Systems and methods for separation of platelets from blood and return of mononuclear cells

Abstract

To provide systems and methods for separating platelets from blood and converting mononuclear cells, and systems and methods for separating platelets from blood.SOLUTION: A blood processing system comprises a centrifugal blood separation device 10 that may be used in combination with a disposable fluid flow circuit. Prior to blood separation, a volume of blood to be processed, a volume of platelets to be collected, and / or a time required to complete a blood draw from a source during a blood separation procedure are determined. Based on that determination, a procedure setpoint is calculated from the completion of the blood draw. Blood is drawn from the source into a separator, in which the blood is separated into a mononuclear cell-containing fraction and a platelet-containing fraction. At least a portion of the platelet-containing fraction is conveyed from the separator, while the volume of the mononuclear cell-containing fraction in the separator increases. The mononuclear cell-containing fraction is conveyed to the source from the separator at the procedure setpoint. The blood draw and separation are then ended.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 230,228, filed August 6, 2021, the contents of which are incorporated herein by reference. [Background technology]

[0002] [Technical field] The present invention relates to blood separation. More particularly, the present invention relates to a system and method for separating platelets from blood during a separation procedure and returning mononuclear cells to the blood source.

[0003] [Description of Related Art] Various blood processing systems allow for the separation of blood into two or more component parts, which can be useful for blood donation purposes and for treating individuals with potentially harmful or deleterious blood conditions or disorders.

[0004] When such systems are used for blood component donation, whole blood is typically drawn from a donor, specific blood components or components are removed and collected, and the remaining blood components are returned to the donor. This removal of specific components may shorten the time it takes for the donor's body to return to normal, allowing blood donations to be made more frequently than if whole blood were drawn. This increases the overall supply of blood components, such as plasma and platelets, available for medical use.

[0005] Typically, whole blood is separated into its components by centrifugation. This requires that the whole blood be passed through a centrifuge after collection and before being returned to the source. To avoid contamination of the blood and potential source infection (when the source is a living donor or patient), the blood is preferably contained within a sealed, sterile fluid flow system throughout the centrifugation process. Thus, a typical blood processing system includes a permanent, reusable centrifuge assembly containing the hardware (drive system, pumps, valve actuators, programmable controls, etc.) that rotates and pumps the blood, and a sealed, sterilized fluid processing assembly mounted in conjunction with the hardware. The centrifuge assembly engages and spins the disposable separation chamber of the fluid processing assembly during the collection or processing procedure. However, the blood only actually comes into contact with the fluid processing assembly, which is used only once and then discarded.

[0006] Centrifugal blood separators are known in the art and are currently in commercial practice. One known separator is shown in Figures 1-7.

[0007] FIG. 1 shows an exemplary commercially available centrifugal blood separator 10 that can be used in combination with a disposable fluid flow circuit 12 (FIG. 2) to form a blood processing system (FIG. 3) for separating blood into two or more fractions. The illustrated blood separator 10 is currently sold as the AMICUS® separator by Fenwall, Inc. of Lake Zurich, Illinois, an affiliate of Fresenius Kabi AG of Bad Homburg, Germany, and is disclosed in U.S. Patent No. 5,868,696, incorporated herein by reference. While the device 10 can be used to process a variety of fluids, it is particularly suited for processing whole blood, blood components, or suspensions of other biological cellular material.

[0008] The device 10 includes a separator configured as a centrifuge 14 (FIG. 3) used to centrifuge blood components. The device 10 can be programmed to separate blood into various components and subcomponents. For example, in an exemplary blood separation procedure, the centrifuge 14 is operated to separate whole blood into platelet-rich plasma and red blood cells, which are then separated into platelet-poor plasma and platelets or platelet concentrate.

[0009] The illustrated centrifuge 14 is of the type shown in U.S. Pat. No. 5,316,667, which is incorporated herein by reference. The centrifuge includes a bowl 16 and a spool 18, which are received within a bucket or housing 20. The bowl 16 and spool 18 are pivoted on a yoke 22 between an operating position and a loading / unloading position. When the bowl 16 and spool 18 are in the loading / unloading position, a separation chamber 26 of the flow circuit 12 is wrapped around the spool 18 ( FIG. 4 ) and positioned within the centrifuge 14 in an annular gap defined between the bowl 16 and the spool 18. Further details of the separation chamber 26 of the type shown in FIG. 4 and its operation can also be found in U.S. Pat. No. 5,316,667.

[0010] Chamber 26 is typically formed from a pair of sheets of flexible, deformable material (e.g., polyvinyl chloride material) sealed together around its periphery. When chamber 26 is attached to centrifuge 14, one of the sheets defines a high-G (outer) wall 90, and the other defines a low-G (inner) wall 92 that is positioned closer to the axis of rotation of centrifuge 14. A plurality of ports 30, 32, 34, 36, and 38 extend through the sealed periphery to allow fluid flow between the interior of chamber 26 and other components of flow circuit 12.

[0011] The illustrated chamber 26 defines a first chamber 40 and a second chamber 42 and further includes a plurality of internal seals that direct the flow of separated blood components within the chamber 26. As shown in FIG. 5, there are three ports 30, 32, and 34 associated with the first stage 40 of the illustrated chamber 26. The port identified by the numeral 32 is used to transport blood from a blood source to the first stage 40. The other two ports, 30 and 34, function as outlet ports for separated blood components exiting the first stage 40. More specifically, the first outlet port 34 transports low-density blood components from the first stage 40, and the second outlet port 30 transports high-density blood components from the first stage 40.

[0012] Other portions of flow circuit 12 can remain outside of bucket 20. In the illustrated embodiment, the various tubing connected to blood separation chamber 26 is bundled into an umbilicus 28 that extends outside of bucket 20 during use ( FIG. 3 ). As shown in FIGS. 4 and 5 , umbilicus 28 of flow circuit 12 can be attached to ports 30, 32, 34, 36, and 38 of blood separation chamber 26 by individual tubing. Umbilicus 28 interconnects first stage 40 and second stage 42 of chamber 26 with each other and with components of flow circuit 12 that are located outside of centrifuge 14 during use.

[0013] The tubing of the umbilicus 28 can be connected to cassettes 50A, 50B, and 50C of the flow circuit 12 (FIG. 2), which are molded parts defining multiple fluid flow segments that can be selectively placed in and out of fluid communication with one another via operation of valve stations defined within the cassettes. The front panel 52 of the blood separation device 10 includes multiple cassette holders 54 (FIG. 1) for receiving the cassettes 50A, 50B, and 50C of the flow circuit 12. Each cassette holder 54 receives and holds a different one of the cassettes 50A, 50B, and 50C of the fluid flow circuit 12 along two opposing side edges in a desired operating position. Each cassette holder 54 includes a pair of peristaltic pumping stations or pumps 56. When a cassette is grasped by cassette holder 54, a tubing loop 58 (FIG. 2) extending from the cassette is operatively engaged with pump 56. Pump 56 is operated under command of the system control to cause fluid to flow through the associated cassette.

[0014] The front panel 52 of the device 10 may include additional components, such as at least one optical line monitor 58. If provided, the optical line monitor 58 may receive the tubes or fluid flow conduits of the flow circuit 12 to optically monitor the fluid flowing therethrough. The front panel 52 may also include various ramps 60 that receive the tubes or fluid flow conduits of the flow circuit 12 and selectively allow and prevent fluid flow through the conduits.

[0015] A user interface screen 62 (e.g., a touch screen) can be located on the front panel 52 (as in FIG. 1 ) or in another location. The user interface screen 62 allows an operator to interact with the system controller (e.g., a microprocessor) of the device 10 to provide instructions to the controller (e.g., to perform a particular procedure) as well as information to be used during a procedure (e.g., a pre-platelet count of the source blood). The user interface screen 62 can provide instructions to the operator (e.g., to connect or disconnect the source blood to the flow circuit 12) and information (e.g., to alert the operator to an occlusion in a fluid flow conduit of the flow circuit 12).

[0016] As previously mentioned, the various components of fluid flow circuit 12 may be connected by flexible tubing or any other suitable fluid flow conduits. The illustrated flow circuit 12 is a "two-needle" system that includes a pair of blood source access devices 64 and 66 (e.g., phlebotomy needles), one serving to draw blood from the source into flow circuit 12 and the other serving to return fluid to the source. In other embodiments, the flow circuit may be configured as a "single-needle" system that uses a single blood source access device (e.g., phlebotomy needle) to withdraw blood from the blood source and deliver fluid to the blood source.

[0017] To begin a separation procedure, the operator may select a procedure from among various procedures that the device 10 can perform (e.g., using the user interface screen 62). The operator may input various information required by the system controller to enable the controller to better perform the procedure. The controller may be provided with the total source blood volume, a pre-platelet count or initial platelet concentration of the source blood, and a post-platelet count or target platelet concentration to be achieved for the source blood by the end of the procedure. The total volume of blood to be processed may also be provided to the system controller.

[0018] Once the system controller has received all necessary inputs and performed the necessary preliminary calculations and status checks (e.g., to ensure that the flow circuit 12 is properly installed and that the various components of the device 10 are functioning properly), the flow circuit 12 can be primed and the separation procedure can begin.

[0019] The system controller directs one or more of the pumps 56 to draw blood from the blood source into the flow circuit 12 via one of the blood source access devices 64. When the centrifuge 14 rotates the chamber 26 about its axis of rotation at a sufficient speed so that the blood is separated into red blood cells (i.e., high-density blood components) and platelet-rich plasma (i.e., low-density blood components), the blood enters the first stage 40 of the separation chamber 26 via the inlet port 32. The red blood cells are returned to the blood source via the outlet port 30, and the platelet-rich plasma is conveyed from the first stage 40 via the outlet port 34 and conveyed to the second stage 42 via the inlet port 38. In the second stage 42, the platelet-rich plasma is separated into platelet-poor plasma and platelets or platelet concentrate. The platelet-poor plasma may be removed from the second stage 42 and returned to the blood source via the outlet port 36, while the platelets / platelet concentrate accumulate in the second stage 42 and are ultimately transferred to a collection container 86.

[0020] More specifically, during the separation procedure, fluid passage 98 associated with inlet port 32 directs blood into a circumferential flow path immediately adjacent to low-density collection region 100. As shown in FIG. 6 , the blood separates into an optically dense layer 106, which forms as cellular components migrate under the influence of centrifugal force toward high-G (outer) wall 90 of chamber 26. Optically dense layer 106 contains red blood cells (and thus is referred to herein as the "RBC layer"), although other cellular components (e.g., larger white blood cells and platelets) may also be present in RBC layer 106, depending on the speed at which centrifuge 14 rotates.

[0021] The movement of the components of the RBC layer 106 causes the less dense blood components to move radially toward the low-G (inner) wall 92 of the chamber 26, forming a second, optically less dense layer 108. The optically less dense layer 108 includes plasma and platelets (and thus is referred to herein as the "PRP layer"), although other components (e.g., smaller white blood cells) may also be present in the PRP layer 108 depending on the speed at which the centrifuge 14 rotates and the length of time the blood resides within the centrifuge 14.

[0022] The transition between the RBC layer 106 and the PRP layer 108 is commonly referred to as the interface 110 (FIG. 6). The location of the interface 110 within the chamber 26 can dynamically change during blood processing. If the interface 110 is positioned too high (i.e., too close to the low-G wall 92 and the exit port 34), red blood cells may spill into the low-density collection region 100, adversely affecting the quality of the platelet-rich plasma. On the other hand, if the interface 110 is positioned too low (i.e., too far from the low-G wall 92), the collection efficiency of the device 10 may be compromised. The blood separation device 10 may include a viewing head or interface sensor assembly for optically viewing and adjusting the position of the interface 110 as viewed on the interface ramp 112.

[0023] While the blood is being separated into the RBC layer 106 and the PRP layer 108 in the first stage 40, as described above, the portion of the PRP layer 108 (received from the first stage 40) in the second stage 42 is separating into platelets or platelet concentrate 126 and platelet-poor plasma 128 ( FIG. 7 ). Concurrently, a buffy coat containing (among other things) mononuclear cells (referred to herein as “MNCs”) and larger platelets develops within the first stage at or adjacent to interface 110. As described above, interface 110 is monitored to ensure it remains in the proper position within the first stage 40, thereby increasing the volume of the buffy coat as it remains within the first stage 40 during blood separation (rather than exiting the first stage 40 with either the RBC layer 106 or the PRP layer 108).

[0024] Blood collection and separation continues until terminated by the system controller. The platelets / platelet concentrate 126 accumulating in the second stage 42 are then harvested or collected, followed by a reinfusion phase in which the fluid remaining in the chamber 26 (including the buffy coat) is returned to the blood source.

[0025] While this type of platelet separation and collection method has proven effective, it has recently been found that donors or patients may experience leukopenia due to insufficient return of the mononuclear cell component within the buffy coat. For example, the above type of procedure may result in a leukopenia of 1 × 10 MNCs rather than 1 × 10 MNCs being returned to the blood source. 8 It is known that MNCs on the order of 100 may remain in the isolation chamber.

[0026] This problem can be even greater in systems that omit the type of post-collection reinfusion step described above. For example, platelet collection or removal procedures performed using the TRIMA ACCEL® collection device sold by Terumo BCT, Inc. of Lakewood, Colorado, can result in platelet counts of 1 x 10 9 ~1×10 10 It has been found that MNCs of this order may not be returned to the patient or donor.

[0027] Procedures that leave fewer MNCs as waste (e.g., 1 × 10 7 MNCs (on the order of 0.01) significantly reduce the incidence of leukopenia. It would therefore be advantageous to provide a platelet depletion or platelet collection procedure capable of such improved MNC return. Summary of the Invention

[0028] There are several aspects of the present subject matter that can be embodied separately or together in the devices and systems described and claimed below. These aspects can be used alone or in combination with other aspects of the subject matter described herein, and describing these aspects together is not intended to exclude the use of these aspects separately in the claims appended hereto or the claiming of such aspects separately or in different combinations as a set.

[0029] In one embodiment, a method for separating platelets from blood from a blood source is provided. The method includes determining a volume of blood to be processed, a volume of platelets to be collected, a time to complete blood collection, and / or a time required to complete blood collection from a source during a blood separation procedure. A procedure setpoint calculated from the completion of blood collection is selected or determined. Blood is then drawn from the source and delivered to a separator. At least a portion of the platelet-containing fraction is transferred from the separator while increasing the volume of the mononuclear cell-containing fraction in the separator. The mononuclear cell-containing fraction is transferred from the separator to the source at the procedure setpoint. Blood collection and blood separation then terminate.

[0030] In another aspect, a blood separation device for use in combination with a fluid flow circuit is provided. The blood separation device includes a separator, a pump system, and a controller. The controller is configured to (a) determine a volume of blood to be processed, a volume of platelets to be collected, a time to complete blood collection, and / or a time required to complete blood collection from a blood source during a separation procedure, (b) select or determine a procedure setpoint calculated from completion of blood collection, (c) execute a blood separation procedure, and (d) terminate blood collection. The blood separation procedure includes operating the pump system to draw blood from a source into a separator, operating the separator to separate the blood into a platelet-containing fraction and a mononuclear cell-containing fraction, operating the pump system to increase the volume of the mononuclear cell-containing fraction within the separator while transporting at least a portion of the platelet-containing fraction from a centrifuge, and operating the pump system to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint. [Brief explanation of the drawings]

[0031] [Figure 1] FIG. 1 is a perspective view of an exemplary commercially available blood separation device.

[0032] [Figure 2] 2 is a schematic diagram of an exemplary disposable fluid flow circuit that can be used in combination with the blood separation device of FIG. 1.

[0033] [Figure 3] 3 is a partially broken-away, cross-sectional side view of the blood separation device of FIG. 1 with the device's centrifuge bowl and spool in an operating position and with the fluid flow circuit of FIG. 2 mounted thereon;

[0034] [Figure 4] 4 is a top perspective view of the spool of the centrifuge shown in FIG. 3 in an upright position and carrying the blood separation chamber of the fluid flow circuit of FIG. 2.

[0035] [Figure 5]FIG. 5 is a plan view of the blood separation chamber shown in FIG. 4 without the spool connected thereto.

[0036] [Figure 6] FIG. 1 is an enlarged perspective view of an interface ramp carried by the centrifuge in association with the blood separation chamber, showing the centrifuged red blood cell layer and platelet-rich plasma layer within the chamber when in a desired position on the ramp.

[0037] [Figure 7] FIG. 12 is an enlarged perspective view of the position of platelets / platelet concentrate and platelet-poor plasma in the second stage of the blood separation chamber during the platelet removal or collection procedure.

[0038] [Figure 8] FIG. 1 is a schematic diagram of a first stage of a blood separation chamber during a portion of a procedure according to the present disclosure.

[0039] [Figure 9] FIG. 1 is a schematic diagram of the first stage of the blood separation chamber during the second part of the procedure according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0040] The embodiments disclosed herein are intended to provide an illustration of the present subject matter, and it is understood that the subject matter may be embodied in various other forms and combinations not specifically shown. Accordingly, the specific designs and features disclosed herein should not be construed as limiting the subject matter defined in the appended claims.

[0041] Platelet collection and removal procedures according to the present disclosure proceed similarly to the procedures described above and may be performed using systems similar to those shown in Figures 1-7. However, it should be understood that the principles described herein are not limited to a particular system configuration and / or a particular sequence of steps or stages. Rather, the MNC return principles described herein can be applied using a variety of differently configured blood processing systems (e.g., the AMICUS® and TRIMA ACCEL® systems described above) that perform platelet collection and / or removal procedures in different ways. Indeed, it is contemplated that the principles described herein can be applied to any blood processing system and platelet collection or removal procedure in which MNCs (e.g., in the buffy coat) accumulate in a separator (configured as a centrifuge or otherwise) during the course of the procedure.

[0042] The platelet collection and removal procedure according to the present disclosure allows for the return of more MNCs to the donor or patient (e.g., 1 x 10 MNCs in the separation chamber when using an AMICUS® type system) by establishing a calculated procedure set point from the end of blood collection and executing the MNC return step at that time. 7 (Leaving only MNCs of the order of 1000). The end of blood collection can be determined according to any suitable approach. This may include the use of one or more pre-counts, such as a platelet pre-count, indicating the platelet content of the patient's or donor's blood before treatment. Other relevant information may include, for example, a target volume or amount of platelets to be collected and / or a target platelet post-count (indicating the platelet content of the patient's or donor's blood at the end of treatment). It should be understood that obtaining information regarding the composition of the patient's or donor's blood before treatment begins is advantageous, but not required. For example, if a platelet pre-count is not available, the platelet content of the blood may be determined during the course of the procedure using any suitable approach.

[0043] Using appropriate information, along with knowledge of the separation efficiency of the separation device, it is possible to determine how much blood must be drawn from the patient or donor to collect a target volume or amount of platelets or to achieve a target platelet post-count. The system controller uses the calculated blood draw volume to determine (based on the expected operating rates of the various components of the system) when blood draw should end (when the start time is known or when the patient or donor is only available until a certain time) and / or the duration of blood draw. It should be understood, therefore, that the blood draw endpoint can be expressed in a variety of ways (e.g., the volume to be drawn, the time when the appropriate volume of blood is drawn, the length of time required to draw the appropriate volume of blood, etc.). The controller can be configured to adjust the end-of-draw calculation during the procedure, as needed, to account for unexpected delays (e.g., if blood draw is slower than expected due to blockages or irregular flow).

[0044] The system controller can then establish a procedure setpoint calculated from the expected end of blood collection. Just as the end of blood collection can be expressed in a variety of ways, the procedure setpoint can also be expressed in a variety of ways (e.g., blood volume, time, length of time, etc.). For example, if the end of blood collection is expressed as the volume of blood collected, the controller can select or be provided with a specific volume from the end of blood collection, which becomes the procedure setpoint at which MNCs will return to the blood source. If volume is selected as the basis for establishing the procedure setpoint, the specific volume can vary (depending on factors such as the configuration of the separation chamber) without departing from the scope of the present disclosure, but it can be advantageous to select this volume large enough to ensure that all, or at least substantially all, of the MNCs in the separation chamber are displaced from the separation chamber by the selected amount of blood entering the chamber. In an exemplary embodiment in which 2 liters of blood are collected from a donor or patient, a volume ranging from approximately 25 mL to approximately 100 mL can be selected. If a volume of 25 mL is selected, the procedure setpoint is set when 1.975 liters of blood is collected from the donor. In another example, if the end of blood collection is expressed in terms of the time that blood collection must end (e.g., if the donor or patient is only available until a certain time of day), the control unit selects or is provided with a specific time from the end of blood collection at which time the MNCs in the separator will be returned to the blood source.

[0045] When time is selected as the basis for establishing a procedure setpoint, the specific volume may vary (depending on factors such as the configuration of the separation chamber) without departing from the scope of the present disclosure, but it may be advantageous to select a time long enough to ensure that all, or at least substantially all, of the MNCs in the separation chamber are displaced from the separation chamber by blood flowing into the chamber during that time. A specific time may be, for example, between about 1 minute and about 5 minutes from the end of the procedure. This may include setting the procedure setpoint at a specific time (e.g., 11:55 if blood collection should end at 12:00 and a 5-minute time is selected) or a specific length of time before blood collection ends (e.g., if blood collection is calculated to last 1 hour, the procedure setpoint may be set 2 minutes from the end of the procedure, i.e., 58 minutes after the end of the procedure). If the calculated blood collection time changes during the procedure, the time at which MNC return is performed may also change. For example, in the previous example where blood collection was initially calculated to last 1 hour, if the procedure setpoint was 2 minutes and there was a 5-minute delay during the procedure, the recalculated blood collection time would be 1 hour and 5 minutes. In this case, the time from the end of blood collection to the return of the MNC at that time will remain the same (2 minutes before the end of blood collection), but the time of return of the MNC will be adjusted (from 58 minutes after the start of blood collection to 1 hour and 3 minutes after the start of blood collection).

[0046] After setting procedure setpoints and performing any pretreatment steps (such as priming the circuit), the system controller directs one or more of the device's pumps to draw blood from the blood source (donor / patient) into the separation chamber. The blood enters the separation chamber, where the buffy coat or MNC-containing fraction is separated from the other blood components, and some or all of the other components are collected or returned to the source, while the volume containing the buffy coat or MNC in the separation chamber increases. As noted above, the configuration of the separation chamber and the method of separating the buffy coat or MNC-containing fraction from the other blood components can be varied without departing from the scope of this disclosure.

[0047] According to an exemplary embodiment, during a platelet collection or removal procedure performed using an AMICUS® separator, blood drawn from a source enters the first stage 240 of the separation chamber shown in FIG. 8 via inlet port 232. It is then separated into red blood cells or red blood cell fraction 206 (i.e., a high-density blood component) and platelet-rich plasma or plasma fraction 208 (i.e., a low-density blood component). The red blood cells are removed from the first stage 240 via outlet port 230 (typically returned to the blood source), and the platelet-rich plasma is conveyed from the first stage 240 via second outlet port 234 and into the second stage via the chamber's inlet port. In the second stage, the platelet-rich plasma is separated into platelet-poor plasma and platelets or platelet concentrate. The platelet-poor plasma is removed from the second stage via the outlet port (possibly returned to the blood source), and the platelets / platelet concentrate accumulate in the second stage and are ultimately transferred to a collection container.

[0048] As described above, as MNCs and other blood cells (i.e., platelets and white blood cells) settle from the red blood cells, a buffy coat or MNC-containing fraction 212 forms at or adjacent to the interface 210 between the red blood cell fraction 206 and the plasma fraction 208. For the majority of the procedure, the MNC-containing fraction 212 resides primarily at the interface 210 while the plasma fraction 208 exits the first stage 240 into the second stage and the red blood cell fraction 206 exits and is returned to the donor / patient. During this time, the interface 210 is maintained in a first position (shown in FIG. 8 ), a specific distance between the high-G wall 290 and the low-G wall 292. This position can be expressed as the percentage of the thickness or height of the first stage 240 occupied by the red blood cell fraction 206, as presented on the interface ramp associated with the first stage 240. In one embodiment, this may be 30-50% (i.e., the red blood cell fraction 206 occupies 30-50% of the space between the high-G wall 290 and the low-G wall 292). In one embodiment, this may be, for example, about 40%.

[0049] The position of interface 210 is regulated by the relative speeds at which red blood cell fraction 206 and plasma fraction 208 are transported from first stage 240. In one embodiment, a pump is associated with plasma outlet 234 but not with red blood cell outlet 230, and the flow of red blood cells from first stage 240 is equal to the difference between the speed at which blood enters first stage 240 and the speed at which plasma fraction 208 exits first stage 240. Thus, the position of interface 210 (and thus MNC-containing fraction 212) can be adjusted by changing the operating speed of the plasma pump; increasing the speed moves interface 210 closer to low-G wall 292, and decreasing the speed moves interface 210 closer to high-G wall 290. It should be understood that this is just one possible approach to adjusting and controlling the position of interface 210, and that other approaches can be used without departing from the scope of the present disclosure.

[0050] Figure 9 shows the positions of various separated blood components within the first stage during MNC return at a procedure setpoint. As described above, at the procedure setpoint, the system controller controls other components of the processing device (e.g., the plasma pump) to move interface 310 from a first position (shown in Figure 8) to a second position (Figure 9) closer to high-G wall 390. The exact position of interface 310 at this point can be varied without departing from the scope of this disclosure, and the second position is appropriate to move MNC-containing fraction 312 close enough to high-G wall 390 to exit first stage 340 via red blood cell outlet 330. MNC-containing fraction 312 exits first stage 340 along with red blood cell fraction 306 via red blood cell outlet 330, and MNC-containing fraction 312 and red blood cell fraction 306 are returned to the donor / patient (before blood collection is complete). In an exemplary embodiment (where the interface is maintained at a first position of 30-50% within the first stage during steady-state separation), the controller can move the interface to a second position of 20-40%. In another exemplary embodiment where the interface is maintained at a first position of 40%, the controller can move the interface to a second position of 30%.

[0051] As mentioned above, the position of the interface can be lowered by any acceptable method, such as slowing the pump at the plasma outlet of the first stage. It will be appreciated that a slower operating speed of the plasma pump will result in a lower volumetric flow rate of the plasma fraction into the second stage of the chamber. Therefore, it may be advantageous to maintain the interface in the second position only for the time necessary to remove the MNC-containing fraction from the separation chamber, so as not to excessively reduce platelet collection efficiency. Therefore, depending on what is required to remove the MNC-containing fraction from the separation chamber, the MNC return phase may need to continue until the end of blood collection (e.g., starting 2 minutes before the end of blood collection and lasting 2 minutes). Alternatively, it may be acceptable to terminate the MNC return phase before the end of blood collection (e.g., starting 2 minutes before the end of blood collection and lasting only 2 minutes before returning to steady-state separation conditions). However, generally speaking, the MNC return phase performed at the procedure setpoint is typically relatively short compared to the duration of blood collection and separation (e.g., 1–2 minutes for a 1-hour procedure). The reduction in platelet collection efficiency is minimal.

[0052] Blood collection and separation continues until terminated by the system controller, followed by harvesting or collection of the platelets / platelet concentrate accumulated in the second stage (e.g., by stopping the centrifuge rotation and pumping the platelets out of the separation chamber), followed by an optional reinfusion step in which the fluid (including the MNC-containing fraction) remaining in the chamber is reinfused back into the blood source (as is done at the end of a conventional platelet collection or removal procedure using an AMICUS® Separator).

[0053] As mentioned above, the conventional procedure is modified by implementing mid-processing MNC return, reducing the number of MNCs remaining in the chamber to 1 × 10 8 order of MNCs (at the end of a conventional platelet collection or removal procedure) to 1 × 10 7 This allows for a reduction in the number of MNCs to the order of 100, allowing for a much larger number of MNCs to be returned to the donor or patient.

[0054] As noted above, the MNC return principles described herein are not limited to use with any particular blood separation system. For example, the TRIMA ACCEL® system uses a leukocyte reduction or "LRS" chamber into which plasma, platelets, white blood cells, and red blood cells are delivered. The LRS chamber separates platelets from white blood cells (including MNCs) and pushes the platelets into a collection compartment as a leukocyte-reduced platelet product. The white blood cells (including MNCs) can be delivered to a separate line or stream that is returned to the donor / patient. Details of this system are described in U.S. Patent No. 7,963,901, incorporated herein by reference.

[0055] Unlike the AMICUS® system, the TRIMA ACCEL® separator does not perform a reinfusion step at the end of processing, but instead schedules the white blood cells to be returned to the blood source at a specific time after the procedure begins. While this approach may appear similar to the approach to MNC return described herein, the difference between an MNC return step scheduled to occur at a specific time before the end of blood collection (according to the present disclosure) and an MNC return step scheduled a fixed time after the start of blood collection is important.

[0056] As discussed above, for any of a number of reasons, blood collection may actually end at a time different from the expected time. In this case, scheduling the MNC return step for a specific time after the start of blood collection (which may be intended to occur just before the end of blood collection) could result in a larger-than-expected gap between MNC return and blood collection, potentially leaving an unacceptably large number of MNCs as waste in the separator. By employing the principles described herein and scheduling the MNC return step to occur at a specific procedure setpoint calculated from the end of blood collection, it is possible to ensure that the MNC return step occurs at a specific time before the end of blood collection. This results in increased return of MNCs to the donor or patient.

[0057] [Aspect] Embodiment 1. A method for separating platelets from blood, the method comprising: determining an amount of blood to be processed, and / or an amount of platelets to be collected, and / or a time to complete blood collection, and / or a time required to complete blood collection from a blood source during a blood separation procedure; selecting or determining a procedure set point calculated from the completion of blood collection; drawing blood from the source and transporting the blood to a separator; separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction; transporting at least a portion of the platelet-containing fraction from the separator to increase the volume of the mononuclear cell-containing fraction in the separator; transporting the mononuclear cell-containing fraction from the separator to the source at the procedure set point; and terminating the blood collection and blood separation.

[0058] Embodiment 2. The method of embodiment 1, comprising performing a reinfusion step after blood collection, the reinfusion step comprising conveying the contents of the separator to a source.

[0059] Embodiment 3. The method of embodiment 1 or embodiment 2, wherein selecting or determining a procedure set point calculated from completion of blood draw comprises selecting or determining a procedure set point that is a set time before completion of blood draw.

[0060] Embodiment 4. The method of embodiment 1 or embodiment 2, wherein selecting or calculating a calculated procedural setpoint from completion of blood collection comprises selecting or determining a procedural setpoint that is a particular time of day.

[0061] Embodiment 5. The method of embodiment 1 or embodiment 2, wherein selecting or calculating a procedure set point calculated from completion of blood draw comprises selecting or determining a procedure set point that is a set volume of blood remaining to be drawn from the source before completion of blood draw.

[0062] Embodiment 6. The method of any one of embodiments 1 to 5, comprising adjusting the calculation or determination of when blood draw is complete, wherein the adjustment changes the time or volume after the start of blood draw at which transfer of the mononuclear cell-containing fraction from the separator to the source occurs at a procedure setpoint, and does not change the time or volume of blood draw before the end of blood draw at which transfer of the mononuclear cell-containing fraction from the separator to the source occurs at a procedure setpoint.

[0063] Embodiment 7. The method of any one of embodiments 1 to 6, wherein separating the blood into a platelet-containing fraction and a mononuclear cell-containing fraction in a separator comprises separating the blood into a plasma fraction, a red blood cell fraction, and a mononuclear cell fraction in a first stage in the separator, conveying the plasma fraction from the first stage in the separator into a second stage in the separator, and separating the plasma fraction in the second stage into a platelet-containing fraction and a substantially cell-free plasma fraction.

[0064] Embodiment 8. The method of embodiment 7, wherein conveying the mononuclear cell-containing fraction from the separator to the source at a procedure set point comprises reducing the rate at which the plasma fraction is conveyed from the first stage to the second stage within the separator.

[0065] Aspect 9. The method of Aspect 8, further comprising detecting a position of an interface between the plasma fraction and the red blood cell fraction within a first stage within the separator, wherein the rate at which the plasma fraction is transported from the first stage to the second stage within the separator is reduced until the interface moves from a first position within the first stage to a second position within the first stage.

[0066] Embodiment 10. The method of embodiment 9, wherein the interface is maintained in the second position for a predetermined length of time calculated to transport substantially all of the mononuclear cell-containing fraction from the separator or while a predetermined volume of blood is drawn from the source.

[0067] Embodiment 11. The method of any one of embodiments 7 to 10, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure set point comprises conveying the mononuclear cell-containing fraction from a first stage within the separator together with the red blood cell fraction.

[0068] Embodiment 12. The method of any one of embodiments 1 to 11, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedural setpoints continues until the end of blood collection.

[0069] Embodiment 13. The method of any one of embodiments 1 to 11, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint does not continue until the end of blood collection.

[0070] Embodiment 14. The method of any one of embodiments 1 to 13, wherein the separator is a centrifuge.

[0071] Aspect 15. A blood separation device for use in combination with a fluid flow circuit, comprising a separator, a pump system, and a controller, the controller configured to (a) determine an amount of blood to be processed, and / or an amount of platelets to be collected, and / or a time to complete blood collection, and / or a time required to complete blood collection from a blood source during a blood separation procedure; (b) select or determine a procedure setpoint calculated from completion of blood collection; (c) perform a blood separation procedure, the blood separation procedure including operating the pump system to draw blood from the source and deliver the blood to a separator, operating the separator to separate the blood into a platelet-containing fraction and a mononuclear cell-containing fraction in the separator, operating the pump system to deliver at least a portion of the platelet-containing fraction from the separator and increase the volume of the mononuclear cell-containing fraction in the separator, and operating the pump system to deliver the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint; and (d) terminate blood collection.

[0072] Aspect 16. A blood separation device as described in aspect 15, wherein the control unit is configured to perform a reinfusion step after completion of blood collection by operating the pump system to transport the contents of the separator to the source.

[0073] Aspect 17. A blood separation device according to aspect 15 or aspect 16, wherein the separator comprises a first stage and a second stage, and the mononuclear cell-containing fraction and the platelet-containing fraction are separated within the first stage of the separator.

[0074] Aspect 18. A blood separation device according to any one of Aspects 15 to 17, wherein the control unit is configured to determine a procedure setpoint that is a set time before completion of blood collection.

[0075] Aspect 19. A blood separation device according to any one of Aspects 15 to 17, wherein the control unit is configured to determine a procedure setpoint that is a specific time of day.

[0076] Aspect 20. A blood separation device described in any one of aspects 15 to 17, wherein the control unit is configured to determine a procedure setpoint, which is a set volume of blood remaining to be drawn from the source before completion of blood collection.

[0077] Aspect 21. A blood separation device described in any one of aspects 15 to 20, wherein the control unit is configured to adjust the determination of when blood collection is complete, and the adjustment changes the time or volume after the start of blood collection at which the pump operates to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint, and does not change the time or volume of blood collection before the end of blood collection at which the pump operates to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint.

[0078] Aspect 22. A blood separation device described in any one of Aspects 15 to 21, wherein the control unit is configured to perform a separation procedure, the separation procedure including operating a separator to separate blood into a plasma fraction, a red blood cell fraction, and a mononuclear cell fraction, operating a pump system to transport the plasma fraction from a first stage in the separator into a second stage in the separator, and operating the separator to separate the plasma fraction in the second stage into a platelet-containing fraction and a substantially cell-free plasma fraction.

[0079] Aspect 23. The separation device of aspect 22, wherein the control unit is configured to execute a separation procedure, the separation procedure including operating the pump system to reduce the rate at which the plasma fraction is transported from the first stage to the second stage within the separator while transporting the mononuclear cell-containing fraction from the separator to the source at a procedure set point.

[0080] Aspect 24. A separation device as described in Aspect 23, wherein the control unit is configured to detect the position of an interface between the plasma fraction and the red blood cell fraction in a first stage in the separator during a separation procedure, and the rate at which the plasma fraction is transported from the first stage to the second stage in the separator is reduced until the interface moves from a first position in the first stage to a second position in the first stage.

[0081] Embodiment 25. A separation device described in any one of embodiments 22 to 24, wherein the control unit is configured to maintain the interface in the second position during a separation procedure for a predetermined length of time calculated to transport substantially all of the mononuclear cell-containing fraction from the separator or while a predetermined volume of blood is drawn from the source.

[0082] Aspect 26. A separation device described in any one of aspects 22 to 25, wherein operating the pump to transport the mononuclear cell-containing fraction from the separator to the source at a procedure set point comprises operating the pump system to transport the mononuclear cell fraction from the first stage within the separator together with the red blood cell fraction.

[0083] Aspect 27. A separation device according to any one of aspects 15 to 26, wherein operation of the pump to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint continues until the end of blood collection.

[0084] Aspect 28. A separation device according to any one of aspects 15 to 26, wherein operation of the pump to transport the mononuclear cell-containing fraction from the separator to the source at the procedure set point does not continue until the end of blood collection.

[0085] Embodiment 29. The separation device of any one of embodiments 15 to 28, wherein the separator is a centrifuge.

[0086] It will be understood that the above-described embodiments and examples illustrate some applications of the principles of the present subject matter. Numerous modifications may be made by those skilled in the art without departing from the spirit and scope of the claimed subject matter, including combinations of features individually disclosed or claimed herein. For these reasons, it will be understood that the scope of the specification is not limited to the above description, but is as set forth in the following claims, which may cover features of the specification, including combinations of features individually disclosed or claimed herein.

Claims

1. 1. A blood separation device for use in combination with a fluid flow circuit, comprising: a separator; A pump system; a control unit; The control unit (a) determining the amount of blood to be processed and / or the amount of platelets to be collected and / or the time to complete blood collection and / or the time required to complete blood collection from a blood source during a blood separation procedure; (b) selecting or determining a procedural set point calculated from the completion of blood collection; (c) performing a blood separation procedure, said blood separation procedure comprising: operating the pump system to draw blood from a source and deliver the blood to a separator; operating the separator to separate the blood into a platelet-containing fraction and a mononuclear cell-containing fraction within the separator; operating the pump system to transport at least a portion of the platelet-containing fraction from the separator and to increase the volume of the mononuclear cell-containing fraction within the separator; operating the pump system to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint; (d) a blood separation device configured to terminate blood collection.

2. 2. The blood separation device of claim 1, wherein the control unit is configured to perform a reinfusion step after completion of blood collection by operating the pump system to transport the contents of the separator to the source.

3. 3. The blood separation device according to claim 1, wherein the separator comprises a first stage and a second stage, and the mononuclear cell-containing fraction and the platelet-containing fraction are separated in the first stage of the separator.

4. 10. The blood separation device of claim 1, wherein the controller is configured to determine a procedure setpoint that is a set time before completion of the blood collection.

5. 10. The blood separation device of claim 1, wherein the controller is configured to determine a procedure setpoint that is a specific time of day.

6. 10. The blood separation device of claim 1, wherein the controller is configured to determine a procedure setpoint that is a set volume of blood remaining to be drawn from the source before the blood collection is completed.

7. 2. The blood separation device of claim 1, wherein the control unit is configured to adjust the determination of when blood collection is complete, the adjustment changing the time or volume after the start of blood collection that the pump operates to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint, but not changing the time or volume of blood collection before the end of blood collection that the pump operates to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint.

8. The control unit is configured to perform a separation procedure, the separation procedure comprising: operating the separator to separate the blood into a plasma fraction, a red blood cell fraction, and a mononuclear cell fraction; operating the pump system to transport the plasma fraction from the first stage in the separator into a second stage in the separator; 2. The blood separation device of claim 1, further comprising operating the separator to separate the plasma fraction in the second stage into the platelet-containing fraction and a substantially cell-free plasma fraction.

9. 9. The blood separation device of claim 8, wherein the control unit is configured to execute a separation procedure, the separation procedure including operating the pump system to decrease the rate at which the plasma fraction is transported from the first stage to the second stage within the separator while transporting the mononuclear cell-containing fraction from the separator to the source at the procedure set point.

10. 10. The blood separation device of claim 9, wherein the control unit is configured to detect the position of an interface between the plasma fraction and the red blood cell fraction in the first stage within the separator during a separation procedure, and the rate at which the plasma fraction is transported from the first stage to the second stage within the separator is reduced until the interface moves from a first position within the first stage to a second position within the first stage.

11. 9. The blood separation device of claim 8, wherein the control unit is configured to maintain the interface in the second position for a predetermined length of time calculated to transport substantially all of the mononuclear cell-containing fraction from the separator or while a predetermined volume of blood is drawn from a source during the separation procedure.

12. 9. The blood separation device of claim 8, wherein operating the pump to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint comprises operating the pump system to transport the mononuclear cell fraction from the first stage within the separator together with the red blood cell fraction.

13. 2. The blood separation device of claim 1, wherein operation of the pump to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint continues until the end of blood collection.

14. 2. The blood separation device of claim 1, wherein operation of the pump to transport the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint does not continue until the end of blood collection.

15. 10. The blood separation device of claim 1, wherein the separator is a centrifuge.

16. 1. A method for separating platelets from blood, comprising: determining the amount of blood to be processed and / or the amount of platelets to be collected and / or the time to complete blood collection and / or the time required to complete blood collection from a blood source during a blood separation procedure; selecting or determining a procedure set point calculated from the completion of blood collection; Drawing blood from a source and conveying said blood to a separator; separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction; removing at least a portion of the platelet-containing fraction from the separator to increase the volume of the mononuclear cell-containing fraction within the separator; conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint; The method includes drawing blood and completing blood separation.

17. 17. The method of claim 16, further comprising performing a reinfusion step after blood collection, said reinfusion step comprising conveying the contents of said separator to said source.

18. 18. The method of claim 16 or claim 17, wherein selecting or determining a procedure set point calculated from completion of the blood draw comprises selecting or determining a procedure set point that is a set time before completion of the blood draw.

19. 18. The method of claim 16 or claim 17, wherein selecting or calculating a procedure setpoint calculated from completion of the blood draw comprises selecting or determining a procedure setpoint that is a particular time of day.

20. 18. The method of claim 16 or claim 17, wherein selecting or calculating a procedure setpoint calculated from completion of the blood draw comprises selecting or determining a procedure setpoint that is a set volume of blood remaining to be drawn from the source before completion of the blood draw.

21. including coordinating the calculation or determination of when blood collection is complete; 17. The method of claim 16, wherein the adjustment changes the time or volume after the start of blood collection at which transfer of the mononuclear cell-containing fraction from the separator to the source occurs at the procedure setpoint, but does not change the time or volume of blood collection before the end of blood collection at which transfer of the mononuclear cell-containing fraction from the separator to the source occurs at the procedure setpoint.

22. Separating the blood into a platelet-containing fraction and a mononuclear cell-containing fraction in the separator includes: separating the blood into a plasma fraction, a red blood cell fraction, and a mononuclear cell fraction in a first stage of the separator; conveying the plasma fraction from the first stage in the separator into a second stage in the separator; and separating the plasma fraction in the second stage into the platelet-containing fraction and a substantially cell-free plasma fraction.

23. 23. The method of claim 22, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure set point comprises decreasing a rate at which the plasma fraction is conveyed from the first stage to the second stage within the separator.

24. 24. The method of claim 23, further comprising detecting a position of an interface between the plasma fraction and the red blood cell fraction within the first stage within the separator, wherein a rate at which the plasma fraction is transported from the first stage to the second stage within the separator is reduced until the interface moves from a first position within the first stage to a second position within the first stage.

25. 25. The method of claim 24, wherein the interface is maintained in the second position for a predetermined length of time calculated to transport substantially all of the mononuclear cell-containing fraction from the separator or while a predetermined volume of blood is drawn from a source.

26. 23. The method of claim 22, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint comprises conveying the mononuclear cell-containing fraction from the first stage within the separator together with the red blood cell fraction.

27. 17. The method of claim 16, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoints continues until the end of blood collection.

28. 17. The method of claim 16, wherein conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint does not continue until the end of the blood collection.

29. 17. The method of claim 16, wherein the separator is a centrifuge.

Images