U.S. patent application number 10/462320 was filed with the patent office on 2003-11-13 for blood processing chamber counter-balanced with blood-free liquid.
This patent application is currently assigned to Baxter International Inc.. Invention is credited to Brown, Richard I., Cantu, Robert J., Min, Kyungyoon, Reitz, Douglas W..
Application Number | 20030211927 10/462320 |
Document ID | / |
Family ID | 25388544 |
Filed Date | 2003-11-13 |
United States Patent
Application |
20030211927 |
Kind Code |
A1 |
Cantu, Robert J. ; et
al. |
November 13, 2003 |
Blood processing chamber counter-balanced with blood-free
liquid
Abstract
Blood processing systems and methods rotate a processing chamber
on a rotating element. The processing chamber includes a first
compartment and a second compartment. Blood is conveyed into the
first compartment for centrifugal separation into components. A
liquid free of blood occupies the second compartment to
counter-balance the first compartment during rotation on the
rotating element. In one embodiment, the second compartment is
served by a single fluid flow access. Prior to use, the single
access is coupled to tubing, through which a vacuum is drawn to
remove air from the second compartment. While the vacuum exists,
communication is opened between the tubing and a source of liquid.
The vacuum draws the liquid into the second compartment through the
single access, thereby priming the second compartment for use.
Inventors: |
Cantu, Robert J.;
(Algonquin, IL) ; Min, Kyungyoon; (Gurnee, IL)
; Reitz, Douglas W.; (Green Oaks, IL) ; Brown,
Richard I.; (Northbrook, IL) |
Correspondence
Address: |
BAXTER HEALTHCARE CORPORATION
Bradford R.L. Price
Fenwal Division RLP-30
Route 120 and Wilson Road
Round Lake
IL
60073
US
|
Assignee: |
Baxter International Inc.
|
Family ID: |
25388544 |
Appl. No.: |
10/462320 |
Filed: |
June 16, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10462320 |
Jun 16, 2003 |
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09669752 |
Sep 26, 2000 |
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6582349 |
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09669752 |
Sep 26, 2000 |
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09377339 |
Aug 19, 1999 |
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6168561 |
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09377339 |
Aug 19, 1999 |
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08886179 |
Jul 1, 1997 |
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6027441 |
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Current U.S.
Class: |
494/3 ; 494/1;
494/10; 494/2; 494/45; 494/5 |
Current CPC
Class: |
B01D 21/34 20130101;
B01D 21/32 20130101; B04B 2005/045 20130101; B04B 2009/143
20130101; B01D 2221/10 20130101; B04B 9/14 20130101; A61M 1/3693
20130101; A61M 1/3696 20140204; B01D 21/262 20130101 |
Class at
Publication: |
494/3 ; 494/1;
494/2; 494/5; 494/10; 494/45 |
International
Class: |
B04B 011/04; B04B
013/00 |
Claims
We claim:
1. A blood processing system comprising a rotating element, a
processing chamber on the rotating element for common rotation with
the rotating element, the processing chamber including a separation
compartment for receiving whole blood for centrifugal separation
into components, the separation compartment including an inlet
region where whole blood enters for separation into packed red
blood cells, a plasma constituent, and an interface carrying
platelets between the packed red blood cells and the plasma
constituent, and a controller for the rotating element operable in
a control mode to convey whole blood into the separation
compartment for centrifugal separation into components, the
controller including an interface control unit operative (i) in a
first condition to retain platelets in the processing chamber to
enable removal of platelet-poor plasma and packed red blood cells
from the processing chamber, and (ii) in a second condition to
enable removal of platelets from the processing chamber enabling
removal of platelet-rich plasma and packed red blood cells from the
processing chamber.
2. A system according to claim 1 wherein the interface control unit
includes a sensing element to locate the interface in the
separation compartment and provide a sensed output.
3. A system according to claim 2 wherein the sensing element
optically locates the interface in the separation compartment.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of copending U.S. patent
application Ser. No. 09/669,752 filed Sep. 26, 2000, which is a
divisional of application Ser. No. 09/377,339 filed Aug. 19, 1999
(now U.S. Pat. No. 6,168,561), which is a divisional of application
Ser. No. 08/886,179 filed Jul. 1, 1997 (now U.S. Pat. No.
6,027,441).
FIELD OF THE INVENTION
[0002] The invention relates to centrifugal processing systems and
apparatus.
BACKGROUND OF THE INVENTION
[0003] Today blood collection organizations routinely separate
whole blood by centrifugation into its various therapeutic
components, such as red blood cells, platelets, and plasma.
[0004] Conventional blood processing systems and methods use
durable centrifuge equipment in association with single use,
sterile processing chambers, typically made of plastic. The
centrifuge equipment introduces whole blood into these chambers
while rotating them to create a centrifugal field.
[0005] Whole blood separates within the rotating chamber under the
influence of the centrifugal field into higher density red blood
cells and platelet-rich plasma. An intermediate layer of leukocytes
forms the interface between the red blood cells and platelet-rich
plasma.
SUMMARY OF THE INVENTION
[0006] One aspect of the invention provides blood processing
systems and methods comprising a processing chamber carried on a
rotating element. The processing chamber includes a first
compartment containing blood for centrifugal separation into
components. The processing chamber also includes a second
compartment containing a liquid free of blood. The liquid in the
second compartment counter-balances the first compartment during
rotation on the rotating element.
[0007] In a preferred embodiment, the second compartment is
substantially free of air, and the liquid in the second compartment
is subject to a positive pressure.
[0008] In one embodiment, the second compartment has a single
access, e.g., a single access port or multiple ports served by a
single access path, such that two way fluid flow simultaneously
into and out of the compartment is not possible. Another aspect of
the invention provides systems and methods to prime the single
access compartment, or any like chamber serviced by a single
access. The systems and methods operate a pump element to draw a
vacuum in the chamber through the single access. While the vacuum
exists, the systems and methods open communication between the
chamber and a source of liquid. The vacuum draws the liquid into
the chamber through the single access to prime the chamber.
[0009] In a preferred embodiment, the systems and methods command a
pump element to convey the liquid into the chamber while the vacuum
also draws the liquid into the chamber. A positive pressure
condition is thereby established in the primed chamber.
[0010] Other features and advantages of the invention will become
apparent upon reviewing the following specification, drawings, and
appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a side section view of a blood centrifuge having a
separation chamber that embodies features of the invention;
[0012] FIG. 2 shows the spool element associated with the
centrifuge shown in FIG. 1, with an associated processing container
wrapped about it for use;
[0013] FIG. 3A is a perspective view of the centrifuge shown in
FIG. 1, with the bowl and spool elements pivoted into their access
position;
[0014] FIG. 3B is a perspective view of the bowl and spool elements
in their mutually separation condition to allow securing the
processing container shown in FIG. 2 about the spool element;
[0015] FIG. 4 is a plan view of the processing container shown in
FIG. 2;
[0016] FIG. 5 is a perspective view of a fluid circuit associated
with the processing container, which comprises cassettes mounted in
association with pump stations on the centrifuge;
[0017] FIG. 6 is a schematic view of the fluid circuit shown in
FIG. 5;
[0018] FIG. 7 is a perspective view of the back side of a cassette
that forms a part of the fluid circuit shown in FIG. 6;
[0019] FIG. 8 is a perspective view of the front side of the
cassette shown in FIG. 7;
[0020] FIG. 9 is a schematic view of the flow channels and valve
stations formed within the cassette shown in FIG. 7;
[0021] FIG. 10 is a schematic view of a pump station intended to
receive a cassette of the type shown in FIG. 7;
[0022] FIG. 11 is a schematic view of the cassette shown in FIG. 9
mounted on the pump station shown in FIG. 10;
[0023] FIG. 12 is a perspective view of a cassette and a pump
station which form a part of the fluid circuit shown in FIG. 6;
[0024] FIG. 13 is a top view of a peristaltic pump that forms a
part of the fluid circuit shown in FIG. 6, with the pump rotor in a
retracted position;
[0025] FIG. 14 is a top view of a peristaltic pump that forms a
part of the fluid circuit shown in FIG. 6, with the pump rotor in
an extended position engaging pump tubing;
[0026] FIG. 15 is a diagrammatic top view of the separation chamber
of the centrifuge shown in FIG. 1, laid out to show the radial
contours of the high-G and low-G walls;
[0027] FIGS. 16A and 16B somewhat diagrammatically show a portion
of the platelet-rich plasma collection zone in the separation
chamber, in which the high-G wall surface forms a tapered wedge for
containing and controlling the position of the interface between
the red blood cells and platelet-rich plasma;
[0028] FIG. 17 is a somewhat diagrammatic view of the interior of
the processing chamber, looking from the low-G wall toward the
high-G wall in the region where whole blood enters the processing
chamber for separation into red blood cells and platelet-rich
plasma, and where platelet-rich plasma is collected in the
processing chamber;
[0029] FIG. 18 is a diagrammatic view showing the dynamic flow
conditions established that confine and "park" MNC within the blood
separation chamber shown in FIG. 17;
[0030] FIG. 19 is a schematic view of the process controller which
configures the fluid circuit shown in FIG. 6 to conduct a
prescribed MNC collection procedure;
[0031] FIG. 20 is a flow chart showing the various cycles and
phases of the MNC collection procedure that the controller shown in
FIG. 19 governs;
[0032] FIG. 21 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the
preliminary processing cycle of the procedure shown in FIG. 20;
[0033] FIG. 22 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the MNC
accumulation phase of the procedure shown in FIG. 20;
[0034] FIG. 23 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the
PRBC collection phase of the procedure shown in FIG. 20;
[0035] FIG. 24A is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 at the
beginning of the MNC removal phase of the procedure shown in FIG.
20;
[0036] FIG. 24B is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the MNC
removal phase of the procedure shown in FIG. 20;
[0037] FIG. 24C is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 at the end of
the MNC removal phase of the procedure shown in FIG. 20;
[0038] FIG. 25 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the PRP
flush phase of the procedure shown in FIG. 20;
[0039] FIG. 26 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the MNC
suspension phase of the procedure shown in FIG. 20;
[0040] FIG. 27 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 6 during the
clean up phase of the procedure shown in FIG. 20;
[0041] FIG. 28 is a schematic view of the optical sensor used in
association with the circuit shown in FIG. 6 to sense and quantify
the MNC region for harvesting;
[0042] FIG. 29 is an alternative embodiment of a fluid circuit
suited for collecting and harvesting MNC;
[0043] FIG. 30 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 29 during the
PRBC collection phase of the procedure shown in FIG. 20; and
[0044] FIG. 31 is a schematic view showing the conveyance of blood
components and fluids in the circuit shown in FIG. 29 during the
MNC removal phase of the procedure shown in FIG. 20.
[0045] The invention may be embodied in several forms without
departing from its spirit or essential characteristics. The scope
of the invention is defined in the appended claims, rather than in
the specific description preceding them. All embodiments that fall
within the meaning and range of equivalency of the claims are
therefore intended to be embraced by the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0046] I. The Centrifuge
[0047] FIG. 1 shows a blood centrifuge 10 having a blood processing
chamber 12 suitable for harvesting mononuclear cells (MNC) from
whole blood. The boundaries of the chamber 12 are formed by a
flexible processing container 14 carried within an annular gap 16
between a rotating spool element 18 and bowl element 20. In the
illustrated and preferred embodiment, the processing container 14
takes the form of an elongated tube (see FIG. 2), which is wrapped
about the spool element 18 before use.
[0048] Further details of the centrifuge 10 are set forth in U.S.
Pat. No. 5,370,802, entitled "Enhanced Yield Platelet Systems and
Methods," which is incorporated herein by reference.
[0049] The bowl and spool elements 18 and 20 are pivoted on a yoke
22 between an upright position, as FIGS. 3A and 3B show, and a
suspended position, as FIG. 1 shows.
[0050] When upright, the bowl and spool elements 18 and 20 are
presented for access by the user. A mechanism permits the spool and
bowl elements 18 and 20 to be opened, as FIG. 3B shows, so that the
operator can wrap the container 14 about the spool element 20, as
FIG. 2 shows. Pins 150 on the spool element 20 engage cutouts on
the container 14 to secure the container 14 on the spool element
20.
[0051] When closed, the spool and bowl elements 18 and 20 can be
pivoted into the suspended position shown in FIG. 1. In operation,
the centrifuge 10 rotates the suspended bowl and spool elements 18
and 20 about an axis 28, creating a centrifugal field within the
processing chamber 12.
[0052] Further details of the mechanism for causing relative
movement of the spool and bowl elements 18 and 20 as just described
are disclosed in U.S. Pat. No. 5,360,542 entitled "Centrifuge With
Separable Bowl and Spool Elements Providing Access to the
Separation Chamber," which is incorporated herein by reference.
[0053] The radial boundaries of the centrifugal field (see FIG. 1)
are formed by the interior wall 24 of the bowl element 18 and the
exterior wall 26 of the spool element 20. The interior bowl wall 24
defines the high-G wall. The exterior spool wall 26 defines the
low-G wall.
[0054] II. The Processing Container
[0055] In the illustrated embodiment (see FIG. 4), a first
peripheral seal 42 forms the outer edge of the container 14. A
second interior seal 44 extends generally parallel to the
rotational axis 28, dividing the container 14 into two compartments
38 and 40.
[0056] In use, whole blood is centrifugally separated in the
compartment 38. In use, the compartment 40 carries a liquid, such
as saline, to counter-balance the compartment 38. In the embodiment
shown in FIG. 4, the compartment 38 is larger than the compartment
40 by a volumetric ratio of about 1 to 1.2.
[0057] Three ports 46, 48, and 50 communicate with the processing
compartment 38, to convey whole blood and its components. Two
additional ports 52 and 54 communicate with the ballast compartment
40 to convey the counter-balancing fluid.
[0058] III. The Fluid Processing Circuit
[0059] A fluid circuit 200 (see FIG. 4) is coupled to the container
14. FIG. 5 shows the general layout of the fluid circuit 200, in
terms of an array of flexible tubing, liquid source and collection
containers, in-line pumps, and clamps, all of which will be
described in greater detail later. FIG. 6 shows the details of the
fluid circuit 200 in schematic form.
[0060] In the illustrated embodiment, left, middle, and right
cassettes, respectively 23L, 23M, and 23R, centralize many of the
valving and pumping functions of the fluid circuit 200. The left,
middle, and right cassettes 23L, 23M, and 23R mate with left,
middle, and right pump stations on the centrifuge 10, which are
designated, respectively, PSL, PSM, and PSR.
[0061] A. The Cassettes
[0062] Each cassette 23L, 23M, and 23R is constructed the same, so
a description of one cassette 23L is applicable to all cassettes.
FIGS. 7 and 8 show the structural details of the cassette 23L.
[0063] The cassette 23L comprises a molded plastic body 202. Liquid
flow channels 208 are integrally molded into on the front side 204
of the body 202. A rigid panel 214 covers and seals the front body
side 204.
[0064] Valve stations 210 are molded into the back side 206 of the
cassette body 202. A flexible diaphragm 212 covers and seals the
back side 206 of the body 202.
[0065] FIG. 9 schematically shows a representative array of flow
channels 208 and valve stations 210 for each cassette. As shown,
channels C1 to C6 intersect to form a star array, radiating from a
central hub H. Channel C7 intersects channel C5; channel C8
intersects channel C6; channel C9 intersects channel C3; and
channel C10 intersects channel C2. Of course, other channel
patterns can be used.
[0066] In this arrangement, valve stations VS1, VS2, VS9, and VS10
are located in, respectively, channels C2, C3, C5, and C6
immediately next to their common intersection at the hub H. Valve
stations VS3, VS4, VS5, VS6, VS7, and VS8 are located at the outer
extremities of channels C8, C1, C2, C5, C4, and C3,
respectively.
[0067] Each cassette 23L carries an upper flexible tubing loop UL,
which extends outside the cassette 23L between channels C7 and C6,
and a lower tubing loop LL, which extends outside the cassette
between channels C3 and C10. In use, the tube loops UL and LL
engage the peristaltic pump rotors of the pumps on the associated
pump station.
[0068] B. The Pumping Stations
[0069] The pump stations PSL, PSM, and PSR are, like the cassettes
23L, 23M, and 23R, identically constructed, so a description of one
station PSL is applicable to all. FIG. 12 shows the structural
details of the left pump station PSL. FIG. 10 shows the left pump
station PSL in a more schematic form.
[0070] The station PSL includes two peristaltic pumps, for a total
of six pumps in the circuit 200, which are designated P1 to P6 (see
FIG. 6). The station PSL also includes an array of ten valve
actuators (which FIG. 10 shows), for a total of thirty valve
actuators in the circuit 200, which designated VA1 to VA30 (see
FIG. 6).
[0071] In use (see FIG. 11), the tube loops UL and LL of cassette
23L engage pumps P1 and P2 of the left pump station PSL. In like
fashion (as FIG. 6 shows), the tube loops UL and LL of the middle
cassette 23M engage pumps P3 and P4. The tube loops UL and LL of
the right cassette 23L engage pumps P5 and P6.
[0072] As FIG. 11 shows, the valve stations VS1 to VS10 of the
cassette 23L align with the valve actuators V1 to V10 of the left
pump station PSL. As FIG. 6 shows, the valve stations of the middle
and right cassettes 23M and 23R likewise align with the valve
actuators of the respective middle and right pump stations PSM and
PSR.
[0073] The following Table 1 summarizes the operative association
of the pump station valve actuators V1 to V30 to the cassette valve
stations S1 to VS10 shown in FIG. 6.
1TABLE 1 Alignment of Cassette Valve Stations to Valve Actuators
Left Cassette Middle Cassette Right Cassette Valve Chambers 23L 23M
23R VS1 Valve Actuator Valve Actuator Valve Actuator V1 V11 V21 VS2
Valve Actuator Valve Actuator Valve Actuator V2 V12 V22 VS3 Valve
Actuator Valve Actuator Valve Actuator V3 V13 V23 VS4 Valve
Actuator Valve Actuator Valve Actuator V4 V14 V24 VS5 Valve
Actuator Valve Actuator Valve Actuator V5 V15 V25 VS6 Valve
Actuator Valve Actuator Valve Actuator V6 V16 V26 VS7 Valve
Actuator Valve Actuator Valve Actuator V7 V17 V27 VS8 Valve
Actuator Valve Actuator Valve Actuator V8 V18 V28 VS9 Valve
Actuator Valve Actuator Valve Actuator V9 V19 V29 VS10 Valve
Actuator Valve Actuator Valve Actuator V10 V20 V30
[0074] The cassettes 23L, 23M, and 23R are mounted on their
respective pump stations PSL, PSM, PSR with their back sides 206
down, so that the diaphragms 212 face and engage the valve
actuators. The valve actuators Vn are solenoid-actuated rams 215
(see FIG. 12), which are biased toward a valve closing position.
The valve actuators Vn are patterned to align with the cassette
valve stations VSn in the manner set forth in Table 1. When a given
ram 215 is energized, the associated cassette valve station is
opened, allowing through-passage of liquid. When the ram 215 is not
energized, it displaces the diaphragm 212 into the associated valve
station, blocking passage of liquid through the associated valve
station.
[0075] In the illustrated embodiment, as FIG. 12 shows, the pumps
P1 to P6 on each pump station PSL, PSM, and PSR include rotating
peristaltic pump rotors 216. The rotors 216 can be moved between a
retracted condition (shown in FIG. 13), out of engagement with the
respective tube loop, and an operating condition (shown in FIG.
14), in which the rotors 216 engage the respective tube loop
against a pump race 218.
[0076] The pumps P1 and P6 can thereby be operated in three
conditions:
[0077] (i) in a pump on condition, during which the pump rotors 216
rotate and are in their operating position to engage the pump
tubing against the pump race 218 (as FIG. 14 shows). The rotating
pump rotors 216 therefore convey fluid in a peristaltic fashion
through the tubing loop.
[0078] (ii) in an opened, pump off condition, during which the pump
rotors 216 are not rotated and are in their retracted position, so
as not to engage the pump tubing loop (as FIG. 13 shows). The
opened, pump off condition therefore permits fluid flow through the
pump tube loop in the absence of pump rotor rotation.
[0079] (iii) in a closed, pump off condition, during which the pump
rotors 216 are not rotated, and the pump rotors are in the
operating condition. The stationary pump rotors 216 thereby engage
the pump tubing loop, and serve as a clamp to block fluid flow
through the pump tubing loop.
[0080] Of course, equivalent combinations of pump conditions can be
achieved using peristaltic pump rotors that do not retract, by
suitable placement of clamps and tubing paths upstream and
downstream of the pump rotors.
[0081] Further structural details of the cassettes 23L, 23M, 23R,
the peristaltic pumps P1 to P6, and the valve actuators V1 to V30
are not essential to the invention. These details are described in
U.S. Pat. No. 5,427,509, entitled "Peristaltic Pump Tube Cassette
with Angle Port Tube Connectors," which is incorporated herein by
reference.
[0082] C. The Fluid Flow Tubing
[0083] The fluid circuit 200 further includes lengths of flexible
plastic tubing, designated T1 to T20 in FIG. 6. The flexible tubing
T1 to T20 couple the cassettes 23L, 23M, and 23R to the processing
container 14, to external source and collection bags or containers,
and to the blood donor/patient.
[0084] The fluid flow function of the tubing T1 to T20 in
connection with collecting and harvesting MNC will be described
later. The following summarizes, from a structural standpoint, the
attachment of the tubing T1 to T20, as shown in FIG. 6:
[0085] Tubing T1 extends from the donor/patient (via a conventional
phlebotomy needle, not shown) through an external clamp C2 to
channel C4 of the left cassette 23L.
[0086] Tubing T2 extends from tube T1 through an external clamp C4
to channel C5 of the middle cassette 23M.
[0087] Tubing T3 extends from an air detection chamber D1 to
channel C9 of the left cassette 23L.
[0088] Tubing T4 extends from the drip chamber D1 to port 48 of the
processing container 14.
[0089] Tubing T5 extends from port 50 of the processing container
14 to channel C4 of the middle cassette 23M.
[0090] Tubing T6 extends from channel C9 of the middle cassette 23M
to join tubing T4 downstream of the chamber D1.
[0091] Tubing T7 extends from channel C8 of the right cassette 23M
to channel C8 of the left cassette 23L.
[0092] Tubing T8 extends from channel C1 of the middle cassette 23M
to join tubing T7.
[0093] Tubing T9 extends from channel C5 of the left cassette 23L
through an air detection chamber D2 and an external clamp C3 to the
donor/patient (via a conventional phlebotomy needle, not
shown).
[0094] Tubing T10 extends from port 46 of the processing container
14, through an in line optical sensor OS to channel C4 of the right
cassette 23R.
[0095] Tubing T11 extends from channel C9 of the right cassette 23R
to the chamber D1.
[0096] Tubing T12 extends from channel C2 of the right cassette 23R
to a container intended to receive platelet-poor plasma, designated
PPP. A weight scale (not shown) senses weight of the container PPP
for the purpose of deriving fluid volume changes.
[0097] Tubing T13 extends from channel C1 of the right cassette 23R
to a container intended to receive mono-nuclear cells, designated
MNC.
[0098] Tubing T14 extends from channel C2 of the middle cassette
23M to a container intended to receive packed red blood cells,
designated PRBC. A weight scale WS senses weight of the container
PRBC for the purpose of deriving fluid volume changes.
[0099] Tubing T15 extends from a container of anticoagulant,
designated ACD, to channel C8 of the middle cassette 23M. A weight
scale (not shown) senses weight of the container ACD for the
purpose of deriving fluid volume changes.
[0100] Tubing T16 and T17 extend from a container of priming
liquid, such as saline, designated PRIME, bypassing all cassettes
23L, 23M, and 23R, through an external clamp C1, and intersecting,
respectively, tubing T9 (between the air detection chamber D2 and
the clamp C3) and tubing T1 (upstream of clamp C3). A weight scale
(not shown) senses weight of the container PRIME for the purpose of
deriving fluid volume changes.
[0101] Tubing T18 extends from the port 52 of the processing
container 14 to channel C5 of the right cassette 23R.
[0102] Tubing T19 extends from the port 54 of the processing
container 14 to intersect tubing T18.
[0103] Tubing T20 extends from channel C2 of the left cassette 23L
to a container intended to receive waste priming fluid, designated
WASTE. A weight scale (not shown) senses weight of the container
WASTE for the purpose of deriving fluid volume changes.
[0104] Portions of the tubing are joined in umbilicus 30 (see FIG.
1). The umbilicus 30 provides fluid flow communication between the
interior of the processing container 14 within the centrifugal
field and other stationary components of the circuit 200 located
outside the centrifugal field. A non-rotating (zero omega) holder
32 holds the upper portion of the umbilicus 30 in a non-rotating
position above the suspended spool and bowl elements 18 and 20. A
holder 34 on the yoke 22 rotates the mid-portion of the umbilicus
30 at a first (one omega) speed about the suspended spool and bowl
elements 18 and 20. Another holder 36 rotates the lower end of the
umbilicus 30 at a second speed twice the one omega speed (the two
omega speed), at which the suspended spool and bowl elements 18 and
20 also rotate. This known relative rotation of the umbilicus 30
keeps it untwisted, in this way avoiding the need for rotating
seals.
[0105] IV. Separation in the Blood Processing Chamber (An
Overview)
[0106] Before explaining the details of the procedure by which MNC
are collected using the container 14 and the fluid circuit 200, the
fluid dynamics of whole blood separation in the processing
compartment 38 will first be generally described, with reference
principally to FIGS. 4 and 15 to 17.
[0107] Referring first to FIG. 4, anticoagulated whole blood (WB)
is drawn from the donor/patient and conveyed into the processing
compartment through the port 48. The blood processing compartment
38 includes a interior seals 60 and 66, which form a WB inlet
passage 72 that leads into a WB entry region 74.
[0108] As WB follows a circumferential flow path in the compartment
38 about the rotational axis 28. The sidewalls of the container 14
expand to conform to the profiles of the exterior (low-G) wall 26
of the spool element 18 and the interior (high-G) wall 24 of the
bowl element 20.
[0109] As FIG. 17 shows, WB separates in the centrifugal field
within the blood processing compartment 38 into packed red blood
cells (PRBC, designated by numeral 96), which move toward the
high-G wall 24, and platelet-rich plasma (PRP, designated by
numeral 98), which are displaced by movement of the PRBC 96 toward
the low-G wall 26. An intermediate layer, called the interface
(designed by numeral 58), forms between the PRBC 96 and PRP 98.
[0110] Referring back to FIG. 4, the interior seal 60 also creates
a PRP collection region 76 within the blood processing compartment
38. As FIG. 17 further shows, the PRP collection region 76 is
adjacent to the WB entry region 74. The velocity at which the PRBC
96 settle toward the high-G wall 24 in response to centrifugal
force is greatest in the WB entry region 74 than elsewhere in the
blood processing compartment 38. There is also relatively more
plasma volume to displace toward the low-G wall 26 in the WB entry
region 74. As a result, relatively large radial plasma velocities
toward the low-G wall 26 occur in the WB entry region 74. These
large radial velocities toward the low-G wall 26 elute large
numbers of platelets from the PRBC 96 into the close-by PRP
collection region 76.
[0111] As FIG. 4 shows, the interior seal 66 also forms a dog-leg
70 that defines a PRBC collection passage 78. A stepped-up barrier
115 (see FIG. 15) extends into the PRBC mass along the high-G wall
24, creating a restricted passage 114 between it and the facing,
iso-radial high-G wall 24. The restricted passage 114 allows PRBC
96 present along the high-G wall 24 to move beyond the barrier 115
into the PRBC collection region 50, for conveyance by the PRBC
collection passage 78 to the PRBC port 50. Simultaneously, the
stepped-up barrier 115 blocks the passage of the PRP 98 beyond
it.
[0112] As FIGS. 15, 16A and 16B show, the high-G wall 24 also
projects toward the low-G wall 26 to form a tapered ramp 84 in the
PRP collection region 76. The ramp 84 forms a constricted passage
90 along the low-G wall 26, along which the PRP 98 layer extends.
The ramp 84 keeps the interface 58 and PRBC 96 away from the PRP
collection port 46, while allowing PRP 98 to reach the PRP
collection port 46.
[0113] In the illustrated and preferred embodiment (see FIG. 16A),
the ramp 84 is oriented at a non-parallel angle .alpha. of less
than 45.degree. (and preferably about 30.degree.) with respect to
the axis of the PRP port 46. The angle .alpha. mediates spill-over
of the interface and PRBC through the constricted passage 90.
[0114] As FIGS. 16A and 16B show, the ramp 84 also displays the
interface 26 for viewing through a side wall of the container 14 by
an associated interface controller 220 (see FIG. 19). The interface
controller 220 controls the relative flow rates of WB, the PRBC,
and the PRP through their respective ports 48, 50, and 46. In this
way, the controller 220 can maintain the interface 58 at prescribed
locations on ramp, either close to the constricted passage 90 (as
FIG. 16A shows) or spaced away from the constricted passage 90 (as
FIG. 16B shows).
[0115] By controlling the position of the interface 58 on the ramp
84 relative to the constricted passage 90, the controller 220 can
also control the platelet content of the plasma collected through
the port 46. The concentration of platelets in the plasma increases
with proximity to the interface 58. By maintaining the interface 58
at a relatively low position on the ramp 84 (as FIG. 16B shows),
the platelet-rich region is kept away from the port 46, and the
plasma conveyed by the port 46 has a relatively low platelet
content. By maintaining the interface 58 at a high position on the
ramp 84 (as FIG. 16A shows), closer to the port 46, the plasma
conveyed by the port 46 is platelet-rich.
[0116] Alternatively, or in combination, the controller could
control the location of the interface 58 by varying the rate at
which WB is introduced into the blood processing compartment 38, or
the rate at which PRBC are conveyed from the blood processing
compartment 134, or both.
[0117] Further details of a preferred embodiment for the interface
controller are described in U.S. Pat. No. 5,316,667, which is
incorporated herein by reference.
[0118] As FIG. 15 shows, radially opposed surfaces 88 and 104 form
a flow-restricting region 108 along the high-G wall 24 of the WB
entry region 74. As FIG. 17 also shows, the region 108 restricts WB
flow in the WB entry region 74 to a reduced passage, thereby
causing more uniform perfusion of WB into the blood processing
compartment 38 along the low-G wall 26. This uniform perfusion of
WB occurs adjacent to the PRP collection region 76 and in a plane
that is approximately the same as the plane in which the preferred,
controlled position of the interface 58 lies. Once beyond the
constricted region 108 of the zone dam 104, the PRBC 96 rapidly
move toward the high-G wall 24 in response to centrifugal
force.
[0119] The constricted region 108 brings WB into the entry region
74 at approximately the preferred, controlled height of the
interface 58. WB brought into the entry region 74 below or above
the controlled height of the interface 58 will immediately seek the
interface height and, in so doing, oscillate about it, causing
unwanted secondary flows and perturbations along the interface 58.
By bringing the WB into the entry region 74 approximately at
interface level, the region 108 reduces the incidence of secondary
flows and perturbations along the interface 58.
[0120] As FIG. 15 shows, the low-G wall 26 tapers outward away from
the axis of rotation 28 toward the high-G wall 24 in the direction
of WB flow, while the facing high-G wall 24 retains a constant
radius. The taper can be continuous (as FIG. 15 shows) or can occur
in step fashion. These contours along the high-G and low-G walls 24
and 26 produces a dynamic circumferential plasma flow condition
generally transverse the centrifugal force field in the direction
of the PRP collection region 76. As depicted schematically in FIG.
18, the circumferential plasma flow condition in this direction
(arrow 214) continuously drags the interface 58 back toward the PRP
collection region 76, where the higher radial plasma flow
conditions already described exist to sweep even more platelets off
the interface 58. Simultaneously, the counterflow patterns serve to
circulate the other heavier components of the interface 58 (the
lymphocytes, monocytes, and granulocytes) back into the PRBC mass,
away from the PRP stream.
[0121] Within this dynamic circumferential plasma flow condition,
MNC (designated as such in FIG. 18) initially settle along the
high-G wall 24, but eventually float up to the surface of the
interface 58 near the high-hematocrit PRBC collection region 50.
The tapering low-G wall creates the plasma counterflow patterns,
shown by arrows 214 in FIG. 18. These counterflow patterns 214 draw
the MNC back toward the low-hematocrit PRP collection region 76.
MNC again resettle near the low-hematocrit PRP collection region 76
toward the high-G wall 24.
[0122] The MNC circulate in this path, designated 216 in FIG. 18,
while WB is separated into PRBC and PRP. The MNC are thus collected
and "parked" in this confined path 216 within the compartment 38
away from both the PRBC collection region 50 and the PRP collection
region 76.
[0123] Further details of the dynamics of separation in the
processing compartment 38 are found in U.S. Pat. No. 5,573,678,
which is incorporated herein by reference.
[0124] V. Mononuclear Cell Processing Procedure
[0125] The centrifuge 10 includes a process controller 222 (see
FIG. 19), which commands operation of the fluid circuit 200 to
carry out a prescribed MNC collection and harvesting procedure 224
using the container 14.
[0126] As FIG. 20 shows, the procedure 224 comprises a
pre-processing priming cycle 226, which primes the fluid circuit
200. The procedure 224 next includes a preliminary processing cycle
228, which processes PPP from whole blood obtained from the
donor/patient for use later in the procedure 224 as a suspension
medium for the harvested MNC. The procedure 224 next includes at
least one main processing cycle 230. The main processing cycle 230
comprises a collection stage 232, followed by a harvesting stage
234.
[0127] The collection stage 232 includes a series of collection
phases 236 and 238, during which whole blood is processed to
accumulate mononuclear cells in the first compartment 38, in the
manner previously described.
[0128] The harvesting stage likewise includes a series of
harvesting phases 240, 242, 244, and 246, during which the
accumulation of mononuclear cells are transferred from the first
compartment 38 into a collection container MNC coupled to the
circuit 200. Suspension medium, collected during the preliminary
processing cycle 228, is added to the MNC.
[0129] Usually, the main processing cycle 230 will be carried out
more than once during a given procedure 224. The number of
processing cycles 230 conducted in a given procedure 224 will
depend upon the total volume of MNC sought to be collected.
[0130] For example, in a representative procedure 224, five main
processing cycles 230 are repeated, one after the other. During
each main processing cycle 230, from about 1500 to about 3000 ml of
whole blood can be processed, to obtain a MNC volume per cycle of
about 3 ml. At the end of the five processing cycles 230, a MNC
volume of about 15 ml can be collected, which is suspended in a
final dilution PPP of about 200 ml.
[0131] A. Pre-Processing Priming/Ballast Sequence
[0132] Before a donor/patient is coupled to the fluid circuit 200
(via tubing T1 and T9), the controller 222 conducts a priming cycle
228. During the priming cycle 228, the controller 222 commands the
centrifuge 10 to rotate the spool and bowl elements 18 and 20 about
the axis 28, while commanding the pumps P1 to P6 to convey a
sterile priming liquid, such as saline, from the container PRIME
and anticoagulant from the container ACD throughout the entire
fluid circuit 15 and container 14. The priming liquid displaces air
from the circuit 15 and container 14.
[0133] The second compartment 40 is served by single tubing T18 and
therefore has, in effect, a single access port. To accomplish
priming, the compartment 40 is isolated from flow communication
with the priming liquid, while pump P5 is operated to draw air from
the compartment 40, thereby creating a negative pressure (vacuum)
condition in the compartment 40. Upon removal of air from the
compartment 40, communication is then opened to the flow of priming
liquid, which is drawn into the compartment 40 by the vacuum. Pump
P5 is also operated to aid in the conveyance of liquid into the
compartment 40 and to create a positive pressure condition in the
compartment 40. The controller 222 retains priming liquid in the
second compartment 40, to counter-balance the first compartment 38
during blood processing.
[0134] It should, of course, be appreciated that this vacuum
priming procedure is applicable to the priming of virtually any
container serviced by a single access port or its equivalent.
[0135] B. Preliminary Processing Cycle
[0136] MNC that is harvested in container MNC is preferably
suspended in a platelet-poor plasma (PPP) media obtained from the
MNC donor/patient. During the preliminary processing cycle 228, the
controller 222 configures the fluid circuit 222 to collect a
preestablished volume of PPP from the donor/patient for retention
in the container PPP. This volume is later used as a suspension
medium for the MNC during processing, as well as added to the MNC
after processing to achieve the desired final dilution volume.
[0137] Once the donor/patient has been phlebotomized, the
controller 222 configures the pump stations PSL, PSM, and PSR to
begin the preliminary processing cycle 228. During this cycle 228,
whole blood is centrifugally separated in the compartment 38 into
packed red blood cells (PRBC) and platelet-rich plasma (PRP), as
before described. PRBC are returned to the donor/patient, while
mononuclear cells accumulate in the compartment 38.
[0138] As MNC accumulate in the compartment 38, a portion of the
separated plasma component is removed and collected for use as a
MNC suspension medium. During this cycle 228, the controller 222
maintains the interface 58 at a relatively low position on the ramp
84 (as depicted in FIG. 16B). As a result, plasma that is conveyed
from the compartment 38 and stored in the container PPP is
relatively poor in platelets, and can thus be characterized as PPP.
The remainder of the PPP conveyed from the compartment 38 is
returned to the donor/patient during this cycle 228.
[0139] The configuration of the fluid circuit 200 during the
preliminary processing cycle 228 is shown in FIG. 21, and is
further summarized in Table 2.
2TABLE 2 Preliminary Processing Cycle V1 .circle-solid. V9
.circle-solid. V17 .largecircle. V25 .largecircle. C1
.circle-solid. P1 .largecircle. V2 .circle-solid. V10 .largecircle.
V18 .circle-solid. V26 .circle-solid. C2 .largecircle. P2 V3
.largecircle. V11 .circle-solid. V19 .circle-solid. V27
.largecircle. C3 .largecircle. P3 V4 .circle-solid. V12
.circle-solid. V20 .circle-solid. V28 .circle-solid. C4
.largecircle. P4 .circle-solid. V5 .circle-solid. V13 .largecircle.
V21 .largecircle. V29 .largecircle. P5 V6 .largecircle. V14
.largecircle. V22 .circle-solid. V30 .circle-solid. P6 V7
.largecircle. V15 .circle-solid. V23 .largecircle. V8 .largecircle.
V16 .largecircle. V24 .circle-solid. Where: .circle-solid.
indicates a tubing occluded or closed condition. .largecircle.
indicates a tubing non-occluded or opened condition. indicates a
pump on condition, during which the pump rotors rotate and engage
the pump tubing to convey fluid in a peristaitic fashion.
.largecircle. indicates an opened, pump off condition, during which
the pump rotors are not rotating and in which the pump rotors do
not engage the pump tubing loop, and therefore permit fluid flow
through the pump tubing loop. .circle-solid. indicates a closed,
pump off condition, during which the pump rotors are not rotating,
and in which the pump rotors do engage with pump tubing loop, and
therefore do not permit fluid flow through the pump tubing
loop.
[0140] During the preliminary cycle 228, pump P2 draws whole blood
(WB) from the donor/patient through tubing T1 into the left
cassette 23L, into tubing T3, through the chamber D1, and into the
blood processing compartment 38 through tubing T4. Pump P3 draws
anticoagulant ACD through tubing T15, into the middle cassette 23M
and into tubing T2, for mixing with the whole blood.
[0141] The anticoagulated whole blood is conveyed into the
compartment 38 through port 48. The whole blood is separated into
PRP, PRBC, and the interface (including MNC), as previously
described.
[0142] The port 50 conveys PRBC 96 from the blood processing
compartment 38, through tubing T5 into the middle cassette 23M. The
PRBC enters tubing T7 through tubing T8, for return to the
donor/patient via the left cassette 23L and tubing T9.
[0143] The port 46 conveys PPP from the blood processing
compartment 38. The PPP follows tubing T10 into the right cassette
23R. Pump P5 conveys a portion of the PPP into tubing T7 for return
with PRBC to the donor/patient. The interface controller 220 sets
the flow rate of pump P5 to maintain the interface at a low
position on the ramp 84 (as shown in FIG. 16B), to thereby minimize
the concentration of platelets conveyed from the compartment 38
during this cycle. Pump P6 conveys a portion of the PPP through
tubing T12 into container PPP, until the volume prescribed for MNC
suspension and final dilution is collected. This volume is
designated VOL.sub.sus.
[0144] C. Main Processing Cycle
[0145] 1. Mononuclear Cell (MNC) Collection Stage
[0146] a. MNC Accumulation Phase
[0147] The controller 222 now switches to the MNC collect stage 232
of the main processing cycle 230. First, the controller 222
configures the fluid circuit 200 for the MNC accumulation phase
236.
[0148] For the phase 236, the controller 222 changes the
configuration of the pump station PSR to stop collection of PPP.
The controller 222 also commands the interface controller 220 to
maintain a flow rate for pump P5 to maintain the interface at a
higher location on the ramp 84 (such as shown in FIG. 16A), thereby
enabling the separation of PRP.
[0149] Due to the changed configuration, the pump P6 also
recirculates a portion of the PRP to the blood processing chamber
38 to enhance platelet separation efficiencies, as will be
described in greater detail later.
[0150] The configuration for the MNC accumulation phase 236 of the
MNC collect stage 232 is shown in FIG. 22, and is further
summarized in Table 3.
3TABLE 3 Mononuclear Cell Collect Condition (MNC Accumulation
Phase) V1 .circle-solid. V9 .circle-solid. V17 .largecircle. V25
.circle-solid. C1 .circle-solid. P1 .largecircle. V2 .circle-solid.
V10 .largecircle. V18 .largecircle. V26 .circle-solid. C2
.largecircle. P2 V3 .largecircle. V11 .circle-solid. V19
.circle-solid. V27 .largecircle. C3 .largecircle. P3 V4
.circle-solid. V12 .circle-solid. V20 .largecircle. V28
.largecircle. C4 .largecircle. P4 V5 .circle-solid. V13
.largecircle. V21 .largecircle. V29 .circle-solid. P5 V6
.largecircle. V14 .largecircle. V22 .circle-solid. V30
.largecircle. P6 V7 .largecircle. V15 .circle-solid. V23
.largecircle. V8 .largecircle. V16 .largecircle. V24 .circle-solid.
Where: .circle-solid. indicates a tubing occluded or closed
condition. .largecircle. indicates a tubing non-occluded or opened
condition. indicates a pump on condition, during which the pump
rotors rotate and engage the pump tubing to convey fluid in a
peristaitic fashion. .largecircle. indicates an opened, pump off
condition, during which the pump rotors are not rotating and in
which the pump rotors do not engage the pump tubing loop, and
therefore permit fluid flow through the pump tubing loop.
.circle-solid. indicates a closed, pump off condition, during which
the pump rotors are not rotating, and in which the pump rotors do
engage with pump tubing loop, and therefore do not permit fluid
flow through the pump tubing loop.
[0151] b. Promoting High Platelet Separation Efficiencies By
Recirculation of PRP
[0152] Normally, platelets are not collected during a MNC
procedure. Instead, it is believed desirable to return them to the
donor/patient. A high mean platelet volume MPV (expressed in
femtoliters, fl, or cubic microns) for separated platelets is
desirable, as it denotes a high platelet separation efficiency. MPV
can be measured by conventional techniques from a PRP sample.
Larger platelets (i.e., larger than about 20 femtoliters) are most
likely to become entrapped in the interface 58 and not enter the
PRP for return to the donor/patient. This results in a reduced
population of larger platelets in the PRP, and therefore a lower
MPV, for return to the donor/patient.
[0153] The establishment of radial plasma flow conditions
sufficient to lift larger platelets from the interface 58, as
previously described, is highly dependent upon the inlet hematocrit
H.sub.i of WB entering the blood processing compartment 38. For
this reason, the pump 6 recirculates a portion of the PRP flowing
in tubing T10 back into the WB inlet port 48. The recirculating PRP
flows through the right cassette 23R into tubing T11, which joins
tubing T4 coupled to the inlet port 48. The recirculating PRP mixes
with WB entering the blood processing compartment 38, thereby
lowering inlet hematocrit H.sub.i.
[0154] The controller sets a PRP recirculation flow rate
Q.sub.Recirc for pump P6 to achieve a desired inlet hematocrit
H.sub.i. In a preferred implementation, H.sub.i is no greater that
about 40%, and, most preferably, is about 32%, which will achieve a
high MPV.
[0155] Inlet hematocrit H.sub.i can be conventionally measured by
an in-line sensor in tubing T4 (not shown). Inlet hematocrit
H.sub.i can also be determined empirically based upon sensed flow
conditions, as disclosed in copending U.S. patent application Ser.
No. 08/471,883, which is incorporated herein by reference.
[0156] 2. Promoting High MNC Concentration and Purity By
Recirculation of PRBC
[0157] As depicted schematically in FIG. 18, the counter flow of
plasma (arrows 214) in the compartment 38 drags the interface 58
back toward the PRP collection region 76, where the enhanced radial
plasma flow conditions sweep platelets off the interface 58 for
return to the donor/patient. The counterflow patterns 214 also
circulate other heavier components of the interface 58, such as
lymphocytes, monocytes, and granulocytes, back for circulation into
the PRBC mass.
[0158] Meanwhile, due to the relatively high hematocrit in the PRBC
collection region 80, MNC float near the region 80 to the surface
of the interface 58. There, the MNC are drawn by the plasma
counter-flow 214 toward the low-hematocrit PRP collection region
76. Due to the lower hematocrit in this region 76, MNC resettle
again toward the high-G wall 24. Arrow 216 in FIG. 18 shows the
desired circulating flow of MNC as it accumulates in the
compartment 38.
[0159] Maintaining a desired PRBC outlet hematocrit H.sub.o in the
PRBC collection region 50 is important. If the outlet hematocrit
H.sub.o, of the PRBC falls below a given low threshold value (e.g.,
below about 60%), the majority of MNC will not circulate as a
cellular mass, as shown by the arrow 216 in FIG. 18. Exposed to a
low H.sub.o all or some of the MNC will fail to float toward the
interface 58. Instead, the MNC will remain congregated along the
high-G wall and will be carried out of the compartment 38 with the
PRBC. An insufficient MNC yield results.
[0160] On the other hand, if H.sub.o exceeds a given high threshold
value (e.g., about 85%), larger numbers of the heavier granulocytes
will float on the interface 58. As a result, fewer granulocytes
will be carried away from the interface 58 for return with the PRBC
to the donor/patient. Instead, more granulocytes will occupy the
interface 58 and contaminate the MNC.
[0161] For this reason, during the MNC collection stage 232, the
process controller 222 commands the pump P4 to recirculate a
portion of the PRBC flowing in tubing T5 back into the WB inlet
port 48. As FIGS. 21 and 22 show, recirculating PRBC flows through
the middle cassette 23M into tubing T6, which joins tubing T4
coupled to the inlet port 48. The recirculating PRBC mixes with WB
entering the blood processing compartment 38.
[0162] Generally speaking, the magnitude of the outlet hematocrit
H.sub.o varies conversely as a function of PRBC recirculation flow
rate Q.sub.r, which is governed by the pump P4 (PRBC) and the pump
P2 (WB). Given a flow rate for WB set by pump P2, the outlet
hematocrit H.sub.o can be increased by lowering Q.sub.r, and,
conversely, outlet hematocrit H.sub.o can be decreased by raising
Q.sub.r. The exact relationship between Q.sub.r and H.sub.o takes
into account the centrifugal acceleration of fluid in the
compartment 38 (governed by the magnitude of centrifugal forces in
the compartment 38), the area of the compartment 38, as well as the
inlet flow rate whole blood (Q.sub.b) into the compartment 38
(governed by pump P2) and the outlet flow rate PRP (Q.sub.p) from
the compartment 38 (governed by the interface control pump P5).
[0163] There are various ways of expressing this relationship and
thereby quantifying Q.sub.r based upon a desired H.sub.o. In the
illustrated embodiment, the controller 222 periodically samples
Q.sub.b, Q.sub.p, and Q.sub.r. Further taking into account the
centrifugal force factors active in the compartment 38, the
controller derives a new PRBC recirculation pump rate Q.sub.r (NEW)
for the pump P4, based upon a targeted H.sub.o, as follows:
[0164] (i) Start at sample time n=0
[0165] (ii) Calculate current Q.sub.r as follows: 1 Q r = [ Q p - Q
b ] + [ k H o - 1 ] [ a * A m ]
[0166] where:
[0167] H.sub.o is the targeted exit hematocrit value, expressed as
a decimal (e.g., 0.75 for 75%).
[0168] a is the acceleration of fluid, governed by centrifugal
forces, calculated at follows: 2 a = r 2 g
[0169] where:
[0170] .OMEGA. is the rate of rotation of the compartment 38,
expressed in radians per second.
[0171] r is the radius of rotation.
[0172] g is unit gravity, equal to 981 cm/sec.sup.2.
[0173] A is the area of the compartment 38.
[0174] k is hematocrit constant and m is a separation performance
constant, which are derived based upon empirical data and/or
theoretical modeling. In the preferred embodiment, the following
theoretical model is used: 3 H o ( 1 - H o ) k + 1 = Q b H i a A C
R
[0175] where:
C.sub.R=1.08 S.sub.I
[0176] and where:
[0177] .beta. is a shear sensitive term defined as: 4 = 1 + b n
[0178] and where:
[0179] based upon empirical data, b=6.0 s.sup.-n and n=0.75, and
shear rate is defined as:
.tau.=du/dy
[0180] in which (u) is the fluid velocity and (y) is a spatial
dimension.
[0181] and where:
[0182] S.sub.r is an empirically derived red blood cell
sedimentation factor, which, upon empirical data, can be set at
95.times.10.sup.-9 s.
[0183] This model is based upon Equation (19) of Brown, "The
Physics of Continuous Flow Centrifugal Cell Separation," Artificial
Organs; 13(1):4-20, Raven Press, Ltd., New York (1989) (the "Brown
Article"), which is incorporated herein by reference. The plot of
the model appears in FIG. 9 of the Brown Article.
[0184] The above model is linearized using simple linear regression
over an expected, practical operating range of blood processing
conditions. Algebraic substitutions are made based upon the
following expressions:
H.sub.iQ.sub.b=H.sub.oQ.sub.o
[0185] where:
[0186] Q.sub.o is the flow rate of PRBC through outlet tubing T5,
which can be expressed as:
Q.sub.o=Q.sub.b-Q.sub.p
[0187] This linearization yields a simplified curve in which the
value of (m) constitutes the slope and the value of (k) constitutes
the y-intercept.
[0188] In the simplified curve, the slope (m) is expressed as
follows: 5 m = 338.3 ( S r )
[0189] where:
[0190] .beta./S.sub.r can, based upon empirical data, be expressed
as a constant value of 1.57/.mu.s.
[0191] Therefore, in the simplified curve, m has a value of 531.13.
A range of values for m between about 500 and about 600 is believed
to be applicable to centrifugal, continuous flow whole blood
separation procedures, in general.
[0192] For the simplified curve, the y-intercept value for (k)
equals 0.9489. A range of values for k between about 0.85 and about
1.0 is believed to be applicable to centrifugal, continuous flow
whole blood separation procedures, in general.
[0193] (iii) Calculate Average Q.sub.r
[0194] Q.sub.r is measured at selected intervals, and these
instantaneous measurements are averaged over the processing period,
as follows:
Q.sub.r(AVG)=[0.95(Q.sub.r(AVG.sub.LAST)]+[0.05 *Q.sub.r]
[0195] (iv) Calculate New Q.sub.r, as Follows:
Q.sub.r(NEW)=Q.sub.r(AVG)*F
[0196] where:
[0197] F is an optional control factor, which enables the control
of Q.sub.r (when F=1), or disables the control of Q.sub.r (when
F=0), or enables a scaling of Q.sub.r based upon system variances
(when F is expressed as a fraction between 0 and 1). F can comprise
a constant or, alternatively, it can vary as a function of
processing time, e.g., starting at a first value at the outset of a
given procedure and changing to a second or more values as the
procedure progresses.
[0198] (v) Keep Q.sub.r within prescribed limits (e.g., between 0
ml/min and 20 ml/min)
[0199] IF
Q.sub.r(NEW)>20 ml/min THEN
Q.sub.r(NEW)=20 ml/min
[0200] ENDIF
[0201] IF
Q.sub.r(NEW)<0 ml/min THEN
Q.sub.r(NEW)=0ml/min
[0202] ENDIF
n=n+1
[0203] During the MNC collect stage 232 (FIG. 22), the controller
222 simultaneously sets and maintains multiple pump flow rates to
achieve processing conditions in the compartment 38 optimal for the
accumulation of a high yield of MNC of high purity. The controller
sets and maintains WB inlet flow rate Q.sub.b (via the pump P2),
PRP outlet flow rate Q.sub.p (via the pump PS), PRP recirculation
flow rate Q.sub.Recirc (via the pump P6), and PRBC recirculation
flow rate Q.sub.r (via the pump P4). Given a WB inlet flow rate
Q.sub.b, which is typically set for donor/patient comfort and the
achievement of an acceptable processing time, the controller
222:
[0204] (i) commands pump PS to maintain a Q.sub.p set to hold a
desired interface position on the ramp 84, and thereby achieve the
desired platelet concentrations in the plasma (PPP or PRP);
[0205] (ii) commands the pump P6 to maintain a Q.sub.Recirc set to
hold the desired inlet hematocrit H.sub.i (e.g., between about 32%
and 34%), and thereby achieve high platelet separation
efficiencies; and
[0206] (iii) commands the pump P4 to maintain a Q.sub.r set to hold
a desired outlet hematocrit H.sub.o (e.g., between about 75% to
85%), and thereby prevent granulocyte contamination and maximize
MNC yields.
[0207] 3. Second Phase (PRBC Collect)
[0208] The controller 222 terminates the MNC accumulation phase 236
when a preestablished volume of whole blood (e.g., 1500 ml to 3000
ml) is processed. Alternatively, the MNC accumulation phase can be
terminated when a targeted volume of MNC is collected.
[0209] The controller 22 then enters the PRBC collection phase 238
of the MNC collection stage 232. In this phase 238, the
configuration of the pump station PSM is altered to stop the return
of PRBC to the donor/patient (by closing V14), stop the
recirculation of PRBC (by closing valve V18 and placing pump P4
into a closed, pump off condition, and instead conveying PRBC to
the container PRBC (by opening V15).
[0210] This new configuration is shown in FIG. 23, and is further
summarized in Table 4.
4TABLE 4 Mononuclear Cell Collect Stage (Collect PRBC Phase) V1
.circle-solid. V9 .circle-solid. V17 .largecircle. V25
.circle-solid. C1 .circle-solid. P1 .largecircle. V2 .circle-solid.
V10 .largecircle. V18 .circle-solid. V26 .circle-solid. C2
.largecircle. P2 V3 .largecircle. V11 .circle-solid. V19
.circle-solid. V27 .largecircle. C3 .largecircle. P3 V4
.circle-solid. V12 .circle-solid. V20 .largecircle. V28
.largecircle. C4 .largecircle. P4 .circle-solid. V5 .circle-solid.
V13 .largecircle. V21 .largecircle. V29 .circle-solid. P5 V6
.largecircle. V14 .circle-solid. V22 .circle-solid. V30
.circle-solid. P6 V7 .largecircle. V15 .largecircle. V23
.largecircle. V8 .largecircle. V16 .largecircle. V24 .circle-solid.
Where: .circle-solid. indicates a tubing occluded or closed
condition. .largecircle. indicates a tubing non-occluded or opened
condition. indicates a pump on condition, during which the pump
rotors rotate and engage the pump tubing to convey fluid in a
peristaitic fashion. .largecircle. indicates an opened, pump off
condition, during which the pump rotors are not rotating and in
which the pump rotors do not engage the pump tubing loop, and
therefore permit fluid flow through the pump tubing loop.
.circle-solid. indicates a closed, pump off condition, during which
the pump rotors are not rotating, and in which the pump rotors do
engage with pump tubing loop, and therefore do not permit fluid
flow through the pump tubing loop.
[0211] In this phase 238, PRBC in line TS is conveyed through the
middle cassette 23M, into line T14, and into the container PRBC.
The controller 222 operates in this phase 238 until a desired
volume of PRBC (e.g., 35 ml to 50 ml) collects in the container
PRBC. This PRBC volume is later used in the MNC removal phase 240
of the MNC harvesting stage 234, as will be described in greater
detail later.
[0212] The controller 222 ends the PRBC collection phase 238 upon
sensing (gravimetrically, using the weight scale WS) that the
container PRBC holds the desired volume of PRBC.
[0213] The ends the MNC collection stage 232 of the main processing
cycle 230.
[0214] 4. Mononuclear Cell Harvesting Stage
[0215] a. First Phase (MNC Removal)
[0216] The controller 222 enters the MNC harvesting stage 234 of
the main processing cycle 230. In the first phase 240 of this stage
234, whole blood is drawn and recirculated back to the
donor/patient without passage through the blood processing
compartment 38. PRBC collected in the container PRBC in the
preceding PRBC collection phase 238 is returned to the processing
compartment 38 through WB inlet tubing T4, while rotation of the
compartment 38 continues. The MNC accumulated in the compartment 38
during the MNC collection stage 232 is conveyed with PRP through
tubing T10 out of the compartment 38.
[0217] The configuration of the fluid circuit 15 during the MNC
removal phase 240 of the MNC harvesting stage 234 is shown in FIG.
24A, and is further summarized in Table 5:
5TABLE 5 Mononuclear Cell Harvesting Stage (MNC Removal Phase) V1
.circle-solid. V9 .largecircle. V17 .largecircle. V25 .largecircle.
C1 .circle-solid. P1 or .circle-solid. V2 .largecircle. V10
.largecircle. V18 .largecircle. V26 .circle-solid. C2 .largecircle.
P2 .circle-solid. V3 .circle-solid. V11 .circle-solid. V19
.circle-solid. V27 .largecircle. C3 .largecircle. P3 V4
.circle-solid. V12 .circle-solid. V20 .circle-solid. V28
.largecircle. C4 .largecircle. P4 V5 .circle-solid. V13
.largecircle. V21 .largecircle. V29 .circle-solid. P5
.circle-solid. V6 .largecircle. V14 .circle-solid. V22
.circle-solid. V30 .largecircle. P6 .circle-solid. V7 .largecircle.
V15 .largecircle. V23 .largecircle. V8 .largecircle. V16
.largecircle. V24 .circle-solid. Where: .circle-solid. indicates a
tubing occluded or closed condition. .largecircle. indicates a
tubing non-occluded or opened condition. indicates a pump on
condition, during which the pump rotors rotate and engage the pump
tubing to convey fluid in a peristaitic fashion. .largecircle.
indicates an opened, pump off condition, during which the pump
rotors are not rotating and in which the pump rotors do not engage
the pump tubing loop, and therefore permit fluid flow through the
pump tubing loop. .circle-solid. indicates a closed, pump off
condition, during which the pump rotors are not rotating, and in
which the pump rotors do engage with pump tubing loop, and
therefore do not permit fluid flow through the pump tubing
loop.
[0218] As FIG. 24A shows, the controller 222 closes PRBC outlet
tubing T5 while PRBC is conveyed by pump P4 from the container PRBC
through tubing T14 and T6 into tubing T4, for introduction into
compartment 38 through the WB inlet port 48. The controller 222
starts a cycle time counter at TCYC.sub.START.
[0219] The inflow of PRBC from the container PRBC through the WB
inlet port 48 increases the hematocrit in the PRP collection region
76. In response, the concentrated region of MNC accumulated in the
compartment 38 (as shown in FIG. 18), float to the surface of the
interface 58. The incoming PRBC volume displaces PRP through the
PRP outlet port 46. The interface 58, and with it, the concentrated
MNC region (designated MNC Region in FIG. 24A) are also displaced
out of the compartment 38 through the PRP outlet port 46. The MNC
Region moves along the PRP tubing T10 toward the optical sensor
OS.
[0220] As FIG. 28 shows, within the tubing T10, a region 112 of PRP
precedes the concentrated MNC Region. The PRP in this region 112 is
conveyed into the container PPP through the right cassette 23R and
tubing T12 (as FIG. 24A shows). A region 114 of PRBC also follows
the concentrated MNC Region within the tubing T10.
[0221] A first transition region 116 exists between the PRP region
112 and concentrated MNC Region. The first transition region 116
consists of a steadily decreasing concentration of platelets (shown
by a square pattern in FIG. 28) and a steadily increasing number of
MNC's (shown by a textured pattern in FIG. 28).
[0222] A second transition region 118 exists between the
concentrated MNC Region and the PRBC region 114. The second
transition region 118 consists of a steadily decreasing
concentration of MNC's (shown by the textured pattern in FIG. 28)
and a steadily increasing number of PRBC's (shown by a wave pattern
in FIG. 28).
[0223] Viewed by the optical sensor OS, the regions 112 and 116
preceding the MNC Region and the regions 118 and 114 trailing the
MNC Region present a transition optical densities in which the MNC
Region can be discerned. The optical sensor OS senses changes in
optical density in the liquid conveyed by the tubing T10 between
the PRP outlet port 46 and the right cassette 23R. As FIG. 28
shows, the optical density will change from a low value, indicating
highly light transmissive (i.e., in the PRP region 112), to a high
value, indicating highly light absorbent (i.e., in the PRBC region
114), as the MNC Region progresses past the optical sensor OS.
[0224] In the illustrated embodiment shown in FIG. 28, the optical
sensor OS is a conventional hemoglobin detector, used, e.g., on the
Autopheresis-C.RTM. blood processing device sold by the Fenwal
Division of Baxter Healthcare Corporation. The sensor OS comprises
a red light emitting diode 102, which emits light through the
tubing T10. Of course, other wavelengths, like green or infrared,
could be used. The sensor OS also includes a PIN diode detector 106
on the opposite side of the tubing T10.
[0225] The controller 222 includes a processing element 100, which
analyzes voltage signals received from the emitter 102 and detector
106 to compute the optical transmission of the liquid in the tubing
T10, which is called OPTTRANS.
[0226] Various algorithms can be used by the processing element 100
to compute OPTTRANS.
[0227] For example, OPTRANS can equal the output of the diode
detector 106 when the red light emitting diode 102 is on and the
liquid flows through the tubing T10 (RED).
[0228] Background optical "noise" can be filtered from RED to
obtain OPTTRANS, as follows: 6 OPTTRANS = COR ( RED SPILL )
CORRREF
[0229] where COR(RED SPILL) is calculated as follows: COR(RED
SPILL)=RED-REDBKGRD
[0230] where:
[0231] RED is the output of the diode detector 106 when the red
light emitting diode 102 is on and the liquid flows through the
tubing T10;
[0232] REDBKGRD is the output of the diode detector 106 when the
red light emitting diode 102 is off and the liquid flows through
the tubing T10;
[0233] and where CORREF is calculated as follows:
CORREF=REF-REFBKGRD
[0234] where:
[0235] REF is the output of the red light emitting diode 102 when
the diode is on; and
[0236] REFBKGRD is the output of the red light emitting diode 102
when the diode is off.
[0237] The processing element 100 normalizes the sensor OS to the
optical density of the donor/patient's PRP, by obtaining data from
the sensor OS during the preceding MNC collection stage 232, as the
donor/patient's PRP conveys through the tubing T10. This data
establishes a baseline optical transmission value for the tubing
and the donor/patient's PRP (OPTTRANS.sub.BASE). For example,
OPTTRANS.sub.BASE can be measured at a selected time during the
collection stage 232, e.g., half way through the stage 232, using
either a filtered or non-filtered detection scheme, as described
above. Alternatively, a set of optical transmission values are
calculated during the MNC collection stage 232 using either a
filtered or non-filtered detection scheme. The set of values are
averaged over the entire collection stage to derive
OPTTRANS.sub.BASE.
[0238] The processing element 100 continues during the subsequent
MNC removal phase 240 to sense one or more optical transmission
values for the tubing T10 and the liquid flowing in it
(OPTTRANS.sub.HARVEST) during the MNC removal phase 240.
OPTTRANS.sub.HARVEST can comprise a single reading sensed at a
selected time of the MNC removal phase 240 (e.g., midway through
the phase 240), or it can comprise an average of multiple readings
taken during the MNC removal phase 240.
[0239] The processing element 100 derives a normalized value
DENSITY by establishing OPTTRANS.sub.BASE as 0.0, establishing the
optical saturation value as 1.0, and fitting the value of
OPTTRANS.sub.HARVEST proportionally into the normalized 0.0 to 1.0
value range.
[0240] As FIG. 28 shows, the processing element 100 retains two
predetermined threshold values THRESH(1) and THRESH(2). The value
of THRESH(1) corresponds to a selected nominal value for DENSITY
(e.g., 0.45 in a normalized scale of 0.0 to 1.0), which has been
empirically determined to occur when the concentration of MNC's in
the first transition region 116 meets a preselected processing
goal. The value of THRESH(2) corresponds to another selected
nominal value for DENSITY (e.g., 0.85 in a normalized scale of 0.0
to 1.0), which has been empirically determined to occur when the
concentration of PRBC in the second transition region 118 exceeds
the preselected processing goal.
[0241] The liquid volume of the tubing T10 between the optical
sensor OS and the valve station V24 in the right cassette 23R
constitutes a known value, which is inputted to the controller 222
as a first offset volume VOL.sub.OFF(1) The controller 222
calculates a first control time value Time.sub.1 based upon
VOL.sub.OFF(1) and the pump rate of pump P4 (Q.sub.P4), as follows:
7 Time 1 = VOL OFF ( 1 ) Q P4 .times. 60
[0242] In the illustrated and preferred embodiment, the operator
can specify and input to the controller 222 a second offset volume
VOL.sub.OFF(2), which represents a nominal additional volume (shown
in FIG. 28) to increase the total MNC harvested volume VOL.sub.MNC.
The quantity VOL.sub.OFF(2) takes into account system and
processing variances, as well as variances among donors/patients in
MNC purity. The controller 222 calculates a second control time
value Time.sub.2 based upon VOL.sub.OFF(2) and the pump rate of
pump P4 (Q.sub.P4), as follows: 8 Time 2 = VOL OFF ( 2 ) Q P4
.times. 60
[0243] As operation of the pump P4 conveys PRBC through the WB
inlet port 48, the interface 58 and MNC Region advance through the
PRP tubing T10 toward the optical sensor OS. PRP preceding the MNC
Region advances beyond the optical sensor OD, through the tubing
T12, and into the container PPP.
[0244] When the MNC Region reaches the optical sensor OS, the
sensor OS will sense DENSITY=THRESH(1). Upon this event, the
controller 222 starts a first time counter TC.sub.1. When the
optical sensor OS senses DENSITY=THRESH(2) the controller 222
starts a second time counter TC.sub.2. The volume of MNC sensed can
be derived based upon the interval between TC.sub.1 and TC.sub.2
for a given QP.sub.4.
[0245] As time advances, the controller 222 compares the magnitudes
of TC.sub.1 to the first control time T.sub.1, as well as compares
TC.sub.2 to the second control time T.sub.2. When TC.sub.1=T.sub.1,
the leading edge of the targeted MNC Region has arrived at the
valve station V24, as FIG. 24B shows. The controller 222 commands
valve station V24 to open, and commands valve station V25 to close.
The controller 222 marks this event on the cycle time counter as
TCYC.sub.SWITCH. The targeted MNC Region is conveyed into the
tubing T13 that leads to the container MNC. When TC.sub.2=T.sub.2,
the second offset volume VOL.sub.OFF(2) has also been conveyed into
the tubing T13, as FIG. 24C shows. The total MNC volume selected
for harvesting (VOL.sub.MNC) for the given cycle is thereby present
in the tubing T13. When TC.sub.2=T.sub.2, the controller 222
commands the pump P4 to stop. Further advancement of VOL.sub.MNC in
the tubing T13 therefore ceases.
[0246] The controller 222 derives the volume of PRP that was
conveyed into the container PPP during the preceding MNC removal
phase. This PRP volume (which is designated VOL.sub.PRP) is
derived, as follows: 9 VOL PRP = TCYC SWITCH - TCYC START Q 4
[0247] In a preferred embodiment, the controller 222 ends the MNC
removal phase, independent of TC.sub.1 and TC.sub.2 when the pump
P4 conveys more than a specified fluid volume of PRBC after
TCYC.sub.START (e.g., more than 60 ml). This time-out circum-stance
could occur, e.g., if the optical sensor OS fails to detect
THRESH(1). In this volumetric time-out circumstance,
VOL.sub.PRP=60-VOL.sub.OFF(1).
[0248] Alternatively, or in combination with a volumetric time-out,
the controller 222 can end the MNC removal phase independent of
TC.sub.1 and TC.sub.2 when the weight scale WS for the container
PRBC senses a weight less than a prescribed value (e.g., less than
4 grams, or the weight equivalent of a fluid volume less than 4
ml).
[0249] b. Second Phase (PRP Flush)
[0250] Once the MNC Region is positioned as shown in FIG. 24C, the
controller 222 enters the PRP flush phase 242 of the MNC harvesting
stage 234. During this phase 242, the controller 222 configures the
circuit 200 to move VOL.sub.PRP out of the container PPP and tubing
T12 and into the blood processing compartment 38.
[0251] The configuration of the fluid circuit 200 during the PRP
flush phase 242 is shown in FIG. 25, and is further summarized in
Table 6.
6TABLE 6 Mononuclear Cell Harvesting Stage (PRP Flush Phase) V1
.circle-solid. V9 .circle-solid. V17 .largecircle. V25
.largecircle. C1 .circle-solid. P1 .largecircle. V2 .circle-solid.
V10 .largecircle. V18 .largecircle. V26 .circle-solid. C2
.circle-solid. P2 .circle-solid. V3 .largecircle. V11
.circle-solid. V19 .circle-solid. V27 .circle-solid. C3
.largecircle. P3 .circle-solid. V4 .circle-solid. V12
.circle-solid. V20 .largecircle. V28 .largecircle. C4
.circle-solid. P4 .circle-solid. V5 .circle-solid. V13
.largecircle. V21 .largecircle. V29 .circle-solid. P5
.circle-solid. V6 .largecircle. V14 .largecircle. V22
.circle-solid. V30 .circle-solid. P6 V7 .largecircle. V15
.circle-solid. V23 .largecircle. V8 .largecircle. V16 .largecircle.
V24 .largecircle. Where: .circle-solid. indicates a tubing occluded
or closed condition. .largecircle. indicates a tubing non-occluded
or opened condition. indicates a pump on condition, during which
the pump rotors rotate and engage the pump tubing to convey fluid
in a peristaitic fashion. .largecircle. indicates an opened, pump
off condition, during which the pump rotors are not rotating and in
which the pump rotors do not engage the pump tubing loop, and
therefore permit fluid flow through the pump tubing loop.
.circle-solid. indicates a closed, pump off condition, during which
the pump rotors are not rotating, and in which the pump rotors do
engage with pump tubing loop, and therefore do not permit fluid
flow through the pump tubing loop.
[0252] During the PRP flush stage 242, the controller 222
configures the pump stations PSL, PSM, and PSR to stop whole blood
recirculation, and, while continuing rotation of the compartment
38, to pump VOL.sub.PRP to the processing compartment 38 through
tubing T11. VOL.sub.PRP is conveyed by the pump P6 through tubing
T12 into the right cassette 23R, and thence to tubing T11, for
entry into the processing compartment 38 through tubing T4 and port
48. PRBC are conveyed from the processing compartment 38 through
port 50 and tubing T5 into the middle cassette 23M, and thence into
tubings T8 and T7 into the left cassette 23L. The PRBC is conveyed
into tubing T9 for return to the donor/patient. No other fluid is
conveyed in the fluid circuit 15 during this phase 242.
[0253] The return of VOL.sub.PRP restores the volume of liquid in
container PPP to VOL.sub.SUS as collected during the preliminary
processing cycle 228 previously described. The return of
VOL.sub.PRP also preserves a low platelet population in the
VOL.sub.SUS in the container PPP slated for suspension of MNC. The
return of VOL.sub.PRP also conveys residual MNC present in the
first transition region 116 before TC.sub.1=T.sub.1 (and therefore
not part of VOL.sub.MNC), back to the processing compartment 38 for
further collection in a subsequent main processing cycle 230.
[0254] C. Third Phase (MNC Suspension)
[0255] With the return of VOL.sub.PRP to the compartment 38, the
controller 222 enters the MNC suspension phase 244 of the MNC
harvesting stage 234. During this phase 244, a portion of the
VOL.sub.SUS in the container PPP is conveyed with VOL.sub.MNC into
the container MNC.
[0256] The configuration of the fluid circuit 200 during the MNC
suspension phase 244 is shown in FIG. 26, and is further summarized
in Table 7.
7TABLE 7 Mononuclear Cell Harvesting Stage (MNC Suspension Phase)
V1 .circle-solid. V9 .circle-solid. V17 .largecircle. V25
.largecircle. C1 .circle-solid. P1 .largecircle. V2 .circle-solid.
V10 .largecircle. V18 .largecircle. V26 .circle-solid. C2
.circle-solid. P2 .circle-solid. V3 .largecircle. V11
.circle-solid. V19 .circle-solid. V27 .circle-solid. C3
.circle-solid. P3 .circle-solid. V4 .circle-solid. V12
.circle-solid. V20 .largecircle. V28 .circle-solid. C4
.circle-solid. P4 .circle-solid. V5 .circle-solid. V13
.largecircle. V21 .largecircle. V29 .largecircle. P5 .circle-solid.
V6 .largecircle. V14 .largecircle. V22 .circle-solid. V30
.circle-solid. P6 V7 .largecircle. V15 .circle-solid. V23
.largecircle. V8 .largecircle. V16 .largecircle. V24 .largecircle.
Where: .circle-solid. indicates a tubing occluded or closed
condition. .largecircle. indicates a tubing non-occluded or opened
condition. indicates a pump on condition, during which the pump
rotors rotate and engage the pump tubing to convey fluid in a
peristaitic fashion. .largecircle. indicates an opened, pump off
condition, during which the pump rotors are not rotating and in
which the pump rotors do not engage the pump tubing loop, and
therefore permit fluid flow through the pump tubing loop.
.circle-solid. indicates a closed, pump off condition, during which
the pump rotors are not rotating, and in which the pump rotors do
engage with pump tubing loop, and therefore do not permit fluid
flow through the pump tubing loop.
[0257] In the MNC suspension phase 244, the controller closes C3 to
stop the return to PRBC to the donor/patient. A predetermined
aliquot of VOL.sub.SUS (e.g., 5 ml to 10 ml) is conveyed by the
pump P6 through tubing T12 into the right cassette 23R and then
into tubing T13. As FIG. 26 shows, the aliquot of VOL.sub.SUS
further advances VOL.sub.MNC through the tubing T13 into the
container MNC.
[0258] d. Fourth Phase (Clean Up)
[0259] At this time, the controller 222 enters the final, clean up
phase 246 of the MNC harvesting stage 234. During this phase 246,
the controller 222 returns PRBC resident in the tubing T10 to the
processing compartment 38.
[0260] The configuration of the fluid circuit 200 during the clean
up phase 246 is shown in FIG. 27, and is further summarized in
Table 7.
8TABLE 7 Mononuclear Cell Harvesting Stage (Clean Up Phase) V1
.circle-solid. V9 .circle-solid. V17 .circle-solid. V25
.circle-solid. C1 .circle-solid. P1 .circle-solid. V2
.circle-solid. V10 .circle-solid. V18 .circle-solid. V26
.circle-solid. C2 .circle-solid. P2 .circle-solid. V3
.circle-solid. V11 .circle-solid. V19 .circle-solid. V27
.largecircle. C3 .circle-solid. P3 .circle-solid. V4 .circle-solid.
V12 .circle-solid. V20 .circle-solid. V28 .largecircle. C4
.circle-solid. P4 .circle-solid. V5 .circle-solid. V13
.circle-solid. V21 .largecircle. V29 .circle-solid. P5
.circle-solid. V6 .circle-solid. V14 .circle-solid. V22
.circle-solid. V30 .largecircle. P6 V7 .circle-solid. V15
.circle-solid. V23 .largecircle. V8 .circle-solid. V16
.circle-solid. V24 .circle-solid. Where: .circle-solid. indicates a
tubing occluded or closed condition. .largecircle. indicates a
tubing non-occluded or opened condition. indicates a pump on
condition, during which the pump rotors rotate and engage the pump
tubing to convey fluid in a peristaitic fashion. .largecircle.
indicates an opened, pump off condition, during which the pump
rotors are not rotating and in which the pump rotors do not engage
the pump tubing loop, and therefore permit fluid flow through the
pump tubing loop. .circle-solid. indicates a closed, pump off
condition, during which the pump rotors are not rotating, and in
which the pump rotors do engage with pump tubing loop, and
therefore do not permit fluid flow through the pump tubing
loop.
[0261] The clean up phase 246 returns any residual MNC present in
the second transition region 118 (see FIG. 28) after
TC.sub.2=T.sub.2 (and therefore not part of VOL.sub.SEN), back to
the processing compartment 38 for further collection in a
subsequent processing cycle.
[0262] In the clean up phase 246, the controller 222 closes all
valve stations in the left and middle cassettes 23L and 23M and
configures the right pump station PSR to circulated PRBC from
tubing T10 back into the processing compartment 38 through tubings
T11 and T4. During this period, no components are being drawn from
or returned to the donor/patient.
[0263] At the end of the clean up phase 246, the controller 222
commences a new main processing cycle 230. The controller 222
repeats a series of main processing cycles 230 until the desired
volume of MNC targeted for the entire procedure is reached.
[0264] At the end of the last main processing cycle 230, the
operator may desire additional VOL.sub.SUS to further dilute the
MNC collected during the procedure. In this circumstance, the
controller 222 can be commanded to configure the fluid circuit 200
to carry out a preliminary processing cycle 228, as above
described, to collect additional VOL.sub.SUS in the container PPP.
The controller 222 then configures the fluid circuit 200 to carry
out an MNC suspension phase 244, to convey additional VOL.sub.SUS
into the container MNC to achieve the desired dilution of
VOL.sub.MNC.
[0265] IV. Alternative Mononuclear Cell Processing Procedure
[0266] FIG. 29 shows an alternative embodiment of a fluid circuit
300, which is suited for collecting and harvesting MNC. The circuit
300 is in most respects the same as the circuit 200, shown in FIG.
6, and common components are given the same reference numbers.
[0267] The circuit 300 differs from the circuit 200 in that the
second compartment 310 of the container 14 is identical to the
compartment 38, and thereby itself comprises a second blood
processing compartment with the same features as compartment 38.
The compartment 310 includes interior seals, as shown for
compartment 38 in FIG. 4, creating the same blood collection
regions for PRP and PRBC, the details of which are not shown in
FIG. 29. The compartment 310 includes a port 304 for conveying
whole blood into the compartment 310, a port 306 for conveying PRP
from the compartment 310, and a port 302 for conveying PRBC from
the compartment 310. Compartment 310 also includes a tapered ramp
84, as shown in FIGS. 16A and 16B and as earlier described in
connection with the compartment 38.
[0268] The fluid circuit 300 also differs from the fluid circuit
200 in that tubings T14, T18, and T19 are not included. In
addition, the container PRBC is not included. Instead, fluid
circuit 300 includes several new tubing paths and clamps, as
follows:
[0269] Tubing path T21 leads from the PRP outlet port 306 of the
compartment 310 through a new clamp C5 to join tubing path T10.
[0270] Tubing path T22 leads from the WB inlet port 306 of the
compartment 310 through a new air detector D3 and a new clamp C6 to
join tubing path T3.
[0271] Tubing path T33 leads from the PRBC outlet port 302 of the
compartment 310 through a new clamp C8 to join tubing T4.
[0272] New clamp C7 is also provided in tubing T3 upstream of the
air detector D1.
[0273] New clamp C9 is also provided in tubing T10 between the
optical sensor OS and the junction of new tubing T21.
[0274] Using circuit 300, the controller 222 proceeds through the
previous described priming cycle 226, preliminary processing cycle
228, and main processing cycle 230 as previously described for
circuit 200, up through the MNC accumulation phase 236. The PRBC
collect phase 238 differs when using the circuit 300, in that PRBC
used for subsequent removal of MNC from the compartment 38 are
processed and collected in the second compartment 310.
[0275] More particularly, as shown in FIG. 30, during the PRBC
collection phase 238, the controller 222 conveys a volume of whole
blood from the donor/patient into the second compartment 310. The
whole blood volume is drawn by pump P2 through tubing T1 into
tubing T3 and thence through open clamp C6 into tubing T22, which
leads to the compartment 310. Clamp C7 is closed, to block
conveyance of whole blood into the compartment 38, where the MNC
have been accumulated for harvesting. Clamp C9 is also closed to
block conveyance of PRP from the compartment 38, thereby keeping
the accumulation of MNC undisturbed in the compartment 38.
[0276] In the compartment 310, the whole blood volume is separated
into PRBC and PRP, in the same fashion that these components are
separated in the compartment 38. PRP is conveyed from the
compartment 310 through tubing T23 and open clamp C5 by operation
of the pump P5, for return to the donor/patient. The clamp C8 is
closed, to retain PRBC in the compartment 310.
[0277] The controller 222 also conducts a different MNC removal
phase 240 using circuit 300. As shown in FIG. 31, during the MNC
removal phase 240, the controller 222 recirculates a portion of the
drawn whole blood back to the donor/patient, while directing
another portion of the whole blood into the compartment 310,
following the same path as previously described in connection with
FIG. 30. The controller 222 opens clamps C8 and C9, while closing
clamp CS. The whole blood entering the compartment 310 displaces
PRBC through the PRBC outlet port 302 into tubing T23. The PRBC
from the compartment 310 enters the WB inlet port 48 of the
compartment 38. As before described, the incoming flow of PRBC from
outside the compartment 38 increases the hematocrit of PRBC within
the compartment 38, causing the accumulated MNC to float to the
interface 58. As before described, the incoming PRBC from outside
the compartment 38 displaces PRP through the PRP port 46, together
with the MNC Region, shown in FIG. 31. This MNC Region is detected
by the optical sensor OS and harvested in subsequent processing
242, 244, and 246 in the same fashion as described for circuit
200.
[0278] Various features of the inventions are set forth in the
following claims.
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