U.S. patent application number 10/156496 was filed with the patent office on 2003-04-17 for systems and methods for sensing red blood cell hematocrit.
This patent application is currently assigned to Baxter International Inc.. Invention is credited to Joie, Michel L.F., Muller, Matthew R., Vandlik, Mark R..
Application Number | 20030070969 10/156496 |
Document ID | / |
Family ID | 23538532 |
Filed Date | 2003-04-17 |
United States Patent
Application |
20030070969 |
Kind Code |
A1 |
Muller, Matthew R. ; et
al. |
April 17, 2003 |
Systems and methods for sensing red blood cell hematocrit
Abstract
Red blood cell sensing systems and methods rely upon
straightforward measurement geometries. the systems and methods
comprise an incident light source, an optical sensor, and a blood
collection tube. The systems and methods hold the blood collection
tube a predetermined radial distance from the incident light source
where a linear relationship exists between sensed reflected light
measured by the optical sensor and red blood cell hematocrit in a
range of at least 10 to 90. The systems and methods make possible
accurate red blood sensing without use of special optical cuvettes,
mirrors, or focusing lenses. The systems and methods also make
possible the use of standard transparent plastic tubing, without
reliance upon special optical cuvettes.
Inventors: |
Muller, Matthew R.;
(Lindenhurst, IL) ; Joie, Michel L.F.; (Ernage,
BE) ; Vandlik, Mark R.; (Mundelein, 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: |
23538532 |
Appl. No.: |
10/156496 |
Filed: |
May 28, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10156496 |
May 28, 2002 |
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09901986 |
Jul 10, 2001 |
|
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6419822 |
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09901986 |
Jul 10, 2001 |
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09389506 |
Sep 3, 1999 |
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6294094 |
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Current U.S.
Class: |
210/91 ; 210/143;
210/541; 210/94; 604/410 |
Current CPC
Class: |
B01D 21/245 20130101;
B01D 17/0217 20130101; A61M 1/3696 20140204; A61M 1/367 20130101;
A61M 2205/3393 20130101; A61M 1/0236 20140204; A61M 1/38 20130101;
B01D 21/302 20130101; A61M 2205/128 20130101; B01D 2221/08
20130101; A61M 2230/207 20130101; B01D 21/2444 20130101; B01D
21/262 20130101; B01D 21/34 20130101; B01D 21/26 20130101; B01D
2221/10 20130101; B01D 21/2444 20130101; B01D 21/245 20130101; B01D
21/26 20130101 |
Class at
Publication: |
210/91 ; 210/94;
210/143; 604/410; 210/541 |
International
Class: |
B01D 017/12 |
Claims
We claim:
1. A blood processing system comprising a separation chamber for
processing blood to obtain a blood suspension containing a quantity
of red blood cells, a sensing assembly outside the separation
chamber to optically sense presence of red blood cells, and a fluid
circuit including an umbilicus coupled to the separation chamber, a
blood inlet tube extending beyond the umbilicus outside the
separation chamber for conveying a flow of blood into the
umbilicus, a component collection tube extending beyond the
umbilicus outside the separation chamber for conveying a flow of
the blood suspension from the umbilicus, and a fixture including a
holder to hold the blood inlet tube and the component collection
tube in an adjacent, spaced-apart relationship for handling as a
bundle outside the separation chamber, the fixture being movable
into releasable engagement with the sensing assembly outside the
separation chamber to hold the component collection tube within the
holder in a predetermined relationship with the sensing assembly so
that presence of red blood cells in the component collection tube
can be sensed.
2. A blood processing system according to claim 1 wherein the
fixture directs the blood inlet tube and the component collection
tube through a bend without substantial kinking.
3. A blood processing system according to claim 1 further including
a controller communicating with the sensing assembly to control
flow of blood suspension through the component collection tube in
response to sensing by the sensing assembly.
4. A blood processing system comprising a separation chamber for
processing blood to obtain first and second blood suspensions, a
sensing station outside the separation chamber including a first
sensor assembly that operates to optically monitor presence of at
least one blood component in the first blood suspension, and a
second sensor assembly that operates to optically monitor presence
of at least one blood component in the second blood suspension, a
fluid circuit including an umbilicus coupled to the separation
chamber, a blood inlet tube extending beyond the umbilicus outside
the separation chamber for conveying a flow of blood into the
umbilicus, a first component collection tube extending beyond the
umbilicus outside the separation chamber for conveying a flow of
the first component from the umbilicus, and a second component
collection tube extending beyond the umbilicus outside the
separation chamber for conveying a flow of the second component
from the separation chamber, and a fixture including a holder to
hold the first component collection tube and the second component
collection tube in an adjacent, spaced-apart relationship for
handling as a bundle outside the separation chamber, the fixture
being movable into releasable engagement with the sensing station
to hold the first component collection tube and the second
component collection tube within the holder in predetermined
relationships with the first sensor assembly and the second sensor
assembly, respectively, so that so that presence of blood
components in the respective first and second component collection
tubes can be sensed.
5. A blood processing system according to claim 4 wherein the
fixture directs the first and second component collection tubes
through a bend without substantial kinking.
6. A blood processing system according to claim 4 wherein the
holder holds the blood inlet tube for handling as a bundle outside
the separation chamber with the first and second component
collection tubes.
7. A blood processing system according to claim 4 further including
a controller communicating with the first and second sensing
assemblies to affect flow of first and second blood suspensions
through the first and second component collection tubes in response
to sensing by the first and second sensing assemblies.
8. A blood processing system according to claim 1 or 4 wherein the
fixture comprises an integral part of the fluid circuit.
9. A blood processing system according to claim 1 or 4 wherein the
fixture is a separately fabricated part of the fluid circuit.
Description
RELATED APPLICATIONS
[0001] This application is a division of co-pending application
Ser. No. 09/901,986 filed Jul. 10, 2001, which is a continuation of
application Ser. No. 09/389,506 filed Sep. 3, 1999.
FIELD OF THE INVENTION
[0002] This invention relates to systems and methods for processing
and collecting blood, blood constituents, or other suspensions of
cellular material.
BACKGROUND OF THE INVENTION
[0003] Today people routinely separate whole blood, usually by
centrifugation, into its various therapeutic components, such as
red blood cells, platelets, and plasma.
[0004] Conventional blood processing methods use durable centrifuge
equipment in association with single use, sterile processing
systems, typically made of plastic. The operator loads the
disposable systems upon the centrifuge before processing and
removes them afterwards.
[0005] Conventional blood centrifuges are of a size that does not
permit easy transport between collection sites. Furthermore,
loading and unloading operations can sometimes be time consuming
and tedious.
[0006] In addition, a need exists for further improved systems and
methods for collecting blood components in a way that lends itself
to use in high volume, on line blood collection environments, where
higher yields of critically needed cellular blood components, like
plasma, red blood cells, and platelets, can be realized in
reasonable short processing times.
[0007] The operational and performance demands upon such fluid
processing systems become more complex and sophisticated, even as
the demand for smaller and more portable systems intensifies. The
need therefore exists for automated blood processing controllers
that can gather and generate more detailed information and control
signals to aid the operator in maximizing processing and separation
efficiencies.
SUMMARY OF THE INVENTION
[0008] The invention provides systems and methods for processing
blood and blood constituents that lend themselves to portable,
flexible processing platforms equipped with straightforward and
accurate control functions.
[0009] More particularly, the invention provides red blood cell
sensing systems and methods that rely upon straightforward
measurement geometries. The systems and methods make possible
accurate red blood sensing without use of special optical cuvettes,
mirrors, or focusing lenses. The systems and methods also make
possible the use of standard transparent plastic tubing, without
reliance upon special optical cuvettes.
[0010] According to one aspect of the invention, the systems and
methods comprise an incident light source, an optical sensor, and a
blood collection tube. The systems and methods hold the blood
collection tube a predetermined radial distance from the incident
light source where a linear relationship exists between sensed
reflected light measured by the optical sensor and red blood cell
hematocrit in a range of at least 10 to 90.
[0011] In one embodiment, the light source has a wavelength of
about 805 nm, and the predetermined radial distance is about 7.5 mm
from the light source.
[0012] According to another aspect of the invention, the systems
and methods are used in association with a device for separating
whole blood into red blood cells and plasma. In this arrangement,
the systems and methods include a sensing assembly outside the
device, which includes an incident light source and an optical
sensor to sense red blood cells. A fluid circuit coupled to the
device includes a component collection tube for conveying a flow of
plasma or red blood cells from the device. The systems and methods
include a fixture that is movable into releasable engagement with
the sensing assembly. The fixture includes a holder to hold the
component collection tube a predetermined radial distance from the
incident light source where a linear relationship exists between
sensed reflected light measured by the optical sensor and red blood
cell hematocrit in a range of at least 10 to 90.
[0013] In one embodiment, the fluid circuit includes a whole blood
inlet tube for conveying a flow of whole blood into the device. In
this embodiment, the holder also holds the whole blood inlet tube,
so that the fixture serves to gather and hold the whole blood inlet
tube and the component collection tube in a bundle.
[0014] In one embodiment, the component collection tube comprises
transparent flexible tubing that interfaces directly with the
sensing assembly and is free of an optical cuvette. The collection
tube can covey red blood cells or plasma from the separation
device.
[0015] Other features and advantages of the inventions are set
forth in the following specification and attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is a perspective view of a system that embodies
features of the invention, with the disposable processing set shown
out of association with the processing device prior to use;
[0017] FIG. 2 is a perspective view of the system shown in FIG. 1,
with the doors to the centrifuge station and pump and valve station
being shown open to accommodate mounting of the processing set;
[0018] FIG. 3 is a perspective view of the system shown in FIG. 1
with the processing set fully mounted on the processing device and
ready for use;
[0019] FIG. 4 is a right perspective front view of the case that
houses the processing device shown in FIG. 1, with the lid closed
for transporting the device;
[0020] FIG. 5 is a schematic view of a blood processing circuit,
which can be programmed to perform a variety of different blood
processing procedures in association with the device shown in FIG.
1;
[0021] FIG. 6 is an exploded perspective view of a cassette, which
contains the programmable blood processing circuit shown in FIG. 5,
and the pump and valve station on the processing device shown in
FIG. 1, which receives the cassette for use;
[0022] FIG. 7 is a plane view of the front side of the cassette
shown in FIG. 6;
[0023] FIG. 8 is an enlarged perspective view of a valve station on
the cassette shown in FIG. 6;
[0024] FIG. 9 is a plane view of the back side of the cassette
shown in FIG. 6;
[0025] FIG. 10 is a plane view of a universal processing set, which
incorporates the cassette shown in FIG. 6, and which can be mounted
on the device shown in FIG. 1, as shown in FIGS. 2 and 3;
[0026] FIG. 11 is a top section view of the pump and valve station
in which the cassette as shown in FIG. 6 is carried for use;
[0027] FIG. 12 is a schematic view of a pneumatic manifold
assembly, which is part of the pump and valve station shown in FIG.
6, and which supplies positive and negative pneumatic pressures to
convey fluid through the cassette shown in FIGS. 7 and 9;
[0028] FIG. 13 is a perspective front view of the case that houses
the processing device, with the lid open for use of the device, and
showing the location of various processing elements housed within
the case;
[0029] FIG. 14 is a schematic view of the controller that carries
out the process control and monitoring functions of the device
shown in FIG. 1;
[0030] FIG. 15A, 15B, and 15C are schematic side view of the blood
separation chamber that the device shown in FIG. 1 incorporates,
showing the plasma and red blood cell collection tubes and the
associated two in-line sensors, which detect a normal operating
condition (FIG. 15A), an over spill condition (FIG. 15B), and an
under spill condition (FIG. 15C);
[0031] FIG. 16 is a perspective view of a fixture that, when
coupled to the plasma and red blood cell collection tubes hold the
tubes in a desired viewing alignment with the in-line sensors, as
shown in FIGS. 15A, 15B, and 15C;
[0032] FIG. 17 is a perspective view of the fixture shown in FIG.
16, with a plasma cell collection tube, a red blood cell collection
tube, and a whole blood inlet tube attached, gathering the tubes in
an organized, side-by-side array;
[0033] FIG. 18 is a perspective view of the fixture and tubes shown
in FIG. 17, as being placed into viewing alignment with the two
sensors shown in FIGS. 15A, 15B, and 15C;
[0034] FIG. 19 is a schematic view of the sensing station, of which
the first and second sensors shown in FIGS. 15A, 15B, and 15C form
a part;
[0035] FIG. 20 is a graph of optical densities as sensed by the
first and second sensors plotted over time, showing an under spill
condition;
[0036] FIG. 21 is an exploded top perspective view of the of a
molded centrifugal blood processing container, which can be used in
association with the device shown in FIG. 1;
[0037] FIG. 22 is a bottom perspective view of the molded
processing container shown in FIG. 21;
[0038] FIG. 23 is a top view of the molded processing container
shown in FIG. 21;
[0039] FIG. 24 is a side section view of the molded processing
container shown in FIG. 21, showing an umbilicus to be connected
the container;
[0040] FIG. 24A is a top view of the connector that connects the
umbilicus to the molded processing container in the manner shown in
FIG. 24, taken generally along line 24A-24A in FIG. 24;
[0041] FIG. 25 is a side section view of the molded processing
container shown in FIG. 24, after connection of the umbilicus to
container;
[0042] FIG. 26 is an exploded, perspective view of the centrifuge
station of the processing device shown in FIG. 1, with the
processing container mounted for use;
[0043] FIG. 27 is a further exploded, perspective view of the
centrifuge station and processing container shown in FIG. 26;
[0044] FIG. 28 is a side section view of the centrifuge station of
the processing device shown in FIG. 26, with the processing
container mounted for use;
[0045] FIG. 29 is a top view of a molded centrifugal blood
processing container as shown in FIGS. 21 to 23, showing a flow
path arrangement for separating whole blood into plasma and red
blood cells;
[0046] FIGS. 31 to 33 are top views of molded centrifugal blood
processing containers as shown in FIGS. 21 to 23, showing other
flow path arrangements for separating whole blood into plasma and
red blood cells;
[0047] FIG. 34 is a schematic view of another blood processing
circuit, which can be programmed to perform a variety of different
blood processing procedures in association with the device shown in
FIG. 1;
[0048] FIG. 35 is plane view of the front side of a cassette, which
contains the programmable blood processing circuit shown in FIG.
34;
[0049] FIG. 36 is a plane view of the back side of the cassette
shown in FIG. 35;
[0050] FIGS. 37A to 37E are schematic views of the blood processing
circuit shown in FIG. 34, showing the programming of the cassette
to carry out different fluid flow tasks in connection with
processing whole blood into plasma and red blood cells;
[0051] FIGS. 38A and 38B are schematic views of the blood
processing circuit shown in FIG. 34, showing the programming of the
cassette to carry out fluid flow tasks in connection with on-line
transfer of an additive solution into red blood cells separated
from whole blood;
[0052] FIGS. 39A and 39B are schematic views of the blood
processing circuit shown in FIG. 34, showing the programming of the
cassette to carry out fluid flow tasks in connection with on-line
transfer of red blood cells separated from whole blood through a
filter to remove leukocytes;
[0053] FIG. 40 is a representative embodiment of a weigh scale
suited for use in association with the device shown in FIG. 1;
[0054] FIG. 41 is a representative embodiment of another weigh
suited for use in association with the device shown in FIG. 1;
[0055] FIG. 42 is a schematic view of flow rate sensing and control
system for a pneumatic pump chamber employing an electrode to
create an electrical field inside the pump chamber; and
[0056] FIG. 43 is a schematic view of a pneumatic manifold
assembly, which is part of the pump and valve station shown in FIG.
6, and which supplies positive and negative pneumatic pressures to
convey fluid through the cassette shown in FIGS. 35 and 36.
[0057] 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
[0058] FIG. 1 shows a fluid processing system 10 that embodies the
features of the invention. The system 10 can be used for processing
various fluids. The system 10 is particularly well suited for
processing whole blood and other suspensions of biological cellular
materials. Accordingly, the illustrated embodiment shows the system
10 used for this purpose.
[0059] I. System Overview
[0060] The system 10 includes three principal components. These are
(i) a liquid and blood flow set 12; (ii) a blood processing device
14 that interacts with the flow set 12 to cause separation and
collection of one or more blood components; and (iii) a controller
16 that governs the interaction to perform a blood processing and
collection procedure selected by the operator.
[0061] The blood processing device 14 and controller 16 are
intended to be durable items capable of long term use. In the
illustrated and preferred embodiment, the blood processing device
14 and controller 16 are mounted inside a portable housing or case
36. The case 36 presents a compact footprint, suited for set up and
operation upon a table top or other relatively small surface. The
case 36 is also intended to be transported easily to a collection
site.
[0062] The case 36 includes a base 38 and a hinged lid 40, which
opens (as FIG. 1 shows) and closes (as FIG. 4 shows). The lid 40
includes a latch 42, for releasably locking the lid 40 closed. The
lid 40 also includes a handle 44, which the operator can grasp for
transporting the case 36 when the lid 40 is closed. In use, the
base 38 is intended to rest in a generally horizontal support
surface.
[0063] The case 36 can be formed into a desired configuration,
e.g., by molding. The case 36 is preferably made from a
lightweight, yet durable, plastic material.
[0064] The flow set 12 is intended to be a sterile, single use,
disposable item. As FIG. 2 shows, before beginning a given blood
processing and collection procedure, the operator loads various
components of the flow set 12 in the case 36 in association with
the device 14. The controller 16 implements the procedure based
upon preset protocols, taking into account other input from the
operator. Upon completing the procedure, the operator removes the
flow set 12 from association with the device 14. The portion of the
set 12 holding the collected blood component or components are
removed from the case 36 and retained for storage, transfusion, or
further processing. The remainder of the set 12 is removed from the
case 36 and discarded.
[0065] The flow set 12 shown in FIG. 1 includes a blood processing
chamber 18 designed for use in association with a centrifuge.
Accordingly, as FIG. 2 shows, the processing device 14 includes a
centrifuge station 20, which receives the processing chamber 18 for
use. As FIGS. 2 and 3 show, the centrifuge station 20 comprises a
compartment formed in the base 38. The centrifuge station 20
includes a door 22, which opens and closes the compartment. The
door 22 opens to allow loading of the processing chamber 18. The
door 22 closes to enclose the processing chamber 18 during
operation.
[0066] The centrifuge station 20 rotates the processing chamber 18.
When rotated, the processing chamber 18 centrifugally separates
whole blood received from a donor into component parts, e.g., red
blood cells, plasma, and buffy coat comprising platelets and
leukocytes.
[0067] It should also be appreciated that the system 10 need not
separate blood centrifugally. The system 10 can accommodate other
types of blood separation devices, e.g., a membrane blood
separation device.
[0068] II. The Programmable Blood Processing Circuit
[0069] The set 12 defines a programmable blood processing circuit
46. Various configurations are possible. FIG. 5 schematically shows
one representative configuration. FIG. 34 schematically shows
another representative configuration, which will be described
later.
[0070] Referring to FIG. 5, the circuit 46 can be programmed to
perform a variety of different blood processing procedures in
which, e.g., red blood cells are collected, or plasma is collected,
or both plasma and red blood cells are collected, or the buffy coat
is collected.
[0071] The circuit 46 includes several pump stations PP(N), which
are interconnected by a pattern of fluid flow paths F(N) through an
array of in line valves V(N). The circuit is coupled to the
remainder of the blood processing set by ports P(N).
[0072] The circuit 46 includes a programmable network of flow
paths, comprising eleven universal ports P1 to P8 and P11 to P13
and three universal pump stations PP1, PP2, and PP3. By selective
operation of the in line valves V1 to V14, V16 to V18, and V21 to
23, any universal port P1 to P8 and P11 to P13 can be placed in
flow communication with any universal pump station PP1, PP2, and
PP3. By selective operation of the universal valves, fluid flow can
be directed through any universal pump station in a forward
direction or reverse direction between two valves, or an in-out
direction through a single valve.
[0073] In the illustrated embodiment, the circuit also includes an
isolated flow path comprising two ports P9 and P10 and one pump
station PP4. The flow path is termed "isolated," because it cannot
be placed into direct flow communication with any other flow path
in the circuit 46 without exterior tubing. By selective operation
of the in line valves V15, V19, and V20, fluid flow can be directed
through the pump station in a forward direction or reverse
direction between two valves, or an in-out direction through a
single valve.
[0074] The circuit 46 can be programmed to assigned dedicated
pumping functions to the various pump stations. For example, in a
preferred embodiment, the universal pump station PP3 can serve as a
general purpose, donor interface pump, regardless of the particular
blood procedure performed, to either draw blood from the donor or
return blood to the donor through the port P8. In this arrangement,
the pump station PP4 can serve as a dedicated anticoagulant pump,
to draw anticoagulant from a source through the port P10 and to
meter anticoagulant into the blood through port P9.
[0075] In this arrangement, the universal pump station PP1 can
serve, regardless of the particular blood processing procedure
performed, as a dedicated in-process whole blood pump, to convey
whole blood into the blood separator. This dedicated function frees
the donor interface pump PP3 from the added function of supplying
whole blood to the blood separator. Thus, the in-process whole
blood pump PP1 can maintain a continuous supply of blood to the
blood separator, while the donor interface pump PP3 is
simultaneously used to draw and return blood to the donor through
the single phlebotomy needle. Processing time is thereby
minimized.
[0076] In this arrangement, the universal pump station PP2 can
serve, regardless of the particular blood processing procedure
performed, as a plasma pump, to convey plasma from the blood
separator. The ability to dedicate separate pumping functions
provides a continuous flow of blood into and out of the separator,
as well as to and from the donor.
[0077] The circuit 46 can be programmed, depending upon the
objectives of the particular blood processing procedure, to retain
all or some of the plasma for storage or fractionation purposes, or
to return all or some of the plasma to the donor. The circuit 46
can be further programmed, depending upon the objectives of the
particular blood processing procedure, to retain all or some of the
red blood cells for storage, or to return all or some of the red
blood cells to the donor. The circuit 46 can also be programmed,
depending upon the objectives of the particular blood processing
procedure, to retain all or some of the buffy coat for storage, or
to return all or some of the buffy coat to the donor.
[0078] In a preferred embodiment, the programmable fluid circuit 46
is implemented by use of a fluid pressure actuated cassette 28 (see
FIG. 6). The cassette 28 provides a centralized, programmable,
integrated platform for all the pumping and valving functions
required for a given blood processing procedure. In the illustrated
embodiment, the fluid pressure comprising positive and negative
pneumatic pressure. Other types of fluid pressure can be used.
[0079] As FIG. 6 shows, the cassette 28 interacts with a pneumatic
actuated pump and valve station 30, which is mounted in the lid of
the 40 of the case 36 (see FIG. 1). The cassette 28 is, in use,
mounted in the pump and valve station 30. The pump and valve
station 30 apply positive and negative pneumatic pressure upon the
cassette 28 to direct liquid flow through the circuit. Further
details will be provided later.
[0080] The cassette 28 can take various forms. As illustrated (see
FIG. 6), the cassette 28 comprises an injection molded body 188
having a front side 190 and a back side 192. For the purposes of
description, the front side 190 is the side of the cassette 28
that, when the cassette 28 is mounted in the pump and valve station
30, faces away from the operator. Flexible diaphragms 194 and 196
overlay both the front side 190 and back sides 192 of the cassette
28, respectively.
[0081] The cassette body 188 is preferably made of a rigid medical
grade plastic material. The diaphragms 194 and 196 are preferably
made of flexible sheets of medical grade plastic. The diaphragms
194 and 196 are sealed about their peripheries to the peripheral
edges of the front and back sides of the cassette body 188.
Interior regions of the diaphragms 194 and 196 can also be sealed
to interior regions of the cassette body 188.
[0082] The cassette body 188 has an array of interior cavities
formed on both the front and back sides 190 and 192 (see FIGS. 7
and 9). The interior cavities define the valve stations and flow
paths shown schematically in FIG. 5. An additional interior cavity
is provided in the back side of the cassette 28 to form a station
that holds a filter material 200. In the illustrated embodiment,
the filter material 200 comprises an overmolded mesh filter
construction. The filter material 200 is intended, during use, to
remove clots and cellular aggregations that can form during blood
processing.
[0083] The pump stations PP1 to PP4 are formed as wells that are
open on the front side 190 of the cassette body 188. Upstanding
edges peripherally surround the open wells of the pump stations.
The pump wells are closed on the back side 192 of the cassette body
188, except for a spaced pair of through holes or ports 202 and 204
for each pump station. The ports 202 and 204 extend through to the
back side 192 of the cassette body 188. As will become apparent,
either port 202 or 204 can serve its associated pump station as an
inlet or an outlet, or both inlet and outlet.
[0084] The in line valves V1 to V23 are likewise formed as wells
that are open on the front side 190 of the cassette. FIG. 8 shows a
typical valve V(N). Upstanding edges peripherally surround the open
wells of the valves on the front side 190 of the cassette body 188.
The valves are closed on the back side 192 of the cassette 28,
except that each valve includes a pair of through holes or ports
206 and 208. One port 206 communicates with a selected liquid path
on the back side 192 of the cassette body 188. The other port 208
communicates with another selected liquid path on the back side 192
of the cassette body 188.
[0085] In each valve, a valve seat 210 extends about one of the
ports 208. The valve seat 210 is recessed below the surface of the
recessed valve well, such that the port 208 is essentially flush
with the surrounding surface of recessed valve well, and the valve
seat 210 extends below than the surface of the valve well.
[0086] The flexible diaphragm 194 overlying the front side 190 of
the cassette 28 rests against the upstanding peripheral edges
surrounding the pump stations and valves. With the application of
positive force uniformly against this side of the cassette body
188, the flexible diaphragm 194 seats against the upstanding edges.
The positive force forms peripheral seals about the pump stations
and valves. This, in turn, isolates the pumps and valves from each
other and the rest of the system. The pump and valve station 30
applies positive force to the front side 190 of the cassette body
188 for this purpose.
[0087] Further localized application of positive and negative fluid
pressures upon the regions of the diaphragm 194 overlying these
peripherally sealed areas serve to flex the diaphragm regions in
these peripherally sealed areas. These localized applications of
positive and negative fluid pressures on these diaphragm regions
overlying the pump stations serve to expel liquid out of the pump
stations (with application of positive pressure) and draw liquid
into the pump stations (with application of negative pressure).
[0088] In the illustrated embodiment, the bottom of each pump
station PP1 to PP4 includes a recessed race 316 (see FIG. 7). The
race 316 extends between the ports 202 and 204, and also includes a
dogleg extending at an angle from the top port 202. The race 316
provides better liquid flow continuity between the ports 202 and
204, particularly when the diaphragm region is forced by positive
pressure against the bottom of the pump station. The race 316 also
prevents the diaphragm region from trapping air within the pump
station. Air within the pump station is forced into the race 316,
where it can be readily venting through the top port 202 out of the
pump station, even if the diaphragm region is bottomed out in the
station.
[0089] Likewise, localized applications of positive and negative
fluid pressure on the diaphragm regions overlying the valves will
serve to seat (with application of positive pressure) and unseat
(with application of negative pressure) these diaphragm regions
against the valve seats, thereby closing and opening the associated
valve port. The flexible diaphragm is responsive to an applied
negative pressure for flexure out of the valve seat 210 to open the
respective port. The flexible diaphragm is responsive to an applied
positive pressure for flexure into the valve seat 210 to close the
respective port. Sealing is accomplished by forcing the flexible
diaphragm to flex into the recessed valve seat 210, to seal about
the port 208, which is flush with wall of the valve well. The
flexible diaphragm forms within the recessed valve seat 210 a
peripheral seal about the valve port 208.
[0090] In operation, the pump and valve station 30 applies
localized positive and negative fluid pressures to these regions of
front diaphragm 104 for opening and closing the valve ports.
[0091] The liquid paths F1 to F38 are formed as elongated channels
that are open on the back side 192 of the cassette body 188, except
for the liquid paths F15, F23, and F24 are formed as elongated
channels that are open on the front side 190 of the cassette body
188. The liquid paths are shaded in FIG. 9 to facilitate their
viewing. Upstanding edges peripherally surround the open channels
on the front and back sides 190 and 192 of the cassette body
188.
[0092] The liquid paths F1 to F38 are closed on the front side 190
of the cassette body 188, except where the channels cross over
valve station ports or pump station ports. Likewise, the liquid
paths F31 to F38 are closed on the back side 192 of the cassette
body 188, except where the channels cross over in-line ports
communicating with certain channels on the back side 192 of the
cassette 28.
[0093] The flexible diaphragms 194 and 196 overlying the front and
back sides 190 and 192 of the cassette body 188 rest against the
upstanding peripheral edges surrounding the liquid paths F1 to F38.
With the application of positive force uniformly against the front
and back sides 190 and 192 of the cassette body 188, the flexible
diaphragms 194 and 196 seat against the upstanding edges. This
forms peripheral seals along the liquid paths F1 to F38. In
operation, the pump and valve station 30 applies positive force to
the diaphragms 194 and 196 for this purpose.
[0094] The pre-molded ports P1 to P13 extend out along two side
edges of the cassette body 188. The cassette 28 is vertically
mounted for use in the pump and valve station 30 (see FIG. 2). In
this orientation, the ports P8 to P13 face downward, and the ports
P1 to P7 are vertically stacked one above the other and face
inward.
[0095] As FIG. 2 shows, the ports P8 to P13, by facing downward,
are oriented with container support trays 212 formed in the base
38, as will be described later. The ports P1 to P7, facing inward,
are oriented with the centrifuge station 20 and a container weigh
station 214, as will also be described in greater detail later. The
orientation of the ports P5 to P7 (which serve the processing
chamber 18) below the ports P1 to P4 keeps air from entering the
processing chamber 18.
[0096] This ordered orientation of the ports provides a
centralized, compact unit aligned with the operative regions of the
case 36.
[0097] B. The Universal Set
[0098] FIG. 10 schematically shows a universal set 264, which, by
selective programming of the blood processing circuit 46
implemented by cassette 28, is capable of performing several
different blood processing procedures.
[0099] The universal set 264 includes a donor tube 266, which is
attached (through y-connectors 272 and 273) to tubing 300 having an
attached phlebotomy needle 268. The donor tube 266 is coupled to
the port P8 of the cassette 28.
[0100] A container 275 for collecting an in-line sample of blood
drawn through the tube 300 is also attached through the y-connector
273.
[0101] An anticoagulant tube 270 is coupled to the phlebotomy
needle 268 via the y-connector 272. The anticoagulant tube 270 is
coupled to cassette port P9. A container 276 holding anticoagulant
is coupled via a tube 274 to the cassette port P10. The
anticoagulant tube 270 carries an external, manually operated in
line clamp 282 of conventional construction.
[0102] A container 280 holding a red blood cell additive solution
is coupled via a tube 278 to the cassette port P3. The tube 278
also carries an external, manually operated in line clamp 282.
[0103] A container 288 holding saline is coupled via a tube 284 to
the cassette port P12.
[0104] FIG. 10 shows the fluid holding containers 276, 280, and 288
as being integrally attached during manufacture of the set 264.
Alternatively, all or some of the containers 276, 280, and 288 can
be supplied separate from the set 264. The containers 276, 280, and
288 may be coupled by conventional spike connectors, or the set 264
may be configured to accommodate the attachment of the separate
container or containers at the time of use through a suitable
sterile connection, to thereby maintain a sterile, closed blood
processing environment. Alternatively, the tubes 274, 278, and 284
can carry an in-line sterilizing filter and a conventional spike
connector for insertion into a container port at time of use, to
thereby maintain a sterile, closed blood processing
environment.
[0105] The set 264 further includes tubes 290, 292, 294, which
extend to an umbilicus 296. When installed in the processing
station, the umbilicus 296 links the rotating processing chamber 18
with the cassette 28 without need for rotating seals. Further
details of this construction will be provided later.
[0106] The tubes 290, 292, and 294 are coupled, respectively, to
the cassette ports P5, P6, and P7. The tube 290 conveys whole blood
into the processing chamber 18. The tube 292 conveys plasma from
the processing chamber 18. The tube 294 conveys red blood cells
from processing chamber 18.
[0107] A plasma collection container 304 is coupled by a tube 302
to the cassette port P3. The collection container 304 is intended,
in use, to serve as a reservoir for plasma during processing.
[0108] A red blood cell collection container 308 is coupled by a
tube 306 to the cassette port P2. The collection container 308 is
intended, in use, to receive a first unit of red blood cells for
storage.
[0109] A whole blood reservoir 312 is coupled by a tube 310 to the
cassette port P1. The collection container 312 is intended, in use,
to serve as a reservoir for whole blood during processing. It can
also serve to receive a second unit of red blood cells for
storage.
[0110] As shown in FIG. 10, no tubing is coupled to the utility
cassette port P13 and buffy port P4.
[0111] C. The Pump and Valve Station
[0112] The pump and valve station 30 includes a cassette holder
216. The door 32 is hinged to move with respect to the cassette
holder 216 between the opened position, exposing the cassette
holder 216 (shown in FIG. 6) and the closed position, covering the
cassette holder 216 (shown in FIG. 3). The door 32 also includes an
over center latch 218 with a latch handle 220. When the door 32 is
closed, the latch 218 swings into engagement with the latch pin
222.
[0113] As FIG. 11 shows, the inside face of the door 32 carries an
elastomeric gasket 224. The gasket 224 contacts the back side 192
of the cassette 28 when the door 32 is closed. An inflatable
bladder 314 underlies the gasket 224. With the door 32 opened (see
FIG. 2), the operator can place the cassette 28 into the cassette
holder 216. Closing the door 32 and securing the latch 218 brings
the gasket 224 into facing contact with the diaphragm 196 on the
back side 192 of the cassette 28. Inflating the bladder 314 presses
the gasket 224 into intimate, sealing engagement against the
diaphragm 196. The cassette 28 is thereby secured in a tight,
sealing fit within the cassette holder 216.
[0114] The inflation of the bladder 314 also fully loads the over
center latch 218 against the latch pin 222 with a force that cannot
be overcome by normal manual force against the latch handle 220.
The door 32 is securely locked and cannot be opened when the
bladder 314 is inflated. In this construction, there is no need for
an auxiliary lock-out device or sensor to assure against opening of
the door 32 during blood processing.
[0115] The pump and valve station 30 also includes a manifold
assembly 226 located in the cassette holder 216. The manifold
assembly 226 comprises a molded or machined plastic or metal body.
The front side 194 of the diaphragm is held in intimate engagement
against the manifold assembly 226 when the door 32 is closed and
bladder 314 inflated.
[0116] The manifold assembly 226 is coupled to a pneumatic pressure
source 234, which supplies positive and negative air pressure. The
pneumatic pressure source 234 is carried inside the lid 40 behind
the manifold assembly 226.
[0117] In the illustrated embodiment, the pressure source 234
comprises two compressors C1 and C2. However, one or several
dual-head compressors could be used as well. As FIG. 12 shows, one
compressor C1 supplies negative pressure through the manifold 226
to the cassette 28. The other compressor C2 supplies positive
pressure through the manifold 226 to the cassette 28.
[0118] As FIG. 12 shows, the manifold 226 contains four pump
actuators PA1 to PA4 and twenty-three valve actuators VA1 to VA23.
The pump actuators PA1 to PA4 and the valve actuators VA1 to VA23
are mutually oriented to form a mirror image of the pump stations
PP1 to PP4 and valve stations V1 to V23 on the front side 190 of
the cassette 28.
[0119] As FIG. 22 also shows, each actuator PA1 to PA4 and VA1 to
VA23 includes a port 228. The ports 228 convey positive or negative
pneumatic pressures from the source in a sequence governed by the
controller 16. These positive and negative pressure pulses flex the
front diaphragm 194 to operate the pump chambers PP1 to PP4 and
valve stations V1 to V23 in the cassette 28. This, in turn, moves
blood and processing liquid through the cassette 28.
[0120] The cassette holder 216 preferably includes an integral
elastomeric membrane 232 (see FIG. 6) stretched across the manifold
assembly 226. The membrane 232 serves as the interface between the
piston element 226 and the diaphragm 194 of the cassette 28, when
fitted into the holder 216. The membrane 232 may include one or
more small through holes (not shown) in the regions overlying the
pump and valve actuators PA1 to PA4 and V1 to V23. The holes are
sized to convey pneumatic fluid pressure from the manifold assembly
226 to the cassette diaphragm 194. Still, the holes are small
enough to retard the passage of liquid. The membrane 232 forms a
flexible splash guard across the exposed face of the manifold
assembly 226.
[0121] The splash guard membrane 232 keeps liquid out of the pump
and valve actuators PA1 to PA4 and VA1 to VA23, should the cassette
diaphragm 194 leak. The splash guard membrane 232 also serves as a
filter to keep particulate matter out of the pump and valve
actuators of the manifold assembly 226. The splash guard membrane
232 can be periodically wiped clean when cassettes 28 are
exchanged.
[0122] The manifold assembly 226 includes an array of solenoid
actuated pneumatic valves, which are coupled in-line with the pump
and valve actuators PA1 to PA4 and VA1 to VA23. The manifold
assembly 226, under the control of the controller 16, selectively
distributes the different pressure and vacuum levels to the pump
and valve actuators PA(N) and VA(N). These levels of pressure and
vacuum are systematically applied to the cassette 28, to route
blood and processing liquids.
[0123] Under the control of a controller 16, the manifold assembly
226 also distributes pressure levels to the door bladder 314
(already described), as well as to a donor pressure cuff (not
shown) and to a donor line occluder 320.
[0124] As FIG. 1 shows, the donor line occluder 320 is located in
the case 36, immediately below the pump and valve station 30, in
alignment with the ports P8 and P9 of the cassette 28. The donor
line 266, coupled to the port P8, passes through the occluder 320.
The anticoagulant line 270, coupled to the port P9, also passes
through the occluder 320. The occluder 320 is a spring loaded,
normally closed pinch valve, between which the lines 266 and 270
pass. Pneumatic pressure from the manifold assembly 234 is supplied
to a bladder (not shown) through a solenoid valve. The bladder,
when expanded with pneumatic pressure, opens the pinch valve, to
thereby open the lines 266 and 270. In the absence of pneumatic
pressure, the solenoid valve closes and the bladder vents to
atmosphere. The spring loaded pinch valve of the occluder 320
closes, thereby closing the lines 266 and 270.
[0125] The manifold assembly 226 maintains several different
pressure and vacuum conditions, under the control of the controller
16. In the illustrated embodiment, the following multiple pressure
and vacuum conditions are maintained:
[0126] (i) Phard, or Hard Pressure, and Pinpr, or In-Process
Pressure are the highest pressures maintained in the manifold
assembly 226. Phard is applied for closing cassette valves V1 to
V23. Pinpr is applied to drive the expression of liquid from the
in-process pump PP1 and the plasma pump PP2. A typical pressure
level for Phard and Pinpr in the context of the preferred
embodiment is 500 mmHg.
[0127] (ii) Pgen, or General Pressure, is applied to drive the
expression of liquid from the donor interface pump PP3 and the
anticoagulant pump PP4. A typical pressure level for Pgen in the
context of the preferred embodiment is 150 mmHg.
[0128] (iii) Pcuff, or Cuff Pressure, is supplied to the donor
pressure cuff. A typical pressure level for Pcuff in the context of
the preferred embodiment is 80 mmHg.
[0129] (iv) Vhard, or Hard Vacuum, is the deepest vacuum applied in
the manifold assembly 226. Vhard is applied to open cassette valves
V1 to V23. A typical vacuum level for Vhard in the context of the
preferred embodiment is -350 mmHg.
[0130] (vi) Vgen, or General Vacuum, is applied to drive the draw
function of each of the four pumps PP1 to PP4. A typical pressure
level for Vgen in the context of the preferred embodiment is -300
mmHg.
[0131] (vii) Pdoor, or Door Pressure, is applied to the bladder 314
to seal the cassette 28 into the holder 216. A typical pressure
level for Pdoor in the context of the preferred embodiment is 700
mmHg.
[0132] For each pressure and vacuum level, a variation of plus or
minus 20 mmHg is tolerated.
[0133] Pinpr is used to operate the in process pump PP1, to pump
blood into the processing chamber 18. The magnitude of Pinpr must
be sufficient to overcome a minimum pressure of approximately 300
mm Hg, which is typically present within the processing chamber
18.
[0134] Similarly, Pinpr is used for the plasma pump PP2, since it
must have similar pressure capabilities in the event that plasma
needs to be pumped backwards into the processing chamber 18, e.g.,
during a spill condition, as will be described later.
[0135] Pinpr and Phard are operated at the highest pressure to
ensure that upstream and downstream valves used in conjunction with
pumping are not forced opened by the pressures applied to operate
the pumps. The cascaded, interconnectable design of the fluid paths
F1 to F38 through the cassette 28 requires Pinpr-Phard to be the
highest pressure applied. By the same token, Vgen is required to be
less extreme than Vhard, to ensure that pumps PP1 to PP4 do not
overwhelm upstream and downstream cassette valves V1 to V23.
[0136] Pgen is used to drive the donor interface pump PP3 and can
be maintained at a lower pressure, as can the AC pump PP4.
[0137] A main hard pressure line 322 and a main vacuum line 324
distribute Phard and Vhard in the manifold assembly 324. The
pressure and vacuum sources 234 run continuously to supply Phard to
the hard pressure line 322 and Vhard to the hard vacuum line
324.
[0138] A pressure sensor S1 monitors Phard in the hard pressure
line 322. The sensor S1 controls a solenoid 38. The solenoid 38 is
normally closed. The sensor S1 opens the solenoid 38 to build Phard
up to its maximum set value. Solenoid 38 is closed as long as Phard
is within its specified pressure range and is opened when Phard
falls below its minimum acceptable value.
[0139] Similarly, a pressure sensor S5 in the hard vacuum line 324
monitors Vhard. The sensor S5 controls a solenoid 39. The solenoid
39 is normally closed. The sensor S5 opens the solenoid 39 to build
Vhard up to its maximum value. Solenoid 39 is closed as long as
Vhard is within its specified pressure range and is opened when
Vhard falls outside its specified range.
[0140] A general pressure line 326 branches from the hard pressure
line 322. A sensor S2 in the general pressure line 326 monitors
Pgen. The sensor 32 controls a solenoid 30. The solenoid 30 is
normally closed. The sensor S2 opens the solenoid 30 to refresh
Pgen from the hard pressure line 322, up to the maximum value of
Pgen. Solenoid 30 is closed as long as Pgen is within its specified
pressure range and is opened when Pgen falls outside its specified
range.
[0141] An in process pressure line 328 also branches from the hard
pressure line 322. A sensor S3 in the in process pressure line 328
monitors Pinpr. The sensor S3 controls a solenoid 36. The solenoid
36 is normally closed. The sensor S3 opens the solenoid 36 to
refresh Pinpr from the hard pressure line 322, up to the maximum
value of Pinpr. Solenoid 36 is closed as long as Pinpr is within
its specified pressure range and is opened when Pinpr falls outside
its specified range.
[0142] A general vacuum line 330 branches from the hard vacuum line
324. A sensor S6 monitors Vgen in the general vacuum line 330. The
sensor S6 controls a solenoid 31. The solenoid 31 is normally
closed. The sensor S6 opens the solenoid 31 to refresh Vgen from
the hard vacuum line 324, up to the maximum value of Vgen. The
solenoid 31 is closed as long as Vgen is within its specified range
and is opened when Vgen falls outside its specified range.
[0143] In-line reservoirs R1 to R5 are provided in the hard
pressure line 322, the in process pressure line 328, the general
pressure line 326, the hard vacuum line 324, and the general vacuum
line 330. The reservoirs R1 to R5 assure that the constant pressure
and vacuum adjustments as above described are smooth and
predictable.
[0144] The solenoids 33 and 34 provide a vent for the pressures and
vacuums, respectively, upon procedure completion. Since pumping and
valving will continually consume pressure and vacuum, the solenoids
33 and 34 are normally closed. The solenoids 33 and 34 are opened
to vent the manifold assembly upon the completion of a blood
processing procedure.
[0145] The solenoids 28, 29, 35, 37 and 32 provide the capability
to isolate the reservoirs R1 to R5 from the air lines that supply
vacuum and pressure to the manifold assembly 226. This provides for
much quicker pressure/vacuum decay feedback, so that testing of
cassette/manifold assembly seal integrity can be accomplished.
These solenoids 28, 29, 35, 37, and 32 are normally opened, so that
pressure cannot be built in the assembly 226 without a command to
close the solenoids 28, 29, 35, 37, and 32, and, further, so that
the system pressures and vacuums can vent in an error mode or with
loss of power.
[0146] The solenoids 1 to 23 provide Phard or Vhard to drive the
valve actuators VA1 to V23. In the unpowered state, these solenoids
are normally opened to keep all cassette valves V1 to V23
closed.
[0147] The solenoids 24 and 25 provide Pinpr and Vgen to drive the
in-process and plasma pumps PP1 and PP2. In the unpowered state,
these solenoids are opened to keep both pumps PP1 and PP2
closed.
[0148] The solenoids 26 and 27 provide Pgen and Vgen to drive the
donor interface and AC pumps PP3 and PP4. In the unpowered state,
these solenoids are opened to keep both pumps PP3 and PP4
closed.
[0149] The solenoid 43 provides isolation of the door bladder 314
from the hard pressure line 322 during the procedure. The solenoid
43 is normally opened and is closed when Pdoor is reached. A sensor
S7 monitors Pdoor and signals when the bladder pressure falls below
Pdoor. The solenoid 43 is opened in the unpowered state to ensure
bladder 314 venting, as the cassette 28 cannot be removed from the
holder while the door bladder 314 is pressurized.
[0150] The solenoid 42 provides Phard to open the safety occluder
valve 320. Any error modes that might endanger the donor will relax
(vent) the solenoid 42 to close the occluder 320 and isolate the
donor. Similarly, any loss of power will relax the solenoid 42 and
isolate the donor.
[0151] The sensor S4 monitors Pcuff and communicates with solenoids
41 (for increases in pressure) and solenoid 40 (for venting) to
maintain the donor cuff within its specified ranges during the
procedure. The solenoid 40 is normally open so that the cuff line
will vent in the event of system error or loss of power. The
solenoid 41 is normally closed to isolate the donor from any Phard
in the event of power loss or system error.
[0152] FIG. 12 shows a sensor S8 in the pneumatic line serving the
donor interface pump actuator PA3. The sensor S8 is a
bi-directional mass air flow sensor, which can monitor air flow to
the donor interface pump actuator PA3 to detect occlusions in the
donor line. Alternatively, as will be described in greater detail
later, electrical field variations can be sensed by an electrode
carried within the donor interface pump chamber PP3, or any or all
other pump chambers PP1, PP2, or PP4, to detect occlusions, as well
as to permit calculation of flow rates and the detection of
air.
[0153] Various alternative embodiments are possible. For example,
the pressure and vacuum available to the four pumping chambers
could be modified to include more or less distinct levels or
different groupings of "shared" pressure and vacuum levels. As
another example, Vhard could be removed from access to the
solenoids 2, 5, 8, 18, 19, 21, 22 since the restoring springs will
return the cassette valves to a closed position upon removal of a
vacuum. Furthermore, the vents shown as grouped together could be
isolated or joined in numerous combinations.
[0154] It should also be appreciated that any of the solenoids used
in "normally open" mode could be re-routed pneumatically to be
realized as "normally closed". Similarly, any of the "normally
closed" solenoids could be realized as "normally open".
[0155] As another example of an alternative embodiment, the hard
pressure reservoir R1 could be removed if Pdoor and Phard were set
to identical magnitudes. In this arrangement, the door bladder 314
could serve as the hard pressure reservoir. The pressure sensor S7
and the solenoid 43 would also be removed in this arrangement.
[0156] III. Other Process Control Components of the System
[0157] As FIG. 13 best shows, the case 36 contains other components
compactly arranged to aid blood processing. In addition to the
centrifuge station 20 and pump and valve station 30, already
described, the case 36 includes a weigh station 238, an operator
interface station 240, and one or more trays 212 or hangers 248 for
containers. The arrangement of these components in the case 36 can
vary. In the illustrated embodiment, the weigh station 238, the
controller 16, and the user interface station 240, like the pump
and valve station 30, are located in the lid 40 of the case 36. The
holding trays 212 are located in base 38 of the case 36, adjacent
the centrifuge station 20.
[0158] A. Container Support Components
[0159] The weigh station 238 comprises a series of container
hangers/weigh sensors 246 arranged along the top of the lid 40. In
use (see FIG. 2), containers 304, 308, 312 are suspended on the
hangers/weigh sensors 246.
[0160] The containers receive blood components separated during
processing, as will be described in greater detail later. The weigh
sensors 246 provide output reflecting weight changes over time.
This output is conveyed to the controller 16. The controller 16
processes the incremental weight changes to derive fluid processing
volumes and flow rates. The controller generates signals to control
processing events based, in part, upon the derived processing
volumes. Further details of the operation of the controller to
control processing events will be provided later.
[0161] The holding trays 212 comprise molded recesses in the base
38. The trays 212 accommodate the containers 276 and 280 (see FIG.
2). In the illustrated embodiment, an additional swing-out hanger
248 is also provided on the side of the lid 40. The hanger 248 (see
FIG. 2) supports the container 288 during processing. In the
illustrated embodiment, the trays 212 and hanger 248 also include
weigh sensors 246.
[0162] The weigh sensors 246 can be variously constructed. In the
embodiment shown in FIG. 40, the scale includes a force sensor 404
incorporated into a housing 400, to which a hanger 402 is attached.
The top surface 420 of hanger 402 engages a spring 406 on the
sensor 404. Another spring 418 is compressed as a load, carried by
the hanger 402, is applied. The spring 418 resists load movement of
the hanger 402, until the load exceeds a predetermined weight
(e.g., 2 kg.). At that time, the hanger 402 bottoms out on
mechanical stops 408 in the housing 400, thereby providing over
load protection.
[0163] In the embodiment shown in FIG. 41, a supported beam 410
transfers force applied by a hanger 416 to a force sensor 412
through a spring 414. This design virtually eliminates friction
from the weight sensing system. The magnitude of the load carried
by the beam is linear in behavior, and the weight sensing system
can be readily calibrated to ascertain an actual load applied to
the hanger 416.
[0164] B. The Controller and Operator Interface Station
[0165] The controller 16 carries out process control and monitoring
functions for the system 10. As FIG. 14 shows schematically, the
controller 16 comprises a main processing unit (MPU) 250, which can
comprise, e.g., a Pentium.TM. type microprocessor made by Intel
Corporation, although other types of conventional microprocessors
can be used. The MPU 250 is mounted inside the lid 40 of the case
36 (as FIG. 13 shows).
[0166] In the preferred embodiment, the MPU 250 employs
conventional real time multi-tasking to allocate MPU cycles to
processing tasks. A periodic timer interrupt (for example, every 5
milliseconds) preempts the executing task and schedules another
that is in a ready state for execution. If a reschedule is
requested, the highest priority task in the ready state is
scheduled. Otherwise, the next task on the list in the ready state
is scheduled.
[0167] As FIG. 14 shows, the MPU 250 includes an application
control manager 252. The application control manager 252
administers the activation of a library of at least one control
application 254. Each control application 254 prescribes procedures
for carrying out given functional tasks using the centrifuge
station 20 and the pump and valve station 30 in a predetermined
way. In the illustrated embodiment, the applications 254 reside as
process software in EPROM's in the MPU 250.
[0168] The number of applications 254 can vary. In the illustrated
embodiment, the applications 254 includes at least one clinical
procedure application. The procedure application contains the steps
to carry out one prescribed clinical processing procedure. For the
sake of example in the illustrated embodiment, the application 254
includes three procedure applications: (1) a double unit red blood
cell collection procedure; (2) a plasma collection procedure; and
(3) a plasma/red blood cell collection procedure. The details of
these procedures will be described later. Of course, additional
procedure applications can be included.
[0169] As FIG. 14 shows, several slave processing units communicate
with the application control manager 252. While the number of slave
processing units can vary, the illustrated embodiment shows five
units 256(1) to 256 (5). The slave processing units 256(1) to
256(5), in turn, communicates with low level peripheral controllers
258 for controlling the pneumatic pressures within the manifold
assembly 226, the weigh sensors 246, the pump and valve actuators
PA1 to PA4 and VA1 to VA23 in the pump and valve station 30, the
motor for the centrifuge station 20, the interface sensing station
332, and other functional hardware of the system.
[0170] The MPU 250 contains in EPROM's the commands for the
peripheral controllers 258, which are downloaded to the appropriate
slave processing unit 256(1) to 256(5) at start-up. The application
control manager 252 also downloads to the appropriate slave
processing unit 256(1) to 256(5) the operating parameters
prescribed by the activated application 254.
[0171] With this downloaded information, the slave processing units
256(1) to 256(5) proceed to generate device commands for the
peripheral controllers 258, causing the hardware to operate in a
specified way to carry out the procedure. The peripheral
controllers 258 return current hardware status information to the
appropriate slave processing unit 256(1) to 256(5), which, in turn,
generate the commands necessary to maintain the operating
parameters ordered by the application control manager 252.
[0172] In the illustrated embodiment, one slave processing unit
256(2) performs the function of an environmental manager. The unit
256(2) receives redundant current hardware status information and
reports to the MPU 250 should a slave unit malfunction and fail to
maintain the desired operating conditions.
[0173] As FIG. 14 shows, the MPU 250 also includes an interactive
user interface 260, which allows the operator to view and
comprehend information regarding the operation of the system 10.
The interface 260 is coupled to the interface station 240. The
interface 260 allows the operator to use the interface station 240
to select applications 254 residing in the application control
manager 252, as well as to change certain functions and performance
criteria of the system 10.
[0174] As FIG. 13 shows, the interface station 240 includes an
interface screen 262 carried in the lid 40. The interface screen
262 displays information for viewing by the operator in
alpha-numeric format and as graphical images. In the illustrated
and preferred embodiment, the interface screen 262 also serves as
an input device. It receives input from the operator by
conventional touch activation.
[0175] C. On-Line Monitoring of Pump Flows
[0176] 1. Gravimetric Monitoring
[0177] Using the weigh scales 246, either upstream or downstream of
the pumps, the controller 16 can continuously determine the actual
volume of fluid that is moved per pump stroke and correct for any
deviations from commanded flow. The controller 16 can also diagnose
exceptional situations, such as leaks and obstructions in the fluid
path. This measure of monitoring and control is desirable in an
automated apheresis application, where anticoagulant has to be
accurately metered with the whole blood as it is drawn from the
donor, and where product quality (e.g., hematocrit, plasma purity)
is influenced by the accuracy of the pump flow rates.
[0178] The pumps PP1 to PP4 in the cassette 28 each provides a
relatively-constant nominal stroke volume, or SV. The flow rate for
a given pump can therefore be expressed as follows: 1 Q = S V ( T
Pump + T Fill + T Idle ) ( 1 )
[0179] where:
[0180] Q is the flow rate of the pump.
[0181] SV is the stroke volume, or volume moved per pump cycle.
[0182] T.sub.Pump is the time the fluid is moved out of the pump
chamber.
[0183] T.sub.Fill is the time the pump is filled with fluid,
and
[0184] T.sub.Idle is the time when the pump is idle, that is, when
no fluid movement occurs.
[0185] The SV can be affected by the interaction of the pump with
attached downstream and upstream fluid circuits. This is analogous,
in electrical circuit theory, to the interaction of a non-ideal
current source with the input impedance of the load it sees.
Because of this, the actual SV can be different than the nominal
SV.
[0186] The actual fluid flow in volume per unit of time
Q.sub.Actual can therefore be expressed as follows: 2 Q Actual = k
.times. S V Ideal T Pump + T Fill + T Idle ( 2 )
[0187] where:
[0188] Q.sub.Actual is the actual fluid flow in volume per unit of
time.
[0189] SV.sub.Ideal is the theoretical stroke volume, based upon
the geometry of the pump chamber.
[0190] k is a correction factor that accounts for the interactions
between the pump and the upstream and downstream pressures.
[0191] The actual flow rate can be ascertained gravimetrically,
using the upstream or downstream weigh scales 246, based upon the
following relationship:
Q.sub.Actual=.DELTA.Wt/.rho..times..DELTA.T (3)
[0192] where:
[0193] .DELTA.Wt is the change in weight of fluid as detected by
the upstream or downstream weigh scale 246 during the time period
.DELTA.T,
[0194] .rho. is the density of fluid.
[0195] .DELTA.T is the time period where the change in weight
.DELTA.Wt is detected in the weigh scale 246.
[0196] The following expression is derived by combining Equations
(2) and (3): 3 k = ( T Pump + T Fill + T Idle ) .times. Wt ( SV
Ideal .times. .times. T ) ( 4 )
[0197] The controller 16 computes k according to Equation (4) and
then adjusts T.sub.Idle so that the desired flow rate is achieved,
as follows:
T.sub.Idle=(k.times.SV.sub.Ideal/Q.sub.Desired)-T.sub.Pump-T.sub.Fill
(5)
[0198] The controller 16 updates the values for k and T.sub.Idle
frequently to adjust the flow rates.
[0199] Alternatively, the controller 16 can change T.sub.Pump
and/or T.sub.Fill and/or T.sub.Idle to adjust the flow rates.
[0200] In this arrangement, one or more of the time interval
components T.sub.Pump, or T.sub.Fill, or T.sub.Idle is adjusted to
a new magnitude to achieve Q.sub.Desired, according to the
following relationship:
T.sub.n(Adjusted)=k(SV.sub.Ideal/Q.sub.Desired)-T.sub.n(NotAdjusted)
[0201] where:
[0202] T.sub.n(Adjusted) is the magnitude of the time interval
component or components after adjustment to achieve the desired
flow rate Q.sub.Desired.
[0203] T.sub.n(NotAdjusted) is the magnitude of the value of the
other time interval component or components of T.sub.Stroke that
are not adjusted. The adjusted stroke interval after adjustment to
achieve the desired flow rate Q.sub.Desired is the sum of
T.sub.n(Adjusted) and T.sub.n(NotAdjusted).
[0204] The controller 16 also applies the correction factor k as a
diagnostics tool to determine abnormal operating conditions. For
example, if k differs significantly from its nominal value, the
fluid path may have either a leak or an obstruction. Similarly, if
computed value of k is of a polarity different from what was
expected, then the direction of the pump may be reversed.
[0205] With the weigh scales 246, the controller 16 can perform
on-line diagnostics even if the pumps are not moving fluid. For
example, if the weigh scales 246 detect changes in weight when no
flow is expected, then a leaky valve or a leak in the set 264 may
be present.
[0206] In computing k and T.sub.idle and/or T.sub.Pump and/or
T.sub.Fill, the controller 16 may rely upon multiple measurements
of .DELTA.Wt and/or .DELTA.T. A variety of averaging or recursive
techniques (e.g., recursive least means squares, Kalman filtering,
etc.) may be used to decrease the error associated with the
estimation schemes.
[0207] The above described monitoring technique is applicable for
use for other constant stroke volume pumps, i.e. peristaltic pumps,
etc.
[0208] 2. Electrical Monitoring
[0209] In an alternative arrangement (see FIG. 42), the controller
16 includes a metal electrode 422 located in the chamber of each
pump station PP1 to PP4 on the cassette 28. The electrodes 422 are
coupled to a current source 424. The passage of current through
each electrode 422 creates an electrical field within the
respective pump chamber PP1 to PP4.
[0210] Cyclic deflection of the diaphragm 194 to draw fluid into
and expel fluid from the pump chamber PP1 to PP4 changes the
electrical field, resulting in a change in total capacitance of the
circuit through the electrode 422. Capacitance increases as fluid
is draw into the pump chamber PP1 to PP4, and capacitance decreases
as fluid is expelled from pump chamber PP1 to PP4.
[0211] The controller 16 includes a capacitive sensor 426 (e.g., a
Qprox E2S)coupled to each electrode 422. The capacitive sensor 426
registers changes in capacitance for the electrode 422 in each pump
chamber PP1 to PP4. The capacitance signal for a given electrode
422 has a high signal magnitude when the pump chamber is filled
with liquid (diaphragm position 194a), has a low signal magnitude
signal when the pump chamber is empty of fluid (diaphragm position
194b), and has a range of intermediate signal magnitudes when the
diaphragm occupies positions between position 194a and 194b.
[0212] At the outset of a blood processing procedure, the
controller 16 calibrates the difference between the high and low
signal magnitudes for each sensor to the maximum stroke volume SV
of the respective pump chamber. The controller 16 then relates the
difference between sensed maximum and minimum signal values during
subsequent draw and expel cycles to fluid volume drawn and expelled
through the pump chamber. The controller 16 sums the fluid volumes
pumped over a sample time period to yield an actual flow rate.
[0213] The controller 16 compares the actual flow rate to a desired
flow rate. If a deviance exists, the controller 16 varies pneumatic
pressure pulses delivered to the actuator PA1 to PA4, to adjust
T.sub.Idle and/or T.sub.Pump and/or T.sub.Fill to minimize the
deviance.
[0214] The controller 16 also operates to detect abnormal operating
conditions based upon the variations in the electric field and to
generate an alarm output. In the illustrated embodiment, the
controller 16 monitors for an increase in the magnitude of the low
signal magnitude over time. The increase in magnitude reflects the
presence of air inside a pump chamber.
[0215] In the illustrated embodiment, the controller 16 also
generates a derivative of the signal output of the sensor 426.
Changes in the derivative, or the absence of a derivative, reflects
a partial or complete occlusion of flow through the pump chamber
PP1 to PP4. The derivative itself also varies in a distinct fashion
depending upon whether the occlusion occurs at the inlet or outlet
of the pump chamber PP1 to PP4.
[0216] IV. The Blood Processing Procedures
[0217] A. Double RBC Collection Procedure (No Plasma
Collection)
[0218] During this procedure, whole blood from a donor is
centrifugally processed to yield up to two units (approximately 500
ml) of red blood cells for collection. All plasma constituent is
returned to the donor. This procedure will, in shorthand, be called
the double red blood cell collection procedure.
[0219] Prior to undertaking the double red blood cell collection
procedure, as well as any blood collection procedure, the
controller 16 operates the manifold assembly 226 to conduct an
appropriate integrity check of the cassette 28, to determine
whether there are any leaks in the cassette 28. Once the cassette
integrity check is complete and no leaks are found, the controller
16 begins the desired blood collection procedure.
[0220] The double red blood cell collection procedure includes a
pre-collection cycle, a collection cycle, a post-collection cycle,
and a storage preparation cycle. During the pre-collection cycle,
the set 264 is primed to vent air prior to venipuncture. During the
collection cycle, whole blood drawn from the donor is processed to
collect two units of red blood cells, while returning plasma to the
donor. During the post-collection cycle, excess plasma is returned
to the donor, and the set is flushed with saline. During the
storage preparation cycle, a red blood cell storage solution is
added.
[0221] 1. The Pre-Collection Cycle
[0222] a. Anticoagulant Prime
[0223] In a first phase of the pre-collection cycle (AC Prime 1),
tube 300 leading to the phlebotomy needle 268 is clamped closed
(see FIG. 10). The blood processing circuit 46 is programmed
(through the selective application of pressure to the valves and
pump stations of the cassette) to operate the donor interface pump
PP3, drawing anticoagulant through the anticoagulant tube 270 and
up the donor tube 266 through the y-connector 272 (i.e., in through
valve V13 and out through valve V11). The circuit is further
programmed to convey air residing in the anticoagulant tube 270,
the donor tube 266, and the cassette and into the in-process
container 312. This phase continues until an air detector 298 along
the donor tube 266 detects liquid, confirming the pumping function
of the donor interface pump PP3.
[0224] In a second phase of the pre-collection cycle (AC Prime 2),
the circuit is programmed to operate the anticoagulant pump PP4 to
convey anticoagulant into the in-process container 312. Weight
changes in the in-process container 312. AC Prime 2 is terminated
when the anticoagulant pump PP4 conveys a predetermined volume of
anticoagulant (e.g., 10 g) into the in-process container 312,
confirming is pumping function.
[0225] b. Saline Prime
[0226] In a third phase of the pre-collection cycle (Saline Prime
1), the processing chamber 46 remains stationary. The circuit is
programmed to operate the in-process pump station PP1 to draw
saline from the saline container 288 through the in-process pump
PP1. This creates a reverse flow of saline through the stationary
processing chamber 46 toward the in-process container 312. In this
sequence saline is drawn through the processing chamber 46 from the
saline container 288 into the in-process pump PP1 through valve
V14. The saline is expelled from the pump station PP1 toward the
in-process container 312 through valve 9. Weight changes in the
saline container 288 are monitored. This phase is terminated upon
registering a predetermined weight change in the saline container
288, which indicates conveyance of a saline volume sufficient to
initially fill about one half of the processing chamber 46 (e.g.,
about 60 g).
[0227] With the processing chamber 46 about half full of priming
saline, a fourth phase of the pre-collection cycle (Saline Prime
2). The processing chamber 46 is rotated at a low rate (e.g., about
300 RPM), while the circuit continues to operate in the same
fashion as in Saline Prime 3. Additional saline is drawn into the
pump station PP1 through valve V14 and expelled out of the pump
station PP1 through valve V9 and into the in-process container 312.
Weight changes in the in-process container 312 are monitored. This
phase is terminated upon registering a predetermined weight change
in the in-process container 312, which indicates the conveyance of
an additional volume of saline sufficient to substantially fill the
processing chamber 46 (e.g., about 80 g).
[0228] In a fifth phase of the pre-collection cycle (Saline Prime
3), the circuit is programmed to first operate the in-process pump
station PP1 to convey saline from the in-process container 312
through all outlet ports of the separation device and back into the
saline container 288 through the plasma pump station PP2. This
completes the priming of the processing chamber 46 and the
in-process pump station PP1 (pumping in through valve V9 and out
through valve V14), as well as primes the plasma pump station PP2,
with the valves V7, V6, V10, and V12 opened to allow passive flow
of saline. During this time, the rate at which the processing
chamber 46 is rotated is successively ramped between zero and 300
RPM. Weight changes in the in process container 312 are monitored.
When a predetermined initial volume of saline is conveyed in this
manner, the circuit is programmed to close valve V7, open valves V9
and V14, and to commence pumping saline to the saline container 288
through the plasma pump PP2, in through valve V12 and out through
valve V10, allowing saline to passively flow through the in-process
pump PP1. Saline in returned in this manner from the in-process
container 312 to the saline container 288 until weight sensing
indicated that a preestablished minimum volume of saline occupies
the in-process container 312.
[0229] In a sixth phase of the pre-collection cycle (Vent Donor
Line), the circuit is programmed to purge air from the venepuncture
needle, prior to venipuncture, by operating the donor interface
pump PP3 to pump anticoagulant through anticoagulant pump PP4 and
into the in process container 312.
[0230] In a seventh phase of the pre-collection cycle
(Venipuncture), the circuit is programmed to close all valves V1 to
V23, so that venipuncture can be accomplished.
[0231] The programming of the circuit during the phases of the
pre-collection cycle is summarized in the following table.
1TABLE Programming of Blood Processing Circuit During Pre-
Collection Cycle (Double Red Blood Cell Collection Procedure) Vent
AC AC Saline Saline Saline Donor Veni- Phase Prime 1 Prime 2 Prime
1 Prime 2 Prime 3 Line puncture V1 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V2 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V3
.smallcircle. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. V4 .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V5 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V6 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid. V7
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. V8 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V9 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump
Pump Pump In Out Out (Stage 1) .smallcircle. (Stage 2) V10
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (Stage 1)
.smallcircle./.circle-solid. Pump Out (Stage 2) V11
.smallcircle./.circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump In V12 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. (Stage 1) .smallcircle./.circle-solid. Pump In
(Stage 2) V13 .smallcircle./.circle-solid. .smallcircle.
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump In Pump Out V14
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. .circle-solid. Pump In Pump Pump In Out (Stage 1)
.smallcircle. (Stage 2) V15 .smallcircle.
.smallcircle./.circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. Pump In Pump Out V16
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V18 .smallcircle. .smallcircle.
.circle-solid. .circle-solid. .circle-solid. .smallcircle.
.circle-solid. V19 .smallcircle. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V20
.smallcircle. .smallcircle./.circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. Pump Out
Pump In V21 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V22
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.smallcircle. .circle-solid. .circle-solid. V23 .circle-solid.
.circle-solid. .smallcircle. .smallcircle. .smallcircle.
.circle-solid. .circle-solid. PP1 .box-solid. .box-solid.
.quadrature. .quadrature. .quadrature. .box-solid. .box-solid.
(Stage 1) PP2 .box-solid. .box-solid. .box-solid. .box-solid.
.quadrature. .box-solid. .box-solid. (Stage 2) PP3 .quadrature.
.box-solid. .box-solid. .box-solid. .box-solid. .quadrature.
.box-solid. PP4 .box-solid. .quadrature. .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. Caption: .smallcircle. denotes
an open valve; .circle-solid. denotes a closed valve;
.smallcircle./.circle-s- olid. denotes a valve opening and closing
during a pumping sequence; .box-solid. denotes an idle pump station
(not in use); and .quadrature. denotes a pump station in use.
[0232] c. The Collection Cycle
[0233] i. Blood Prime
[0234] With venipuncture, tube 300 leading to the phlebotomy needle
268 is opened. In a first phase of the collection cycle (Blood
Prime 1), the blood processing circuit 46 is programmed (through
the selective application of pressure to the valves and pump
stations of the cassette) to operate the donor interface pump PP3
(i.e., in through valve V13 and out through valve V11) and the
anticoagulant pump PP4 (i.e., in through valve V20 and out through
valve V15) to draw anticoagulated blood through the donor tube 270
into the in process container 312. This phase continues until an
incremental volume of anticoagulated whole blood enters the in
process container 312, as monitored by the weigh sensor.
[0235] In a next phase (Blood Prime 2), the blood processing
circuit 46 is programmed to operate the in-process pump station PP1
to draw anticoagulated blood from the in-process container 312
through the separation device. During this phase, saline displaced
by the blood is returned to the donor. This phase primes the
separation device with anticoagulated whole blood. This phase
continues until an incremental volume of anticoagulated whole blood
leaves the in process container 312, as monitored by the weigh
sensor.
[0236] B. Blood Separation While Drawing Whole Blood or Without
Drawing Whole Blood
[0237] In a next phase of the blood collection cycle (Blood
Separation While Drawing Whole Blood), the blood processing circuit
46 is programmed to operate the donor interface pump station PP3
(i.e., in through valve V13 and out through valve V11); the
anticoagulant pump PP4 (i.e., in through valve V20 and out through
valve V15); the in-process pump PP1 (i.e., in through valve V9 and
out through valve V14); and the plasma pump PP2 (i.e., in through
valve V12 and out through valve V10). This arrangement draws
anticoagulated blood into the in-process container 312, while
conveying the blood from the in-process container 312 into the
processing chamber for separation. This arrangement also removes
plasma from the processing chamber into the plasma container 304,
while removing red blood cells from the processing chamber into the
red blood cell container 308. This phase continues until an
incremental volume of plasma is collected in the plasma collection
container 304 (as monitored by the weigh sensor) or until a
targeted volume of red blood cells is collected in the red blood
cell collection container (as monitored by the weigh sensor).
[0238] If the volume of whole blood in the in-process container 312
reaches a predetermined maximum threshold before the targeted
volume of either plasma or red blood cells is collected, the
circuit is programmed for another phase (Blood Separation Without
Drawing Whole Blood), to terminate operation of the donor interface
pump station PP3 (while also closing valves V13, V11, V18, and V13)
to terminate collection of whole blood in the in-process container
312, while still continuing blood separation. If the volume of
whole blood reaches a predetermined minimum threshold in the
in-process container 312 during blood separation, but before the
targeted volume of either plasma or red blood cells is collected,
the circuit is programmed to return to the Blood Separation While
Drawing Whole Blood Phase, to thereby allow whole blood to enter
the in-process container 312. The circuit is programmed to toggle
between the Blood Separation While Drawing Whole Blood Phase and
the Blood Separation Without Drawing Whole Blood Phase according to
the high and low volume thresholds for the in-process container
312, until the requisite volume of plasma has been collected, or
until the target volume of red blood cells has been collected,
whichever occurs first.
[0239] C. Return Plasma and Saline
[0240] If the targeted volume of red blood cells has not been
collected, the next phase of the blood collection cycle (Return
Plasma With Separation) programs the blood processing circuit 46 to
operate the donor interface pump station PP3 (i.e., in through
valve V11 and out through valve V13); the in-process pump PP1
(i.e., in through valve V9 and out through valve V14); and the
plasma pump PP2 (i.e., in through valve V12 and out through valve
V10). This arrangement conveys anticoagulated whole blood from the
in-process container 312 into the processing chamber for
separation, while removing plasma into the plasma container 304 and
red blood cells into the red blood cell container 308. This
arrangement also conveys plasma from the plasma container 304 to
the donor, while also mixing saline from the container 288 in line
with the returned plasma. The in line mixing of saline with plasma
raises the saline temperature and improves donor comfort. This
phase continues until the plasma container 304 is empty, as
monitored by the weigh sensor.
[0241] If the volume of whole blood in the in-process container 312
reaches a specified low threshold before the plasma container 304
empties, the circuit is programmed to enter another phase (Return
Plasma Without Separation), to terminate operation of the
in-process pump station PP1 (while also closing valves V9, V10,
V12, and V14) to terminate blood separation. The phase continues
until the plasma container 304 empties.
[0242] Upon emptying the plasma container 304, the circuit is
programmed to enter a phase (Fill Donor Line), to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V13) to draw whole blood from the in process
container 312 to fill the donor tube 266, thereby purge plasma
(mixed with saline) in preparation for another draw whole blood
cycle.
[0243] The circuit is then programmed to conduct another Blood
Separation While Drawing Whole Blood Phase, to refill the in
process container 312. The circuit is programmed in successive
Blood Separation and Return Plasma Phases until the weigh sensor
indicates that a desired volume of red blood cells have been
collected in the red blood cell collection container 308. When the
targeted volume of red blood cells has not been collected, the
post-collection cycle commences.
[0244] The programming of the circuit during the phases of the
collection cycle is summarized in the following table.
2TABLE Programming of Blood Processing Circuit During The
Collection Cycle (Double Red Blood Cell Collection Procedure) Blood
Separation While Drawing Return Whole Blood Plasma/ (Without with
Drawing Separation Whole (Without Phase Blood Prime 1 Blood Prime 2
Blood) Separation) Fill Donor Line V1 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. V2 .circle-solid.
.circle-solid. .smallcircle. .smallcircle.(.circle-solid.)
.circle-solid. V3 .smallcircle. .circle-solid. .smallcircle.
.circle-solid. .circle-solid. (.circle-solid.) V4 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V5
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.circle-solid. V6 .circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Alternates with V23 V7
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.smallcircle. V8 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V9 .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump In Pump In Pump In
(.circle-solid.) V10 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump Out (.circle-solid.) V11
.smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump Out Pump Out Pump In Pump In
(.circle-solid.) V12 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In (.circle-solid.) V13
.smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump In Pump In Pump Out Pump Out
(.circle-solid.) V14 .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump Out Pump Out (.circle-solid.) V15
.smallcircle./.circle-sol- id. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump Out (.circle-solid.) V16 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V18
.smallcircle. .smallcircle. .smallcircle. .smallcircle.
.smallcircle. (.circle-solid.) V19 .smallcircle. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (.circle-solid.) V20
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump In (.circle-solid.) V21 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V22 .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V23
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Alternates with V6 PP1
.box-solid. .quadrature. .quadrature. .quadrature. .box-solid.
(.box-solid.) PP2 .box-solid. .box-solid. .quadrature. .quadrature.
.box-solid. (.box-solid.) PP3 .quadrature. .box-solid. .quadrature.
.quadrature. .quadrature. (.box-solid.) PP4 .quadrature.
.box-solid. .quadrature. .box-solid. .box-solid. (.box-solid.)
[0245] D. The Post-Collection Cycle
[0246] Once the targeted volume of red blood cells has been
collected (as monitored by the weigh sensor), the circuit is
programmed to carry out the phases of the post-collection
cycle.
[0247] 1. Return Excess Plasma
[0248] In a first phase of the post-collection cycle (Excess Plasma
Return), the circuit is programmed to terminate the supply and
removal of blood to and from the processing chamber, while
operating the donor interface pump station PP3 (i.e., in through
valve V11 and out through valve V13) to convey plasma remaining in
the plasma container 304 to the donor. The circuit is also
programmed in this phase to mix saline from the container 288 in
line with the returned plasma. This phase continues until the
plasma container 304 is empty, as monitored by the weigh
sensor.
[0249] 2. Saline Purge
[0250] In the next phase of the post-collection cycle (Saline
Purge), the circuit is programmed to operate the donor interface
pump station PP3 (i.e., in through valve V11 and out through valve
V11) to convey saline from the container 288 through the separation
device, to displace the blood contents of the separation device
into the in-process container 312, in preparation for their return
to the donor. This phase reduces the loss of donor blood. This
phase continues until a predetermined volume of saline is pumped
through the separation device, as monitored by the weigh
sensor.
[0251] 3. Final Return to Donor
[0252] In the next phase of the post-collection cycle (Final
Return), the circuit is programmed to operate the donor interface
pump station PP3 (i.e., in through valve V11 and out through valve
V13) to convey the blood contents of the in-process container 312
to the donor. Saline is intermittently mixed with the blood
contents. This phase continues until the in-process container 312
is empty, as monitored by the weigh sensor.
[0253] In the next phase (Fluid Replacement), the circuit is
programmed to operate the donor interface pump station PP3 (i.e.,
in through valve V11 and out through valve V13) to convey the
saline to the donor. This phase continues until a prescribed
replacement volume amount is infused, as monitored by the weigh
sensor.
[0254] In the next phase of the post-collection cycle (Empty In
Process Container), the circuit is programmed to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V13) to convey all remaining contents of the
in-process container 312 to the donor, in preparation of splitting
the contents of the red blood cell container 308 for storage in
both containers 308 and 312. This phase continues until a zero
volume reading for the in-process container 312 occurs, as
monitored by the weigh sensor, and air is detected at the air
detector.
[0255] At this phase, the circuit is programmed to close all valves
and idle all pump stations, so that the phlebotomy needle 268 can
be removed from the donor.
[0256] The programming of the circuit during the phases of the
post-collection cycle is summarized in the following table.
3TABLE Programming of Blood Processing Circuit During The
Post-Collection Cycle (Double Red Blood Cell Collection Procedure)
Excess Empty In Plasma Saline Final Fluid Process Phase Return
Purge Return Replacement Container V1 .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .smallcircle. V2 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V3
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V4 .circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. V5 .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V5
.smallcircle./.circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. Alternates with V23 V7 .circle-solid.
.circle-solid. .smallcircle./.circle-so- lid. .circle-solid.
.smallcircle. Alternates with V23 V8 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V9 .smallcircle.
.smallcircle. .circle-solid. .circle-solid. .circle-solid. V10
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V11 .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid. Pump In
Pump Pump In Pump In Pump In In/ Pump Out V12 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V13
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump Out Pump Out Pump Out Pump Out
V14 .circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. V15 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V16 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V18
.smallcircle. .circle-solid. .smallcircle. .smallcircle.
.smallcircle. V19 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V20 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V21 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V22
.smallcircle. .smallcircle. .smallcircle. .smallcircle.
.circle-solid. V23 .smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle. .circle-solid.
Alternates Alternates with V6 with V7 PP1 .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. PP2 .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. PP3 .quadrature. .quadrature.
.quadrature. .quadrature. .quadrature. PP4 .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid.
[0257] E. The Storage Preparation Cycle
[0258] 1. Split RBC
[0259] In the first phase of the storage preparation cycle (Split
RBC), the circuit is programmed to operate the donor interface pump
station PP3 to transfer half of the contents of the red blood cell
collection container 308 into the in-process container 312. The
volume pumped is monitored by the weigh sensors for the containers
308 and 312.
[0260] 2. Add RBC Preservative
[0261] In the next phases of the storage preparation cycle (Add
Storage Solution to the In Process Container and Add Storage
Solution to the Red Blood Cell Collection Container), the circuit
is programmed to operate the donor interface pump station PP3 to
transfer a desired volume of red blood cell storage solution from
the container 280 first into the in-process container 312 and then
into the red blood cell collection container 308. The transfer of
the desired volume is monitored by the weigh scale.
[0262] In the next and final phase (End Procedure), the circuit is
programmed to close all valves and idle all pump stations, so that
the red blood cell containers 308 and 312 can be separated and
removed for storage. The remainder of the disposable set can now be
removed and discarded.
[0263] The programming of the circuit during the phases of the
storage preparation cycle is summarized in the following table.
4TABLE Programming of Blood Processing Circuit During The Storage
Preparation Cycle (Double Red Blood Cell Collection Procedure)
Split RBC Between RBC Add Storage End Collection Add Storage
Solution to Procedure and In Solution to In RBC (Remove Process
Process Collection Veni- Phase Containers Container Container
puncture) V1 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V2 .largecircle. .circle-solid. .largecircle.
.circle-solid. V3 .largecircle./.circle-solid. .largecircle.
.circle-solid. .circle-solid. Alternates with V11 and V4 V4
.largecircle./.circle-solid. .circle-solid. .largecircle.
.circle-solid. Alternates with V11 and V4 V5 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V6 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V7 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V8 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V9 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V10 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V11
.largecircle./.circle-solid. .largecircle./.circle-solid.
.largecircle./.circle-solid. .circle-solid. Pump In/ Pump In/ Pump
In/ Pump Out Pump Out Pump Out V12 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V13 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V14 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V15 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V16 .circle-solid. .largecircle.
.largecircle. .circle-solid. V17 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V18 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V19 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V20 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V21 .circle-solid. .largecircle.
.largecircle. .circle-solid. V22 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V23 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. PP1 .box-solid. .box-solid.
.box-solid. .box-solid. PP2 .box-solid. .box-solid. .box-solid.
.box-solid. PP3 .quadrature. .quadrature. .quadrature. .box-solid.
PP4 .box-solid. .box-solid. .box-solid. .box-solid. Caption:
.largecircle. denotes an open valve; .circle-solid. denotes a
closed valve; .largecircle./.circle-soli- d. denotes a valve
opening and closing during a pumping sequence; .box-solid. denotes
an idle pump station (not in use); and .quadrature. denotes a pump
station in use.
[0264] F. Plasma Collection (No Red Blood Cell Collection)
[0265] During this procedure, whole blood from a donor is
centrifugally processed to yield up to 880 ml of plasma for
collection. All red blood cells are returned to the donor. This
procedure will, in shorthand, be called the plasma collection
procedure.
[0266] Programming of the blood processing circuit 46 (through the
selective application of pressure to the valves and pump stations
of the cassette) makes it possible to use the same universal set
264 as in the double red blood cell collection procedure.
[0267] The procedure includes a pre-collection cycle, a collection
cycle, and a post-collection cycle.
[0268] During the pre-collection cycle, the set 264 is primed to
vent air prior to venipuncture. During the collection cycle, whole
blood drawn from the donor is processed to collect plasma, while
returning red blood cells to the donor. During the post-collection
cycle, excess plasma is returned to the donor, and the set is
flushed with saline.
[0269] 1. The Pre-Collection Cycle
[0270] a. Anticoagulant Prime
[0271] In the pre-collection cycle for the plasma collection (no
red blood cells) procedure, the cassette is programmed to carry out
AC Prime 1 and AC Prime 2 Phases that are identical to the AC Prime
1 and AC Prime 2 Phases of the double red blood cell collection
procedure.
[0272] b. Saline Prime
[0273] In the pre-collection cycle for the plasma collection (no
red blood cell) procedure, the cassette is programmed to carry out
Saline Prime 1, Saline Prime 2, Saline Prime 3, Vent Donor Line,
and Venipuncture Phases that are identical to the Saline Prime 1,
Saline Prime 2, Saline Prime 3, Vent Donor Line, and Venipuncture
Phases of the double red blood cell collection procedure.
[0274] The programming of the circuit during the phases of the
pre-collection cycle is summarized in the following table.
5TABLE Programming of Blood Processing Circuit During Pre-
Collection Phase (Plasma Collection Procedure) Vent AC AC Saline
Saline Saline Donor Veni- Phase Prime 1 Prime 2 Prime 1 Prime 2
Prime 3 Line puncture V1 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V2 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V3
.smallcircle. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. V4 .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V5 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V6 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid. V7
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. V8 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V9 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump
Pump Pump In Out Out (Stage 1) .smallcircle. (Stage 2) V10
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (Stage 1)
.smallcircle./.circle-solid. Pump Out (Stage 2) V11
.smallcircle./.circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Pump In Out V12 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. (Stage 1) .smallcircle./.circle-solid. Pump In
(Stage 2) V13 .smallcircle./.circle-solid. .smallcircle.
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump In Pump Out V14
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. .circle-solid. Pump In Pump In Pump Out (Stage 1)
.smallcircle. (Stage 2) V15 .smallcircle.
.smallcircle./.circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. Pump In Pump Out V16
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V18 .smallcircle. .smallcircle.
.circle-solid. .circle-solid. .circle-solid. .smallcircle.
.circle-solid. V19 .smallcircle. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V20
.smallcircle. .smallcircle./.circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. Pump Out
Pump In V21 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V22
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.smallcircle. .circle-solid. .circle-solid. V23 .circle-solid.
.circle-solid. .smallcircle. .smallcircle. .smallcircle.
.circle-solid. .circle-solid. PP1 .box-solid. .box-solid.
.quadrature. .quadrature. .quadrature. .box-solid. .box-solid.
(Stage 1) PP2 .box-solid. .box-solid. .box-solid. .box-solid.
.quadrature. .box-solid. .box-solid. (Stage 2) PP3 .quadrature.
.box-solid. .box-solid. .box-solid. .box-solid. .quadrature.
.box-solid. PP4 .box-solid. .quadrature. .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. Caption: .smallcircle. denotes
an open valve; .circle-solid. denotes a closed valve;
.smallcircle./.circle-s- olid. denotes a valve opening and closing
during a pumping sequence; .box-solid. denotes an idle pump station
(not in use); and .quadrature. denotes a pump station in use.
[0275] 2. The Collection Cycle
[0276] a. Blood Prime
[0277] With venipuncture, tube 300 leading to the phlebotomy needle
268 is opened. In a first phase of the collection cycle (Blood
Prime 1), the blood processing circuit 46 is programmed to operate
the donor interface pump PP3 (i.e., in through valve V13 and out
through valve V11) and the anticoagulant pump PP4 (i.e., in through
valve V20 and out through valve V15) to draw anticoagulated blood
through the donor tube 270 into the in process container 312, in
the same fashion as the Blood Prime 1 Phase of the the double red
blood cell collection procedure, as already described.
[0278] In a next phase (Blood Prime 2), the blood processing
circuit 46 is programmed to operate the in-process pump station PP1
to draw anticoagulated blood from the in-process container 312
through the separation device, in the same fashion as the Blood
Prime 2 Phase for the double red blood cell collection procedure,
as already described. During this phase, saline displaced by the
blood is returned to the donor.
[0279] b. Blood Separation While Drawing Whole Blood or Without
Drawing Whole Blood
[0280] In a next phase of the blood collection cycle (Blood
Separation While Drawing Whole Blood), the blood processing circuit
46 is programmed to operate the donor interface pump station PP3
(i.e., in through valve V13 and out through valve V11); the
anticoagulant pump PP4 (i.e., in through valve V20 and out through
valve V15); the in-process pump PP1 (i.e., in through valve V9 and
out through valve V14); and the plasma pump PP2 (i.e., in through
valve V12 and out through valve V10), in the same fashion as the
Blood Separation While Drawing Whole Blood Phase for the double red
blood cell collection procedure, as already described. This
arrangement draws anticoagulated blood into the in-process
container 312, while conveying the blood from the in-process
container 312 into the processing chamber for separation. This
arrangement also removes plasma from the processing chamber into
the plasma container 304, while removing red blood cells from the
processing chamber into the red blood cell container 308. This
phase continues until the targeted volume of plasma is collected in
the plasma collection container 304 (as monitored by the weigh
sensor) or until a targeted volume of red blood cells is collected
in the red blood cell collection container (as monitored by the
weigh sensor).
[0281] As in the double red blood cell collection procedure, if the
volume of whole blood in the in-process container 312 reaches a
predetermined maximum threshold before the targeted volume of
either plasma or red blood cells is collected, the circuit is
programmed to enter another phase (Blood Separation Without Drawing
Whole Blood), to terminate operation of the donor interface pump
station PP3 (while also closing valves V13, V11, V18, and V13) to
terminate collection of whole blood in the in-process container
312, while still continuing blood separation. If the volume of
whole blood reaches a predetermined minimum threshold in the
in-process container 312 during blood separation, but before the
targeted volume of either plasma or red blood cells is collected,
the circuit is programmed to return to the Blood Separation While
Drawing Whole Blood Phase, to thereby refill the in-process
container 312. The circuit is programmed to toggle between the
Blood Separation Phases while drawing whole blood and without
drawing whole blood, according to the high and low volume
thresholds for the in-process container 312, until the requisite
volume of plasma has been collected, or until the target volume of
red blood cells has been collected, whichever occurs first.
[0282] C. Return Red Blood Cells/Saline
[0283] If the targeted volume of plasma has not been collected, the
next phase of the blood collection cycle (Return Red Blood Cells
With Separation) programs the blood processing circuit 46 to
operate the donor interface pump station PP3 (i.e., in through
valve V11 and out through valve V13); the in-process pump PP1
(i.e., in through valve V9 and out through valve V14); and the
plasma pump PP2 (i.e., in through valve V12 and out through valve
V10). This arrangement conveys anticoagulated whole blood from the
in-process container 312 into the processing chamber for
separation, while removing plasma into the plasma container 304 and
red blood cells into the red blood cell container 308. This
arrangement also conveys red blood cells from the red blood cell
container 308 to the donor, while also mixing saline from the
container 288 in line with the returned red blood cells. The in
line mixing of saline with the red blood cells raises the saline
temperature and improves donor comfort. The in line mixing of
saline with the red blood cells also lowers the hematocrit of the
red blood cells being returned to the donor, thereby allowing a
larger gauge (i.e., smaller diameter) phlebotomy needle to be used,
to further improve donor comfort. This phase continues until the
red blood cell container 308 is empty, as monitored by the weigh
sensor.
[0284] If the volume of whole blood in the in-process container 312
reaches a specified low threshold before the red blood cell
container 308 empties, the circuit is programmed to enter another
phase (Red Blood Cell Return Without Separation), to terminate
operation of the in-process pump station PP1 (while also closing
valves V9, V10, V12, and V14) to terminate blood separation. The
phase continues until the red blood cell container 308 empties.
[0285] Upon emptying the red blood cell container 308, the circuit
is programmed to enter another phase (Fill Donor Line), to operate
the donor interface pump station PP3 (i.e., in through valve V11
and out through valve V13) to draw whole blood from the in process
container 312 to fill the donor tube 266, thereby purge red blood
cells (mixed with saline) in preparation for another draw whole
blood cycle.
[0286] The circuit is then programmed to conduct another Blood
Separation While Drawing Whole Blood Phase, to refill the in
process container 312. The circuit is programmed to conduct
successive draw whole blood and return red blood cells/saline
cycles, as described, until the weigh sensor indicates that a
desired volume of plasma has been collected in the plasma
collection container 304. When the targeted volume of plasma has
been collected, the post-collection cycle commences.
[0287] The programming of the circuit during the phases of the
collection cycle is summarized in the following table.
6TABLE Programming of Blood Processing Circuit During The
Collection Cycle (Plasma Collection Procedure) Blood Separation
While Return Red Drawing Blood Cells/ Whole Blood Saline (Without
with Drawing Separation Whole (Without Phase Blood Prime 1 Blood
Prime 2 Blood) Separation) Fill Donor Line V1 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .smallcircle. V2
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.circle-solid. V3 .smallcircle. .circle-solid. .smallcircle.
.circle-solid. .circle-solid. (.circle-solid.) V4 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V5
.circle-solid. .circle-solid. .smallcircle.
.smallcircle.(.circle-solid.) .circle-solid. V6 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V7
.circle-solid. .smallcircle. .circle-solid.
.smallcircle./.circle-solid. .smallcircle. Alternates with V23 V8
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V9 .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In Pump In (.circle-solid.) V10
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump Out Pump Out
(.circle-solid.) V11 .smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump Out Pump Out Pump In Pump In
(.circle-solid.) V12 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In (.circle-solid.) V13
.smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump In Pump In Pump Out Pump Out
(.circle-solid.) V14 .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump Out Pump Out (.circle-solid.) V15
.smallcircle./.circle-sol- id. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump Out (.circle-solid.) V16 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V18
.smallcircle. .smallcircle. .smallcircle. .smallcircle.
.smallcircle. (.circle-solid.) V19 .smallcircle. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (.circle-solid.) V20
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump In (.circle-solid.) V21 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V22 .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V23
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Alternates with V7 PP1
.box-solid. .quadrature. .quadrature. .quadrature. .box-solid.
(.box-solid.) PP2 .box-solid. .box-solid. .quadrature. .quadrature.
.box-solid. (.box-solid.) PP3 .quadrature. .box-solid. .quadrature.
.quadrature. .quadrature. (.box-solid.) PP4 .quadrature.
.box-solid. .quadrature. .box-solid. .box-solid. (.box-solid.)
Caption: .smallcircle. denotes an open valve; .circle-solid.
denotes a closed valve; .smallcircle./.circle-solid. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0288] d. The Post-Collection Cycle
[0289] Once the targeted volume of plasma has been collected (as
monitored by the weigh sensor), the circuit is programmed to carry
out the phases of the post-collection cycle.
[0290] 3. Return Excess Red Blood Cells
[0291] In a first phase of the post-collection cycle (Remove Plasma
Collection Container), the circuit is programmed to close all
valves and disable all pump stations to allow separation of the
plasma collection container 304 from the set 264.
[0292] In the second phase of the post-collection cycle (Return Red
Blood Cells), the circuit is programmed to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V13) to convey red blood cells remaining in the red
blood cell collection container 308 to the donor. The circuit is
also programmed in this phase to mix saline from the container 288
in line with the returned red blood cells. This phase continues
until the red blood cell container 308 is empty, as monitored by
the weigh sensor.
[0293] 4. Saline Purge
[0294] In the next phase of the post-collection cycle (Saline
Purge), the circuit is programmed to operate the donor interface
pump station PP3 (i.e., in through valve V11 and out through valve
V11) to convey saline from the container 288 through the separation
device, to displace the blood contents of the separation device
into the in-process container 312, in preparation for their return
to the donor. This phase reduces the loss of donor blood. This
phase continues until a predetermined volume of saline in pumped
through the separation device, as monitored by the weigh
sensor.
[0295] 5. Final Return to Donor
[0296] In the next phase of the post-collection cycle (Final
Return), the circuit is programmed to operate the donor interface
pump station PP3 (i.e., in through valve V11 and out through valve
V13) to convey the blood contents of the in-process container 312
to the donor. Saline is intermittently mixed with the blood
contents. This phase continues until the in-process container 312
is empty, as monitored by the weigh sensor.
[0297] In the next phase (Fluid Replacement), the circuit is
programmed to operate the donor interface pump station PP3 (i.e.,
in through valve V11 and out through valve V13) to convey the
saline to the donor. This phase continues until a prescribed
replacement volume amount is infused, as monitored by the weigh
sensor.
[0298] In the final phase (End Procedure), the circuit is
programmed to close all valves and idle all pump stations, so that
venipuncture can be terminated, and the plasma container can be
separated and removed for storage. The remaining parts of the
disposable set can be removed and discarded.
[0299] The programming of the circuit during the phases of the
post-collection cycle is summarized in the following table.
7TABLE Programming of Blood Processing Circuit During The
Post-Collection Cycle (Plasma Collection Procedure) Remove Plasma
Collection Return Saline Final Fluid End Phase Container RBC Purge
Return Replacement Procedure V1 .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid. V2
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V3 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V4
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. V5 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V6
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V7 .circle-solid.
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Altern
Altern ates ates with with V23 V23 V8 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V9
.circle-solid. .smallcircle. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. V10 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V11
.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump Pump Pump Pump In
In In/ In Pump Out V12 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V13 .circle-solid.
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Pump Pump Out Out Out V14 .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. V15 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V16 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V17 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V18 .circle-solid.
.circle-solid. .smallcircle. .smallcircle. .circle-solid. V19
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V20 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V21
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V22 .circle-solid. .smallcircle.
.smallcircle. .smallcircle. .smallcircle. .circle-solid. V23
.circle-solid. .smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle. .circle-solid. Altern
Altern ates ates with with V6 V7 PP1 .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. .box-solid. PP2 .box-solid.
.box-solid. .box-solid. .box-solid. .box-solid. .box-solid. PP3
.box-solid. .quadrature. .quadrature. .quadrature. .quadrature. PP4
.box-solid. .box-solid. .box-solid. .box-solid. .box-solid.
Caption: .smallcircle. denotes an open valve; .circle-solid.
denotes a closed valve; .smallcircle./.circle-solid. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0300] G. Red Blood Cell and Plasma Collection
[0301] During this procedure, whole blood from a donor is
centrifugally processed to collect up to about 550 ml of plasma and
up to about 250 ml of red blood cells. This procedure will, in
shorthand, be called the red blood cell/plasma collection
procedure.
[0302] The portion of the red blood cells not retained for
collection are periodically returned to the donor during blood
separation. Plasma collected in excess of the 550 ml target and red
blood cells collected in excess of the 250 ml target are also
returned to the donor at the end of the procedure.
[0303] Programming of the blood processing circuit 46 (through the
selective application of pressure to the valves and pump stations
of the cassette) makes it possible to use the same universal set
264 used to carry out the double red blood cell collection or the
plasma collection procedure.
[0304] The procedure includes a pre-collection cycle, a collection
cycle, and a post-collection cycle, and a storage preparation
cycle.
[0305] During the pre-collection cycle, the set 264 is primed to
vent air prior to venipuncture. During the collection cycle, whole
blood drawn from the donor is processed to collect plasma and red
blood cells, while returning a portion of the red blood cells to
the donor. During the post-collection cycle, excess plasma and red
blood cells are returned to the donor, and the set is flushed with
saline. During the storage preparation cycle, a red blood cell
storage solution added to the collected red blood cells.
[0306] (1) The Pre-Collection Cycle
[0307] a. Anticoagulant Prime
[0308] In the pre-collection cycle for the red blood cell/plasma
collection procedure, the cassette is programmed to carry out AC
Prime 1 and AC Prime 2 Phases that are identical to the AC Prime 1
and AC Prime 2 Phases of the double red blood cell collection
procedure.
[0309] b. Saline Prime
[0310] In the pre-collection cycle for the red blood cell/plasma
collection procedure, the cassette is programmed to carry out
Saline Prime 1, Saline Prime 2, Saline Prime 3, Vent Donor Line,
and Venipuncture Phases that are identical to the Saline Prime 1,
Saline Prime 2, Saline Prime 3, Vent Donor Line, and Venipuncture
Phases of the double red blood cell collection procedure.
[0311] The programming of the circuit during the phases of the
pre-collection cycle is summarized in the following table.
8TABLE Programming of Blood Processing Circuit During Pre-
Collection Cycle (Red Blood Cell/Plasma Collection Procedure) Vent
AC AC Saline Saline Saline Donor Veni- Phase Prime 1 Prime 2 Prime
1 Prime 2 Prime 3 Line puncture V1 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V2 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V3
.smallcircle. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. V4 .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V5 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V6 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. .circle-solid. V7
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. V8 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V9 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump
Pump Pump In Out Out (Stage 1) .smallcircle. (Stage 2) V10
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (Stage 1)
.smallcircle./.circle-solid. Pump Out (Stage 2) V11
.smallcircle./.circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Pump In Out V12 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. (Stage 1) .smallcircle./.circle-solid. Pump In
(Stage 2) V13 .smallcircle./.circle-solid. .smallcircle.
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump In Pump Out V14
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. .circle-solid. Pump In Pump In Pump Out (Stage 1)
.smallcircle. (Stage 2) V15 .smallcircle.
.smallcircle./.circle-solid. .circle-solid. .circle-solid.
.circle-solid. .smallcircle. .circle-solid. Pump In Pump Out V16
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V18 .smallcircle. .smallcircle.
.circle-solid. .circle-solid. .circle-solid. .smallcircle.
.circle-solid. V19 .smallcircle. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V20
.smallcircle. .smallcircle./.circle-solid. .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. Pump Out
Pump In V21 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V22
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.smallcircle. .circle-solid. .circle-solid. V23 .circle-solid.
.circle-solid. .smallcircle. .smallcircle. .smallcircle.
.circle-solid. .circle-solid. PP1 .box-solid. .box-solid.
.quadrature. .quadrature. .quadrature. .box-solid. .box-solid.
(Stage 1) PP2 .box-solid. .box-solid. .box-solid. .box-solid.
.quadrature. .box-solid. .box-solid. (Stage 2) PP3 .quadrature.
.box-solid. .box-solid. .box-solid. .box-solid. .quadrature.
.box-solid. PP4 .box-solid. .quadrature. .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. Caption: .smallcircle. denotes
an open valve; .circle-solid. denotes a closed valve;
.smallcircle./.circle-s- olid. denotes a valve opening and closing
during a pumping sequence; .box-solid. denotes an idle pump station
(not in use); and .quadrature. denotes a pump station in use.
[0312] 2. The Collection Cycle
[0313] a. Blood Prime
[0314] With venipuncture, tube 300 leading to the phlebotomy needle
268 is opened. The collection cycle of the red blood cell/plasma
collection procedure programs the circuit to carry out Blood Prime
1 and Blood Prime 2 Phases that are identical to the Blood Prime 1
and Blood Prime 2 Phases of the Double Red Blood Cell Collection
Procedure, already described.
[0315] b. Blood Separation While Drawing Whole Blood or Without
Drawing Whole Blood
[0316] In the blood collection cycle for the red blood cell/plasma
collection procedure, the circuit is programmed to conduct a Blood
Separation While Drawing Whole Blood Phase, in the same fashion
that the Blood Separation While Drawing Whole Blood Phase is
conducted for the double red blood cell collection procedure. This
arrangement draws anticoagulated blood into the in-process
container 312, while conveying the blood from the in-process
container 312 into the processing chamber for separation. This
arrangement also removes plasma from the processing chamber into
the plasma container 304, while removing red blood cells from the
processing chamber into the red blood cell container 308. This
phase continues until the desired maximum volumes of plasma and red
blood cells have been collected in the plasma and red blood cell
collection containers 304 and 308 (as monitored by the weigh
sensor).
[0317] As in the double red blood cell collection procedure and the
plasma collection procedure, if the volume of whole blood in the
in-process container 312 reaches a predetermined maximum threshold
before the targeted volume of either plasma or red blood cells is
collected, the circuit is programmed to enter a phase (Blood
Separation Without Whole Blood Draw) to terminate operation of the
donor interface pump station PP3 (while also closing valves V13,
V11, V18, and V13) to terminate collection of whole blood in the
in-process container 312, while still continuing blood separation.
If the volume of whole blood reaches a predetermined minimum
threshold in the in-process container 312 during blood separation,
but before the targeted volume of either plasma or red blood cells
is collected, the circuit is programmed to return to the Blood
Separation With Whole Blood Draw, to thereby refill the in-process
container 312. The circuit is programmed to toggle between the
Blood Separation cycle with whole blood draw and without whole
blood draw according to the high and low volume thresholds for the
in-process container 312, until the requisite maximum volumes of
plasma and red blood cells have been collected.
[0318] c. Return Red Blood Cells and Saline
[0319] If the targeted volume of plasma has not been collected, and
red blood cells collected in the red blood cell container 308
exceed a predetermined maximum threshold, the next phase of the
blood collection cycle (Return Red Blood Cells With Separation)
programs the blood processing circuit 46 to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V13); the in-process pump PP1 (i.e., in through valve
V9 and out through valve V14); and the plasma pump PP2 (i.e., in
through valve V12 and out through valve V10). This arrangement
continues to convey anticoagulated whole blood from the in-process
container 312 into the processing chamber for separation, while
removing plasma into the plasma container 304 and red blood cells
into the red blood cell container 308. This arrangement also
conveys all or a portion of the red blood cells collected in the
red blood cell container 308 to the donor. This arrangement also
mixes saline from the container 288 in line with the returned red
blood cells. The in line mixing of saline with the red blood cells
raises the saline temperature and improves donor comfort. The in
line mixing of saline with the red blood cells also lowers the
hematocrit of the red blood cells being returned to the donor,
thereby allowing a larger gauge (i.e., smaller diameter) phlebotomy
needle to be used, to further improve donor comfort.
[0320] This phase can continue until the red blood cell container
308 is empty, as monitored by the weigh sensor, thereby
corresponding to the Return Red Blood Cells With Separation Phase
of the plasma collection procedure. Preferably, however, the
processor determines how much additional plasma needs to be
collected to meet the plasma target volume. From this, the
processor derives the incremental red blood cell volume associated
with the incremental plasma volume. In this arrangement, the
processor returns a partial volume of red blood cells to the donor,
so that, upon collection of the next incremental red blood cell
volume, the total volume of red blood cells in the container 308
will be at or slightly over the targeted red blood cell collection
volume.
[0321] If the volume of whole blood in the in-process container 312
reaches a specified low threshold before return of the desired
volume of red blood cells, the circuit is programmed to enter a
phase (Return Red Blood Cells Without Separation), to terminate
operation of the in-process pump station PP1 (while also closing
valves V9, V10, V12, and V14) to terminate blood separation. This
phase corresponds to the Return Red Blood Cells Without Separation
Phase of the plasma collection procedure.
[0322] Upon returning the desired volume of red blood cells from
the container 308, the circuit is programmed to enter a phase (Fill
Donor Line), to operate the donor interface pump station PP3 (i.e.,
in through valve V11 and out through valve V13) to draw whole blood
from the in process container 312 to fill the donor tube 266,
thereby purge red blood cells (mixed with saline) in preparation
for another draw whole blood cycle.
[0323] The circuit is then programmed to conduct another Blood
Separation While Drawing Whole Blood Phase, to refill the in
process container 312. If required, the circuit is capable of
performing successive draw whole blood and return red blood cells
cycles, until the weigh sensors indicate that volumes of red blood
cells and plasma collected in the containers 304 and 308 are at or
somewhat greater than the targeted values. The post-collection
cycle then commences.
[0324] The programming of the circuit during the phases of the
collection cycle is summarized in the following table.
9TABLE Programming of Blood Processing Circuit During The
Collection Cycle (Red Blood Cell/Plasma Collection Procedure) Blood
Separation While Return Red Drawing Blood Cells/ Whole Blood Saline
(Without with Drawing Separation Whole (Without Phase Blood Prime 1
Blood Prime 2 Blood) Separation) Fill Donor Line V1 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .smallcircle. V2
.circle-solid. .circle-solid. .smallcircle. .smallcircle.
.circle-solid. V3 .smallcircle. .circle-solid. .smallcircle.
.circle-solid. .circle-solid. (.circle-solid.) V4 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V5
.circle-solid. .circle-solid. .smallcircle.
.smallcircle.(.circle-solid.) .circle-solid. V6 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V7
.circle-solid. .smallcircle. .circle-solid.
.smallcircle./.circle-solid. .smallcircle. Alternates with V23 V8
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V9 .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In Pump In (.circle-solid.) V10
.circle-solid. .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid. Pump Out Pump Out
(.circle-solid.) V11 .smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump Out Pump Out Pump In Pump In
(.circle-solid.) V12 .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In (.circle-solid.) V13
.smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. Pump In Pump In Pump Out Pump Out
(.circle-solid.) V14 .circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump Out Pump Out (.circle-solid.) V15
.smallcircle./.circle-sol- id. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump Out (.circle-solid.) V16 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V18
.smallcircle. .smallcircle. .smallcircle. .smallcircle.
.smallcircle. (.circle-solid.) V19 .smallcircle. .circle-solid.
.smallcircle. .circle-solid. .circle-solid. (.circle-solid.) V20
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. .circle-solid. Pump Out
Pump In (.circle-solid.) V21 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V22 .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid. V23
.circle-solid. .circle-solid. .circle-solid.
.smallcircle./.circle-solid. .circle-solid. Alternates with V7 PP1
.box-solid. .quadrature. .quadrature. .quadrature. .box-solid.
(.box-solid.) PP2 .box-solid. .box-solid. .quadrature. .quadrature.
.box-solid. (.box-solid.) PP3 .quadrature. .box-solid. .quadrature.
.quadrature. .quadrature. (.box-solid.) PP4 .quadrature.
.box-solid. .quadrature. .box-solid. .box-solid. (.box-solid.)
Caption: .smallcircle. denotes an open valve; .circle-solid.
denotes a closed valve; .smallcircle./.circle-solid. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0325] d. The Post-Collection Cycle
[0326] Once the targeted maximum volumes of plasma and red blood
cells have been collected (as monitored by the weigh sensor), the
circuit is programmed to carry out the phases of the
post-collection cycle.
[0327] i. Return Excess Plasma
[0328] If the volume of plasma collected in the plasma collection
container 304 is over the targeted volume, a phase of the
post-collection cycle (Excess Plasma Return) is entered, during
which the circuit is programmed to terminate the supply and removal
of blood to and from the processing chamber, while operating the
donor interface pump station PP3 (i.e., in through valve V11 and
out through valve V13) to convey plasma in the plasma container 304
to the donor. The circuit is also programmed in this phase to mix
saline from the container 288 in line with the returned plasma.
This phase continues until the volume of plasma in the plasma
collection container 304 is at the targeted value, as monitored by
the weigh sensor.
[0329] ii. Return Excess Red Blood Cells
[0330] If the volume of red blood cells collected in the red blood
cell collection container 308 is also over the targeted volume, a
phase of the post-collection cycle (Excess RBC Return) is entered,
during which the circuit is programmed to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V13) to convey red blood cells remaining in the red
blood cell collection container 308 to the donor. The circuit is
also programmed in this phase to mix saline from the container 288
in line with the returned red blood cells. This phase continues
until the volume of red blood cells in the container 308 equals the
targeted value, as monitored by the weigh sensor.
[0331] iii. Saline Purge
[0332] When the volumes of red blood cells and plasma collected in
the containers 308 and 304 equal the targeted values, the next
phase of the post-collection cycle (Saline Purge) is entered,
during which the circuit is programmed to operate the donor
interface pump station PP3 (i.e., in through valve V11 and out
through valve V11) to convey saline from the container 288 through
the separation device, to displace the blood contents of the
separation device into the in-process container 312, in preparation
for their return to the donor. This phase reduces the loss of donor
blood. This phase continues until a predetermined volume of saline
in pumped through the separation device, as monitored by the weigh
sensor.
[0333] iv. Final Return to Donor
[0334] In the next phase of the post-collection cycle (Final
Return), the circuit is programmed to operate the donor interface
pump station PP3 (i.e., in through valve V11 and out through valve
V13) to convey the blood contents of the in-process container 312
to the donor. Saline is intermittently mixed with the blood
contents. This phase continues until the in-process container 312
is empty, as monitored by the weigh sensor.
[0335] In the next phase (Fluid Replacement), the circuit is
programmed to operate the donor interface pump station PP3 (i.e.,
in through valve V11 and out through valve V13) to convey the
saline to the donor. This phase continues until a prescribed
replacement volume amount is infused, as monitored by the weigh
sensor.
[0336] In the next phase (End Venipuncture), the circuit is
programmed to close all valves and idle all pump stations, so that
venipuncture can be terminated.
[0337] The programming of the circuit during the phases of the
post-collection cycle is summarized in the following table.
10TABLE Programming of Blood Processing Circuit During The
Post-Collection Cycle (Red Blood Cell/Plasma Collection Procedure)
Excess End Plasma Excess RBC Fluid Veni- Phase Return Return Saline
Purge Final Return Replacement puncture V1 .circle-solid.
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. V2 .circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V3 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V4 .circle-solid. .circle-solid. .smallcircle.
.circle-solid. .circle-solid. .circle-solid. V5 .smallcircle.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V6 .smallcircle./.circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
Alternates with V23 V7 .circle-solid. .smallcircle./.circle-solid.
.circle-solid. .smallcircle./.circle-solid. .circle-solid.
.circle-solid. Alternates Alternates with V23 with V23 V8
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V9 .smallcircle. .smallcircle.
.smallcircle. .circle-solid. .circle-solid. .circle-solid. V10
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V11 .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump In Pump In Pump Pump In Pump In In/ Pump Out
V12 .circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V13 .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .circle-solid.
.smallcircle./.circle-solid. .smallcircle./.circle-solid.
.circle-solid. Pump Out Pump Out Pump Out Pump Out V14
.circle-solid. .circle-solid. .smallcircle. .circle-solid.
.circle-solid. .circle-solid. V15 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V16
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. V17 .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid. V18
.smallcircle. .circle-solid. .smallcircle. .smallcircle.
.circle-solid. V19 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V20 .circle-solid.
.circle-solid. .circle-solid. .circle-solid. .circle-solid.
.circle-solid. V21 .circle-solid. .circle-solid. .circle-solid.
.circle-solid. .circle-solid. .circle-solid. V22 .smallcircle.
.smallcircle. .smallcircle. .smallcircle. .smallcircle.
.circle-solid. V23 .smallcircle./.circle-solid.
.smallcircle./.circle-solid. .smallcircle.
.smallcircle./.circle-solid. .smallcircle. .circle-solid.
Alternates Alternates Alternates with V6 with V6 with V7 PP1
.box-solid. .box-solid. .box-solid. .box-solid. .box-solid.
.box-solid. PP2 .box-solid. .box-solid. .box-solid. .box-solid.
.box-solid. .box-solid. PP3 .quadrature. .quadrature. .quadrature.
.quadrature. .quadrature. .box-solid. PP4 .box-solid. .box-solid.
.box-solid. .box-solid. .box-solid. .box-solid. Caption:
.smallcircle. denotes an open valve; .circle-solid. denotes a
closed valve; .smallcircle./.circle-solid. denotes a valve opening
and closing during a pumping sequence; .box-solid. denotes an idle
pump station (not in use); and .quadrature. denotes a pump station
in use.
[0338] e. The Storage Preparation Cycle
[0339] i. RBC Preservative Prime
[0340] In the first phase of the storage preparation cycle (Prime
Storage Solution), the circuit is programmed to operate the donor
interface pump station PP3 to transfer a desired volume of red
blood cell storage solution from the container 280 into the
in-process container 312. The transfer of the desired volume is
monitored by the weigh scale.
[0341] In the next phase (Transfer Storage Solution), the circuit
is programmed to operate the donor interface pump station PP3 to
transfer a desired volume of red blood cell storage solution from
the in-process container 312 into the red blood cell collection
container 308. The transfer of the desired volume is monitored by
the weigh scale.
[0342] In the next and final phase (End Procedure), the circuit is
programmed to close all valves and idle all pump stations, so that
the plasma and red blood cell storage containers 304 and 308 can be
separated and removed for storage. The remainder of the disposable
set can now be removed and discarded.
[0343] The programming of the circuit during the phases of the
storage preparation cycle is summarized in the following table.
11TABLE Programming of Blood Processing Circuit During The Storage
Preparation Cycle (Red Blood Cell/Plasma Collection Procedure)
Prime Storage Transfer Storage Phase Solution Solution End
Procedure V1 .circle-solid. .circle-solid. .circle-solid. V2
.circle-solid. .largecircle. .circle-solid. V3 .largecircle.
.circle-solid. .circle-solid. V4 .circle-solid. .largecircle.
.circle-solid. V5 .circle-solid. .circle-solid. .circle-solid. V6
.circle-solid. .circle-solid. .circle-solid. V7 .circle-solid.
.circle-solid. .circle-solid. V8 .circle-solid. .circle-solid.
.circle-solid. V9 .circle-solid. .circle-solid. .circle-solid. V10
.circle-solid. .circle-solid. .circle-solid. V11
.largecircle./.circle-solid. .largecircle./.circle-solid.
.circle-solid. Pump In/ Pump In/ Pump Out Pump Out V12
.circle-solid. .circle-solid. .circle-solid. V13 .circle-solid.
.circle-solid. .circle-solid. V14 .circle-solid. .circle-solid.
.circle-solid. V15 .circle-solid. .circle-solid. .circle-solid. V16
.largecircle. .largecircle. .circle-solid. V17 .circle-solid.
.circle-solid. .circle-solid. V18 .circle-solid. .circle-solid.
.circle-solid. V19 .circle-solid. .circle-solid. .circle-solid. V20
.circle-solid. .circle-solid. .circle-solid. V21 .largecircle.
.largecircle. .circle-solid. V22 .circle-solid. .circle-solid.
.circle-solid. V23 .circle-solid. .circle-solid. .circle-solid. PP1
.box-solid. .box-solid. .box-solid. PP2 .box-solid. .box-solid.
.box-solid. PP3 .quadrature. .quadrature. .box-solid. PP4
.box-solid. .box-solid. .box-solid. Caption: .largecircle. denotes
an open valve; .circle-solid. denotes a closed valve;
.largecircle./.circle-solid. denotes a valve opening and closing
during a pumping sequence; .box-solid. denotes an idle pump station
(not in use); and .quadrature. denotes a pump station in use.
[0344] Caption: .circle-solid. denotes an open valve; .smallcircle.
denotes a closed valve; .circle-solid./.smallcircle. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0345] V. Interface Control
[0346] A. Underspill and Overspill Detection
[0347] In any of the above-described procedures, the centrifugal
forces present within the processing chamber 18 separate whole
blood into a region of packed red blood cells and a region of
plasma (see FIG. 15A). The centrifugal forces cause the region of
packed red blood cells to congregate along the outside or high-G
wall of the chamber, while the region of plasma is transported to
the inside or low-G wall of the chamber.
[0348] An intermediate region forms an interface between the red
blood cell region and the plasma region. Intermediate density
cellular blood species like platelets and leukocytes populate the
interface, arranged according to density, with the platelets closer
to the plasma layer than the leukocytes. The interface is also
called the "buffy coat," because of its cloudy color, compared to
the straw color of the plasma region and the red color of the red
blood cell region.
[0349] It is desirable to monitor the location of the buffy coat,
either to keep the buffy coat materials out of the plasma or out of
the red blood cells, depending on the procedure, or to collect the
cellular contents of the buffy coat. The system includes a sensing
station 332 comprising two optical sensors 334 and 336 for this
purpose.
[0350] In the illustrated and preferred embodiment (see FIG. 13),
the sensing station 332 is located a short distance outside the
centrifuge station 20. This arrangement minimizes the fluid volume
of components leaving the chamber before monitoring by the sensing
station 332.
[0351] The first sensor 334 in the station 332 optically monitors
the passage of blood components through the plasma collection tube
292. The second sensor 336 in the station 332 optically monitors
the passage of blood components through the red blood cell
collection tube 294.
[0352] The tubes 292 and 294 are made from plastic (e.g.
polyvinylchloride) material that is transparent to the optical
energy used for sensing, at least in the region where the tubes 292
and 294 are to be placed into association with the sensing station
332.
[0353] In the illustrated embodiment, the set 264 includes a
fixture 338 (see FIGS. 16 to 18) to hold the tubes 292 and 294 in
viewing alignment with its respective sensor 334 and 336. The
fixture 338 gathers the tubes 292 and 294 in a compact, organized,
side-by-side array, to be placed and removed as a group in
association with the sensors 334 and 336, which are also arranged
in a compact, side-by-side relationship within the station 332.
[0354] In the illustrated embodiment, the fixture 338 also holds
the tube 290, which conveys whole blood into the centrifuge station
20, even though no associated sensor is provided. The fixture 338
serves to gather and hold all tubes 290, 292, and 294 that are
coupled to the umbilicus 296 in a compact and easily handled
bundle.
[0355] The fixture 338 can be an integral part of the umbilicus
296, formed, e.g., by over molding. Alternatively, the fixture 338
can be a separately fabricated part, which snap fits about the
tubes 290, 292, and 294 for use.
[0356] In the illustrated embodiment (as FIG. 2 shows), the
containers 304, 308, and 312 coupled to the cassette 28 are
suspended during use above the centrifugation station 20. In this
arrangement, the fixture 338 directs the tubes 290, 292, and 294
through an abrupt, ninety degree bend immediately beyond the end of
the umbilicus 296 to the cassette 28. The bend imposed by the
fixture 338 directs the tubes 290, 292, and 294 in tandem away from
the area immediately beneath the containers 304, 308, and 312,
thereby preventing clutter in this area. The presence of the
fixture 338 to support and guide the tubes 290, 292, and 294
through the bend also reduces the risk of kinking or
entanglement.
[0357] The first sensor 334 is capable of detecting the presence of
optically targeted cellular species or components in the plasma
collection tube 292. The components that are optically targeted for
detection vary depending upon the procedure.
[0358] For a plasma collection procedure, the first sensor 334
detects the presence of platelets in the plasma collection tube
292, so that control measures can be initiated to move the
interface between the plasma and platelet cell layer back into the
processing chamber. This provides a plasma product that can be
essentially platelet-free or at least in which the number of
platelets is minimized.
[0359] For a red blood cell-only collection procedure, the first
sensor 334 detects the interface between the buffy coat and the red
blood cell layer, so that control measures can be initiated to move
this interface back into the processing chamber. This maximizes the
red blood cell yield.
[0360] For a buffy coat collection procedure (which will be
described later), the first sensor 334 detects when the leading
edge of the buffy coat (i.e., the plasma/platelet interface) begins
to exit the processing chamber, as well as detects when the
trailing edge of the buffy coat (i.e., the buffy coat/red blood
cell interface) has completely exited the processing chamber.
[0361] The presence of these cellular components in the plasma, as
detected by the first sensor 334, indicates that the interface is
close enough to the low-G wall of the processing chamber to allow
all or some of these components to be swept into the plasma
collection line (see FIG. 15B). This condition will also be called
an "over spill."
[0362] The second sensor 336 is capable of detecting the hematocrit
of the red blood cells in the red blood cell collection tube 294.
The decrease of red blood hematocrit below a set minimum level
during processing that the interface is close enough to the high-G
wall of the processing chamber to allow plasma to enter the red
blood cell collection tube 294 (see FIG. 15C). This condition will
also be called an "under spill."
[0363] B. The Sensing Circuit
[0364] The sensing station 332 includes a sensing circuit 340 (see
FIG. 19), of which the first sensor 334 and second sensor 336 form
a part.
[0365] The first sensor 334 includes one green light emitting diode
(LED) 350, one red LED 352, and two photodiodes 354 and 355. The
photodiode 354 measures transmitted light, and the photodiode 355
measures reflected light.
[0366] The second sensor 336 includes one red LED 356 and two
photodiodes 358 and 360. The photodiode 358 measures transmitted
light, and the photodiode 360 measures reflected light.
[0367] The sensing circuit 340 further includes an LED driver
component 342. The driver component 342 includes a constant current
source 344, coupled to the LED's 350, 352, and 356 of the sensors
334 and 336. The constant current source 344 supplies a constant
current to each LED 350, 352, and 356, independent of temperature
and the power supply voltage levels. The constant current source
344 thereby provides a constant output intensity for each LED 350,
352, and 356.
[0368] The LED drive component 342 includes a modulator 346. The
modulator 346 modulates the constant current at a prescribed
frequency. The modulation 346 removes the effects of ambient light
and electromagnetic interference (EMI) from the optically sensed
reading, as will be described in greater detail later.
[0369] The sensing circuit 340 also includes a receiver circuit 348
coupled to the photodiodes 354, 355, 358, and 360. The receiver
circuit 348 includes, for each photodiode 354, 355, 358, and 360, a
dedicated current-to-voltage (I-V) converter 362. The remainder of
the receiver circuit 348 includes a bandpass filter 364, a
programmable amplifier 366, and a full wave rectifier 368. These
components 364, 366, and 368 are shared, e.g., using a
multiplexer.
[0370] Ambient light typically contains frequency components less
than 1000 Hz, and EMI typically contains frequency components above
2 Khz. With this in mind, the modulator 346 modulates the current
at a frequency below the EMI frequency components, e.g., at about 2
Khz. The bandpass filter 364 has a center frequency of about the
same value, i.e., about 2 Khz. The sensor circuit 340 eliminates
frequency components above and below the ambient light source and
EMI components from the sensed measurement. In this way, the
sensing circuit 340 is not sensitive to ambient lighting conditions
and EMI.
[0371] More particularly, transmitted or reflected light from the
tube 292 or 294 containing the fluid to be measured is incident on
photodiodes 354 and 355 (for the tube 292) or photodiodes 358 and
360 (for tube 294). Each photodiode produces a photocurrent
proportional to the received light intensity. This current is
converted to a voltage. The voltage is fed, via the multiplexer
370, to the bandpass filter 364. The bandpass filter 364 has a
center frequency at the carrier frequency of the modulated source
light (i.e., 2 Khz in the illustrated embodiment).
[0372] The sinusoidal output of the bandpass filter 364 is sent to
the variable gain amplifier 366. The gain of the amplifier is
preprogrammed in preestablished steps, e.g., X1, X10, X100, and
X1000. This provides the amplifier with the capability to respond
to a large dynamic range.
[0373] The sinusoidal output of the amplifier 366 is sent to the
full wave rectifier 368, which transforms the sinusoidal output to
a DC output voltage proportional to the transmitted light
energy.
[0374] The controller 16 generates timing pulses for the sensor
circuit 340. The timing pulses comprise, for each LED, (i) a
modulation square wave at the desired modulation frequency (i.e., 2
Khz in the illustrated embodiment), (ii) an enable signal, (iii)
two sensor select bits (which select the sensor output to feed to
the bandpass filter 364), and (iv) two bits for the receiver
circuit gain selection (for the amplifier 366).
[0375] The controller 16 conditions the driver circuit 342 to
operate each LED in an ON state and an OFF state.
[0376] In the ON state, the LED enable is set HIGH, and the LED is
illuminated for a set time interval, e.g., 100 ms. During the first
83.3 ms of the ON state, the finite rise time for the incident
photodiode and receiver circuit 348 are allowed to stabilize.
During the final 16.7 ms of the ON state, the output of the circuit
340 is sampled at twice the modulation rate (i.e., 4 Khz in the
illustrated embodiment). The sampling interval is selected to
comprises one complete cycle of 60 Hz, allowing the main frequency
to be filtered from the measurement. The 4 Khz sampling frequency
allows the 2 Khz ripple to be captured for later removal from the
measurement.
[0377] During the OFF state, the LED is left dark for 100 ms. The
LED baseline due to ambient light and electromagnetic interference
is recorded during the final 16.7 ms.
[0378] 1. The First Sensor: Platelet/RBC Differentiation
[0379] In general, cell free ("free") plasma has a straw color. As
the concentration of platelets in the plasma increases, the clarity
of the plasma decreases. The plasma looks "cloudy." As the
concentration of red blood cells in the plasma increases, the
plasma color turns from straw to red.
[0380] The sensor circuit 340 includes a detection/differentiation
module 372, which analyses sensed attenuations of light at two
different wavelengths from the first sensor 334 (using the
transmitted light sensing photodiode 354). The different
wavelengths are selected to possess generally the same optical
attenuation for platelets, but significantly different optical
attentuations for red blood cells.
[0381] In the illustrated embodiment, the first sensor 334 includes
an emitter 350 of light at a first wavelength (.lambda..sub.1),
which, in the illustrated embodiment, is green light (570 nm and
571 nm). The first sensor 334 also includes an emitter 352 of light
at a second wavelength (.lambda..sub.2), which, in the illustrated
embodiment, is red light (645 nm to 660 nm).
[0382] The optical attenuation for platelets at the first
wavelength (.epsilon..sub.platelets.sup..lambda..sub.1) and the
optical attenuation for platelets at the second wavelength
(.epsilon..sub.platelets.sup..lamb- da..sub.2) are generally the
same. Thus, changes in attenuation over time, as affected by
increases or decreases in platelet concentration, will be
similar.
[0383] However, the optical attenuation for hemoglobin at the first
wavelength (.epsilon..sub.Hb.sup..lambda..sub.1) is about ten times
greater than the optical attenuation for hemoglobin at the second
wavelength (.epsilon..sub.Hb.sup..lambda..sub.2). Thus, changes in
attenuation over time, as affected by the presence of red blood
cells, will not be similar.
[0384] The tube 294, through which plasma to be sensed, is
transparent to light at the first and second wavelengths. The tube
294 conveys the plasma flow past the first and second emitters 350
and 352.
[0385] The light detector 354 receives light emitted by the first
and second emitters 350 and 352 through the tube 294. The detector
354 generates signals proportional to intensities of received
light. The intensities vary with optical attenuation caused by the
presence of platelets and/or red blood cells.
[0386] The module 372 is coupled to the light detector 354 to
analyze the signals to derive intensities of the received light at
the first and second wavelengths. The module 372 compares changes
of the intensities of the first and second wavelengths over time.
When the intensities of the first and second wavelengths change
over time in substantially the same manner, the module 372
generates an output representing presence of platelets in the
plasma flow. When the intensities of the first and second
wavelengths change over time in a substantially different manner,
the module 372 generates an output representing presence of red
blood cells in the plasma flow. The outputs therefore differentiate
between changes in intensity attributable to changes in platelet
concentration in the plasma flow and changes in intensity
attributable to changes in red blood cell concentration in the
plasma flow.
[0387] There are various ways to implement the module 372. In a
preferred embodiment, the detection/differentiation module 372
considers that the attenuation of a beam of monochromatic light of
wavelength .lambda. by a plasma solution can be described by the
modified Lambert-Beer law, as follows: 4 I = I o e - [ ( H b c H b
H + platelets c platelets ) d + G platelets + G RBC ] ( 1 )
[0388] where:
[0389] I is transmitted light intensity.
[0390] I.sub.O is incident light intensity.
[0391] .epsilon..sub.Hb.sup..lambda. is the optical attenuation of
hemoglobin (Hb) (gm/dl) at the applied wavelength.
[0392] .epsilon..sub.platelets.sup..lambda. is the optical
attenuation of platelets at the applied wavelength.
[0393] C.sub.Hb is the concentration of hemoglobin in a red blood
cell, taken to be 34 gm/dl.
[0394] C.sub.platelets is the concentration of platelets in the
sample.
[0395] d is thickness of the plasma stream through the tube
294.
[0396] G.sup..lambda. is the path length factor at the applied
wavelength, which accounts for additional photon path length in the
plasma sample due to light scattering.
[0397] H is whole blood hematocrit, which is percentage of red
blood cells in the sample.
[0398] G.sub.RBC.sup..lambda. and G.sub.platelets.sup..lambda. are
a function of the concentration and scattering coefficients of,
respectively, red blood cells and platelets at the applied
wavelengths, as well as the measurement geometry.
[0399] For wavelengths in the visible and near infrared spectrum,
.epsilon..sub.platelets.sup..lambda..apprxeq.0, therefore: 5 L n (
I I O ) = L n ( T ) - [ ( H b C H b H ) d + G platelets + G RBC ] (
2 )
[0400] In an over spill condition (shown in FIG. 15B), the first
cellular component to be detected by the first sensor 334 in the
plasma collection line 294 will be platelets. Therefore, for the
detection of platelets,
Ln(T.sup..lambda.).apprxeq.G.sub.platelets.sup..lambda..
[0401] To detect the buffy coat interface between the platelet
layer and the red blood cell layer, the two wavelengths
(.lambda..sub.1 and .lambda..sub.2) are chosen based upon the
criteria that (i) .lambda..sub.1 and .lambda..sub.2 have
approximately the same path length factor (G.sup..lambda.), and
(ii) one wavelength .lambda..sub.1 or .lambda..sub.2 has a much
greater optical attenuation for hemoglobin than the other
wavelength.
[0402] Assuming the wavelengths .lambda..sub.1 and .lambda..sub.2
have the same G.sup..lambda., Equation (2) reduces to: 6 L n ( T 1
) - L n ( T 2 ) H d c H b ( H b 2 - H b 1 ) ( 3 )
[0403] In the preferred embodiment, .lambda..sub.1=660 nm (green)
and .lambda..sub.2=571 nm (red). The path length factor
(G.sup..lambda.) for 571 nm light is greater than for 660 nm light.
Therefore the path length factors have to be modified by
coefficients .alpha. and .beta., as follows:
G.sub.RBC.sup..lambda..sup..sub.1=.alpha.G.sub.RBC.sup..lambda..sup..sub.2
G.sub.platelets.sup..lambda..sup..sub.1=.beta.G.sub.platelets.sup..lambda.-
.sup..sub.2
[0404] Therefore, Equation (3) can be reexpressed as follows:
Ln(T.sup..lambda..sup..sub.1)-Ln(T.sup..lambda..sup..sub.2).apprxeq.Hdc.su-
b.Hb(.epsilon..sub.Hb.sup..lambda..sup..sub.2-.epsilon..sub.Hb.sup..lambda-
..sup..sub.1)+(.alpha.-1)G.sub.RBC.sup..lambda..sup..sub.1+(.beta.-1)G.sub-
.platelets.sup..lambda..sup..sub.2 (4)
[0405] In the absence of red blood cells, Equation (3) causes a
false red blood cell detect with increasing platelet
concentrations, as Equation (5) demonstrates:
Ln(T.sup..lambda..sup..sub.1)-Ln(T.sup..lambda..sup..sub.2)=(.beta.-1)G.su-
b.platelets.sup..lambda..sup..sub.1 (5)
[0406] For the detection of platelets and the interface between the
platelet/red blood cell layer, Equation (4) provides a better
resolution. The module 372 therefore applies Equation (4). The
coefficient (.beta.-1) can be determined by empirically measuring
G.sub.platelets.sup..lambda..s- up..sub.1 and G.sub.platelets
.sup..lambda..sup..sub.2 in the desired measurement geometry for
different known concentrations of platelets in prepared
platelet-spiked plasma.
[0407] The detection/differentiation module 372 also differentiates
between intensity changes due to the presence of red blood cells in
the plasma or the presence of free hemoglobin in the plasma due to
hemolysis. Both circumstances will cause a decrease in the output
of the transmitted light sensing photodiode 354. However, the
output of the reflected light sensing photodiode 355 increases in
the presence of red blood cells and decreases in the presence of
free hemoglobin. The detection/differentiati- on module 372 thus
senses the undesired occurrence of hemolysis during blood
processing, so that the operator can be alerted and corrective
action can be taken.
[0408] 2. The Second Sensor: Packed Red Blood Cell Measurement
[0409] In an under spill condition (shown in FIG. 15C), the
hematocrit of red blood cells exiting the processing chamber 18
will dramatically decrease, e.g., from a targeted hematocrit of
about 80 to a hematocrit of about 50, as plasma (and the buffy
coat) mixes with the red blood cells. An under spill condition is
desirable during a plasma collection procedure, as it allows the
return of the buffy coat to the donor with the red blood cells. An
under spill condition is not desired during a red blood cell-only
collection procedure, as it jeopardizes the yield and quality of
red blood cells that are collected for storage.
[0410] In either situation, the ability to sense when an under
spill condition exists is desireable.
[0411] Photon wavelengths in the near infrared spectrum (NIR)
(approximately 540 nm to 1000 nm) are suitable for sensing red
blood cells, as their intensity can be measured after transmission
through many millimeters of blood.
[0412] The sensor circuit 340 includes a red blood cell detection
module 374. The detection module 374 analyses sensed optical
transmissions of the second sensor 336 to discern the hematocrit
and changes in the hematocrit of red blood cells exiting the
processing chamber 18.
[0413] The detection module 374 considers that the attenuation of a
beam of monochromatic light of wavelength .lambda. by blood may be
described by the modified Lambert-Beer law, as follows:
I=I.sub.Oe.sup.-[(.epsilon..sup..sub.Hb.sup..sup..lambda..sup.c.sup..sub.H-
b.sup.H)d+G.sup..sub.RBC.sup..sup..lambda..sup.] (6)
[0414] where:
[0415] I is transmitted light intensity.
[0416] I.sub.O is incident light intensity.
[0417] .epsilon..sub.Hb.sup..lambda.is the extinction coefficient
of hemoglobin (Hb) (gm/dl) at the applied wavelength.
[0418] C.sub.Hb is the concentration of hemoglobin in a red blood
cell, taken to be 34 gm/dl.
[0419] d is the distance between the light source and light
detector.
[0420] G.sup..lambda. is the path length factor at the applied
wavelength, which accounts for additional photon path length in the
media due to light scattering.
[0421] H is whole blood hematocrit, which is percentage of red
blood cells in the sample.
[0422] G.sub.RBC.sup..lambda. is a function of the hematocrit and
scattering coefficients of red blood cells at the applied
wavelengths, as well as the measurement geometry.
[0423] Given Equation (6), the optical density O.D. of the sample
can be expressed as follows:
Ln(I.sup..lambda./I.sub.O.sup..lambda.)=O.D..apprxeq.-[(.epsilon..sub.Hb.s-
up..lambda.C.sub.HbH)d+G.sub.RBC.sup..lambda.] (7)
[0424] The optical density of the sample can further be expressed
as follows:
O.D.=O.D..sub.Absorption+O.D..sub.Scattering (8)
[0425] where:
[0426] O.D..sub.Absorption is the optical density due to absorption
by red blood cells, expressed as follows:
O.D..sub.Absorption=-(.epsilon..sub.Hb.sup..lambda.C.sub.HbH)d
(9)
[0427] O.D..sub.Scattering is the optical density due to scattering
of red blood cells, expressed as follows:
O.D..sub.Scattering=G.sub.RBC.sup..lambda. (10)
[0428] From Equation (9), O.D..sub.Absorption increases linearly
with hematocrit (H). For transmittance measurements in the red and
NIR spectrum, G.sub.RBC.sup..lambda. is generally parabolic,
reaching a maximum at a hematocrit of between 50 and 75 (depending
on illumination wavelength and measurement geometry) and is zero at
hematocrits of 0 and 100 (see, e.g., Steinke et al., "Diffusion
Model of the Optical Absorbance of Whole Blood," J. Opt. Soc. Am.,
Vol 5, No. 6, June 1988). Therefore, for light transmission
measurements, the measured optical density is a nonlinear function
of hematocrit.
[0429] Nevertheless, it has been discovered that
G.sub.RBC.sup..lambda. for reflected light measured at a
predetermined radial distance from the incident light source is
observed to remain linear for the hematocrit range of at least 10
to 90. Thus, with the second sensor 336 so configured, the
detection module can treat the optical density of the sample for
the reflected light to be a linear function of hematocrit. The same
relationship exists for the first sensor 334 with respect to the
detection of red blood cells in plasma.
[0430] This arrangement relies upon maintaining straightforward
measurement geometries. No mirrors or focusing lenses are required.
The LED or photodiode need not be positioned at an exact angle with
respect to the blood flow tube. No special optical cuvettes are
required. The second sensor 336 can interface directly with the
transparent plastic tubing 294. Similarly, the first sensor 334 can
interface directly with the transparent tubing 292.
[0431] In the illustrated embodiment, the wavelength 805 nm is
selected, as it is an isobestic wavelength for red blood cells,
meaning that light absorption by the red blood cells at this
wavelength is independent of oxygen saturation. Still, other
wavelengths can be selected within the NIR spectrum.
[0432] In the illustrated embodiment, for a wavelength of 805 nm,
the preferred set distance is 7.5 mm from the light source. The
fixture 338, above described (see FIG. 18), facilitates the
placement of the tube 294 in the desired relation to the light
source and the reflected light detector of the second sensor 336.
The fixture 338 also facilitates the placement of the tube 292 in
the desired relation to the light source and the reflected light
detector of the first sensor 334.
[0433] Measurements at a distance greater than 7.5 mm can be made
and will show a greater sensitivity to changes in the red blood
cell hematocrit. However a lower signal to noise ratio will be
encountered at these greater distances. Likewise, measurements at a
distance closer to the light source will show a greater signal to
noise ratio, but will be less sensitive to changes in the red blood
cell hematocrit. The optimal distance for a given wavelength in
which a linear relationship between hematocrit and sensed intensity
exists for a given hematocrit range can be empirically
determined.
[0434] The second sensor 336 detects absolute differences in the
mean transmitted light intensity of the signal transmitted through
the red blood cells in the red blood cell collection line. The
detection module analyzes these measured absolute differences in
intensities, along with increases in the standard deviation of the
measured intensities, to reliably signal an under spill condition,
as FIG. 20 shows.
[0435] At a given absolute hematocrit, G.sub.RBC.sup..lambda.
varies slightly from donor to donor, due to variations in the mean
red blood cell volume and/or the refractive index difference
between the plasma and red blood cells. Still, by measuring the
reflected light from a sample of a given donor's blood having a
known hematocrit, G.sub.RBC.sup..lambda. may be calibrated to
yield, for that donor, an absolute measurement of the hematocrit of
red blood cells exiting the processing chamber.
[0436] C. Pre-Processing Calibration of the Sensors
[0437] The first and second sensors 334 and 336 are calibrated
during the saline and blood prime phases of a given blood
collection procedure, the details of which have already
described.
[0438] During the saline prime stage, saline is conveyed into the
blood processing chamber 18 and out through the plasma collection
line 292. During this time, the blood processing chamber 18 is
rotated in cycles between 0 RPM and 200 RPM, until air is purged
from the chamber 18. The speed of rotation of the processing
chamber 18 is then increased to full operational speed.
[0439] The blood prime stage follows, during which whole blood is
introduced into the processing chamber 18 at the desired whole
blood flow rate (Q.sub.WB) The flow rate of plasma from the
processing chamber through the plasma collection line 292 is set at
a fraction (e.g., 80%) of the desired plasma flow rate (Q.sub.P)
from the processing chamber 18, to purge saline from the chamber
18. The purge of saline continues under these conditions until the
first sensor 334 optically senses the presence of saline in the
plasma collection line 292.
[0440] 1. For Plasma Collection Procedures (Induced Under
Spill)
[0441] If the procedure to be performed collects plasma for storage
(e.g., the Plasma Collection Procedure or the Red Blood Cell/Plasma
Collection Procedure), an under spill condition is induced during
calibration. The under spill condition is created by decreasing or
stopping the flow of plasma through the plasma collection line 292.
This forces the buffy coat away from the low-G side of the chamber
18 (as FIG. 15C) to assure that a flow of "clean" plasma exists in
the plasma collection line 292, free or essentially free of
platelets and leukocytes. The induced under spill allows the first
sensor 334 to be calibrated and normalized with respect to the
physiologic color of the donor's plasma, taking into account the
donor's background lipid level, but without the presence of
platelets or leukocytes. The first sensor 334 thereby possesses
maximum sensitivity to changes brought about by the presence of
platelets or leukocytes in the buffy coat, should an over spill
subsequently occur during processing.
[0442] Forcing an under spill condition also positions the
interface close to the high-G wall at the outset of blood
processing. This creates an initial offset condition on the high-G
side of the chamber, to prolong the ultimate development of an over
spill condition as blood processing proceeds.
[0443] 2. Red Blood Cell Collection Procedures
[0444] If a procedure is to be performed in which no plasma is to
be collected (e.g., the Double Unit Red Blood Cell Collection
Procedure), an under spill condition is not induced during the
blood purge phase. This is because, in a red blood cell only
collection procedure, the first sensor 334 need only detect, during
an over spill, the presence of red blood cells in the plasma. The
first sensor 334 does not need to be further sensitized to detect
platelets. Furthermore, in a red blood cell only collection
procedure, it may be desirable to keep the interface as near the
low-G wall as possible. The desired condition allows the buffy coat
to be returned to the donor with the plasma and maximizes the
hematocrit of the red blood cells collected.
[0445] D. Blood Cell Collection
[0446] 1. Plasma Collection Procedures
[0447] In procedures where plasma is collected (e.g., the Plasma
Collection Procedure or the Red Blood Cell/Plasma Collection
Procedure), Q.sub.p is set at Q.sub.P(Ideal), which is an
empirically determined plasma flow rate that allows the system to
maintain a steady state collection condition, with no underspills
and no overspills.
[0448] Q.sub.P(Ideal) (in grams/ml) is a function of the
anticogulated whole blood inlet flow rate Q.sub.WB, the
anticoagulant whole blood inlet hematocrit HCT.sub.WB, and the red
blood cell exit hematocrit HCT.sub.RBC (as estimated or measured),
expressed as follows: 7 Q P ( Ideal ) = ( Plasma Q WB * ( 1 - HCT
WB ) - [ WB RBC ( 1 - HCT RBC ) ] ( 1 - Plasma RBC ) ( 1 - HCT RBC
)
[0449] where:
[0450] .rho..sub.Plasma is the density of plasma (in g/ml)=1.03
[0451] .rho..sub.WB is the density of whole blood (in
g/ml)=1.05
[0452] .rho..sub.RBC is the density of red blood cells=1.08
[0453] Q.sub.WB is set to the desired whole blood inlet flow rate
for plasma collection, which, for a plasma only collection
procedure, is generally about 70 ml/min. For a red blood
cell/plasma collection procedure, Q.sub.WB is set at about 50
ml/min, thereby providing packed red blood cells with a higher
hematocrit than in a traditional plasma collection procedure.
[0454] The system controller 16 maintains the pump settings until
the desired plasma collection volume is achieved, unless an under
spill condition or an over spill condition is detected.
[0455] If set Q.sub.P is too high for the actual blood separation
conditions, or, if due to the physiology of the donor, the buffy
coat volume is larger (i.e., "thicker") than expected, the first
sensor 334 will detect the presence of platelets or leukocytes, or
both in the plasma, indicating an over spill condition.
[0456] In response to an over spill condition caused by a high
Q.sub.P, the system controller 16 terminates operation of the
plasma collection pump PP2, while keeping set Q.sub.WB unchanged.
In response to an over spill condition caused by a high volume
buffy coat, the system controller 16 terminates operation of the
plasma collection pump PP2, until an under spill condition is
detected by the red blood cell sensor 336. This serves to expel the
buffy coat layer from the separation chamber through the red blood
cell tube 294.
[0457] To carry out the over spill response, the blood processing
circuit 46 is programmed to operate the in-process pump PP1 (i.e.,
drawing in through the valve V9 and expelling out of the valve
V14), to draw whole blood from the in-process container 312 into
the processing chamber 18 at the set Q.sub.WB. Red blood cells exit
the chamber 18 through the tube 294 for collection in the
collection container 308. The flow rate of red blood cells directly
depends upon the magnitude of Q.sub.WB.
[0458] During this time, the blood processing circuit 46 is also
programmed to cease operation of the plasma pump PP2 for a
preestablished time period (e.g., 20 seconds). This forces the
interface back toward the middle of the separation chamber. After
the preestablished time period, the operation of the plasma pump
PP2 is resumed, but at a low flow rate (e.g., 10 ml/min) for a
short time period (e.g., 10 seconds). If the spill has been
corrected, clean plasma will be detected by the first sensor 334,
and normal operation of the blood processing circuit 46 is resumed.
If clean plasma is not sensed, indicating that the over spill has
not been corrected, the blood processing circuit 46 repeats the
above-described sequence.
[0459] The programming of the circuit to relieve an over spill
condition is summarized in the following table.
12TABLE Programming of Blood Processing Circuit To Relive an Over
Spill Condition (Plasma Collection Procedures) V1 .circle-solid. V2
.largecircle. V3 .circle-solid. V4 .circle-solid. V5 .largecircle.
V6 .circle-solid. V7 .circle-solid. V8 .circle-solid. V9
.circle-solid./.largecircle. Pump In V10 .circle-solid. V11
.circle-solid. V12 .circle-solid. V13 .circle-solid. V14
.circle-solid./.largecircle. Pump Out V15 .circle-solid. V16
.circle-solid. V17 .circle-solid. V18 .circle-solid. V19
.circle-solid. V20 .circle-solid. V21 .circle-solid. V22
.circle-solid. V23 .circle-solid. PP1 .quadrature. PP2 .box-solid.
PP3 .box-solid. PP4 .box-solid. Caption: .largecircle. denotes an
open valve; .circle-solid. denotes a closed valve;
.largecircle./.circle-solid. denotes a valve opening and closing
during a pumping sequence; .box-solid. denotes an idle pump station
(not in use); and .quadrature. denotes a pump station in use.
[0460] Caption: .circle-solid. denotes an open valve; .smallcircle.
denotes a closed valve; .circle-solid./.smallcircle. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0461] Upon correction of an over spill condition, the controller
16 returns the blood processing circuit 46 to resume normal blood
processing, but applies a percent reduction factor (%RF) to the
Q.sub.P set at the time the over spill condition was initially
sensed. The reduction factor (%RF) is a function of the time
between over spills, i.e., %RF increases as the frequency of over
spills increases, and vice versa.
[0462] If set Q.sub.P is too low, the second sensor 336 will detect
a decrease in the red blood cell hematocrit below a set level,
which indicates an under spill condition.
[0463] In response to an under spill condition, the system
controller 16 resets Q.sub.P close to the set Q.sub.WB. As
processing continues, the interface will, in time, move back toward
the low-G wall. The controller 16 maintains these settings until
the second sensor 336 detects a red blood cell hematocrit above the
desired set level. At this time, the controller 16 applies a
percent enlargement factor (%EF) to the Q.sub.P set at the time the
under spill condition was initially sensed. The enlargement factor
(%EF) is a function of the time between under spills, i.e., %EF
increases as the frequency of under spills increases.
[0464] Should the controller 16 be unable to correct a given under
or over spill condition after multiple attempts (e.g., three
attempts), an alarm is commanded.
[0465] 2. Red Blood Cell Only Collection Procedures
[0466] In procedures where only red blood cells and no plasma is
collected (e.g., the Double Unit Red Blood Cell Collection
Procedure), Q.sub.p is set to no greater than Q.sub.P(Ideal), and
Q.sub.WB is set to the desired whole blood inlet flow rate into the
processing chamber 18 for the procedure, which is generally about
50 ml/min for a double unit red blood cell collection
procedure.
[0467] It may be desired during a double unit red blood cell
collection procedure that over spills occur frequently. This
maximizes the hematocrit of the red blood cells for collection and
returns the buffy coat to the donor with the plasma. Q.sub.p is
increased over time if over spills occur at less than a set
frequency. Likewise, Q.sub.P is decreased over time if over spills
occur above the set frequency. However, to avoid an undesirably
high hematocrit, it may be just as desirable to operate at
Q.sub.P(Ideal).
[0468] The system controller 16 controls the pump settings in this
way until the desired red blood cell collection volume is achieved,
taking care of under spills or over spills as they occur.
[0469] The first sensor 334 detects an over spill by the presence
of red blood cells in the plasma. In response to an over spill
condition, the system controller 16 terminates operation of the
plasma collection pump to draw plasma from the processing chamber,
while keeping the set Q.sub.WB unchanged.
[0470] To implement the over spill response, the blood processing
circuit 46 is programmed (through the selective application of
pressure to the valves and pump stations) to operate the plasma
pump PP2 and in-process pump PP1 in the manner set forth in the
immediately preceding Table. The red blood cells detected in the
tube 292 are thereby returned to the processing chamber 18, and are
thereby prevented from entering the plasma collection container
304.
[0471] The interface will, in time, move back toward the high-G
wall. The controller 16 maintains these settings until the second
sensor 336 detects a decrease in the red blood cell hematocrit
below a set level, which indicates an under spill condition.
[0472] In response to an under spill condition, the system
controller 16 increases Q.sub.P until the second sensor 336 detects
a red blood cell hematocrit above the desired set level. At this
time, the controller 16 resets Q.sub.P to the value at the time the
most recent overspill condition was sensed.
[0473] 3. Buffy Coat Collection
[0474] If desired, an over spill condition can be periodically
induced during a given plasma collection procedure to collect the
buffy coat in a buffy coat collection container 376 (see FIG. 10).
As FIG. 10 shows, in the illustrated embodiment, the buffy coat
collection container 376 is coupled by tubing 378 to the buffy port
P4 of the cassette 28. The buffy coat collection container 376 is
suspended on a weigh scale 246, which provides output reflecting
weight changes over time, from which the controller 16 derives the
volume of buffy coat collected.
[0475] In this arrangement, when the induced over spill condition
is detected, the blood processing circuit 46 is programmed (through
the selective application of pressure to the valves and pump
stations) to operate the plasma pump PP2 (i.e., drawing in through
valve V12 and expelling out through valve V10), to draw plasma from
the processing chamber 18 through the tube 378, while valves V4 and
V6 are closed and valve V8 is opened. The buffy coat in the tube
378 is conveyed into the buffy coat collection container 376. The
blood processing circuit 46 is also programmed during this time to
operate the in-process pump PP1 (i.e., drawing in through the valve
V9 and expelling out of the valve V14), to draw whole blood from
the in-process container 312 into the processing chamber 18 at the
set Q.sub.WB. Red blood cells exit the chamber 18 through the tube
294 for collection in the collection container 308.
[0476] The programming of the circuit to relieve an over spill
condition by collecting the buffy coat in the buffy coat collection
container 376 is summarized in the following table.
13TABLE Programming of Blood Processing Circuit To Relive an Over
Spill Condition by Collecting the Buffy Coat (Plasma Collection
Procedures) V1 .circle-solid. V2 .circle-solid. V3 .circle-solid.
V4 .largecircle. V5 .circle-solid. V6 .circle-solid. V7
.circle-solid. V8 .circle-solid. V9 .circle-solid./.largecircle.
Pump In V10 .circle-solid./.largecir- cle. Pump Out V11
.circle-solid. V12 .circle-solid./.largecircle. Pump In V13
.circle-solid. V14 .circle-solid./.largecircle. Pump Out V15
.circle-solid. V16 .circle-solid. V17 .circle-solid. V18
.circle-solid. V19 .circle-solid. V20 .circle-solid. V21
.circle-solid. V22 .circle-solid. V23 .circle-solid. PP1
.quadrature. PP2 .quadrature. PP3 .box-solid. PP4 .box-solid.
Caption: .largecircle. denotes an open valve; .circle-solid.
denotes a closed valve; .largecircle./.circle-solid. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0477] Caption: .circle-solid. denotes an open valve; .smallcircle.
denotes a closed valve; .circle-solid./.smallcircle. denotes a
valve opening and closing during a pumping sequence; .box-solid.
denotes an idle pump station (not in use); and .quadrature. denotes
a pump station in use.
[0478] After a prescribed volume of buffy coat is conveyed into the
buffy coat collection container 376 (as monitored by the weigh
scale 246), normal blood processing conditions are resumed. Over
spill conditions causing the movement of the buffy coat into the
tube 378 can be induced at prescribed intervals during the process
period, until a desired buffy coat volume is collected in the buffy
coat collection container.
[0479] VI. Another Programmable Blood Processing Circuit
[0480] A. Circuit Schematic
[0481] As previously mentioned, various configurations for the
programmable blood processing circuit 46 are possible. FIG. 5
schematically shows one representative configuration 46, the
programmable features of which have been described. FIG. 34 shows
another representative configuration of a blood processing circuit
46' having comparable programmable features.
[0482] Like the circuit 46, the circuit 46' includes several pump
stations PP(N), which are interconnected by a pattern of fluid flow
paths F(N) through an array of in line valves V(N). The circuit is
coupled to the remainder of the blood processing set by ports
P(N).
[0483] The circuit 46' includes a programmable network of flow
paths F1 to F33. The circuit 46' includes eleven universal ports P1
to P8 and P11 to P13 and four universal pump stations PP1, PP2,
PP3, and PP4. By selective operation of the in line valves V1 to
V21 and V23 to V25, any universal port P1 to P8 and P11 to P13 can
be placed in flow communication with any universal pump station
PP1, PP2, PP3, and PP4. By selective operation of the universal
valves, fluid flow can be directed through any universal pump
station in a forward direction or reverse direction between two
valves, or an in-out direction through a single valve.
[0484] In the illustrated embodiment, the circuit 46' also includes
an isolated flow path (comprising flow paths F9, F23, F24, and F10)
with two ports P9 and P10 and one in line pump station PP5. The
flow path is termed "isolated," because it cannot be placed into
direct flow communication with any other flow path in the circuit
46' without exterior tubing. By selective operation of the in line
valves V21 and V22, fluid flow can be directed through the pump
station PP5 in a forward direction or reverse direction between two
valves, or an in-out direction through a single valve.
[0485] Like circuit 46, the circuit 46' can be programmed to
assigned dedicated pumping functions to the various pump stations.
In a preferred embodiment, the universal pump stations PP3 and PP4
in tandem serve as a general purpose, donor interface pump,
regardless of the particular blood procedure performed. The dual
donor interface pump stations PP3 and PP4 in the circuit 46' work
in parallel. One pump station draws fluid into its pump chamber,
while the other pump station is expels fluid from its pump chamber.
The pump station PP3 and PP4 alternate draw and expel
functions.
[0486] In a preferred arrangement, the draw cycle for the drawing
pump station is timed to be longer than the expel cycle for the
expelling pump station. This provides a continuous flow of fluid on
the inlet side of the pump stations and a pulsatile flow in the
outlet side of the pump stations. In one representative embodiment,
the draw cycle is ten seconds, and the expel cycle is one second.
The expelling pump station performs its one second cycle at the
beginning of the draw cycle of the drawing pump, and then rests for
the remaining nine seconds of the draw cycle. The pump stations
then switch draw and expel functions. This creates a continuous
inlet flow and a pulsatile outlet flow. The provision of two
alternating pump stations PP3 and PP4 serves to reduce overall
processing time, as fluid is continuously conducted into a drawing
pump station through out the procedure.
[0487] In this arrangement, the isolated pump station PP5 of the
circuit 46' serves as a dedicated anticoagulant pump, like pump
station PP4 in the circuit 46, to draw anticoagulant from a source
through the port P10 and to meter anticoagulant into the blood
through port P9.
[0488] In this arrangement, as in the circuit 46, the universal
pump station PP1 serves, regardless of the particular blood
processing procedure performed, as a dedicated in-process whole
blood pump, to convey whole blood into the blood separator. As in
the circuit 46, the dedicated function of the pump station PP1
frees the donor interface pumps PP3 and PP4 from the added function
of supplying whole blood to the blood separator. Thus, the
in-process whole blood pump PP1 can maintain a continuous supply of
blood to the blood separator, while the donor interface pumps PP3
and PP4 operate in tandem to simultaneously draw and return blood
to the donor through the single phlebotomy needle. The circuit 46'
thus minimizes processing time.
[0489] In this arrangement, as in circuit 46, the universal pump
station PP2 of the circuit 46' serves, regardless of the particular
blood processing procedure performed, as a plasma pump, to convey
plasma from the blood separator. As in the circuit 46, the ability
to dedicate separate pumping functions in the circuit 46' provides
a continuous flow of blood into and out of the separator, as well
as to and from the donor.
[0490] The circuit 46' can be programmed to perform all the
different procedures described above for the circuit 46. Depending
upon the objectives of the particular blood processing procedure,
the circuit 46' can be programmed to retain all or some of the
plasma for storage or fractionation purposes, or to return all or
some of the plasma to the donor. The circuit 46' can be further
programmed, depending upon the objectives of the particular blood
processing procedure, to retain all or some of the red blood cells
for storage, or to return all or some of the red blood cells to the
donor. The circuit 46' can also be programmed, depending upon the
objectives of the particular blood processing procedure, to retain
all or some of the buffy coat for storage, or to return all or some
of the buffy coat to the donor.
[0491] In a preferred embodiment (see FIG. 34), the circuit 46'
forms a part of a universal set 264', which is coupled to the ports
P1 to P13.
[0492] More particularly, a donor tube 266', with attached
phlebotomy needle 268' is coupled to the port P8 of the circuit
46'. An anticoagulant tube 270', coupled to the phlebotomy needle
268' is coupled to port P9. A container 276' holding anticoagulant
is coupled via a tube 274' to the port P10.
[0493] A container 280' holding a red blood cell additive solution
is coupled via a tube 278' to the port P3. A container 288' holding
saline is coupled via a tube 284' to the port P12. A storage
container 289' is coupled via a tube 291' to the port P13. An
in-line leukocyte depletion filter 293' is carried by the tube 291'
between the port P13 and the storage container 289'. The containers
276', 280', 288', and 289' can be integrally attached to the ports
or can be attached at the time of use through a suitable sterile
connection, to thereby maintain a sterile, closed blood processing
environment.
[0494] Tubes 290', 292', and 294', extend to an umbilicus 296'
which is coupled to the processing chamber 18'. The tubes 290',
292', and 294 are coupled, respectively, to the ports P5, P6, and
P7. The tube 290' conveys whole blood into the processing chamber
18 under the operation of the in-process pump station PP1. The tube
292' conveys plasma from the processing chamber 18' under the
operation of the plasma pump chamber PP2. The tube 294' conveys red
blood cells from processing chamber 18'.
[0495] A plasma collection container 304' is coupled by a tube 302'
to the port P3. The collection container 304' is intended, in use,
to serve as a reservoir for plasma during processing.
[0496] A red blood cell collection container 308' is coupled by a
tube 306' to the port P2. The collection container 308' is
intended, in use, to receive a unit of red blood cells for
storage.
[0497] A buffy coat collection container 376' is coupled by a tube
377' to the port P4. The container 376' is intended, in use, to
receive a volume of buffy coat for storage.
[0498] A whole blood reservoir 312' is coupled by a tube 310' to
the port P1. The collection container 312' is intended, in use, to
receive whole blood during operation of the donor interface pumps
PP3 and PP4, to serve as a reservoir for whole blood during
processing. It can also serve to receive a second unit of red blood
cells for storage.
[0499] B. The Cassette
[0500] As FIGS. 35 and 36 show, the programmable fluid circuit 46'
can be implemented as an injection molded, pneumatically controlled
cassette 28'. The cassette 28' interacts with the pneumatic pump
and valve station 30, as previously described, to provide the same
centralized, programmable, integrated platform as the cassette
28.
[0501] FIG. 35 and 36 show the cassette 28' in which the fluid
circuit 46' (schematically shown in FIG. 34) is implemented. As
previously described for the cassette 28, an array of interior
wells, cavities, and channels are formed on both the front and back
sides 190' and 192' of the cassette body 188', to define the pump
stations PP1 to PP5, valve stations V1 to V25, and flow paths F1 to
F33 shown schematically in FIG. 34. In FIG. 36, the flow paths F1
to F33, are shaded to facilitate their viewing. Flexible diaphragms
194' and 196' overlay the front and back sides 190' and 192' of the
cassette body 188', resting against the upstanding peripheral edges
surrounding the pump stations PP1 to PP5, valves V1 to V25, and
flow paths F1 to F33. The pre-molded ports P1 to P13 extend out
along two side edges of the cassette body 188'.
[0502] The cassette 28' is vertically mounted for use in the pump
and valve station 30 in the same fashion shown in FIG. 2. In this
orientation (which Fog. 36 shows), the side 192' faces outward,
ports P8 to P13 face downward, and the ports P1 to P7 are
vertically stacked one above the other and face inward.
[0503] As previously described, localized application by the pump
and valve station 30 of positive and negative fluid pressures upon
the diaphragm 194' serves to flex the diaphragm to close and open
the valve stations V1 to V 25 or to expel and draw liquid out of
the pump stations PP1 to PP5.
[0504] An additional interior cavity 200' is provided in the back
side 192' of the cassette body 188'. The cavity 200' forms a
station that holds a blood filter material to remove clots and
cellular aggregations that can form during blood processing. As
shown schematically in FIG. 34, the cavity 200' is placed in the
circuit 46' between the port P8 and the donor interface pump
stations PP3 and PP4, so that blood returned to the donor passes
through the filter. Return blood flow enters the cavity 200'
through flow path F27 and exits the cavity 200' through flow path
F8. The cavity 200' also serves to trap air in the flow path to and
from the donor.
[0505] Another interior cavity 201' (see FIG. 35) is also provided
in the back side 192' of the cassette body 188'. The cavity 201' is
placed in the circuit 46' between the port P5 and the valve V16 of
the in-process pumping station PP1. Blood enters the cavity 201'
from flow path F16 through opening 203' and exits the cavity 201'
into flow path F5 through opening 205' The cavity 201' serves as
another air trap within the cassette body 188' in the flow path
serving the separation chamber 26'. The cavity 201' also serves as
a capacitor to dampen the pulsatile pump strokes of the in-process
pump PP1 serving the separation chamber.
[0506] C. Associated Pneumatic Manifold Assembly
[0507] FIG. 43 shows a pneumatic manifold assembly 226' that can be
used in association with the cassette 28', to supply positive and
negative pneumatic pressures to convey fluid through the cassette
28'. The front side 194' of the diaphragm is held in intimate
engagement against the manifold assembly 226' when the door 32 of
the pump station 20 is closed and bladder 314 inflated. The
manifold assembly 226', under the control of the controller 16,
selectively distributes the different pressure and vacuum levels to
the pump and valve actuators PA(N) and VA(N) of the cassette 28'.
These levels of pressure and vacuum are systematically applied to
the cassette 28', to route blood and processing liquids. Under the
control of a controller 16, the manifold assembly 226 also
distributes pressure levels to the door bladder 314 (already
described), as well as to a donor pressure cuff (also already
described) and to a donor line occluder 320 (also already
described). The manifold assembly 226' for the cassette 28' shown
in FIG. 43 shares many attributes with the manifold assembly 226
previously described for the cassette 28, as shown in FIG. 12.
[0508] Like the manifold assembly 226, the manifold assembly 226'
is coupled to a pneumatic pressure source 234', which is carried
inside the lid 40 behind the manifold assembly 226'. As in manifold
assembly 226, the pressure source 234' for the manifold assembly
226 comprises two compressors C1' and C2', although one or several
dual-head compressors could be used as well. Compressor C1 supplies
negative pressure through the manifold 226' to the cassette 28'.
The other compressor C2' supplies positive pressure through the
manifold 226' to the cassette 28.
[0509] As FIG. 43 shows, the manifold 226' contains five pump
actuators PA1 to PA4 and twenty-five valve actuators VA1 to VA25.
The pump actuators PA1 to PAS and the valve actuators VA1 to VA25
are mutually oriented to form a mirror image of the pump stations
PP1 to PP5 and valve stations V1 to V25 on the front side 190' of
the cassette 28'.
[0510] Like the manifold assembly 226, the manifold assembly 226'
shown in FIG. 43 includes an array of solenoid actuated pneumatic
valves, which are coupled in-line with the pump and valve actuators
PA1 to PA5 and VA1 to VA25.
[0511] Like the manifold assembly 226, the manifold assembly 226'
maintains several different pressure and vacuum conditions, under
the control of the controller 16.
[0512] As previously described in connection with the manifold
assembly 226, Phard, or Hard Pressure, and Pinpr, or In-Process
Pressure are high positive pressures (e.g., +500 mmHg) maintained
by the manifold assembly 226' for closing the cassette valves V1 to
V25 and to drive the expression of liquid from the in-process pump
PP1 and the plasma pump PP2. As before explained, the magnitude of
Pinpr must be sufficient to overcome a minimum pressure of
approximately 300 mm Hg, which is typically present within the
processing chamber 18. Pinpr and Phard are operated at the highest
pressure to ensure that upstream and downstream valves used in
conjunction with pumping are not forced opened by the pressures
applied to operate the pumps.
[0513] Pgen, or General Pressure (+300 mmHg), is applied to drive
the expression of liquid from the donor interface pumps PP3 and PP4
and the anticoagulant pump PP5.
[0514] Vhard, or Hard Vacuum (-350 mmHg), is the deepest vacuum
applied in the manifold assembly 226' to open cassette valves V1 to
V25. Vgen, or General Vacuum (-300 mmHg), is applied to drive the
draw function of each of the pumps PP1 to PP5. Vgen is required to
be less extreme than Vhard, to ensure that pumps PP1 to PP5 do not
overwhelm upstream and downstream cassette valves V1 to V25.
[0515] A main hard pressure line 322' and a main vacuum line 324'
distribute Phard and Vhard in the manifold assembly 324. The
pressure and vacuum sources 234' run continuously to supply Phard
to the hard pressure line 322' and Vhard to the hard vacuum line
324'. A pressure sensor S2 monitors Phard in the hard pressure line
322'. The sensor S2 opens and closes the solenoid 38 to build Phard
up to its maximum set value.
[0516] Similarly, a pressure sensor S6 in the hard vacuum line 324'
monitors Vhard. The sensor S6 controls a solenoid 43 to maintain
Vhard as its maximum value.
[0517] A general pressure line 326' branches from the hard pressure
line 322'. A sensor S4 in the general pressure line 326' monitors
Pgen. The sensor S2 controls a solenoid 34 to maintain Pgen within
its specified pressure range.
[0518] A general vacuum line 330' branches from the hard vacuum
line 324'. A sensor S5 monitors Vgen in the general vacuum line
330'. The sensor S5 controls a solenoid 45 to keep Vgen within its
specified vacuum range.
[0519] In-line reservoirs R1 to R4 are provided in the hard
pressure line 322, the general pressure line 326', the hard vacuum
line 324', and the general vacuum line 330'. The reservoirs R1 to
R4 assure that the constant pressure and vacuum adjustments as
above described are smooth and predictable.
[0520] The solenoids 32 and 43 provide a vent for the pressures and
vacuums, respectively, upon procedure completion.
[0521] The solenoids 41, 2, 46, and 47 provide the capability to
isolate the reservoirs R1 to R4 from the air lines that supply
vacuum and pressure to the pump and valve actuators. This provides
for much quicker pressure/vacuum decay feedback, so that testing of
cassette/manifold assembly seal integrity can be accomplished.
[0522] The solenoids 1 to 25 provide Phard or Vhard to drive the
valve actuators VA1 to V25. The solenoids 27 and 28 provide Pinpr
and Vgen to drive the in-process and plasma pumps PP1 and PP2. The
solenoids 30 and 31 provide Pgen and Vgen to drive the donor
interface pumps actuators PA3 and PA4. The solenoid 29 provides
Pgen and Vgen to drive the AC pump actuator PP5.
[0523] The solenoid 35 provides isolation of the door bladder 314
from the hard pressure line 322' during the procedure. A sensor S1
monitors Pdoor and control the solenoid 35 to keep the pressure
within its specified range.
[0524] The solenoid 40 provides Phard to open the safety occluder
valve 320'. Any error modes that might endanger the donor will
relax (vent) the solenoid 40 to close the occluder 320' and isolate
the donor. Similarly, any loss of power will relax the solenoid 40
and isolate the donor.
[0525] The sensor S3 monitors Pcuff and communicates with solenoids
36 (for increases in pressure) and solenoid 37 (for venting) to
maintain the donor cuff within its specified ranges during the
procedure.
[0526] As before explained, any solenoid can be operated in
"normally open" mode or can be re-routed pneumatically to be
operated in a "normally closed" mode, and vice versa.
[0527] D. Exemplary Pumping Functions
[0528] Based upon the foregoing description of the programming of
the fluid circuit 46 implemented by the cassette 28, one can
likewise program the fluid circuit 46' implemented by the cassette
28' to perform all the various blood process functions already
described. Certain pumping functions for the fluid circuit 46',
common to various blood processing procedures, will be described by
way of example.
[0529] 1. Whole Blood Flow To the In-Process Container
[0530] In a first phase of a given blood collection cycle, the
blood processing circuit 46' is programmed (through the selective
application of pressure to the valves and pump stations of the
cassette 28' ) to jointly operate the donor interface pumps PP3 and
PP4 to transfer anticoagulated whole blood into the in-process
container 312' prior to separation.
[0531] In a first phase (see FIG. 37A) the pump PP3 is operated in
a ten second draw cycle (i.e., in through valves V12 and V13, with
valves V6, V14, V18, and V15 closed) in tandem with the
anticoagulant pump PP5 (i.e., in through valve V22 and out through
valve V21) to draw anticoagulated blood through the donor tube 270
into the pump PP3. At the same time, the donor interface pump PP4
is operated in a one second expel cycle to expel (out through valve
V7) anticoagulant blood from its chamber into the process container
312' through flow paths F20 and F1 (through opened valve V4).
[0532] At the end of the draw cycle for pump PP3 (see FIG. 37B),
the blood processing circuit 46' is programmed to operate the donor
interface pump PP4 in a ten second draw cycle (i.e., in through
valves V12 and V14, with valves V13, V18, and V18 closed) in tandem
with the anticoagulant pump PP5 to draw anticoagulated blood
through the donor tube 270 into the pump PP4. At the same time, the
donor interface pump PP3 is operated in a one second expel cycle to
expel (out through valve V6) anticoagulant blood from its chamber
into the process container 312' through the flow paths F20 and F1
(through opened valve V4).
[0533] These alternating cycles continue until an incremental
volume of anticoagulated whole blood enters the in process
container 312', as monitored by a weigh sensor. As FIG. 37C shows,
the blood processing circuit 46' is programmed to operate the
in-process pump station PP1 (i.e., in through valve V1 and out
through valve V16) and the plasma pump PP2 (i.e., in through valve
V17 and out through valve V11, with valve V9 opened and valve V10
closed) to convey anticoagulated whole blood from the in-process
container 312 into the processing chamber 18' for separation, while
removing plasma into the plasma container 304 (through opened valve
V9) and red blood cells into the red blood cell container 308
(through open valve V2), in the manner previously described with
respect to the circuit 46. This phase continues until an
incremental volume of plasma is collected in the plasma collection
container 304 (as monitored by the weigh sensor) or until a
targeted volume of red blood cells is collected in the red blood
cell collection container (as monitored by the weigh sensor). The
donor interface pumps PP3 and PP4 toggle to perform alternating
draw and expel cycles as necessary to keep the volume of
anticoagulated whole blood in the in-process container 312' between
prescribed minimum and maximum levels, as blood processing
proceeds.
[0534] 2. Red Blood Cell Return with In-Line Addition of Saline
[0535] When it is desired to return red blood cells to the donor
(see FIG. 37D), the blood processing circuit 46' is programmed to
operate the donor interface pump station PP3 in a ten second draw
cycle (i.e., in through valve V6, with valves V13 and V7 closed) to
draw red blood cells from the red blood cell container 308' into
the pump PP3 (through open valves V2, V3, and V5, valve V10 being
closed). At the same time, the donor interface pump PP4 is operated
in a one second expel cycle to expel (out through valves V14 and
V18, with valves V12 and V21 closed) red blood cells from its
chamber to the donor through the filter cavity 200'.
[0536] At the end of the draw cycle for pump PP3 (see FIG. 37E),
the blood processing circuit 46' is programmed to operate the donor
interface pump PP4 in a ten second draw cycle (i.e., in through
valve V7, with valves V6 and V14 closed) to draw red blood cells
from the red blood cell container 308' into the pump PP4. At the
same time, the donor interface pump PP3 is operated in a one second
expel cycle to expel (out through valves V13 and V18, with valve
V12 closed) red blood cells from its chamber to the donor through
the filter chamber 200'. These alternating cycles continue until a
desired volume of red blood cells are returned to the donor.
[0537] Simultaneously, valves V24, V20, and V8 are opened, so that
the drawing pump station PP3 or PP4 also draws saline from the
saline container 288' for mixing with red blood cells drawn into
the chamber. As before explained, the in line mixing of saline with
the red blood cells raises the saline temperature and improves
donor comfort, while also lowering the hematocrit of the red blood
cells.
[0538] Simultaneously, the in-process pump PP1 is operated (i.e.,
in through valve V1 and out through valve V16) and the plasma pump
PP2 (i.e., in through valve V17 and out through valve V11, with
valve V9 open) to convey anticoagulated whole blood from the
in-process container 312 into the processing chamber for
separation, while removing plasma into the plasma container 304, in
the manner previously described with respect to the fluid circuit
46.
[0539] 3. In-Line Addition of Red Blood Cell Additive Solution
[0540] In a blood processing procedure where red blood cells are
collected for storage (e.g., the Double Red Blood Cell Collection
Procedure or the Red Blood Cell and Plasma Collection Procedure)
the circuit 46' is programmed to operate the donor interface pump
station PP3 in a ten second draw cycle (in through valves V15 and
V13, with valve V23 opened and valves V8, V12 and V18 closed) to
draw red blood cell storage solution from the container 280' into
the pump PP3 (see FIG. 38A). Simultaneously, the circuit 46' is
programmed to operate the donor interface pump station PP4 in a one
second expel cycle (out through valve V7, with valves V14 and V18
closed) to expel red blood cell storage solution to the
container(s) where red blood cells reside (e.g., the in-process
container 312 (through open valve V4) or the red blood cell
collection container 308' (through open valves V5, V3, and V2, with
valve V10 closed).
[0541] At the end of the draw cycle for pump PP3 (see FIG. 38B),
the blood processing circuit 46' is programmed to operate the donor
interface pump PP4 in a ten second draw cycle (i.e., in through
valve V14, with valves V7, V18, V12, and V13 closed) to draw red
blood cell storage solution from the container 280' into the pump
PP4. At the same time, the donor interface pump PP3 is operated in
a one second expel cycle to expel (out through valve V6, with
valves V13 and V12 closed) red blood cell storage solution to the
container(s) where red blood cells reside. These alternating cycles
continue until a desired volume of red blood cell storage solution
is added to the red blood cells.
[0542] 4. In-Line Leukocyte Depletion
[0543] Circuit 46' provides the capability to conduct on-line
depletion of leukocytes from collected red blood cells. In this
mode (see FIG. 39A), the circuit 46' is programmed to operate the
donor interface pump station PP3 in a ten second draw cycle (in
through valve V6, with valves V13 and V12 closed) to draw red blood
cells from the container(s) where red blood cells reside (e.g., the
in-process container 312' (through open valve V4) or the red blood
cell collection container 308 (through open valves V5, V3, and V2,
with valve V10 closed) into the pump PP3. Simultaneously, the
circuit 46' is programmed to operate the donor interface pump
station PP4 in a one second expel cycle (out through valve V14,
with valves V18 and V8 closed and valves V15 and V25 opened) to
expel red blood cells through tube 291' through the in-line
leukocyte depletion filter 293' to the leukocyte-depleted red blood
cell storage container 289'.
[0544] At the end of the draw cycle for pump PP3 (see FIG. 39B),
the blood processing circuit 46' is programmed to operate the donor
interface pump PP4 in a ten second draw cycle (i.e., in through
valve V7, with valves V14 and V18 closed) to draw red blood cells
from the container 312' or 308' into the pump PP4. At the same
time, the donor interface pump PP3 is operated in a one second
expel cycle to expel (out through valve V13, with valve V12 closed
and valves V15 and V25 opened) red blood cells through tube 291'
through the in-line leukocyte depletion filter 293' to the
leukocyte-depleted red blood cell storage container 289'. These
alternating cycles continue until a desired volume of red blood
cells are transfered through the filter 293 into the container
289'.
[0545] 5. Staged Buffy Coat Harvesting
[0546] In circuit 46 (see FIG. 5), buffy coat is collected through
port P4, which is served by flow line F4, which branches from flow
line F26, which conveys plasma from the plasma pump station PP2 to
the plasma collection container 304 (also see FIG. 10). In the
circuit 46' (see FIG. 34), the buffy coat is collected through the
port P4 from the flow path F6 as controlled by valve V19. The buffy
coat collection path bypasses the plasma pump station PP2, keeping
the plasma pump station PP2 free of exposure to the buffy coat,
thereby keeping the collected plasma free of contamination by the
buffy coat components.
[0547] During separation, the system controller (already described)
maintains the buffy coat layer within the separation chamber 18' at
a distance spaced from the low-G wall, away from the plasma
collection line 292 (see FIG. 15A). This allows the buffy coat
component to accumulate during processing as plasma is conveyed by
operation of the plasma pump PP2 from the chamber into the plasma
collection container 304'.
[0548] To collect the accumulated buffy coat component, the
controller opens the buffy coat collection valve V19, and closes
the inlet valve V17 of the plasma pump station PP2 and the red
blood cell collection valve V2. The in-process pump PP1 continues
to operate, bringing whole blood into the chamber 18'. The flow of
whole blood into the chamber 18' moves the buffy coat to the low-G
wall, inducing an over spill condition) (see FIG. 15B). The buffy
coat component enters the plasma collection line 292' and enters
flow path F6 through the port P6. The circuit 46' conveys the buffy
coat component in F6 through the opened valve V19 directly into
path F4 for passage through the port P4 into the collection
container 376'.
[0549] The valve V19 is closed when the sensing station 332 senses
the presence of red blood cells. The plasma pumping station PP2 can
be temporarily operated in a reverse flow direction (in through the
valve V11 and out through the valve V17, with valve V9 opened) to
flow plasma from the collection container 302' through the tube
292' toward the separation chamber, to flush resident red blood
from the tube 292' back into the separation chamber. The controller
can resume normal plasma and red blood cell collection, by opening
the red blood cell collection valve V2 and operating the plasma
pumping station PP2 (in through valve V17 and out through valve
V11) to resume the conveyance of plasma from the separation chamber
to the collection container 302'.
[0550] Over spill conditions causing the movement of the buffy coat
for collection can be induced at prescribed intervals during the
process period, until a desired buffy coat volume is collected in
the buffy coat collection container.
[0551] 6. Miscellaneous
[0552] As FIG. 43 shows in phantom lines, the manifold assembly
226' can include an auxiliary pneumatic actuator A.sub.AUX
selectively apply P.sub.HARD to the region of the flexible
diaphragm that overlies the interior cavity 201' (see FIG. 35). As
previously described, whole blood expelled by the pumping station
PP1 (by application of P.sub.HARD by actuator PA2), enters flow
path F5 through openings 203' and 205' into the processing chamber
18'. During the next subsequent stroke of the PP1, to draw whole
blood into the pumping chamber PP1 by application of V.sub.GEN by
actuator PA2, residual whole blood residing in the cavity 201' is
expelled into flow path F5 through opening 205', and into the
processing chamber 18' by application of P.sub.HARD by A.sub.AUX.
The cavity 201' also serves as a capacitor to dampen the pulsatile
pump strokes of the in-process pump PP1 serving the separation
chamber 18'.
[0553] It is desirable to conduct seal integrity testing of the
cassette 28' shown in FIG. 35 and 36 prior to use. The integrity
test determines that the pump and valve stations within the
cassette 28' function without leaking. In this situation, it is
desirable to isolate the cassette 28' from the separation chamber
26'. Valves V19 and V16 (see FIG. 34) in circuit 264' provide
isolation for the whole blood inlet and plasma lines 292' and 296'
of the chamber 18'. To provide the capability of also isolating the
red blood cell line 294', an extra valve fluid actuated station V26
can be added in fluid flow path F7 serving port P7. As further
shown in phantom lines in FIG. 43, an addition valve actuator VA26
can be added to the manifold assembly 26', to apply positive
pressure to the valve V26, to close the valve V26 when isolation is
required, and to apply negative pressure to the valve V26, to open
the valve when isolation is not required.
[0554] VII. Blood Separation Elements
[0555] A. Molded Processing Chamber
[0556] FIGS. 21 to 23 show an embodiment of the centrifugal
processing chamber 18, which can be used in association with the
system 10 shown in FIG. 1.
[0557] In the illustrated embodiment, the processing chamber 18 is
preformed in a desired shape and configuration, e.g., by injection
molding, from a rigid, biocompatible plastic material, such as a
non-plasticized medical grade acrilonitrile-butadiene-styrene
(ABS).
[0558] The preformed configuration of the chamber 18 includes a
unitary, molded base 388. The base 388 includes a center hub 120.
The hub 120 is surrounded radially by inside and outside annular
walls 122 and 124 (see FIGS. 21 and 23). Between them, the inside
and outside annular walls 122 and 124 define a circumferential
blood separation channel 126. A molded annular wall 148 closes the
bottom of the channel 126 (see FIG. 22).
[0559] The top of the channel 126 is closed by a separately molded,
flat lid 150 (which is shown separated in FIG. 21 for the purpose
of illustration). During assembly, the lid 150 is secured to the
top of the chamber 18, e.g., by use of a cylindrical sonic welding
horn.
[0560] All contours, ports, channels, and walls that affect the
blood separation process are preformed in the base 388 in a single,
injection molded operation. Alternatively, the base 388 can be
formed by separate molded parts, either by nesting cup shaped
subassemblies or two symmetric halves.
[0561] The lid 150 comprises a simple flat part that can be easily
welded to the base 388. Because all features that affect the
separation process are incorporated into one injection molded
component, any tolerance differences between the base 388 and the
lid 150 will not affect the separation efficiencies of the chamber
18.
[0562] The contours, ports, channels, and walls that are preformed
in the base 388 can vary. In the embodiment shown in FIGS. 21 to
23, circumferentially spaced pairs of stiffening walls 128, 130,
and 132 emanate from the hub 120 to the inside annular wall 122.
The stiffening walls 128, 130, 132 provide rigidity to the chamber
18.
[0563] As seen in FIG. 23, the inside annular wall 122 is open
between one pair 130 of the stiffening walls. The opposing
stiffening walls form an open interior region 134 in the hub 120,
which communicates with the channel 126. Blood and fluids are
introduced from the umbilicus 296 into and out of the separation
channel 126 through this region 134.
[0564] In this embodiment (as FIG. 23 shows), a molded interior
wall 136 formed inside the region 134 extends entirely across the
channel 126, joining the outside annular wall 124. The wall 136
forms a terminus in the separation channel 126, which interrupts
flow circumferentially along the channel 126 during separation.
[0565] Additional molded interior walls divide the region 124 into
three passages 142, 144, and 146. The passages 142, 144, and 146
extend from the hub 120 and communicate with the channel 126 on
opposite sides of the terminus wall 136. Blood and other fluids are
directed from the hub 120 into and out of the channel 126 through
these passages 142, 144, and 146. As will be explained in greater
detail later, the passages 142, 144, and 146 can direct blood
components into and out of the channel 126 in various flow
patterns.
[0566] The underside of the base 388 (see FIG. 22) includes a
shaped receptacle 179. Three preformed nipples 180 occupy the
receptacle 179. Each nipple 180 leads to one of the passages 142,
144, 146 on the opposite side of the base 388.
[0567] The far end of the umbilicus 296 includes a shaped mount 178
(see FIGS. 24 and 24A). The mount 178 is shaped to correspond to
the shape of the receptacle 179. The mount 178 can thus be plugged
into the receptacle 179 (as FIG. 25 shows). The mount 178 includes
interior lumens 398 (see FIG. 24A), which slide over the nipples
180 in the hub 120, to couple the umbilicus 296 in fluid
communication with the channel 126.
[0568] Ribs 181 within the receptacle 179 (see FIG. 22) uniquely
fit within a key way 183 formed on the mount 178 (see FIG. 24A).
The unique fit between the ribs 181 and the key way 183 is arranged
to require a particular orientation for plugging the shaped mount
178 into the shaped receptacle 179. In this way, a desired flow
orientation among the umbilicus 296 and the passages 142, 144, and
146 is assured.
[0569] In the illustrated embodiment, the umbilicus 296 and mount
178 are formed from a material or materials that withstand the
considerable flexing and twisting forces, to which the umbilicus
296 is subjected during use. For example, a Hytrel.RTM. polyester
material can be used.
[0570] This material, while well suited for the umbilicus 296, is
not compatible with the ABS plastic material of the base 388, which
is selected to provide a rigid, molded blood processing
environment. The mount 178 thus cannot be attached by conventional
by solvent bonding or ultrasonic welding techniques to the
receptacle 179.
[0571] In this arrangement (see FIGS. 24 and 25), the dimensions of
the shaped receptacle 179 and the shaped mount 178 are preferably
selected to provide a tight, dry press fit. In addition, a
capturing piece 185, formed of ABS material (or another material
compatible with the material of the base 388), is preferably placed
about the umbilicus 296 outside the receptacle in contact with the
peripheral edges of the receptacle 179. The capturing piece 185 is
secured to the peripheral edges of the receptacle 179, e.g., by
swaging or ultrasonic welding techniques. The capturing piece 185
prevents inadvertent separation of the mount 178 from the
receptacle 181. In this way, the umbilicus 296 can be integrally
connected to the base 388 of the chamber 18, even though
incompatible plastic materials are used.
[0572] The centrifuge station 20 (see FIGS. 26 to 28) includes a
centrifuge assembly 48. The centrifuge assembly 48 is constructed
to receive and support the molded processing chamber 18 for
use.
[0573] As illustrated, the centrifuge assembly 48 includes a yoke
154 having bottom, top, and side walls 156, 158, 160. The yoke 154
spins on a bearing element 162 attached to the bottom wall 156. An
electric drive motor 164 is coupled via an axle to the bottom wall
156 of the collar 154, to rotate the yoke 154 about an axis 64. In
the illustrated embodiment, the axis 64 is tilted about fifteen
degrees above the horizontal plane of the base 38, although other
angular orientations can be used.
[0574] A rotor plate 166 spins within the yoke 154 about its own
bearing element 168, which is attached to the top wall 158 of the
yoke 154. The rotor plate 166 spins about an axis that is generally
aligned with the axis of rotation 64 of the yoke 154.
[0575] The top of the processing chamber 18 includes an annular lip
380, to which the lid 150 is secured. Gripping tabs 382 carried on
the periphery of the rotor plate 166 make snap-fit engagement with
the lip 380, to secure the processing chamber 18 on the rotor plate
166 for rotation.
[0576] A sheath 182 on the near end of the umbilicus 296 fits into
a bracket 184 in the centrifuge station 20. The bracket 184 holds
the near end of the umbilicus 296 in a non-rotating stationary
position aligned with the mutually aligned rotational axes 64 of
the yoke 154 and rotor plate 166.
[0577] An arm 186 protruding from either or both side walls 160 of
the yoke 154 contacts the mid portion of the umbilicus 296 during
rotation of the yoke 154. Constrained by the bracket 184 at its
near end and the chamber 16 at its far end (where the mount 178 is
secured inside the receptacle 179), the umbilicus 296 twists about
its own axis as it rotates about the yoke axis 64. The twirling of
the umbilicus 296 about its axis as it rotates at one omega with
the yoke 154 imparts a two omega rotation to the rotor plate 166,
and thus to the processing chamber 18 itself.
[0578] The relative rotation of the yoke 154 at a one omega
rotational speed and the rotor plate 166 at a two omega rotational
speed, keeps the umbilicus 296 untwisted, avoiding the need for
rotating seals. The illustrated arrangement also allows a single
drive motor 164 to impart rotation, through the umbilicus 296, to
the mutually rotating yoke 154 and rotor plate 166. Further details
of this arrangement are disclosed in Brown et al U.S. Pat. No.
4,120,449, which is incorporated herein by reference.
[0579] Blood is introduced into and separated within the processing
chamber 18 as it rotates.
[0580] In one flow arrangement (see FIG. 29), as the processing
chamber 18 rotates (arrow R in FIG. 29), the umbilicus 296 conveys
whole blood into the channel 126 through the passage 146. The whole
blood flows in the channel 126 in the same direction as rotation
(which is counterclockwise in FIG. 29). Alternatively, the chamber
18 can be rotated in a direction opposite to the circumferential
flow of whole blood, i.e., clockwise. The whole blood separates as
a result of centrifugal forces in the manner shown in FIG. 15A. Red
blood cells are driven toward the high-G wall 124, while lighter
plasma constituent is displaced toward the low-G wall 122. In this
flow pattern, a dam 384 projects into the channel 126 toward the
high-G wall 124. The dam 384 prevents passage of plasma, while
allowing passage of red blood cells into a channel 386 recessed in
the high-G wall 124. The channel 386 directs the red blood cells
into the umbilicus 296 through the radial passage 144. The plasma
constituent is conveyed from the channel 126 through the radial
passage 142 into umbilicus 296.
[0581] Because the red blood cell exit channel 386 extends outside
the high-g wall 124, being spaced further from the rotational axis
than the high-g wall, the red blood cell exit channel 386 allows
the positioning of the interface between the red blood cells and
the buffy coat very close to the high-g wall 124 during blood
processing, without spilling the buffy coat into the red blood cell
collection passage 144 (creating an over spill condition). The
recessed exit channel 386 thereby permits red blood cell yields to
be maximized (in a red blood cell collection procedure) or an
essentially platelet-free plasma to be collected (in a plasma
collection procedure).
[0582] In an alternative flow arrangement (see FIG. 30), the
umbilicus 296 conveys whole blood into the channel 126 through the
passage 142. The processing chamber 18 rotates (arrow R in FIG. 30)
in the same direction as whole blood flow (which is clockwise in
FIG. 30). Alternatively, the chamber 18 can be rotated in a
direction opposite to the circumferential flow of whole blood,
i.e., clockwise. The whole blood separates as a result of
centrifugal forces in the manner shown in FIG. 15A. Red blood cells
are driven toward the high-G wall 124, while lighter plasma
constituent is displaced toward the low-G wall 122.
[0583] In this flow pattern, the dam 384 (previously described)
prevents passage of plasma, while allowing passage of red blood
cells into the recessed channel 386. The channel 386 directs the
red blood cells into the umbilicus 296 through the radial passage
144. The plasma constituent is conveyed from the opposite end of
the channel 126 through the radial passage 146 into umbilicus
296.
[0584] In another alternative flow arrangement (see FIG. 31), the
umbilicus 296 conveys whole blood into the channel 126 through the
passage 144. The processing chamber 18 is rotated (arrow R in FIG.
31) in the same direction as blood flow (which is clockwise in FIG.
31). Alternatively, the chamber 18 can be rotated in a direction
opposite to the circumferential flow of whole blood, i.e.,
counterclockwise. The whole blood separates as a result of
centrifugal forces in the manner shown in FIG. 15A. Red blood cells
are driven toward the high-G wall 124, while lighter plasma
constituent is displaced toward the low-G wall 122.
[0585] In this flow pattern, a dam 385 at the opposite end of the
channel 126 prevents passage of plasma, while allowing passage of
red blood cells into a recessed channel 387. The channel 387
directs the red blood cells into the umbilicus 296 through the
radial passage 146. The plasma constituent is conveyed from the
other end of the channel 126 through the radial passage 142 into
umbilicus 296. In this arrangement, the presence of the dam 384 and
the recessed passage 386 (previously described) separates incoming
whole blood flow (in passageway 144) from outgoing plasma flow (in
passageway 142). This flow arrangement makes possible the
collection of platelet-rich plasma, if desired.
[0586] In another alternative flow arrangement (see FIG. 32), the
passage 144 extends from the hub 120 into the channel 126 in a
direction different than the passages 142 and 146. In this
arrangement, the terminus wall 136 separates the passages 142 and
146, and the passage 144 communicates with the channel 126 at a
location that lays between the passages 142 and 146. In this
arrangement, the umbilicus 296 conveys whole blood into the channel
126 through the passage 146. The processing chamber 18 is rotated
(arrow R in FIG. 32) in the same direction as blood flow (which is
clockwise in FIG. 32). Alternatively, the chamber 18 can be rotated
in a direction opposite to the circumferential flow of whole blood,
i.e., counterclockwise. The whole blood separates as a result of
centrifugal forces in the manner shown in FIG. 15A. Red blood cells
are driven toward the high-G wall 124, while lighter plasma
constituent is displaced toward the low-G wall 122.
[0587] In this flow pattern, the passage 144 conveys plasma from
the channel 126, while the passage 142 conveys red blood cells from
the channel 126.
[0588] As previously mentioned, in any of the flow patterns shown
in FIGS. 28 to 32, the chamber 18 can be rotated in the same
direction or in an opposite direction to circumferential flow of
whole blood in the channel 126. Blood separation as described will
occur in either circumstance. Nevertheless, it has been discovered
that, rotating the chamber 18 in the same direction as the flow of
whole blood in the channel 126 during separation, appears to
minimize disturbances due, e.g., Coriolis effects, resulting in
increased separation efficiencies.
EXAMPLE
[0589] Whole blood was separated during various experiments into
red blood cells and plasma in processing chambers 18 like that
shown in FIG. 28. In one chamber (which will be called Chamber 1),
whole blood circumferentially flowed in the channel 126 in the same
direction as the chamber 18 was rotated (i.e., the chamber 18 was
rotated in a counterclockwise direction). In the other chamber 18
(which will be called Chamber 2), whole blood circumferentially
flowed in the channel 126 in a direction opposite to chamber
rotation (i.e., the chamber 18 was rotated in a clockwise
direction).
[0590] The average hematocrit for red blood cells collected were
measured for various blood volume samples, processed at different
combinations of whole blood inlet flow rates and plasma outlet flow
rates. The following Tables summarize the results for the various
experiments.
14TABLE 1 (Flow in the Same Direction as Rotation) Number of Blood
Average Hematocrit of Samples Average Whole Blood Red Blood Cells
Processed Hematocrit (%) Collected 7 45.4 74.8 4 40 78.8
[0591]
15TABLE 2 (Flow in the Opposite Direction as Rotation) Number of
Blood Average Hematocrit of Samples Average Whole Blood Red Blood
Cells Processed Hematocrit (%) Collected 3 43.5 55.5 2 42.25
58.25
[0592] Tables 1 and 2 show that, when blood flow in the chamber is
in the same direction as rotation, the hematocrit of red blood
cells is greater than when blood flow is in the opposite direction.
A greater yield of red blood cells also means a greater yield of
plasma during the procedure.
[0593] FIG. 33 shows a chamber 18' having a unitary molded base
388' like that shown in FIGS. 21 to 23, but in which two flow paths
126' and 390 are formed. The flow paths 126' and 390 are shown to
be concentric, but they need not be. The chamber 18' shares many
other structural features in common with the chamber 18 shown in
FIG. 23. Common structural features are identified by the same
reference number marked with an asterisk.
[0594] The base 388' includes a center hub 120' which is surrounded
radially by the inside and outside annular walls 122' and 124',
defining between them the circumferential blood separation channel
126'. In this embodiment, a second inside annular wall 392 radially
surrounds the hub 120'. The second circumferential blood separation
channel 390 is defined between the inside annular walls 122' and
392. This construction forms the concentric outside and inside
separation channels 126' and 390.
[0595] An interruption 394 in the annular wall 122' adjacent to the
dam 384' establishes flow communication between the outside channel
126' and the inside channel 390. An interior wall 396 blocks flow
communication between the channels 126' and 390 at their opposite
ends.
[0596] As the processing chamber 18' rotates (arrow R in FIG. 33),
the umbilicus 296 conveys whole blood into the outside channel 126'
through the passage 144'. The whole blood flows in the channel 126'
in the same direction as rotation (which is counterclockwise in
FIG. 33). Alternatively, the chamber 18' can be rotated in a
direction opposite to the circumferential flow of whole blood,
i.e., clockwise. The whole blood separates in the outside channel
126' as a result of centrifugal forces in the manner shown in FIG.
15A. Red blood cells are driven toward the high-G wall 124', while
lighter plasma constituent is displaced toward the low-G wall
122'.
[0597] As previously described, the dam 384' prevents passage of
plasma, while allowing passage of red blood cells into a channel
386' recessed in the high-G wall 124'. The channel 386' directs the
red blood cells into the umbilicus 296 through the radial passage
142'. The plasma constituent is conveyed from the channel 126'
through the interruption 394 into the inside separation channel
390.
[0598] The plasma flows circumferentially flow through the inside
channel 390 in a direction opposite to the whole blood in the
outside channel 126'. Platelets remaining in the plasma migrate in
response to centrifugal forces against the annular wall 124'. The
channel 390 directs the plasma constituent to the same end of the
chamber 18' where whole blood is initially introduced. The plasma
constituent is conveyed from the channel 390 by the passage
146'.
[0599] VIII. Other Blood Processing Functions
[0600] The many features of the invention have been demonstrated by
describing their use in separating whole blood into component parts
for storage and blood component therapy. This is because the
invention is well adapted for use in carrying out these blood
processing procedures. It should be appreciated, however, that the
features of the invention equally lend themselves to use in other
blood processing procedures.
[0601] For example, the systems and methods described, which make
use of a programmable cassette in association with a blood
processing chamber, can be used for the purpose of washing or
salvaging blood cells during surgery, or for the purpose of
conducting therapeutic plasma exchange, or in any other procedure
where blood is circulated in an extracorporeal path for
treatment.
[0602] Features of the invention are set forth in the following
claims.
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