/or activating desirable immune responses.
MNC treatments are used for blood or solid organ/tissue cancers,
photopheresis treatments, autologous and allogeneic stem cell
transplants, donor lymphocyte infusions, research collections,
etc.
SUMMARY
[0008] According to an exemplary embodiment, the present disclosure
is directed to a method of collecting mononuclear cells, comprising
separating whole blood into plasma and cellular components,
combining the cellular components with plasma replacement fluid to
form a first mixture, and separating the first mixture into
mononuclear cells and at least one component.
[0009] According to an exemplary embodiment, the present disclosure
is directed to a method of collecting mononuclear cells, comprising
separating whole blood into plasma and cellular components,
purifying the plasma through a plasma adsorption column to create
purified plasma, combining the cellular components with the
purified plasma to form a first mixture, and separating the first
mixture into mononuclear cells and at least one component.
[0010] According to an exemplary embodiment, the present disclosure
is directed to a method of collecting mononuclear cells, comprising
providing an adsorption column through which whole blood is flowed
to create purified whole blood, and separating the purified whole
blood into mononuclear cells and at least one component.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Features, aspects, and advantages of the present embodiments
will become apparent from the following description, appended
claims, and the accompanying exemplary embodiments shown in the
drawings, which are briefly described below.
[0012] FIG. 1 is a diagrammatic depiction of a separation system
useful in the separation and collection of mononuclear cells,
according to an exemplary embodiment;
[0013] FIG. 2 is a perspective view of the front panel of a
separation system with a disposable processing set for collecting
mononuclear cells mounted on the device, according to an exemplary
embodiment;
[0014] FIG. 3 is a diagram showing the disposable processing set of
FIG. 2, according to an exemplary embodiment;
[0015] FIG. 4 is a flow diagram illustrating an improved method for
obtaining mononuclear cells, according to an exemplary
embodiment;
[0016] FIG. 5 is a flow diagram illustrating an improved method for
obtaining mononuclear cells, according to another exemplary
embodiment; and
[0017] FIG. 6 is a flow diagram illustrating an improved method for
obtaining mononuclear cells, according to another exemplary
embodiment.
DETAILED DESCRIPTION
[0018] There are several aspects of the present subject matter
which may be embodied separately or together in the devices and
systems described and claimed below. These aspects may be employed
alone or in combination with other aspects of the subject matter
described herein, and the description of these aspects together is
not intended to preclude the use of these aspects separately or the
claiming of such aspects separately or in different combinations as
set forth in the claims appended hereto.
[0019] Some embodiments may provide for collecting MNCs with
reduced plasma lipid interference during MNC harvest.
[0020] Some embodiments may provide for more accurate collection
and harvest of MNCs by allowing for a clearer interface between
blood component layers.
[0021] During harvest of MNCs, non-target substances may be present
in the MNC product that can interfere with accurate harvesting of
the target MNCs. Plasma proteins and lipids may interfere, for
example, in the event that the donor/patient has certain disease
states or medications, such as elevated bilirubin levels and drugs
such as mycophenolate mofetil (MMF) and cyclosporine, which cause
hyperlipidemia.
[0022] FIG. 1 is a diagrammatic depiction of a separation system 10
useful in the separation and collection of mononuclear cells, as
described herein, and FIG. 2 shows an exemplary embodiment of the
separation system 10, The system 10 may include a separation
component 12 and a disposable processing kit 14 (FIG. 2) that is
mounted thereon. Flow direction and rate may be controlled by a
plurality of pumps 15 engaged with the processing kit 14, In one
embodiment, the separation principle used by the separator 12 is
based on centrifugation, but an automated separator based on a
different separation principle (e.g., spinning membrane, etc.) may
also be used.
[0023] A patient may be connected to the fluid circuit 14, which
may provide a sterile closed pathway between the separation
component 12 and the remainder of the processing kit 14, Whole
blood that is withdrawn from the patient may be introduced into the
separation component 12, where the whole blood may be separated to
provide a target cell population, which in the context of the
present disclosure may be mononuclear cells. Other components
separated from the whole blood, such as red blood cells and
platelets may be returned to the patient or collected in
pre-attached containers of the blood processing set. The separated
target cell population, e.g., mononuclear cells, may then be
collected for future use or prepared for various therapies. One
example of a therapy involving MNCs that may benefit from reducing
plasma lipid interference during MNC harvest is extracorporeal
photopheresis or "ECP". ECP involves the extracorporeal exposure of
MNCs combined with a photoactive compound, such as
8-methoxypsoralen or "8-MOP" which is then photoactivated by
ultraviolet light, followed by re-infusion of the treated MNCs.
Removal of plasma lipids, which absorb UV light during irradiation,
may lead to generally more consistent and less variable irradiation
procedures, thereby enhancing accuracy of irradiation dosing and
shortening procedure time.
[0024] Apparatus useful in the collection of mononuclear cells, and
providing the separation component 12 of FIG. 1, include for
example the Amicus.RTM. Separator made and sold by Fenwal, Inc., of
Lake Zurich, Ill. Mononuclear cell collections using a device such
as the Amicus.RTM. are described in greater detail in U.S. Pat. No.
6,027,657, the contents of which are incorporated by reference
herein in its entirety. The fluid circuit 14 (FIG. 3) may include a
blood processing container 16 defining a separation chamber
suitable for harvesting MNCs from whole blood.
[0025] As shown in FIG. 2, a disposable processing set or fluid
circuit 14 (which includes container 16) may be mounted on the
front panel of the separation component 12. The processing set
(fluid circuit 14) may include a plurality of processing fluid flow
cassettes 23L, 23M and 23R with tubing loops for association with
peristaltic pumps 15 on the separation component 12. Fluid circuit
14 may also include a network of tubing and pre-connected
containers for establishing flow communication with the patient and
for processing and collecting fluids and blood and blood
components, as shown in greater detail in FIG. 3.
[0026] As seen in FIG. 3, the disposable processing set 14 may
include a container 60 for supplying anticoagulant, an in-process
container 62, a container 64 for holding a crystalloid solution,
such as saline, a container 66 for collecting plasma, and a
container 68 for collecting the mononuclear cells.
[0027] With reference to FIG. 3, fluid circuit 14 may include inlet
line 72, an anticoagulant (AC) line 74 for delivering AC from
container 60, an RBC line 76 for conveying red blood cells from
chamber 16 of set 14 to container 67, a platelet-poor plasma (PPP)
line 78 for conveying PPP to container 66 and line 80 for conveying
mononuclear cells to and from separation chamber 16 and collection
container 68.
[0028] The blood processing set may also include one or more
venipuncture needle(s) for accessing the circulatory system of the
patient. As shown in FIG. 3, fluid circuit 14 may include inlet
needle 70 and return needle 82. In an alternative embodiment, a
single needle may serve as both the inlet and outlet needle.
[0029] Fluid flow through fluid circuit 14 may be driven,
controlled and adjusted by a microprocessor-based controller in
cooperation with the valves, pumps, weight scales and sensors of
separation component 12 and fluid circuit 14, the details of which
are described in the previously mentioned U.S. Pat. No.
6,027,657.
[0030] A separation chamber may be defined by the walls of the
processing container 16. The processing container 16 may comprise
two different compartments 16a and 16b (FIG. 3). Using both
compartments 16a and 16b for separation in a procedure may enable
multiple target products to be separated simultaneously and/or
multiple steps to be completed simultaneously. If only one
compartment is used for separation, the other compartment may
optionally be used as an in-process, waste, or storage container.
In operation, the separation device 12 may rotate the processing
container 16 about an axis, creating a centrifugal field within the
processing container 16. Details of the mechanism for rotating the
processing container 16 are disclosed in U.S. Pat. No. 5,360,542
titled "Centrifuge with Separable Bowl and Spool Elements Providing
Access to the Separation Chamber," which is also incorporated
herein by reference in its entirety.
[0031] In one embodiment, an apheresis device or system 10 may
include a programmable controller that is pre-programmed with one
or more selectable protocols. A user/operator may select a
particular processing protocol to achieve a desired outcome or
objective. The pre-programmed selectable protocol(s) may be based
on one or more fixed and/or adjustable parameters. During a
particular processing procedure, the pre-programmed controller may
operate the separator 12 and processing chamber 16 associated
therewith to separate blood into its various components, as well as
operate one or more pumps to move blood, blood components and/or
solutions through the various openable valves and tubing segments
of a processing set, such as processing set 14 illustrated in FIG.
3. The various processing steps performed by the pre-programmed
automated apheresis device may occur separately, in series,
simultaneously or any combination of these.
[0032] An automated apheresis device may be used to perform MNC
collection in a batch process in which MNCs continuously collect in
the chamber 16 until the target cycle volume is reached. During the
continuous collection of MNCs within the chamber 16, different
blood components separate into layers that may be detected by an
optical interface detector that monitors the location and presence
of the interface between layers. Details of an exemplary mechanism
for interface detection are disclosed in U.S. Pat. No. 6,027,657,
the contents of which are incorporated by reference herein in its
entirety. Before and during the transfer of the MNCs out of the
chamber 16, MNCs and other blood components (e.g., plasma, etc.)
may pass through an optical sensor 17, located downstream of the
chamber 16, which detects the presence of cells in the tubing line
to determine the start and end of the MNC harvest (i.e. when to
open and close the valves leading to the product container). The
term "downstream" describes an event proximal to post-separation,
and the term "upstream" describes an event proximal to
pre-separation. "Downstream" and "upstream" are relative terms,
with the reference point being the time/location of separation.
After MNC harvest is complete, the remaining cells in the line may
be flushed into the product container with a predetermined volume
of plasma known as the "plasma flush".
[0033] The ability of the interface detector to accurately detect
the interface between blood component layers may be facilitated by
removal of non-target substances (e.g., plasma proteins and lipids)
that may be present in the blood that can interfere with the
separation procedure. Additionally, the removal of non-target
substances may improve the ability of the optical sensor 17 to
accurately detect the presence of cells in the tubing line to
determine the start and end of the MNC harvest to facilitate
precise harvesting of the target MNCs.
EXAMPLES
[0034] Without limiting any of the foregoing, the subject matter
described herein may be found in one or more methods, systems
and/or products. For example, in a first aspect of the present
subject matter, an improved system and method for obtaining MNCs is
set forth in FIG. 4. The inlet needle 70 of FIG. 3 attached to
inlet line 72 may first be connected to a blood source 5 (e.g,
donor, patient, blood bag, etc.). Whole blood may enter the
separation chamber 16 of the separator 12, which separates the
whole blood into plasma and cellular components. The plasma may be
separated and directed into a plasma container 66, and the cellular
components may be separated and directed into a different container
67. The separated cellular contents may be combined with a
replacement fluid 69 that has minimal non-target content (e.g.,
plasma proteins and/or lipids) that may interfere with optical
sensor readings. Examples of suitable replacement fluids include
fresh frozen plasma, immunoglobulin solution, albumin, and/or other
colloid solutions. The cellular components mixed with replacement
fluid may then be returned to the separation chamber 16, where
target MNCs may be collected. The target MNCs may be harvested into
a designated container 68 to be processed for further treatment.
Non-target components may be collected or returned to the
patient/donor.
[0035] The process and steps of whole blood initially entering the
separation chamber 16 and the cellular components and replacement
fluid mix returning to the separation chamber 16 portrayed in FIG.
4 may take place substantially in series if only one compartment
16a or 16b is utilized. Alternatively, the process and steps of
whole blood entering the separation chamber 16 and the fluid mix
returning to the separation chamber 16 may take place substantially
at the same time if both compartments 16a and 16b are utilized. In
an embodiment in which the processes take place substantially in
series, whole blood entering one of the compartments 16a or 16b may
separate into plasma and cellular components, both of which may be
directed to separate containers until separation of plasma and
cellular components is complete. An optical sensor 17 may
optionally be placed downstream of the separation chamber 16a
and/or 16b at a tubing line leading to the MNC product container 68
and/or leading to the plasma container 66 to determine when plasma
is clear enough and plasma diversion can stop. Subsequently, the
cellular components may combine with the replacement fluid within
one of the compartments 16a or 16b, and further separation into
target MNCs and non-target components may take place.
[0036] In an embodiment in which the steps of whole blood entering
the separation chamber 16 and the fluid mix returning to the
separation chamber 16 take place substantially at the same time,
whole blood entering a first compartment (e.g., 16a) may separate
into plasma and cellular components, with the plasma being sent to
an plasma container 62. Simultaneously, the cellular components may
join the replacement fluid and together enter a second compartment
(e.g., 16b) and there further separate into target MNCs and
non-target components. An optical sensor 17 may optionally be
placed downstream of the separation chamber 16a at a tubing line
leading to the MNC product container 68 and/or leading to the
plasma container 66 to determine when plasma is clear enough and
plasma diversion can stop. As the replacement fluid continues to
enter compartment 16b and the clarity of the plasma leaving
compartment 16a improves sufficiently as determined by the optical
sensor 17, the plasma diversion from compartment 16a into the
plasma container 66 can be stopped, and any unseparated whole
blood, including the contents of compartment 16a, may be directed
to compartment 16b to continue MNC collection.
[0037] In another aspect of the present subject matter, an improved
method for obtaining MNCs is set forth in FIG. 5. An inlet needle
may first be connected to a blood source 5 (e.g, donor, patient,
blood bag, etc.) at step 100 of FIG. 5. In step 200, whole blood
enters a separator, which separates the whole blood into plasma
(step 300a) and cellular components (step 300b). In the embodiment
in FIG. 5, the separator of step 200 may be a centrifugal or
spinning membrane separator. An exemplary spinning membrane and
hardware is disclosed in greater detail in PCT Patent Application
No. PCT/US2012/28492, which is incorporated herein by reference in
its entirety, although any suitable membrane assembly may be used,
Plasma separated in step 300a may be flowed through an adsorption
column in step 400. An exemplary adsorption column is the MONET
filter made and sold by Fresenius Medical Care. Another exemplary
adsorption column is disclosed in greater detail in International
Publication No, WO 2012/141697 and U.S. Pat. No. 6,569,112, each of
which is hereby incorporated by reference herein in its entirety,
although any suitable column may be used. In step 500, purified
plasma from the adsorption column in step 400 may be combined with
the cellular components of step 300b. The combined product of step
500 may then be separated in a separation chamber of a separator in
step 600 to collect and harvest MNC target cells separated from
non-target components.
[0038] In another aspect of the present subject matter, an improved
method for obtaining MNCs is set forth in FIG. 6. An inlet needle
may first be connected to a blood source 5 (e.g, donor, patient,
blood bag, etc.) at step 101 of FIG. 6. In step 201, whole blood
enters a whole blood adsorption column, which removes certain
lipids, proteins, antibodies, and/or fatty acids in step 301. An
exemplary whole blood adsorption column is the DALI.RTM. adsorber
made and sold by Fresenius Medical Care, although any suitable
whole blood adsorption column may be used. Purified whole blood
exiting from the WB adsorption column of step 201 may then be
separated in a separation chamber 16 of a separator in step 401 to
collect and harvest MNC target cells separated from non-target
components.
[0039] The embodiments disclosed herein are for the purpose of
providing a description of the present subject matter, and it is
understood that the subject matter may be embodied in various other
forms and combinations not shown in detail. Therefore, specific
embodiments and features disclosed herein are not to be interpreted
as limiting the subject matter as defined in the accompanying
claims.
* * * * *