SYSTEMS AND METHODS FOR SEPARATION OF PLATELETS FROM BLOOD AND RETURN OF MONONUCLEAR CELLS

Abstract

Systems and methods are provided for separating platelets from blood. 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 blood draw from a source during a blood separation procedure is determined. Based on that determination, a procedure setpoint is calculated from the completion of the blood draw. Blood is subsequently drawn from a 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.

Claims

1. A method for separating platelets from blood, comprising: determining a volume of blood to be processed, and/or a volume of platelets to be collected, and/or a time at which to complete blood draw, and/or a time required to complete blood draw from a source during a blood separation procedure; selecting or determining a procedure setpoint calculated from the completion of blood draw; drawing blood from the source and conveying the blood to a separator; separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction; conveying at least a portion of the platelet-containing fraction from the separator while increasing a volume of the mononuclear cell-containing fraction in the separator; conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint; and ending blood draw and blood separation.

2. The method of claim 1, further comprising executing a reinfusion phase after the completion of blood draw, the reinfusion phase comprising conveying the contents of the separator to the source.

3. The method of claim 1, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a set time before the completion of blood draw.

4. The method of claim 1, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a particular time of day.

5. The method of claim 1, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a set volume of blood remaining to be drawn from the source before the completion of blood draw.

6. The method of claim 1, further comprising adjusting the calculation or determination of when blood draw will be completed, with such adjustment changing the time or volume of blood drawn after the beginning of blood draw at which said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs without changing the time or volume of blood drawn before the end of blood draw at which said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs.

7. The method of claim 1, wherein said separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction includes separating the blood in a first stage within the separator into a plasma fraction, a red blood cell fraction, and the mononuclear cell-containing fraction, conveying the plasma fraction from the first stage within the separator to a second stage within the separator, and separating the plasma fraction in the second stage into the platelet-containing fraction and a substantially cell-free plasma fraction.

8-11. (canceled)

12. The method of claim 1, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint lasts until the end of blood draw.

13. The method of claim 1, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint does not last until the end of blood draw.

14. The method of claim 1, wherein the separator is a centrifuge.

15. A blood separation device for use in combination with a fluid flow circuit, comprising: a separator; a pump system; and a controller configured to (a) determine a volume of blood to be processed, and/or a volume of platelets to be collected, and/or a time at which to complete blood draw, and/or a time required to complete blood draw from a source during a blood separation procedure, (b) select or determine a procedure setpoint calculated from the completion of the blood draw, (c) execute a blood separation procedure comprising operating the pump system to draw blood from a source into a separator, operating the separator to separate the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction, operating the pump system to convey at least a portion of the platelet-containing fraction from the separator while increasing a volume of the mononuclear cell-containing fraction in the separator, and operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint, and (d) end blood draw.

16. The blood separation device of claim 15, wherein the controller is further configured to execute a refusion phase after the end of the blood draw by operating the pump system to convey the contents of the separator to the source.

17. The blood separation device of claim 15, wherein the separator includes a first and second stage and the mononuclear cell-containing fraction and the platelet-containing fraction are separated in the first stage within the separator.

18. The blood separation device of claim 15, wherein the controller is configured to determine a procedure setpoint that is a set time before the completion of the blood draw.

19. The blood separation device of claim 15, wherein the controller is configured to determine a procedure setpoint that is a particular time of day.

20. The blood separation device of claim 15, 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 completion of the blood draw.

21. The blood separation device of claim 15, wherein the controller is configured to adjust the determination of when blood draw will be completed, with such adjustment changing the time or volume of blood drawn after the beginning of blood draw at which the pump operates to convey the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs without changing the time or volume of blood drawn before the end of blood draw at which the pump operates to convey the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs.

22-26. (canceled)

27. The separation device of claim 15, wherein the operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint lasts until the end of the blood draw.

28. The separation device of claim 15, wherein the operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint does not last until the end of the blood draw.

29. The separation device of claim 15, wherein the separator is a centrifuge.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG. 1 is a is a perspective view of an exemplary commercial blood separation device;

[0032] FIG. 2 is a diagrammatic view of an exemplary disposable fluid flow circuit that may be used in combination with the blood separation device of FIG. 1;

[0033] FIG. 3 is a side elevation view, with portions broken away and in section, of the blood separation device of FIG. 1, with a centrifuge bowl and spool of the device being shown in their operating position and with the fluid flow circuit of FIG. 2 mounted thereon;

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

[0035] FIG. 5 is a plan view of the blood separation chamber shown in FIG. 4, out of association with the spool;

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

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

[0038] FIG. 8 is a schematic view of the first stage of the blood separation chamber during a portion of a procedure according to the present disclosure; and

[0039] FIG. 9 is a schematic view of the first stage of the blood separation chamber during a second portion of a procedure according to the present disclosure.

DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

[0040] The embodiments disclosed herein are for the purpose of providing a description of the present subject matter, and it is understood that the subject matter may be embodied in various other forms and combinations not shown in detail. Therefore, specific designs and features disclosed herein are not to be interpreted as limiting the subject matter as defined in the accompanying claims.

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

[0042] Platelet collection and depletion procedures according to the present disclosure are able to return more MNCs to a donor or patient (leaving only on the order of 1×10.sup.7 MNCs in a separation chamber when using an AMICUS®-type system, for example) by establishing a procedure setpoint calculated from the end of blood draw and executing an MNC-return step at that time. The end of blood draw may be determined according to any suitable approach. This may include the use of one or more pre-counts, such as a platelet pre-count, which is indicative of the platelet content of the blood of a patient or donor before a procedure. Other relevant information may include, for example, a target volume or amount of platelets to be harvested and/or a target platelet post-count (which is indicative of the platelet content of the blood of a patient or donor at the end of a procedure). While it may be advantageous to have information regarding the composition of the blood of a patient or donor prior to beginning a procedure, it should be understood that it is not required. For example, if a platelet pre-count is unavailable, the platelet content of the blood may be determined during the course of a procedure using any suitable approach.

[0043] With the 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 in order to harvest a target volume or amount of platelets or to achieve a target platelet post-count. A system controller may use that calculated volume of drawn blood to determine (based on the expected operational rates of the various components of the system) the time at which blood draw will end (when the starting time is known or when a patient or donor is only available until a particular time of day) and/or the duration of blood draw. Thus, it should be understood that the end point of blood draw may be expressed in a variety of ways—the volume of blood to be drawn, the time at which the proper volume of blood will have been drawn, the amount of time required to draw the proper volume of blood, etc. The controller may be configured to adjust its calculation of the end of blood draw during the course of a procedure, as necessary, such as if there are any unexpected delays (e.g., if blood draw is slower than expected due to a blockage or other flow irregularity).

[0044] The system controller may then establish a procedure setpoint that is calculated from the expected end of blood draw. Just as the end of blood draw may be expressed in a variety of ways, the procedure setpoint may be expressed in a variety of ways—a volume of blood, a time of day, an amount of time, etc. For example, when the end of blood draw is expressed in terms of the volume of blood to be drawn, the controller may select or be provided with a specific volume from the end of blood draw, which becomes the procedure setpoint at which point MNCs are returned to the blood source. If a volume is selected as a basis for establishing a procedure setpoint, the specific volume may vary without departing from the scope of the present disclosure (depending on factors such as the configuration of the separation chamber), though it may be advantageous to select a volume that is sufficiently large to ensure that all or at least substantially all of the MNCs in the separation chamber will be displaced from the separation chamber by the chosen volume of blood flowing into the chamber. In an exemplary embodiment in which 2 liters of blood are to be drawn from the donor or patient, a volume in the range of about 25 mL to about 100 mL may be selected. If a volume of 25 mL is selected, the procedure setpoint will be set to be when 1.975 liters of blood have been drawn from the donor. In another example, when the end of blood draw is expressed in terms of a time at which blood draw must end (e.g., when a donor or patient is only available until a certain time of day), the controller may select or be provided with a specific time from the end of blood draw at which to return MNCs in the separation chamber to the blood source.

[0045] If a time is selected as a basis for establishing a procedure setpoint, the specific volume may vary without departing from the scope of the present disclosure (depending on factors such as the configuration of the separation chamber), though it may be advantageous to select a time that is sufficiently long to ensure that all or at least substantially all of the MNCs in the separation chamber will be displaced from the separation chamber by the blood flowing into the chamber during that time. The specific time may be from about one minute to about five minutes from the end of the procedure, for example. This may include setting the procedure setpoint at a particular time (e.g., at 11:55 when blood draw must be ended at 12:00 and a time of five minutes is selected) or at a certain amount of time before the end of blood draw (e.g., if blood draw is calculated to continue for one hour, the procedure setpoint can be set to two minutes from end of the procedure, or after fifty-eight minutes have passed). If the calculated duration of blood draw changes during the course of the procedure, the time at which MNC return is executed may also be changed. For example, in the preceding example in which blood draw is initially calculated to last for one hour, with a procedure setpoint of two minutes, if there is a delay of five minutes during the course of the procedure, the recalculated duration of blood draw will be one hour and five minutes. In this case, the time from the end of blood draw at which MNC return will remain the same (two minutes before the end of blood draw), but the time at which MNC return will be adjusted (from fifty-eight minutes after blood draw has begun to one hour and three minutes after blood draw has begun).

[0046] After setting the procedure setpoint and performing any pre-procedure steps (such as priming the circuit), the system controller instructs one or more of the pumps of the device to draw blood from the blood source (donor/patient) into a separation chamber. The blood enters the separation chamber and the buffy coat or MNC-containing fraction is separated from the other blood components, with some or all of the other components being collected or returned to the source while the volume of the buffy coat or MNC-containing within the separation chamber increases. As noted above, the configuration of the separation chamber and the manner in which the buffy coat or MNC-containing fraction is separated from the other blood components may vary without departing from the scope of the present disclosure.

[0047] By way of an exemplary embodiment, during a platelet collection or depletion procedure carried out using the AMICUS® separator, the blood drawn from the source enters the first stage 240 of the separation chamber illustrated in FIG. 8 via an inlet port 232 and is separated into red blood cells, or a red blood cell fraction 206 (i.e., the high density blood component), and platelet-rich plasma, or a plasma fraction 208 (i.e., the low density blood component). The red blood cells are removed from the first stage 240 (and typically returned to the blood source) via an outlet port 230, while the platelet-rich plasma is conveyed out of the first stage 240 a second outlet port 234 and into the second stage of the chamber via an 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 (and may be returned to the blood source) via an outlet port, leaving the platelets/platelet concentrate to accumulate in the second stage for eventual transfer to a collection container.

[0048] As described above, at or adjacent to the interface 210 between the red blood cell fraction 206 and the plasma fraction 208, a buffy coat or MNC-containing fraction 212 will arise, as the MNCs and other blood cells (namely, platelets and leukocytes) are sedimented from the red blood cells. For the bulk of the procedure, the MNC-containing fraction 212 resides largely at the interface 210 while the plasma fraction 208 exits from the first stage 240 to the second stage and the red blood cell fraction 206 exits to be returned to the donor/patient. The interface 210 is kept at a first position (illustrated in FIG. 8) that is a particular distance between the high-G wall 290 and the low-G wall 292 during this time. This position may be expressed as the percentage of the thickness or height of the first stage 240 that is occupied by the red blood cell fraction 206, as presented on an interface ramp associated with the first stage 240. In one embodiment, this can be from 30-50% (i.e., with the red blood cell fraction 206 occupying 30-50% of the space between the high-G wall 290 and the low-G wall 292), and in a further embodiment it can be about 40%, for example.

[0049] The position of the interface 210 is regulated by the relative rates at which the red blood cell fraction 206 and the plasma fraction 208 are conveyed from the first stage 240. In one embodiment, a pump is associated with the plasma outlet 234, while there is no pump associated with the red blood cell outlet 230, with the flow of red blood cells from the first stage 240 being equal to the difference in the rate at which blood flows into the first stage 240 and the rate at which the plasma fraction 208 is pumped out of the first stage 240. Thus, the position of the interface 210 (and, hence the MNC-containing fraction 212) may be adjusted by changing the rate of operation of the plasma pump, with an increased rate causing the interface 210 to move closer to the low-G wall 292 and a decreased rate causing the interface 210 to move closer to the high-G wall 290. It should be understood that this is merely one possible approach to adjusting and controlling the position of the interface 210 and that other approaches may be employed without departing from the scope of the present disclosure.

[0050] FIG. 9 illustrates the positions of the various separated blood components within the first stage during MNC-return at a procedure setpoint. At the procedure setpoint, as described above, the system controller controls the other components of the processing device (e.g., a plasma pump) to cause the interface 310 to move from the first position (shown in FIG. 8) to a second position closer to the high-G wall 390 (FIG. 9). The exact position of the interface 310 at this time may vary without departing from the scope of the present disclosure, with the second position being whatever is appropriate to bring the MNC-containing fraction 312 close enough to the high-G wall 390 so as to exit the first stage 340 via the red blood cell outlet 330. The MNC-containing fraction 312 flows out of the first stage 340 with the red blood cell fraction 306 via the red blood cell outlet 330, with the MNC-containing fraction 312 and the red blood cell fraction 306 being returned to the donor/patient (before blood draw is complete). In an exemplary embodiment (in which the interface is maintained at a 30-50% first position within the first stage during steady state separation), the controller may move the interface to a 20-40% second position. In another exemplary embodiment in which the interface is maintained at a 40% first position, the controller may move the interface to a 30% second position.

[0051] As noted above, the position of the interface may be lowered by any acceptable method, such as slowing the pump at the plasma outlet of the first stage. It will be seen that, when the operational rate of a plasma pump is decreased, the volumetric flow rate of the plasma fraction into the second stage of the chamber will be decreased. As such, it may be advantageous to maintain the interface in its second position for only as long as necessary to clear the MNC-containing fraction from the separation chamber so as to not unduly decrease platelet collection efficiency. Thus, depending on what is required to clear the MNC-containing fraction from the separation chamber, it may be necessary for the MNC-return stage to last until the end of blood draw (e.g., beginning two minutes before the end of blood draw and lasting two minutes) or it may instead be acceptable for the MNC-return stage to be ended some time before blood draw ends (e.g., beginning two minutes before the end of blood draw and lasting only one minute before returning to steady state separation conditions). Generally speaking, though, the MNC-return stage executed at the procedure setpoint will typically be relatively brief compared to the duration of blood draw and separation (e.g., one or two minutes for an hour-long procedure), such that the decrease in platelet collection efficiency will be nominal.

[0052] Blood draw and separation continue until they are ended by the system controller. The platelets/platelet concentrate accumulating in the second stage are then harvested or collected (e.g., by stopping rotation of the centrifuge and pumping the platelets out of the separation chamber), followed by an optional reinfusion stage in which the fluid that remains in the chamber (including the MNC-containing fraction) is returned to the blood source (as in does at the end of a conventional platelet collection or depletion procedure using the AMICUS® separator).

[0053] As described above, modifying a conventional procedure by performing a mid-processing MNC return allows a much higher number of the MNCs to be returned to the donor or patient, reducing the number of MNCs left in the chamber from on the order of 1×10.sup.8 MNCs (at the end of a conventional platelet collection or depletion procedure) to on the order of 1×10.sup.7 MNCs.

[0054] As described above, the MNC-return principles described herein are not limited to use with a particular blood separation system. For example, the TRIMA ACCEL® system employs a leukoreduction or “LRS” chamber into which plasma, platelets, white blood cells, and red blood cells are conveyed. The LRS chamber separates the platelets from the white blood cells (including MNCs) and pushes the platelets out to a collection compartment as a leukoreduced platelet product. The white blood cells (including MNCs) can be conveyed into a separate line or stream which is directed back to the donor/patient. Further details for this system can be found in U.S. Pat. No. 7,963,901, which is hereby incorporated herein by reference.

[0055] Unlike the AMICUS® system, the TRIMA ACCEL® separator does not execute a reinfusion stage at the end of processing, instead scheduling white blood cells to be returned to the blood source at particular time after the procedure has begun. While this approach may appear to be similar to the approach to MNC-return described herein, the distinction between an MNC-return stage scheduled to take place a certain time before the end of blood draw (per the present disclosure) and an MNC-return stage scheduled to take place a certain time after the beginning of blood draw is significant.

[0056] As noted above, for any of a number of reasons, blood draw may actually end at a time that differs from an expected time. In this case, scheduling an MNC-return stage to take place a particular time after the beginning of blood draw (which may be intended to occur shortly before the end of blood draw) may result in a larger than expected gap between MNC return and the end of blood draw, with an unacceptably large volume of MNCs remaining in the separator as waste. By employing the principles described herein and scheduling an MNC-return stage to be executed at a particular procedure setpoint calculated from the end of blood draw, it can be ensured that the MNC-return stage will take place a particular time before the end of blood draw, resulting in increased MNC return to the donor or patient.

Aspects

[0057] Aspect 1. A method for separating platelets from blood, comprising: determining a volume of blood to be processed, and/or a volume of platelets to be collected, and/or a time at which to complete blood draw, and/or a time required to complete blood draw from a source during a blood separation procedure; selecting or determining a procedure setpoint calculated from the completion of blood draw; drawing blood from the source and conveying the blood to a separator; separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction; conveying at least a portion of the platelet-containing fraction from the separator while increasing a volume of the mononuclear cell-containing fraction in the separator; conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint; and ending the blood draw and blood separation.

[0058] Aspect 2. The method of Aspect 1, further comprising executing a reinfusion phase after the completion of blood draw, the reinfusion phase comprising conveying the contents of the separator to the source.

[0059] Aspect 3. The method of any one of the preceding Aspects, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a set time before the completion of blood draw.

[0060] Aspect 4. The method of any one of Aspects 1-2, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a particular time of day.

[0061] Aspect 5. The method of any one of Aspects 1-2, wherein said selecting or determining a procedure setpoint calculated from the completion of blood draw comprises selecting or determining a procedure setpoint that is a set volume of blood remaining to be drawn from the source before the completion of blood draw.

[0062] Aspect 6. The method of any one of the preceding Aspects, further comprising adjusting the calculation or determination of when blood draw will be completed, with such adjustment changing the time or volume of blood drawn after the beginning of blood draw at which said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs without changing the time or volume of blood drawn before the end of blood draw at which said conveying the mononuclear cell-containing fraction from the separation chamber to the source at the procedure setpoint occurs.

[0063] Aspect 7. The method of any one of the preceding Aspects, wherein said separating the blood in the separator into a platelet-containing fraction and a mononuclear cell-containing fraction includes separating the blood in a first stage within the separator into a plasma fraction, a red blood cell fraction, and the mononuclear cell-containing fraction, conveying the plasma fraction from the first stage within the separator to a second stage within the separator, and separating the plasma fraction in the second stage into the platelet-containing fraction and a substantially cell-free plasma fraction.

[0064] Aspect 8. The method of Aspect 7, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint includes decreasing a rate at which the plasma fraction is conveyed from the first stage within the separator to the second stage.

[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 in the first stage within the separator, wherein the rate at which the plasma fraction is conveyed from the first stage to the second stage is decreased until the interface moves from a first position within the first stage to a second position within the first stage.

[0066] Aspect 10. The method of Aspect 9, wherein the interface is maintained at the second position for a predetermined amount of time or volume of blood drawn from the source calculated to convey substantially all of the mononuclear cell-containing fraction from the separator.

[0067] Aspect 11. The method of any one of Aspects 7-10, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint includes conveying the mononuclear cell-containing fraction from the first stage within the separator with the red blood cell fraction.

[0068] Aspect 12. The method of any one of the preceding Aspects, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint lasts until the end of blood draw.

[0069] Aspect 13. The method of any one of Aspects 1-11, wherein said conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint does not last until the end of blood draw.

[0070] Aspect 14. The method of any one of the preceding Aspects, 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 configured to (a) determine a volume of blood to be processed, and/or a volume of platelets to be collected, and/or a time at which to complete blood draw, and/or a time required to complete blood draw from a source during a blood separation procedure, (b) select or determine a procedure setpoint calculated from the completion of the blood draw, (c) execute a blood separation procedure comprising operating the pump system to draw blood from a source into the separator, operating the separator to separate the blood into a platelet-containing fraction and a mononuclear cell-containing fraction, operating the pump system to convey at least a portion of the platelet-containing fraction from the separator while increasing a volume of the mononuclear cell-containing fraction in the separator, and operating the pump system to convey the mononuclear cell-containing fraction out of the blood separator to the source at the procedure setpoint, and (d) end blood draw.

[0072] Aspect 16. The blood separation device of Aspect 15, wherein the controller is further configured to execute a refusion phase after the end of the blood draw by operating the pump system to convey the contents of the blood separator to the source.

[0073] Aspect 17. The blood separation device of any of Aspects 15 and 16, wherein the separator includes a first and second stage and the mononuclear cell-containing fraction and the platelet-containing fraction are separated in the first stage within the separator.

[0074] Aspect 18. The blood separation device of any of Aspects 15-17, wherein the controller is configured to determine a procedure setpoint that is a set time before the end of the blood draw.

[0075] Aspect 19. The blood separation device of any of Aspects 15-17, wherein the controller is configured to determine a procedure setpoint that is a particular time of day.

[0076] Aspect 20. The blood separation device of any of Aspects 15-17, 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 completion of the blood draw.

[0077] Aspect 21. The blood separation device of any of Aspects 15-20, wherein the controller is configured to adjust the determination of when blood draw will be completed, with such adjustment changing the time or volume of blood drawn after the beginning of blood draw at which the pump operates to convey the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs without changing the time or volume of blood drawn before the end of blood draw at which the pump operates to convey the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint occurs.

[0078] Aspect 22. The blood separation device of any of Aspects 15-21, wherein the controller is configured to execute a separation procedure further comprising operating the separator to separate the blood into a plasma fraction, a red blood cell fraction, and the mononuclear cell-containing fraction, operating the pump system to convey the plasma fraction from the first stage within the separator to a second stage within the separator, and operating the separator to separate the plasma fraction in the second stage into the platelet-containing fraction and a substantially cell-free plasma fraction.

[0079] Aspect 23. The separation device of Aspect 22, wherein the controller is configured to execute a separation procedure further comprising operating the pump system to decrease the rate at which the plasma fraction is conveyed from the first stage within the separator to the second stage while conveying the mononuclear cell-containing fraction from the separator to the source at the procedure setpoint.

[0080] Aspect 24. The separation device of Aspect 23, wherein the controller is further configured during a separation procedure to detect a position of an interface between the plasma fraction and the red blood cell fraction in the first stage within the separator, wherein the rate at which the plasma fraction is conveyed from the first stage of the separation stage to the second state is decreased until the interface moves from a first position within the first stage to a second position within the first stage.

[0081] Aspect 25. The separation device of any of Aspects 22-24, wherein the controller is further configured during the separation procedure to maintain the interface at the second position for a predetermined amount of time or volume of blood drawn from the source calculated to convey substantially all of the mononuclear cell-containing fraction from the separator.

[0082] Aspect 26. The separation device of any of Aspects 22-25, wherein the operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint includes operating the pump system to convey the mononuclear cell-containing fraction from the first stage within the separator with the red blood cell fraction.

[0083] Aspect 27. The separation device of any of Aspects 15-26, wherein the operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint lasts until the end of the blood draw.

[0084] Aspect 28. The separation device of any of Aspects 15-26, wherein the operating the pump system to convey the mononuclear cell-containing fraction out of the separator to the source at the procedure setpoint does not last until the end of the blood draw.

[0085] Aspect 29. The separation device of any of Aspects 15-28, wherein the separator is a centrifuge.

[0086] It will be understood that the embodiments and examples described above are illustrative of some of the 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 those combinations of features that are individually disclosed or claimed herein. For these reasons, the scope hereof is not limited to the above description but is as set forth in the following claims, and it is understood that claims may be directed to the features hereof, including as combinations of features that are individually disclosed or claimed herein.