Blood separation systems and methods using a multiple function pump station to perform different on-line processing tasks

[0001] This invention relates to systems and methods for processing and collecting blood, blood constituents, or other suspensions of cellular material.

[0002] Today people routinely separate whole blood, usually by centrifugation, into its various therapeutic components, such as red blood cells, platelets, and plasma.

[0003] 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.

[0004] 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.

[0005] 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.

[0006] 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.

[0007] 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.

[0008] More particularly, the invention provides blood separation systems and methods, which employ a multiple function pump station to perform different on-line processing tasks. For example, a pump station that is operated in one mode to draw blood from a donor can, in another mode, be operated to return blood to the donor. As other examples, the pump station used to draw blood from a donor can also be used to perform subsequent blood processing tasks, such as mixing processing or additive fluids with the blood, or transferring a harvested blood component to a storage container, or finishing the processing of a harvested blood component, e.g., by passage through a filter to remove leukocytes.

[0009] The provision of a multiple function pump station makes consolidation of different processing tasks possible, and leads to a reduction in the overall size and complexity of a blood separation system. The use of a multiple function pump station also makes possible the performance of different blood processing procedures using the same blood separation system.

[0010] According to one aspect of the invention, a blood processing system and related method provides a donor flow channel to convey fluid to and from a donor, a blood processing flow channel including a blood separation chamber to separate a blood component from donor blood, and a blood component collection flow channel including a blood component collection container. A multiple function pump station communicates with all these flow channels. The pump station is operated in multiple modes. In a processing mode, the pump station is operated to convey blood in the donor flow channel into the blood processing flow channel for separation of the blood component in the blood separation chamber. In a collection mode, the pump station is operated to convey at least some of the blood component in the blood processing flow channel into the blood component collection flow channel for collection in the blood component collection container.

[0011] In one embodiment, the blood component collection flow channel includes a filter to remove undesired materials, e.g., leukocytes, from the blood component before entering the blood component collection container.

[0012] In one embodiment, the pump station is also operated in a blood component return mode, to convey at least some of the blood component in the blood processing flow channel into the donor flow channel for return to the donor.

[0013] In one embodiment, the pump station also communicates with a utility flow channel, which includes a container holding a processing fluid, e.g., saline. The pump station is operated in the blood component return mode, to convey processing fluid in the utility flow channel into the donor flow channel for mixing with the blood component returned to the donor. The on-line mixing of a processing fluid improves donor comfort by, e.g., raising the temperature of the processing fluid before entering the circulatory system of the donor, or by lowering the hematocrit of a returned cellular blood component, thereby allowing a larger gauge (i.e., smaller diameter) phlebotomy needle to be used.

[0014] In one embodiment, the pump station is operated in a processing fluid transfer mode, during which processing fluid in the utility flow channel into the blood processing flow channel for mixing with the blood component. In this arrangement, the processing fluid can includes a blood component additive to enhance storage of the blood component.

[0015] In one embodiment, the pump station includes a fluid pressure actuated pump and an actuator to apply fluid pressure to the pump. In this embodiment, the pump station and all the flow channels with which the pump station communicates are centralized within a cassette.

[0016] According to another aspect of the invention, a blood processing system and related method couple a pump station to a donor flow channel to convey fluid to and from a donor, a blood processing flow channel including a blood separation chamber to separate red blood cells from donor whole blood, and a blood component collection flow channel including a red blood cell collection container and an in-line filter to remove leukocytes from the red blood cells before entering the red blood cell collection container. The pump station is operated in a processing mode to convey whole blood in the donor flow channel into the blood processing flow channel for separation of the red blood cells in the blood separation chamber. The pump station is also operated in a collection mode, to convey at least some of the red blood cells in the blood processing flow channel into the blood component collection flow channel for on-line removal of leukocytes and collection in the red blood cell collection container.

[0017] In one embodiment applicable to each aspect of the invention, the pump station comprises first and second fluid pressure actuated pump stations. A fluid pressure actuator operates to selectively apply fluid pressure pump strokes in tandem to the first and second pump stations to convey fluid from a source to a destination. During at least one of the multiple modes, operation of the pump station is switched between a first flow state and a second flow state. In the first flow state, the pump strokes draw a fluid volume into the first pump station from the source and expel a fluid volume from the second pump station to the destination. In the second flow state, the pump strokes draw a fluid volume into the second pump station from the source and expel a fluid volume from the first pump station to the destination. A control function operates to synchronize the pump strokes so that fluid flow from the source is essentially continuous while fluid flow to the destination is pulsatile.

[0018] Other features and advantages of the inventions are set forth in the following specification and attached drawings.

[0060] 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.

[0061] 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.

I. System Overview

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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.

[0067] 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.

[0068] 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.

[0069] 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.

II. The Programmable Blood Processing Circuit

[0070] 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.

[0071] 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.

[0072] 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).

[0073] 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.

[0074] 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.

[0075] The circuit 46 can be programmed to assigned dedicated pumping functions to the various pump stations. For example, in a preferrred 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.

[0076] 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.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] 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.

[0083] 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.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] 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.

[0088] 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).

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] This ordered orientation of the ports provides a centralized, compact unit aligned with the operative regions of the case 36.

[0098] B. The Universal Set

[0099] 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.

[0100] 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.

[0101] A container 275 for collecting an in-line sample of blood drawn through the tube 300 is also attached through the y-connector 273.

[0102] 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.

[0103] 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.

[0104] A container 288 holding saline is coupled via a tube 284 to the cassette port P12.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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.

[0110] 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.

[0111] As shown in FIG. 10, no tubing is coupled to the utility cassette port P13 and buffy port P4.

[0112] C. The Pump and Valve Station

[0113] 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.

[0114] 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.

[0115] 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.

[0116] 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.

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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.

[0121] 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.

[0122] 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.

[0123] 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.

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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:

• • [0128] (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.
  • [0129] (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.
  • [0130] (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.
  • [0131] (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.
  • [0132] (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.
  • [0133] (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.

[0134] For each pressure and vacuum level, a variation of plus or minus 20 mmHg is tolerated.

[0135] 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.

[0136] 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.

[0137] 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.

[0138] Pgen is used to drive the donor interface pump PP3 and can be maintained at a lower pressure, as can the AC pump PP4.

[0139] 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.

[0140] 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.

[0141] 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.

[0142] 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.

[0143] 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.

[0144] 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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] 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.

[0149] 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.

[0150] 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.

[0151] 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.

[0152] 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.

[0153] 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.

[0154] 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.

[0155] 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.

[0156] 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”.

[0157] 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.

III. Other Process Control Components of the System

[0158] 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.

[0159] A. Container Support Components

[0160] 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.

[0161] 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.

[0162] 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.

[0163] 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.

[0164] 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.

[0165] B. The Controller and Operator Interface Station

[0166] 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™ 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).

[0167] 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.

[0168] 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.

[0169] 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.

[0170] 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.

[0171] 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.

[0172] 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.

[0173] 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.

[0174] 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.

[0175] 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.

[0176] C. On-Line Monitoring of Pump Flows

[0177] 1. Gravimetric Monitoring

[0178] 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.

[0179] 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:

[0180] $\begin{array}{cc}Q=\frac{\mathrm{SV}}{\left(T_{\mathrm{Pump}}+T_{\mathrm{Fill}}+T_{\mathrm{Idle}}\right)}& \left(1\right)\end{array}$

• • [0181] where:
  • [0182] Q is the flow rate of the pump.
  • [0183] SV is the stroke volume, or volume moved per pump cycle.
  • [0184] T_Pump is the time the fluid is moved out of the pump chamber.
  • [0185] T^Fill is the time the pump is filled with fluid, and
  • [0186] T_Idle is the time when the pump is idle, that is, when no fluid movement occurs.

[0187] 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.

[0188] The actual fluid flow in volume per unit of time Q_Actual can therefore be expressed as follows:

[0189] $\begin{array}{cc}{Q}_{\mathrm{Actual}}=k\times \frac{{\mathrm{SV}}_{\mathrm{Ideal}}}{T_{\mathrm{Pump}}+T_{\mathrm{Fill}}+T_{\mathrm{Idle}}}& \left(2\right)\end{array}$

• • [0190] where:
  • [0191] Q_Actual is the actual fluid flow in volume per unit of time.
  • [0192] SV_Ideal is the theoretical stroke volume, based upon the geometry of the pump chamber. k is a correction factor that accounts for the interactions between the pump and the upstream and downstream pressures.

[0193] The actual flow rate can be ascertained gravimetrically, using the upstream or downstream weigh scales 246, based upon the following relationship:

[0194] $\begin{array}{cc}{Q}_{\mathrm{Actual}}=\frac{\Delta \mathrm{Wt}}{\rho \times \Delta T}& \left(3\right)\end{array}$

• • [0195] where:
  • [0196] ΔWt is the change in weight of fluid as detected by the upstream or downstream weigh scale 246 during the time period ΔT,
  • [0197] ρ is the density of fluid.
  • [0198] ΔT is the time period where the change in weight Δwt is detected in the weigh scale 246.

[0199] The following expression is derived by combining

Equations (2) and (3):

[0200] $\begin{array}{cc}k=\left(T_{\mathrm{Pump}}+T_{\mathrm{Fill}}+T_{\mathrm{Idle}}\right)\times \frac{\Delta \mathrm{Wt}}{\left({\mathrm{SV}}_{\mathrm{Ideal}}\times \rho \times \Delta T\right)}& \left(4\right)\end{array}$

[0201] The controller 16 computes k according to Equation (4) and then adjusts T_Idle so that the desired flow rate is achieved, as follows:

[0202] $\begin{array}{cc}{T}_{\mathrm{Idle}}=\left(k\times \frac{{\mathrm{SV}}_{\mathrm{Ideal}}}{Q_{\mathrm{Desired}}}\right)-T_{\mathrm{Pump}}-T_{\mathrm{Fill}}& \left(5\right)\end{array}$

[0203] The controller 16 updates the values for k and T_Idle frequently to adjust the flow rates.

[0204] Alternatively, the controller 16 can change T_Pump and/or T_Fill and/or T_Idle to adjust the flow rates.

[0205] In this arrangement, one or more of the time interval components T_Pump, or T_Fill, or T_Idle is adjusted to a new magnitude to achieve Q_Desired, according to the following relationship:

[0206] $T_{n\left(\mathrm{Adjusted}\right)}=k\left(\frac{{\mathrm{SV}}_{\mathrm{Ideal}}}{Q_{\mathrm{Desired}}}\right)-T_{n\left(\mathrm{NotAdjusted}\right)}$
where:

• • [0207] T_n(Adjusted) is the magnitude of the time interval component or components after adjustment to achieve the desired flow rate Q_Desired.
  • [0208] T_{n(NotAdjusted)} is the magnitude of the value of the other time interval component or components of T_Stroke that are not adjusted. The adjusted stroke interval after adjustment to achieve the desired flow rate Q_Desired is the sum of T_n(Adjusted) and T_{n(NotAdjusted)}.

[0209] 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.

[0210] 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.

[0211] In computing k and T_idle and/or T_Pump and/or T_Fill, the controller 16 may rely upon multiple measurements of ΔWt and/or ΔT. 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.

[0212] The above described monitoring technique is applicable for use for other constant stroke volume pumps, i.e. peristaltic pumps, etc.

[0213] 2. Electrical Monitoring

[0214] 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.

[0215] 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.

[0216] 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.

[0217] 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.

[0218] 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_Idle and/or T_Pump and/or T_Fill to minimize the deviance.

[0219] 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.

[0220] 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.

IV. The Blood Processing Procedures

[0221] A. Double RBC Collection Procedure (No Plasma Collection)

[0222] 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.

[0223] 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.

[0224] 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.

[0225] 1. The Pre-Collection Cycle

[0226] a. Anticoagulant Prime

[0227] 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.

[0228] 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.

[0229] b. Saline Prime

[0230] 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).

[0231] 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).

[0232] 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.

[0233] 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.

[0234] 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.

[0235] The programming of the circuit during the phases of the pre-collection cycle is summarized in the following table.

[0236]

TABLE
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	●	●	●	●	●	●	●
V2	●	●	●	●	●	●	●
V3	∘	∘	●	●	●	∘	●
V4	●	●	∘	●	●	●	●
V5	●	●	●	●	●	●	●
V6	●	●	●	●	∘	●	●
V7	●	●	●	●	∘	●	●
V8	●	●	●	●	●	●	●
V9	●	●	∘/●	∘/●	∘/●	●	●
			Pump	Pump	Pump In
			Out	Out	(Stage
					1)
					∘
					(Stage
					2)
V10	●	●	●	●	∘	●	●
					(Stage
					1)
					∘/●
					Pump
					Out
					(Stage
					2)
V11	∘/●	∘	●	●	●	∘/●	●
	Pump					Pump In
	Out
V12	●	●	●	●	∘	●	●
					(Stage
					1)
					∘/●
					Pump In
					(Stage
					2)
V13	∘/●	∘	●	●	●	∘/●	●
	Pump In					Pump
						Out
V14	●	●	∘/●	∘/●	∘/●	●	●
			Pump In	Pump In	Pump
					Out
					(Stage
					1)
					∘
					(Stage
					2)
V15	∘	∘/●	●	●	●	∘	●
		Pump In
		Pump
		Out
V16	●	●	●	●	●	●	●
V17	●	●	●	●	●	●	●
V18	∘	∘	●	●	●	∘	●
V19	∘	∘	●	●	●	∘	●
V20	∘	∘/●	●	●	●	∘	●
		Pump
		Out
		Pump In
V21	●	●	●	●	●	●	●
V22	●	●	∘	∘	∘	●	●
V23	●	●	∘	∘	∘	●	●
PP1	▪	▪	□	□	□	▪	▪
					(Stage
					1)
PP2	▪	▪	▪	▪	□	▪	▪
					(Stage
					2)
PP3	□	▪	▪	▪	▪	□	▪
PP4	▪	□	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0237] C. The Collection Cycle

[0238] i. Blood Prime

[0239] 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.

[0240] 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.

[0241] B. Blood Separation While Drawing Whole Blood or Without Drawing Whole Blood

[0242] 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).

[0243] 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.

[0244] C. Return Plasma and Saline

[0245] 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.

[0246] 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.

[0247] 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.

[0248] 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 selected, the post-collection cycle commences.

[0249] The programming of the circuit during the phases of the collection cycle is summarized in the following table.

[0250]

TABLE
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
	Blood		Drawing	Separation
	Prime	Blood Prime	Whole	(Without	Fill Donor
Phase	1	2	Blood)	Separation)	Line
V1	●	●	●	●	∘
V2	●	●	∘	∘ (●)	●
V3	∘	●	∘	●	●
			(●)
V4	●	●	●	●	●
V5	●	●	∘	∘	●
V6	●	●	●	∘/●	●
				Alternates
				with V23
V7	●	∘	●	●	∘
V8	●	●	●	●	●
V9	●	∘/●	∘/●	∘/●	●
		Pump In	Pump In	Pump In
				(●)
V10	●	●	∘/●	∘/●	●
			Pump Out	Pump Out
				(●)
V11	∘/●	∘	∘/●	∘/●	∘/●
	Pump Out		Pump Out	Pump In	Pump In
			(●)
V12	●	●	∘/●	∘/●	●
			Pump In	Pump In
				(●)
V13	∘/●	∘	∘/●	∘/●	∘/●
	Pump In		Pump In	Pump Out	Pump Out
			(●)
V14	●	∘/●	∘/●	∘/●	●
		Pump Out	Pump Out	Pump Out
				(●)
V15	∘/●	●	∘/●	●	●
	Pump Out		Pump Out
			(●)
V16	●	●	●	●	●
V17	●	●	●	●	●
V18	∘	∘	∘	∘	∘
			(●)
V19	∘	●	∘	●	●
			(●)
V20	∘/●	●	∘/●	●	●
	Pump Out		Pump In
			(●)
V21	●	●	●	●	●
V22	●	●	●	∘	●
V23	●	●	●	∘/●	●
				Alternates
				with V6
PP1	▪	□	□	□	▪
				(▪)
PP2	▪	▪	□	□	▪
				(▪)
PP3	□	▪	□	□	□
			(▪)
PP4	□	▪	□	▪	▪
			(▪)
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0251] D. The Post-Collection Cycle

[0252] 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.

[0253] 1. Return Excess Plasma

[0254] 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.

[0255] 2. Saline Purge

[0256] 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.

[0257] 3. Final Return to Donor

[0258] 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.

[0259] 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.

[0260] 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.

[0261] 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.

[0262] The programming of the circuit during the phases of the post-collection cycle is summarized in the following table.

[0263]

TABLE
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	●	●	∘	●	∘
V2	●	●	●	●	●
V3	●	●	●	●	●
V4	●	∘	●	●	●
V5	∘	●	●	●	●
V6	∘/●	●	●	●	●
	Alternates
	with V23
V7	●	●	∘/●	●	∘
			Alternates
			with V23
V8	●	●	●	●	●
V9	∘	∘	●	●	●
V10	●	●	●	●	●
V11	∘/●	∘/●	∘/●	∘/●	∘/●
	Pump In	Pump In/	Pump In	Pump In	Pump In
		Pump Out
V12	●	●	●	●	●
V13	∘/●	●	∘/●	∘/●	∘/●
	Pump Out		Pump Out	Pump Out	Pump Out
V14	●	∘	●	●	●
V15	●	●	●	●	●
V16	●	●	●	●	●
V17	●	●	●	●	●
V18	∘	●	∘	∘	∘
V19	●	●	●	●	●
V20	●	●	●	●	●
V21	●	●	●	●	●
V22	∘	∘	∘	∘	●
V23	∘/●	∘	∘/●	∘	●
	Alternates		Alternates
	with V6		with V7
PP1	▪	▪	▪	▪	▪
PP2	▪	▪	▪	▪	▪
PP3	□	□	□	□	□
PP4	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0264] E. The Storage Preparation Cycle

[0265] 1. Split RBC

[0266] 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.

[0267] 2. Add RBC Preservative

[0268] 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.

[0269] 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.

[0270] The programming of the circuit during the phases of the storage preparation cycle is summarized in the following table.

[0271]

TABLE
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	●	●	●	●
V2	∘	●	∘	●
V3	∘/●	∘	●	●
	Alternates
	with V11 and
	V4
V4	∘/●	●	∘	●
	Alternates
	with V11 and
	V4
V5	●	●	●	●
V6	●	●	●	●
V7	●	●	●	●
V8	●	●	●	●
V9	●	●	●	●
V10	●	●	●	●
V11	∘/●	∘/●	∘/●	●
	Pump In/	Pump In/	Pump In/
	Pump Out	Pump Out	Pump Out
V12	●	●	●	●
V13	●	●	●	●
V14	●	●	●	●
V15	●	●	●	●
V16	●	∘	∘	●
V17	●	●	●	●
V18	●	●	●	●
V19	●	●	●	●
V20	●	●	●	●
V21	●	∘	∘	●
V22	●	●	●	●
V23	●	●	●	●
PP1	▪	▪	▪	▪
PP2	▪	▪	▪	▪
PP3	□	□	□	▪
PP4	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0272] F. Plasma Collection (No Red Blood Cell Collection)

[0273] 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.

[0274] 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.

[0275] The procedure includes a pre-collection cycle, a collection cycle, and a post-collection cycle.

[0276] 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.

[0277] 1. The Pre-Collection Cycle

[0278] a. Anticoagulant Prime

[0279] 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.

• • [0280] b. Saline Prime

[0281] 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.

[0282] The programming of the circuit during the phases of the pre-collection cycle is summarized in the following table.

[0283]

TABLE
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	●	●	●	●	●	●	●
V2	●	●	●	●	●	●	●
V3	∘	∘	●	●	●	∘	●
V4	●	●	∘	●	●	●	●
V5	●	●	●	●	●	●	●
V6	●	●	●	●	∘	●	●
V7	●	●	●	●	∘	●	●
V8	●	●	●	●	●	●	●
V9	●	●	∘/●	∘/●	∘/●	●	●
			Pump	Pump	Pump In
			Out	Out	(Stage
					1)
					∘
					(Stage
					2)
V10	●	●	●	●	∘	●	●
					(Stage
					1)
					∘/●
					Pump
					Out
					(Stage
					2)
V11	∘/●	∘	●	●	●	∘/●	●
	Pump					Pump In
	Out
V12	●	●	●	●	∘	●	●
					(Stage
					1)
					∘/●
					Pump In
					(Stage
					2)
V13	∘/●	∘	●	●	●	∘/●	●
	Pump In					Pump
						Out
V14	●	●	∘/●	∘/●	∘/●	●	●
			Pump In	Pump In	Pump
					Out
					(Stage
					1)
					∘
					(Stage
					2)
V15	∘	∘/●	●	●	●	∘	●
		Pump In
		Pump
		Out
V16	●	●	●	●	●	●	●
V17	●	●	●	●	●	●	●
V18	∘	∘	●	●	●	∘	●
V19	∘	∘	●	●	●	∘	●
V20	∘	∘/●	●	●	●	∘	●
		Pump
		Out
		Pump In
V21	●	●	●	●	●	●	●
V22	●	●	∘	∘	∘	●	●
V23	●	●	∘	∘	∘	●	●
PP1	▪	▪	□	□	□	▪	▪
					(Stage
					1)
PP2	▪	▪	▪	▪	□	▪	▪
					(Stage
					2)
PP3	□	▪	▪	▪	▪	□	▪
PP4	▪	□	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0284] 2. The Collection Cycle

[0285] a. Blood Prime

[0286] 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.

[0287] 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.

[0288] b. Blood Separation While Drawing Whole Blood or Without Drawing Whole Blood

[0289] 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).

[0290] 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.

[0291] c. Return Red Blood Cells/Saline

[0292] 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.

[0293] 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.

[0294] 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.

[0295] 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.

[0296] The programming of the circuit during the phases of the collection cycle is summarized in the following table.

[0297]

TABLE
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
		Blood	Drawing	Separation
	Blood Prime	Prime	Whole	(Without	Fill Donor
Phase	1	2	Blood)	Separation)	Line
V1	●	●	●	●	∘
V2	●	●	∘	∘	●
V3	∘	●	∘	●	●
			(●)
V4	●	●	●	●	●
V5	●	●	∘	∘ (●)	●
V6	●	●	●	●	●
V7	●	∘	●	∘/●	∘
				Alternates
				with V23
V8	●	●	●	●	●
V9	●	∘/●	∘/●	∘/●	●
		Pump In	Pump In	Pump In
				(●)
V10	●	●	∘/●	∘/●	●
			Pump Out	Pump Out
				(●)
V11	∘/●	∘	∘/●	∘/●	∘/●
	Pump Out		Pump Out	Pump In	Pump In
			(●)
V12	●	●	∘/●	∘/●	●
			Pump In	Pump In
				(●)
V13	∘/●	∘	∘/●	∘/●	∘/●
	Pump In		Pump In	Pump Out	Pump Out
			(●)
V14	●	∘/●	∘/●	∘/●	●
		Pump Out	Pump Out	Pump Out
				(●)
V15	∘/●	●	∘/●	●	●
	Pump Out		Pump Out
			(●)
V16	●	●	●	●	●
V17	●	●	●	●	●
V18	∘	∘	∘	∘	∘
			(●)
V19	∘	●	∘	●	●
			(●)
V20	∘/●	●	∘/●	●	●
	Pump Out		Pump In
			(●)
V21	●	●	●	●	●
V22	●	●	●	∘	●
V23	●	●	●	∘/●	●
				Alternates
				with V7
PP1	▪	□	□	□	▪
				(▪)
PP2	▪	▪	□	□	▪
				(▪)
PP3	□	▪	□	□	□
			(▪)
PP4	□	▪	□	▪	▪
			(▪)
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0298] d. The Post-Collection Cycle

[0299] 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.

[0300] 3. Return Excess Red Blood Cells

[0301] 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.

[0302] 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.

[0303] 4. Saline Purge

[0304] 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.

[0305] 5. Final Return to Donor

[0306] 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.

[0307] 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.

[0308] 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.

[0309] The programming of the circuit during the phases of the post-collection cycle is summarized in the following table.

[0310]

TABLE
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	●	●	●	∘	●	●
V2	●	∘	●	●	●	●
V3	●	●	●	●	●	●
V4	●	●	∘	●	●	●
V5	●	●	●	●	●	●
V6	●	●	●	●	●	●
V7	●	∘/●	●	∘/●	●	●
		Alter-		Alter-
		nates		nates
		with		with
		V23		V23
V8	●	●	●	●	●	●
V9	●	∘	∘	●	●	●
V10	●	●	●	●	●	●
V11	●	∘/●	∘/●	∘/●	∘/●	●
		Pump	Pump	Pump	Pump In
		In	In/	In
			Pump
			Out
V12	●	●	●	●	●	●
V13	●	∘/●	●	∘/●	∘/●	●
		Pump		Pump	Pump Out
		Out		Out
V14	●	●	∘	●	●	●
V15	●	●	●	●	●	●
V16	●	●	●	●	●	●
V17	●	●	●	●	●	●
V18	●		●	∘	∘	●
V19	●	●	●	●	●	●
V20	●	●	●	●	●	●
V21	●	●	●	●	●	●
V22	●	∘	∘	∘	∘	●
V23	●	∘/●	∘	∘/●	∘	●
		Alter-		Alter-
		nates		nates
		with		with
		V6		V7
PP1	▪	▪	▪	▪	▪	▪
PP2	▪	▪	▪	▪	▪	▪
PP3	▪	□	□	□	□
PP4	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0311] G. Red Blood Cell and Plasma Collection

[0312] 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.

[0313] 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.

[0314] 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.

[0315] The procedure includes a pre-collection cycle, a collection cycle, and a post-collection cycle, and a storage preparation cycle.

[0316] 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.

[0317] (1) The Pre-Collection Cycle

[0318] a. Anticoagulant Prime

[0319] 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.

[0320] b. Saline Prime

[0321] 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.

[0322] The programming of the circuit during the phases of the pre-collection cycle is summarized in the following table.

[0323]

TABLE
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	•	•	•	•	•	•	•
V2	•	•	•	•	•	•	•
V3	∘	∘	•	•	•	∘	•
V4	•	•	∘	•	•	•	•
V5	•	•	•	•	•	•	•
V6	•	•	•	•	∘	•	•
V7	•	•	•	•	∘	•	•
V8	•	•	•	•	•	•	•
V9	•	•	∘/•	∘/•	∘/•	•	•
			Pump	Pump	Pump In
			Out	Out	(Stage
					1)
					∘
					(Stage
					2)
V10	•	•	•	•	∘	•	•
					(Stage
					1)
					∘/•
					Pump
					Out
					(Stage
					2)
V11	∘/•	∘	•	•	•	◯/•	•
	Pump					Pump In
	Out
V12	•	•	•	•	∘	•	•
					(Stage
					1)
					∘/•
					Pump In
					(Stage
					2)
V13	∘/•	∘	•	•	•	∘/•	•
	Pump In					Pump
						Out
V14	•	•	∘/•	∘/•	∘/•	•	•
			Pump In	Pump In	Pump
					Out
					(Stage
					1)
					∘
					(Stage
					2)
V15	∘	∘/•	•	•	•	∘	•
		Pump In
		Pump
		Out
V16	•	•	•	•	•	•	•
V17	•	•	•	•	•	•	•
V18	∘	∘	•	•	•	∘	•
V19	∘	∘	•	•	•	∘	•
V20	∘	∘/•	•	•	•	∘	•
		Pump
		Out
		Pump In
V21	•	•	•	•	•	•	∘
V22	•	•	∘	∘	∘	•	•
V23	•	•	∘	∘	∘	•	•
PP1	▪	▪	□	□	□	▪	▪
					(Stage
					1)
PP2	▪	▪	▪	▪	□	▪	▪
					(Stage
					2
PP3	□	▪	▪	▪	▪	□	▪
PP4	▪	□	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
• denotes a closed valve;
∘/• denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0324] 2. The Collection Cycle

[0325] a. Blood Prime

[0326] 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.

[0327] b. Blood Separation While Drawing Whole Blood or Without Drawing Whole Blood

[0328] 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).

[0329] 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.

[0330] c. Return Red Blood Cells and Saline

[0331] 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.

[0332] 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.

[0333] 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.

[0334] 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.

[0335] 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.

[0336] The programming of the circuit during the phases of the collection cycle is summarized in the following table.

[0337]

TABLE
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
	Blood		Drawing	Separation
	Prime	Blood Prime	Whole	(Without	Fill Donor
Phase	1	2	Blood)	Separation)	Line
V1	●	●	●	●	∘
V2	●	●	∘	∘	●
V3	∘	●	∘	●	●
			(●)
V4	●	●	●	●	●
V5	●	●	∘	∘ (●)	●
V6	●	●	●	●	●
V7	●	∘	●	∘/●	∘
				Alternates
				with V23
V8	●	●	●	●	●
V9	●	∘/●	∘/●	∘/●	●
		Pump In	Pump In	Pump In
				(●)
V10	●	●	∘/●	∘/●	●
			Pump Out	Pump Out
				(●)
V11	∘/●	∘	∘/●	∘/●	∘/●
	Pump Out		Pump Out	Pump In	Pump In
			(●)
V12	●	●	∘/●	∘/●	●
			Pump In	Pump In
				(●)
V13	∘/●	∘	∘/●	∘/●	∘/●
	Pump In		Pump In	Pump Out	Pump Out
			(●)
V14	●	∘/●	∘/●	∘/●	●
		Pump Out	Pump Out	Pump Out
				(●)
V15	∘/●	●	∘/●	●	●
	Pump Out		Pump Out
			(●)
V16	●	●	●	●	●
V17	●	●	●	●	●
V18	∘	∘	∘	∘	∘
			(●)
V19	∘	●	∘	●	●
			(●)
V20	∘/●	●	∘/●	●	●
	Pump Out		Pump In
			(●)
V21	●	●	●	●	●
V22	●	●	●	∘	●
V23	●	●	●	∘/●	●
				Alternates
				with V7
PP1	▪	□	□	□	▪
				(▪)
PP2	▪	▪	□	□	▪
				(▪)
PP3	□	▪	□	□	□
			(▪)
PP4	□	▪	□	▪	▪
			(▪)
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0338] d. The Post-Collection Cycle

[0339] 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.

[0340] i. Return Excess Plasma

[0341] 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.

[0342] ii. Return Excess Red Blood Cells

[0343] 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.

[0344] iii. Saline Purge

[0345] 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.

[0346] iv. Final Return to Donor

[0347] 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.

[0348] 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.

[0349] 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.

[0350] The programming of the circuit during the phases of the post-collection cycle is summarized in the following table.

[0351]

TABLE
Programming of Blood Processing Circuit During The Post-
Collection Cycle
(Red Blood Cell/Plasma Collection Procedure)
						End
	Excess				Fluid	Veni-
	Plasma	Excess RBC	Saline	Final	Replace-	punc-
Phase	Return	Return	Purge	Return	ment	ture
V1	●	●	●	∘	●	●
V2	●	∘	●	●	●	●
V3	●	●	●	●	●	●
V4	●	●	∘	●	●	●
V5	∘	●	●	●	●	●
V6	∘/●	●	●	●	●	●
	Alternates
	with V23
V7	●	∘/●	●	∘/●	●	●
		Alternates		Alternates
		with V23		with V23
V8	●	●	●	●	●	●
V9	∘	∘	∘	●	●	●
V10	●	●	●	●	●	●
V11	∘/●	∘/●	∘/●	∘/●	∘/●	●
	Pump In	Pump In	Pump	Pump In	Pump In
			In/
			Pump
			Out
V12	●	●	●	●	●	●
V13	∘/●	∘/●	●	∘/●	∘/●	●
	Pump Out	Pump Out		Pump Out	Pump Out
V14	●	●	∘	●	●	●
V15	●	●	●	●	●	●
V16	●	●	●	●	●	●
V17	●	●	●	●	●	●
V18	∘		●	∘	∘	●
V19	●	●	●	●	●	●
V20	●	●	●	●	●	●
V21	●	●	●	●	●	●
V22	∘	∘	∘	∘	∘	●
V23	∘/●	∘/●	∘	∘/●	∘	●
	Alternates	Alternates		Alternates
	with V6	with V6		with V7
PP1	▪	▪	▪	▪	▪	▪
PP2	▪	▪	▪	▪	▪	▪
PP3	□	□	□	□	□	▪
PP4	▪	▪	▪	▪	▪	▪
Caption:
∘ denotes an open valve;
● denotes a closed valve;
∘/● denotes a valve opening and closing during a pumping sequence;
▪ denotes an idle pump station (not in use); and
□ denotes a pump station in use.

[0352] e. The Storage Preparation Cycle

[0353] i. RBC Preservative Prime

[0354] 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.

[0355] 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.

[0356] 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.

[0357] The programming of the circuit during the phases of the storage preparation cycle is summarized in the following table.

[0358]

TABLE
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	●	●	●
	V2	●	∘	●
	V3	∘	●	●
	V4	●	∘	●
	V5	●	●	●
	V6	●	●	●
	V7	●	●	●
	V8	●	●	●
	V9	●	●	●
	V10	●	●	●
	V11	∘/●	∘/●	●
		Pump In/	Pump In/
		Pump Out	Pump Out
	V12	●	●	●
	V13	●	●	●
	V14	●	●	●
	V15	●	●	●
	V16	∘	∘	●
	V17	●	●	●
	V18	●	●	●
	V19	●	●	●
	V20	●	●	●
	V21	∘	∘	●
	V22	●	●	●
	V23	●	●	●
	PP1	▪	▪	▪
	PP2	▪	▪	▪
	PP3	□	□	▪
	PP4	▪	▪	▪
	Caption:
	∘ denotes an open valve;
	● denotes a closed valve;
	∘/● denotes a valve opening and closing during a pumping sequence;
	▪ denotes an idle pump station (not in use); and
	□ denotes a pump station in use.

V. Interface Control

[0359] A. Underspill and Overspill Detection

[0360] 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.

[0361] 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.

[0362] 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.

[0363] 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.

[0364] 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.

[0365] 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.

[0366] 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.

[0367] 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.

[0368] 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.

[0369] 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.

[0370] 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.

[0371] 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.

[0372] 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.

[0373] 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.

[0374] 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.”

[0375] 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.”

[0376] B. The Sensing Circuit

[0377] 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.

[0378] 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.

[0379] 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.

[0380] 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.

[0381] 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.

[0382] 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.

[0383] 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.

[0384] 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).

[0385] 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.

[0386] 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.

[0387] 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).

[0388] The controller 16 conditions the driver circuit 342 to operate each LED in an ON state and an OFF state.

[0389] 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.

[0390] 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.

[0391] 1. The First Sensor: Platelet/RBC Differentiation

[0392] 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.

[0393] 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.

[0394] In the illustrated embodiment, the first sensor 334 includes an emitter 350 of light at a first wavelength (λ₁), 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 (λ₂), which, in the illustrated embodiment, is red light (645 nm to 660 nm)

[0395] The optical attenuation for platelets at the first wavelength (ε_platelet^λ₁) and the optical attenuation for platelets at the second wavelength (ε_platelets^λ₂) are generally the same. Thus, changes in attenuation over time, as affected by increases or decreases in platelet concentration, will be similar.

[0396] However, the optical attenuation for hemoglobin at the first wavelength (ε_Hb^λ₁) is about ten times greater than the optical attenuation for hemoglobin at the second wavelength (ε_Hb^λ₂). Thus, changes in attenuation over time, as affected by the presence of red blood cells, will not be similar.

[0397] 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.

[0398] 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.

[0399] 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.

[0400] 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 λ by a plasma solution can be described by the modified Lambert-Beer law, as follows:

[0401] $\begin{array}{cc}I=I_O{e}^{-\left[\left({\varepsilon }_{\mathrm{Hb}}^{\lambda }{c}_{\mathrm{Hb}}H+{\varepsilon }_{\mathrm{platelets}}^{\lambda }{c}_{\mathrm{platelets}}\right)d+G_{\mathrm{platelets}}^{\lambda }+G_{\mathrm{RBC}}^{\lambda }\right]}& \left(1\right)\end{array}$

• • [0402] where:
  • [0403] I is transmitted light intensity.
  • [0404] I_O is incident light intensity.
  • [0405] ε_Hb^λ is the optical attenuation of hemoglobin (Hb) (gm/dl) at the applied wavelength.
  • [0406] ε_platelets^λ is the optical attenuation of platelets at the applied wavelength.
  • [0407] C_Hb is the concentration of hemoglobin in a red blood cell, taken to be 34 gm/dl.
  • [0408] C_platelets is the concentration of platelets in the sample.
  • [0409] d is thickness of the plasma stream through the tube 294.
  • [0410] G^λ is the path length factor at the applied wavelength, which accounts for additional photon path length in the plasma sample due to light scattering.
  • [0411] H is whole blood hematocrit, which is percentage of red blood cells in the sample.
  • [0412] G_RBC^λ and G_platelets^λ 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.

[0413] For wavelengths in the visible and near infrared spectrum, ε_platelets^λ≈0, therefore:

[0414] $\begin{array}{cc}Ln\left(\frac{I^{\lambda }}{I_O^{\lambda }}\right)=Ln\left(T^{\lambda }\right)\approx -\left[\left({\varepsilon }_{\mathrm{Hb}}^{\lambda }{C}_{\mathrm{Hb}}H\right)d+G_{\mathrm{platelets}}^{\lambda }+G_{\mathrm{RBC}}^{\lambda }\right]& \left(2\right)\end{array}$

[0415] 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^λ)≈G_platelets^λ.

[0416] To detect the buffy coat interface between the platelet layer and the red blood cell layer, the two wavelengths (λ₁ and λ₂) are chosen based upon the criteria that (i) λ₁ and λ₂ have approximately the same path length factor (G^λ), and (ii) one wavelength λ₁ or λ₂ has a much greater optical attenuation for hemoglobin than the other wavelength.

[0417] Assuming the wavelengths λ₁ and λ₂ have the same G^λ, Equation (2) reduces to:

[0418] $\begin{array}{cc}Ln\left(T^{{\lambda }_1}\right)-Ln\left(T^{{\lambda }_2}\right)\approx {\mathrm{Hdc}}_{\mathrm{Hb}}\left({\varepsilon }_{\mathrm{Hb}}^{{\lambda }_2}-{\varepsilon }_{\mathrm{Hb}}^{{\lambda }_1}\right)& \left(3\right)\end{array}$

[0419] In the preferred embodiment, λ₁=660 nm (green) and λ₂=571 nm (red). The path length factor (G^λ) for 571 nm light is greater than for 660 nm light. Therefore the path length factors have to be modified by coefficients α and β, as follows:

[0420] $\begin{array}{c}{G}_{\mathrm{RBC}}^{{\lambda }_1}=\alpha G_{\mathrm{RBC}}^{{\lambda }_2}\\ G_{\mathrm{platelets}}^{{\lambda }_1}=\beta G_{\mathrm{platelets}}^{{\lambda }_2}\end{array}$