Determination of the presence of cellular material in a fluid

Abstract

An optical detection assembly for monitoring a fluid in a vessel includes a light source, a light detector array and a controller programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

Description

DETERMINATION OF THE PRESENCE OF CELLULAR MATERIAL IN A FLUIDThe present application claims the benefit of and priority to U.S. Provisional Application 63 / 679,082, filed August 2, 2024, which is hereby incorporated herein by reference.Field of the Disclosure

[0001] The present disclosure relates to optical monitoring of fluids. More particularly, the present disclosure relates to determination of the presence of a cellular material in a fluid being optically monitored using a light source and a light detector array.Description of Related Art

[0002] It is known to employ an optical detection assembly to monitor the flow of blood, blood components, and other biological fluids through a fluid flow circuit to determine various characteristics of the flow. A typical optical detection assembly includes a light source (e.g., a laser or a light-emitting diode) configured to emit light into a fluid-containing vessel of the fluid flow circuit, with a light detector (e.g., a photodiode) configured to receive light exiting the vessel. The light detector transmits a signal to a controller based upon the light it has received, with the controller using the signal to determine one or more properties of the fluid.

[0003] For example, plasma may be separated from cellular material (e.g., red blood, platelets) in a blood separation procedure to produce a plasma product. Thus, it may be desirable to detect the presence of cellular material in plasma exiting a spinning membrane in the blood separation procedure to ensure the quality of the plasma product. The presence of platelets in the plasma may be indicative of an error in the spinning membrane.

[0004] U.S. Patent Application Serial No. 18 / 101 ,275 (the disclosure of which is hereby incorporated herein by reference) describes an optical detection assembly that improves upon such conventional optical detection assemblies. The optical detection assembly described in U.S. Patent Application Serial No. 18 / 101 ,275 is based upon the principle that light exiting a turbid media (such as blood or a blood component) will bedispersed, such that the light may be detected at multiple positions using a light detector array, rather than at a single location by a single light detector (e.g., an individual photodiode). Different fluids (e.g., ones having different concentrations of a target substance) result in emerging light beams having different dispersion patterns, with individual light detectors or light-sensing elements of a light detector array receiving various amounts of light that has been transmitted through the fluid. Based on the maximum intensity of light received by one of the individual light detectors, a summation of the intensity of light received by at least two of the individual light detectors, or the width of the dispersion pattern (corresponding to the number of the individual light detectors that have received some minimum amount of light), the controller may determine the concentration of a substance (e.g., platelets) in the subject fluid. U.S. Provisional Patent Application No. 63 / 547,710 relates o an optical-based sensor and s incorporated herein in its entirety.Summary

[0005] There are several aspects of the present subject matter which may be embodied separately or together in the devices and methods described and claimed below. These aspects may be employed alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to preclude the use of these aspects separately or the claiming of such aspects separately as set forth in the claims appended hereto.

[0006] In one aspect, an optical detection assembly for monitoring a fluid in a vessel includes a light source configured and oriented to emit a light into a fluid in a vessel, a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors, and a controller. The controller is programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval, comparethe calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0007] In another aspect, a biological fluid processing device includes a pump system, a valve system and a controller programmed to control the operation of the pump system and the valve system to execute a biological fluid processing procedure. The device also includes an optical detection assembly having a light source configured and oriented to emit a light into a fluid in a vessel, and a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors. Thee controller is further programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0008] In yet another aspect, a method of determining the presence of cellular material in a fluid in a vessel includes emitting a light into a fluid in a vessel, receiving at least a portion of the light exiting the vessel with a plurality of light detectors of a light detector array and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors over a predetermined time interval, and measuring light transmission intensity over the predetermined time interval based on the light transmission intensity signals. The method also includes calculating a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval, comparing the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude; and determining whether cellular materialis present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0009] In still another aspect, a method of determining the presence of cellular material in a fluid using an optical detection assembly having a light source, a light detector array, and a controller, includes measuring, by the controller, light transmission intensity over a predetermined time interval based on light transmission intensity signals received from the light detector array, calculating, by the controller, a frequency and an amplitude of the light transmission intensity signals, comparing, by the controller, the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determining, by the controller, whether cellular content is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.Brief Description of the Drawings

[0010] Fig. 1 is a perspective view of an exemplary hardware component of a biological fluid processing system according to an aspect of the present disclosure;

[0011] Fig. 2 is a schematic view of an exemplary disposable component that may be mounted to the hardware component of Fig. 1 to complete a biological fluid processing system according to an aspect of the present disclosure;

[0012] Fig. 3 is a perspective view of an exemplary optical detection assembly of the hardware component of Fig. 1 , with a lid thereof in an open position;

[0013] Fig. 4 is a perspective view of the optical detection assembly of Fig. 3, with the lid in a closed position;

[0014] Fig. 5 is a perspective view of selected components of the optical detection assembly of Fig. 3;

[0015] Fig. 6 is a diagrammatic view of the optical detection assembly of Fig. 3, monitoring a fluid having a low cellular concentration;

[0016] Fig. 7 is a diagrammatic view of the optical detection assembly of Fig. 3, monitoring a fluid having a high cellular concentration;

[0017] Fig. 8 is a chart illustrating and example of the frequency and amplitude of a light transmission intensity signal with respect to time;

[0018] Fig. 9 is a block diagram illustrating an example of a method for determining the presence of cellular material in a fluid using the optical detection assembly of Fig. 3; and

[0019] Fig. 10 is a block diagram illustrating another example of a method for determining the presence of cellular material in fluid.Description of the Illustrated Embodiments

[0020] The embodiments disclosed herein are for the purpose of providing an exemplary description of the present subject matter. They are, however, only exemplary, and the present subject matter may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting the subject matter as defined in the accompanying claims.

[0021] Figs. 1 and 2 show components of a biological fluid processing system that embodies various aspects of the present subject matter. Use of the system for separating blood into two or more components and collecting at least one of the components will be described herein, though it should be understood that systems according to the present disclosure can be used for processing a variety of different biological fluids.

[0022] Generally speaking, the system includes two principal components, a durable and reusable biological fluid processing device 10 (Fig. 1 ) and a disposable fluid flow circuit 12 (Fig. 2). The illustrated biological fluid processing device 10 includes a spinning membrane separator drive unit 14, a centrifuge or centrifugal separator 16, additional components that control fluid flow through the disposable fluid flow circuit 12, and a controller 18, which governs the operation of the other components of the biological fluid processing device 10 to perform a biological fluid processing procedure. While the principles described herein may be employed when using the biological fluid processing device 10 of Fig. 1 , it should be understood that these same principles may be applied to other biological fluid processing devices, including devices employing single separation technologies or approaches.I. The Durable Biological Fluid Processing Device

[0023] The biological fluid processing device 10 (Fig. 1 ) is configured as a durable item that is capable of long-term use. It should be understood that the biological fluid processing device 10 of Fig. 1 is merely exemplary of one possible configuration and that biological fluid processing devices according to the present disclosure may be differently configured.

[0024] In the illustrated embodiment, the biological fluid processing device 10 is embodied in a single housing or case 20. The illustrated case 20 includes a generally horizontal portion 22 (which may include an inclined or angled face or upper surface for enhanced visibility and ergonomics) and a generally vertical portion 24. The spinning membrane separator drive unit 14 and the centrifugal separator 16 are shown as being incorporated into the generally horizontal portion 22 of the case 20, while the controller 18 is shown as being incorporated into the generally vertical portion 24.A. Spinning Membrane Separator Drive Unit

[0025] The biological fluid processing device 10 includes a spinner support or spinning membrane separator drive unit 14 for accommodating a generally cylindrical spinning membrane separator 26 of the fluid flow circuit 12. U.S. Patent No. 5,194,145 (which is hereby incorporated herein by reference) describes an exemplary spinning membrane separator drive unit that would be suitable for incorporation into the fluid processing device 10, but it should be understood that the spinning membrane separator drive unit 14 may be differently configured without departing from the scope of the present disclosure.

[0026] The illustrated spinning membrane separator drive unit 14 has a base 28 configured to receive a lower portion of the spinning membrane separator 26 and an upper end cap 30 to receive an upper portion of the spinning membrane separator 26. Preferably, the upper end cap 30 is positioned directly above the base 28 to orient a spinning membrane separator 26 received by the spinning membrane separator drive unit 14 vertically and to define a vertical axis about which the spinning membrane separator 26 is spun. While it may be advantageous for the spinning membrane separator drive unit 14 to vertically orient a spinning membrane separator 26, it is alsowithin the scope of the present disclosure for the spinning membrane separator 26 to be differently oriented when mounted to the biological fluid processing device 10.

[0027] In one embodiment, one of the base 28 and upper end cap 30 of the spinning membrane separator drive unit 14 is movable with respect to the other, which may allow differently sized spinning membrane separators 26 to be received by the spinning membrane separator drive unit 14. For example, the upper end cap 30 may be translated vertically with respect to the base 28 and locked in a plurality of different positions, with each locking position corresponding to a differently sized spinning membrane separator 26.

[0028] At least one of the base 28 and the upper end cap 30 is configured to spin one or more components of the spinning membrane separator 26 about the axis defined by the spinning membrane separator drive unit 14. The mechanism by which the spinning membrane separator drive unit 14 spins one or more components of the spinning membrane separator 26 may vary without departing from the scope of the present disclosure. In one embodiment, a component of the spinning membrane separator 26 to be spun includes at least one element configured to be acted upon by a magnet (e.g., a metallic material), while the spinning membrane separator drive unit 14 includes a magnet (e.g., a series of magnetic coils or semi-circular arcs). By modulating the magnetic field acting upon the aforementioned element of the spinning membrane separator 26, the component or components of the spinning membrane separator 26 may be made to spin in different directions and at varying speeds. In other embodiments, different mechanisms may be employed to spin the component or components of the spinning membrane separator 26.

[0029] Regardless of the mechanism by which the spinning membrane separator drive unit 14 spins the component or components of the spinning membrane separator 26, the component or components of the spinning membrane separator 26 is / are preferably spun at a speed that is sufficient to create Taylor vortices in a gap between the spinning component and a stationary component of the spinning membrane separator 26 (or a component that spins at a different speed). Fluid to be separated within the spinning membrane separator 26 flows through this gap, and filtration may be dramatically improved by the creation of Taylor vortices.B. Centrifugal Separator

[0030] As for the centrifugal separator 16, it includes a centrifuge compartment 32 that receives a centrifugal separation chamber 36 of the fluid flow circuit 12, as well as other components of the centrifugal separator 16. Further details as to the centrifugal separator are set forth in PCT Patent Application Publication No. WO 2018 / 053217 A1 , which is hereby incorporated herein by reference.

[0031] Fluid (e.g., anticoagulated whole blood) is introduced into the centrifugal separation chamber 36 by an umbilicus, with the fluid being separated into a layer of less dense components (e.g., platelet-rich plasma, in the case of blood being separated) and a layer of more dense components (e.g., packed red blood cells) within the centrifugal separation chamber 36 as a result of centrifugal forces as it rotates. Components of an interface monitoring system may be positioned within the centrifuge compartment 32 to oversee separation of fluid within the centrifugal separation chamber 36. The interface monitoring system may include a light source 50 and a light detector 52, which is positioned and oriented to receive at least a portion of the light emitted by the light source 50.

[0032] The orientation of the various components of the interface monitoring system depends at least in part on the particular configuration of the centrifugal separation chamber 36. In general, though, the light source 50 emits a light beam (e.g., a laser light beam) through the separated fluid components within the centrifugal separation chamber 36 (which may be formed of a material that substantially transmits the light or at least a particular wavelength of the light without absorbing it). A portion of the light reaches the light detector 52, which transmits a signal to the controller 18 that is indicative of the location of an interface between the separated fluid components. If the controller 18 determines that the interface is in the wrong location (which can affect the separation efficiency of the centrifugal separator 16 and / or the quality of the separated fluid components), then it can issue commands to the appropriate components of the biological fluid processing device 10 to modify their operation so as to move the interface to the proper location.C. Other Components Of The Biological Fluid Processing Device

[0033] In addition to the spinning membrane separator drive unit 14 and the centrifugal separator 16, the biological fluid processing device 10 may include other components compactly arranged to aid fluid processing.

[0034] The generally horizontal portion 22 of the case 20 of the illustrated fluid processing device 10 includes a cassette station 54, which accommodates a flow control cassette of the fluid flow circuit 12. In one embodiment, the cassette station 54 is similarly configured to the cassette station of U.S. Patent No. 5,868,696 (which is hereby incorporated herein by reference), but is adapted to include additional components and functionality. The illustrated cassette station 54 includes a plurality of clamps or valves V1 -V9 (which are collectively referred to herein as the “valve system” of the biological fluid processing system 10), which move between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact or otherwise interact with corresponding valve stations of the flow control cassette of the fluid flow circuit 12. Depending on the configuration of the fluid flow circuit 12, its cassette may not include a valve station for each valve V1 -V9 of the cassette station 54, in which case fewer than all of the valves V1 -V9 will be used in a fluid processing procedure.

[0035] In the actuated position, a valve V1 -V9 engages the associated valve station to prevent fluid flow through that valve station (e.g., by closing one or more ports associated with the valve station, thereby preventing fluid flow through that port or ports). In the retracted position, a valve V1 -V9 is disengaged from the associated valve station (or less forcefully contacts the associated valve station than when in the actuated position) to allow fluid flow through that valve station (e.g., by opening one or more ports associated with the valve station, thereby allowing fluid flow through that port or ports). Additional clamps or valves V10 and V1 1 of the valve system may be positioned outside of the cassette station 54 to interact with portions of valve stations (which may be lengths of tubing) of the fluid flow circuit 12 to selectively allow and prevent fluid flow therethrough. The valves V1 -V9 and corresponding valve stations of the cassette station 54 and cassette may be differently configured and operatedifferently from the valves V10 and V11 and the valve stations that are spaced away from the cassette station 54.

[0036] The cassette station 54 may be provided with additional components, such as pressure sensors A1 -A4, which interact with sensor stations of the cassette to monitor the pressure at various locations of the fluid flow circuit 12. For example, if the fluid source is a human donor, one or more of the pressure sensors A1 -A4 may be configured to monitor the pressure of the donor’s vein during blood draw and return. Other pressure sensors A1 -A4 may monitor the pressure of the spinning membrane separator 26 and the centrifugal separation chamber 36. The controller 18 may receive signals from the pressure sensors A1 -A4 that are indicative of the pressure within the fluid flow circuit 12 and, if a signal indicates a low- or high-pressure condition, the controller 18 may initiate an alarm or error condition to alert an operator to the condition and / or to attempt to bring the pressure to an acceptable level without operator intervention.

[0037] The biological fluid processing device 10 may also include a plurality of pumps P1 -P6 (which are collectively referred to herein as the “pump system” of the biological fluid processing device 10) to cause fluid to flow through the fluid flow circuit 12. The pumps P1 -P6 may be differently or similarly configured and / or function similarly or differently from each other. In the illustrated embodiment, the pumps P1 -P6 are configured as peristaltic pumps, which may be generally configured as described in U.S. Patent No. 5,868,696. Each pump P1 -P6 engages a different tubing loop extending from a side surface of the flow control cassette and may be selectively operated under command of the controller 18 to cause fluid to flow through a portion of the fluid flow circuit 12. In one embodiment, all or a portion of the cassette station 54 may be capable of translational motion in and out of the case 20 to allow for automatic loading of the tubing loops into the associated pump P1 -P6. In another exemplary embodiment, rather than employing peristaltic pumps, pneumatic pumps may be employed, with actuators incorporated into the cassette station 54 interacting with suitably configured portions of the fluid flow circuit 12 (e.g., pump stations of a cassette mounted to the cassette station 54) to convey fluid through the fluid flow circuit 12.

[0038] The illustrated biological fluid processing device 10 also includes a spinner inlet sensor M1 for determining one or more properties of a fluid flowing into a spinning membrane separator 26 mounted within the spinning membrane separator drive unit 14. If the fluid flowing into the spinning membrane separator 26 is whole blood (which may include anticoagulated whole blood), the spinner inlet sensor M1 may be configured to determine the hematocrit of the blood flowing into the spinning membrane separator 26. If the fluid flowing into the spinning membrane separator 26 is platelet-rich plasma, the spinner inlet sensor M1 may be configured to determine the platelet concentration of platelet-rich plasma flowing into the spinning membrane separator 26. The spinner inlet sensor M1 may detect the one or more properties of a fluid by optically monitoring the fluid as it flows through tubing of the fluid flow circuit 12, or by any other suitable approach. The controller 18 may receive signals from the spinner inlet sensor M1 that are indicative of the one or more properties of fluid flowing into the spinning membrane separator 26 and use the signals to optimize the fluid processing procedure based upon that property or properties. If the property or properties is / are outside of an acceptable range, then the controller 18 may initiate an alarm or error condition to alert an operator to the condition. A suitable device and method for monitoring hematocrit and / or platelet concentration is described in U.S. Patent No. 6,419,822 (which is hereby incorporated herein by reference), but it should be understood that a different approach may also be employed for monitoring one or more properties of a fluid or fluid component flowing into the spinning membrane separator 26.

[0039] The illustrated biological fluid processing device 10 further includes a spinner outlet sensor M2, which accommodates tubing of the fluid flow circuit 12 that flows a separated fluid component out of the spinning membrane separator 26. The spinner outlet sensor M2 monitors the separated fluid component to determine one or more properties thereof, and may do so by optically monitoring the separated fluid component as it flows through the tubing or by any other suitable approach. In one embodiment, separated plasma flows through the tubing, in which case the spinner outlet sensor M2 may be configured to determine the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic. This may be done using an optical monitor of the type described in U.S. Patent No.8,556,793 (which is hereby incorporated herein by reference) that measures the optical density of the fluid in the associated tubing, or by any other suitable device and / or method.

[0040] The illustrated fluid processing device also includes an air detector M3 (e.g., an ultrasonic bubble detector), which accommodates tubing of the fluid flow circuit 12 that flows fluid to a recipient. It may be advantageous to prevent air from reaching the recipient, whether a human recipient (e.g., the same human that serves as the blood source) or a non-human recipient (e.g., a storage bag or container), so the air detector M3 may transmit signals to the controller 18 that are indicative of the presence or absence of air in the tubing. If the signal is indicative of air being present in the tubing, the controller 18 may initiate an alarm or error condition to alert an operator to the condition and / or to take corrective action to prevent the air from reaching the recipient (e.g., by reversing the flow of fluid through the tubing or diverting flow to a vent location).

[0041] The generally vertical portion 24 of the case 20 may include a plurality of volume measurement systems W1 -W6 (six are shown, but more or fewer may be provided), each configured to be associated with one or more fluid containers F1 -F7 of the fluid flow circuit 12 (Fig. 2). Each volume measurement system W1 -W6 is configured to work in combination with the controller 18 to measure a current volume of fluid within an associated fluid container F1 -F7 and to calculate a change in that volume between two or more points in time. The individual volume measurement systems W1 - W6 may be variously configured without departing from the scope of the present disclosure, which may include two or more of the volume measurement systems W1 - W6 being differently configured. In one exemplary embodiment, a volume measurement system W1 -W6 may be configured as or include a weight scale configured to support and measure the weight of a fluid within an associated fluid container F1 -F7 (with the measured weight being converted to a volume by a component of the volume measurement system W1 -W6 or by the controller 18). In another exemplary embodiment, a volume measurement system W1 -W6 may include one or more sensors configured to detect a volume and / or a change in volume of a fluid within an associated fluid container F1 -F7. Volume measurement systems including additional components(e.g., both a weight scale and a sensor) and / or alternative components may also be employed without departing from the scope of the present disclosure.

[0042] Regardless of its particular configuration, each volume measurement system W1 -W6 transmits to the controller 18 a signal that is indicative of the volume of the fluid within the associated container F1 -F7 to track the change of volume during the course of a procedure. This allows the controller 18 to process the incremental volume changes to derive fluid processing volumes and flow rates and subsequently generate signals to control processing events based, at least in part, upon the derived processing volumes. For example, the controller 18 may diagnose leaks and obstructions in the fluid flow circuit 12 and alert an operator.

[0043] The illustrated case 20 is also provided with a plurality of hooks or supports H1 and H2 that may support various components of the fluid flow circuit 12 or other suitably sized and configured objects.D. Controller

[0044] According to an aspect of the present disclosure, the biological fluid processing device 10 includes a controller 18, which is suitably configured and / or programmed to control operation of the biological fluid processing device 10. In one embodiment, the controller 18 comprises a main processing unit (MPU), which can comprise, e.g., a Pentium™ type microprocessor made by Intel Corporation, although other types of conventional microprocessors can be used. In one embodiment, the controller 18 may be mounted inside the generally vertical portion 24 of the case 20, adjacent to or incorporated into an operator interface station (e.g., a touchscreen). In other embodiments, the controller 18 and operator interface station may be associated with the generally horizontal portion 22 or may be incorporated into a separate device that is connected (either physically, by a cable or the like, or wirelessly) to the biological fluid processing device 10.

[0045] The controller 18 is configured and / or programmed to execute at least one biological fluid processing procedure but, more advantageously, is configured and / or programmed to execute a variety of different biological fluid processing procedures. For example, the controller 18 may be configured and / or programmed to carry out one ormore of the following: a double unit red blood cell collection procedure, a plasma collection procedure, a plasma / red blood cell collection procedure, a red blood cell / platelet / plasma collection procedure, a platelet collection procedure, and a platelet / plasma collection procedure.

[0046] More particularly, in carrying out these fluid processing procedures, the controller 18 is configured and / or programmed to control one or more of the following tasks: drawing fluid into a fluid flow circuit 12 mounted to the biological fluid processing device 10, conveying fluid through the fluid flow circuit 12 to a location for separation (i.e., into a spinning membrane separator 26 or centrifugal separation chamber 36 of the fluid flow circuit 12), separating the fluid into two or more components as desired, and conveying the separated components into storage containers, to a second location for further separation (e.g., into whichever of the spinning membrane separator 26 and centrifugal separation chamber 36 that was not used in the initial separation stage), or to a recipient (which may be a source from which the fluid was originally drawn).

[0047] This may include instructing the spinning membrane separator drive unit 14 and / or the centrifugal separator 16 to operate at a particular rotational speed and instructing a pump P1 -P6 to convey fluid through a portion of the fluid flow circuit 12 at a particular flow rate. Hence, while it may be described herein that a particular component of the biological fluid processing device 10 (e.g., the spinning membrane separator drive unit 14 or the centrifugal separator 16) performs a particular function, it should be understood that that component is being controlled by the controller 18 to perform that function.

[0048] Before, during, and after a procedure, the controller 18 may receive signals from various components of the biological fluid processing device 10 (e.g., the pressure sensors A1 -A4) to monitor various aspects of the operation of the biological fluid processing device 10 and characteristics of the fluid and separated fluid components as they flow through the fluid flow circuit 12. If the operation of any of the components and / or one or more characteristics of the fluid or separated fluid components is outside of an acceptable range, then the controller 18 may initiate an alarm or error condition to alert the operator and / or take action to attempt to correct the condition. The appropriate corrective action will depend upon the particular errorcondition and may include action that is carried out with or without the involvement of an operator.

[0049] For example, the controller 18 may include an interface control module, which receives signals from the light detector 52 of the interface monitoring system. The signals that the controller 18 receives from the light detector 52 are indicative of the location of an interface between the separated fluid components within the centrifugal separation chamber 36. If the controller 18 determines that the interface is in the wrong location, then it can issue commands to the appropriate components of the biological fluid processing device 10 to modify their operation so as to move the interface to the proper location. For example, the controller 18 may instruct one of the pumps P1 -P6 to cause fluid to flow into the centrifugal separation chamber 36 at a different rate and / or for a separated fluid component to be removed from the centrifugal separation chamber 36 at a different rate and / or for the centrifugal separation chamber 36 to be spun at a different speed by the centrifugal separator 16.

[0050] If provided, an operator interface station associated with the controller 18 allows the operator to view on a screen or display (in alpha-numeric format and / or as graphical images) information regarding the operation of the system. The operator interface station also allows the operator to select applications to be executed by the controller 18, as well as to change certain functions and performance criteria of the system. If configured as a touchscreen, the screen of the operator interface station can receive input from an operator via touch-activation. Otherwise, if the screen is not a touchscreen, then the operator interface station may receive input from an operator via a separate input device, such as a computer mouse or keyboard. It is also within the scope of the present disclosure for the operator interface station to receive input from both a touchscreen and a separate input device, such as a keypad.IL The Disposable Fluid Flow Circuit

[0051] As for the fluid flow circuit or flow set 12 (Fig. 2), it is intended to be a sterile, single use, disposable item. Before beginning a given fluid processing procedure, the operator loads various components of the fluid flow circuit 12 in the case 20 in association with the biological fluid processing device 10. The controller 18implements the procedure based upon preset protocols, taking into account other input from the operator. Upon completing the procedure, the operator removes the fluid flow circuit 12 from association with the biological fluid processing device 10. The portions of the fluid flow circuit 12 holding the collected fluid component or components (e.g., collection containers or bags) are removed from the case 20 and retained for storage, transfusion, or further processing. The remainder of the fluid flow circuit 12 is removed from the case 20 and discarded.

[0052] In the illustrated embodiment, the fluid flow circuit 12 includes a cassette, to which the other components of the fluid flow circuit 12 are connected by flexible tubing. The other components may include a plurality of fluid containers F1 -F7. In the context of the present disclosure these containers include an anticoagulant container F1 , a saline container F2, an in-process container F3, a return container F4, a plasma collection container F5, a platelet collection container F6, and an (optional) additive container F7. The illustrated flow circuit 12 further includes one or more fluid source access devices (e.g., a connector for accessing blood within a fluid container or a phlebotomy needle), a spinning membrane separator 26 and a centrifugal separation chamber 36.

[0053] The flow control cassette provides a centralized, programmable, integrated platform for all the pumping and many of the valving functions required for a given fluid processing procedure. In one embodiment, the cassette is similarly configured to the cassette of U.S. Patent No. 5,868,696, but is adapted to include additional components (e.g., more tubing loops) and functionality.

[0054] In use, the cassette is mounted to the cassette station 54 of the biological fluid processing device 10 so as to align each sensor station with an associated pressure sensor A1 -A4 of the cassette station 54 and its valve stations with an associated valve V1 -V9. Each valve station may define one or more ports that allow fluid communication between the valve station and another interior cavity of the cassette (e.g., a flow path). As described above, each valve V1 -V9 is movable under command of the controller 18 to move between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact the valve stations of the cassette. In the actuated position, a valve V1 -V9 engages the associatedvalve station to close one or more of its ports to prevent fluid flow therethrough. In the retracted position, a valve V1 -V9 is disengaged from the associated valve station (or less forcefully contacts the associated valve station than when in the actuated position) to open one or more ports associated with the valve station, thereby allowing fluid flow therethrough.

[0055] A plurality of tubing loops extend from the side surface of the cassette to interact with pumps P1 -P6 of the biological fluid processing device 10. The different pumps P1 -P6 may interact with the tubing loops of the cassette to perform different tasks during a procedure, but in the context of the present disclosure, a different one of the pumps P1 -P6 may be configured to serve as an anticoagulant pump P1 , a source pump P2, a centrifuge pump P3, an outlet pump P4, a recirculation pump P5, and a plasma pump P6. If the pumps P1 -P6 are differently configured (e.g., if they are configured as pneumatic pumps), then the cassette may be differently configured (e.g., with pump stations aligned with pneumatic pump actuators) to allow for the pumps PI PS to convey fluid through the cassette.

[0056] Additional tubing extends from the side surface of the cassette to connect to the other components of the fluid flow circuit 12, such as the various fluid containers F1 -F7, the spinning membrane separator 26, and the centrifugal separation chamber 36. The tubing connected to the centrifugal separator chamber 36 (which includes one inlet tube and two outlet tubes) may be aggregated into an umbilicus.

[0057] Various additional components may be incorporated into the tubing leading out of the cassette or into one of the cavities of the cassette. For example, a manual clamp 56 may be associated with a line or lines leading to the fluid source, a return line filter 58 (e.g., a microaggregate filter) may be associated with a line leading to a fluid recipient, and / or an air trap 62 may be positioned on a line upstream of the centrifugal separation chamber 36.III. Exemplary Biological Fluid Processing Procedure

[0058] An exemplary biological fluid processing procedure according to the present disclosure will now be described.

[0059] Prior to processing, an operator selects the desired protocol (e.g., using an operator interface station, if provided), which informs the controller 18 of the manner in which it is to control the other components of the biological fluid processing device 10 during the procedure. This may include first selecting one of a plurality of possible procedures that the system is capable of executing and then, after selecting the nature of the procedure, selecting one or more parameters to be in effect during the procedure. For example, this may include selecting a platelet collection procedure from among a variety of blood separation procedures and then selecting a total volume of blood to be processed or a target volume of platelets to be collected during the procedure. If the fluid source is a living source (e.g., a donor or patient), the operator may proceed to enter various parameters, such as the sex / height / weight of the source. In one embodiment, the operator may also enter one or more characteristics of the fluid to be processed, such as a platelet pre-count.

[0060] Once the controller 18 has received the necessary input, it may proceed to instruct the operator to mount the fluid flow circuit 12 to the biological fluid processing device 10. If there are any fluid containers (e.g., a platelet additive solution container) that are not integrally formed with the fluid flow circuit 12, they may be connected to the fluid flow circuit 12 (e.g., by piercing a septum of a tube of the fluid flow circuit 12 or via a luer connector), with the fluid flow circuit 12 then being mounted to the biological fluid processing device 10 (including the fluid containers F1 -F7 being associated with the volume measurement systems W1 -W6, as appropriate). In one exemplary embodiment, each volume measurement system W1 -W6 includes a weight scale associated with a hook from which a fluid container may be hung. In another exemplary embodiment, at least one of the volume measurement systems W1 -W6 includes a weight scale associated with a horizontal platform or surface, with a container being placed onto the platform or surface for support while the weight scale sends signals indicative of the weight of the container (and its contents) to be sent to the controller 18 throughout the course of a procedure. In other embodiments, a fluid container may be associated with a volume measurement system omitting a weight scale, but including other means for measuring the volume of fluid within the container (e.g., one or more sensors).

[0061] Once the fluid flow circuit 12 has been fully mounted to the biological fluid processing device 10, the controller 18 may proceed with an integrity check of the fluid flow circuit 12 to ensure that the various components of the fluid flow circuit 12 are properly connected and functioning. Following a successful integrity check, the fluid source is connected to the fluid flow circuit 12 (e.g., by connecting to a container of previously collected fluid or by phlebotomizing a donor), and the fluid flow circuit 12 may be primed (e.g., using saline pumped from a saline container F2 by operation of one or more of the pumps P1-P6 of the biological fluid processing device 10).

[0062] After the fluid flow circuit 12 has been primed, fluid processing may begin. In a first phase of an exemplary platelet collection procedure, blood is drawn into the fluid flow circuit 12 from a blood source. If the blood source is a donor, then blood may be drawn into the fluid flow circuit 12 through a single needle that is connected to the cassette by line L1 . Line L1 may include a manual clamp 56 that may initially be in a closed position to prevent fluid flow through line L1 . When processing is to begin, an operator may move the manual clamp 56 from its closed position to an open position to allow fluid flow through line L1 .

[0063] The blood is drawn into line L1 by the source pump P2 of the biological fluid processing device 10. Anticoagulant from the anticoagulant container F1 may be drawn through line L2 under action of the anticoagulant pump P1 and added to the blood at a junction of lines L1 and L2.

[0064] In the illustrated embodiment, valve V10 is open to allow anticoagulated blood to flow through line L3 and a cassette sensor station associated with pressure sensor A1 , while valve V1 1 is closed to prevent fluid flow through line L4. If the blood source is a living body (e.g., a donor), the pressure sensor A1 may communicate with the controller 18 to monitor the pressure within the vein of the blood source.

[0065] The cassette includes two valve stations downstream of the source pump P2, with valve V2 being closed to prevent flow through line L5 and valve V1 being open to allow flow through line L6. A portion of the blood is directed through line L7 and a cassette sensor station associated with pressure sensor A3 to the in-process container F3 and the remainder is directed through line L8 toward the centrifuge pump P3, which controls the amount of blood that is directed to the centrifugal separation chamber 36instead of the in-process container F3. In particular, the flow rate of the source pump P2 is greater than the flow rate of the centrifuge pump P3, with the difference therebetween being equal to the flow rate of blood into the in-process container F3. The flow rates may be selected such that the in-process container F3 is partially or entirely filled with blood at the end of the draw phase.

[0066] The blood pumped through line L8 by the centrifuge pump P3 passes through line L19, an air trap 62, and a cassette sensor station associated with pressure sensor A2 (which works in combination with the controller 18 of the biological fluid processing device 10 to monitor the pressure in the centrifugal separation chamber 36) before reaching the centrifugal separation chamber 36 of the fluid flow circuit 12. The centrifugal separator 16 of the biological fluid processing device 10 manipulates the centrifugal separation chamber 36 to separate the blood in the centrifugal separation chamber 36 into platelet-rich plasma and packed red blood cells. In one embodiment, the centrifugal separation chamber 36 is rotated nominally at 4,500 rpm, but the particular rotational speed may vary depending on the flow rates of fluids into and out of the centrifugal separation chamber 36.

[0067] The packed red blood cells exit the centrifugal separation chamber 36 via line L10 and flow through line L1 1 into the return container F4. Platelet-rich plasma is drawn out of the centrifugal separation chamber 36 via line L12 by the combined operation of the recirculation and outlet pumps P5 and P4 of the biological fluid processing device 10. The platelet-rich plasma travels through line L12 until it reaches a junction, which splits into lines L13 and L14. The recirculation pump P5 is associated with line L13 and redirects a portion of the platelet-rich plasma to a junction, where it mixes with blood in line L8 that is being conveyed into the centrifugal separation chamber 36 by the centrifuge pump P3. Recirculating a portion of the platelet-rich plasma into the centrifugal separation chamber 36 with inflowing blood decreases the hematocrit of the blood entering the centrifugal separation chamber 36, which may improve separation efficiency. By such an arrangement, the flow rate of the fluid entering the centrifugal separation chamber 36 is equal to the sum of the flow rates of the centrifuge pump P3 and the recirculation pump P5. As the platelet-rich plasma drawn out of the centrifugal separation chamber 36 into line L13 by the recirculationpump P5 is immediately added back into the centrifugal separation chamber 36, the bulk or net platelet-rich plasma flow rate out of the centrifugal separation chamber 36 is equal to the flow rate of the outlet pump P4.

[0068] Line L14 ends at a junction, where it joins with lines L15 and L16. Valve V6 is closed to prevent fluid flow through line L16, thereby directing the separated platelet-rich plasma to the spinning membrane separator 26 via line L15. Before reaching the spinning membrane separator 26, the portion of the platelet-rich plasma conveyed through line L15 passes the spinner inlet sensor M1 and a cassette sensor station associated with pressure sensor A4. The spinner inlet sensor M1 may detect the concentration of platelets in the platelet-rich plasma entering the spinning membrane separator 26, while the pressure sensor A4 may monitor the pressure of the spinning membrane separator 26.

[0069] While valve V6 is typically closed, it may be selectively opened to divert all or a portion of the platelet-rich plasma from line L14 into and through line L16 and to the return container F4, if necessary. An example would be at the start of a procedure when separation is initializing and platelets are not yet exiting the centrifugal separation chamber 36, in which case the fluid conveyed through line L14 by the outlet pump P4 could be diverted to the return container F4.

[0070] The spinning membrane separator drive unit 14 of the biological fluid processing device 10 manipulates the spinning membrane separator 26 to separate the platelet-rich plasma into platelet-poor plasma (“plasma”) and platelet concentrate (“platelets”). Plasma is pumped out of the spinning membrane separator 26 via line L17 by the plasma pump P6 of the biological fluid processing device 10. Valves V5, V6, V8, and V9 are closed to direct the separated plasma along line L18, through valve V4, and into the return container F4 (with the separated red blood cells). On the way to the return container F4, the plasma passes through spinner outlet sensor M2, which may cooperate with the controller 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0071] The platelet concentrate is conveyed out of the spinning membrane separator 26 via line L19. There is no pump associated with line L19, so instead theflow rate at which the platelets exit the spinning membrane separator 26 is equal to the difference between the flow rates of the outlet pump P4 and plasma pump P6. Valve V8 is closed to prevent fluid flow through the line L20, thereby directing the flow of platelets along line L19, through valve V7, and into the platelet collection container F6. Valve V8 may be selectively opened to allow fluid flow through line L20 and to a junction, where it joins the plasma flowing through line L18 to the return container F4, if necessary.

[0072] Depending on the volume of platelets to be collected, the above-described draw stage may be repeated, with draw stages being alternated with return stages in which blood from the in-process container F3 is separated in the centrifugal separation chamber 36 while previously collected blood components in the return container F4 are returned to the blood source. During such return stages, the separated red blood cells and platelet-rich plasma may be variously routed through the fluid flow circuit 12, typically with an additional volume of platelets being collected in the platelet collection container F6 after being separated from platelet-poor plasma in the spinning membrane separator 26 (as during the draw stage). A platelet additive solution from the additive container F7 may be added to the collected platelets in the platelet collection container F6 before ending the procedure.IV. Determination of Cellular Material Presence in Fluid

[0073] As noted above, the spinner inlet sensor M1 may be used in combination with the controller 18 to determine one or more properties of a fluid flowing into a spinning membrane separator 26, while the spinner outlet sensor M2 may be used to determine one or more properties of a fluid flowing out of the spinning membrane separator 26. Figs. 3-5 illustrate an exemplary optical detection assembly 100 that may be incorporated into the biological fluid processing device 10 to perform the functions of the spinner inlet sensor M1 or the spinner outlet sensor M2. In one embodiment, two such optical detection assemblies 100 may be incorporated into the biological fluid processing device 10, with one acting as the spinner inlet sensor M1 and the other acting as the spinner outlet sensor M2. While the optical detection assembly 100 of Figs. 3-5 will be described herein as being a component of the biological fluidprocessing device 10 of Fig. 1 , it should be understood that optical detection assemblies according to the present disclosure may be incorporated into differently configured biological fluid processing devices or be provided as standalone devices that are not incorporated into a biological fluid processing device.

[0074] In the illustrated embodiment, the optical detection assembly 100 includes a light source 102 and a light detector array 104, which are spaced apart to accommodate a vessel “B” therebetween. When the optical detection assembly 100 is employed as a spinner inlet sensor M1 , the vessel B may be line L15 of the fluid flow circuit 12, with the vessel B being line L17 of the fluid flow circuit 12 when the optical detection assembly 100 is instead employed as a spinner outlet sensor M2. It should be understood that the configuration of the vessel B used in combination with the optical detection assembly 100 may vary without departing from the scope of the present disclosure, provided that the vessel B is suitable for containing a fluid (which may include the vessel B being configured to accommodate the flow of a fluid therethrough) and formed of a material that is configured to transmit light emitted by the light source 102.

[0075] The illustrated optical detection assembly 100 includes a base 106 defining a slot or channel 108 configured to receive the vessel B. The channel 108 is configured to secure the vessel B in a desired orientation with respect to the light source 102 and the light detector array 104. The optical detection assembly 100 may also include a lid 110 (which is shown in Figs. 3 and 4 as being hingedly or pivotally associated to the base 106) to block external light from interfering with analysis of a fluid within the vessel B.

[0076] Referring now to FIGS. 6 and 7, light D emitted by the light source 102 (which may be variously configured without departing from the scope of the present disclosure) enters and then exits the vessel B after passing through a fluid within the vessel B. Transmitted light exits the vessel B and the light detector array 104 is positioned and oriented to receive at least a portion of the transmitted light. The light detector array 104 is comprised of a plurality of light detectors or light-sensing elements (e.g., 256 photodiodes in a linear array).

[0077] A controller associated with the light detector array 104 (which may be the controller 18 of the biological fluid processing device 10 or a different, dedicated controller) receives signals from each of the individual light detectors of the light detector array 104, with each signal being indicative of the intensity of light received by the individual light detector that transmitted the signal to the controller. Figs. 6 and 7 include charts generated by the controller based on the signals from the light detector array 104 (which are referred to herein as “scattering profiles”) that reflect the intensity of the signal received by the controller from each individual light detector, with the results ordered by the relative positions of the individual light detectors (i.e. , the signal from the light detector at the left end of the light detector array 104 is presented at the left end of each chart, with the signal from the adjacent light detector being presented just to the right of the signal from the first light detector and so on until the signal from the light detector at the right end of the light detector array 104 is presented at the right end of each chart). As can be seen in Figs. 6 and 7, the light detectors at the center of the light detector array 104 will tend to receive the most intense light, with the light detectors at each end of the light detector array 104 receiving little to no light.

[0078] In the illustrated embodiment, platelets within the fluid cause light to scatter, rather than being transmitted straight through the fluid and vessel B (along its initial path). As there are more cells in the fluid F, there is more scattering of the light, with more individual light detectors receiving at least some of the light, though with a relatively low maximum intensity compared to the maximum intensity of the light received by an individual light detector. Stated differently, light passing through the less concentrated fluid f is narrowly distributed or dispersed, while light passing through the more highly concentrated fluid F is more widely or broadly distributed or dispersed. Thus, by providing a light detector array 104, the intensity of light received by multiple individual light detectors (i.e., the light distribution or the scattering profile) may be assessed to determine one or more properties of a subject fluid, such as a concentration of a substance (e.g., platelets) in the fluid.

[0079] In one embodiment, a frequency and amplitude of the light transmission intensity through the fluid may be monitored over time to determine whether the optical density of the fluid is due to inherent contents of the fluid or the presence of cellularcontents. For example, the frequency and amplitude of the light transmission intensity through plasma exiting the spinning membrane may be monitored over time to determine whether the optical density of the plasma is due to inherent plasma contents, e.g., proteins and lipids, or the presence of the cellular contents, such as platelets.

[0080] FIG. 8 is a graph showing the detected light transmission intensity signal over time, as detected by the light detector array 104. The light transmission intensity signal is indicative of a light intensity of at least a portion of the light received by one or more of the light detectors 104. In one example, the light transmission intensity signal may be indicative of the maximum intensity of light received by one of the plurality of the light detectors. In general, as the cellular material concentration decreases, the amplitude and frequency of the light transmission intensity decrease as well. Conversely, as the cellular material concentration increases, the amplitude and frequency of the light transmission intensity will increase.

[0081] In the example of FIG. 8, when a relatively higher concentration of cellular material is present in the fluid, for example, about 92e3 / uL, both the amplitude and frequency of the light transmission intensity signal are relatively high. When a relatively lower concentration of cellular material is present in the fluid, for example, about 0e3 / uL (considered to be cell free plasma), both the amplitude and frequency of the light transmission intensity signal are relatively low. In the illustrated example, the cellular material concentration decreases with time, and thus, the amplitude and frequency of the light transmission intensity signal also decrease with time.

[0082] Cellular material creates a light scattering phenomenon with a fluid which impacts the frequency and amplitude of the light transmission intensity signal through the fluid due the larger size of the cells (urn range) with respect to the wavelength of light. Conversely, lipids and proteins will not have a significant light scatter impact due to the relatively small size of the particles (< nm range). Thus, when the frequency and amplitude of the transmitted light intensity vary with time, it can be determined that cellular material is present in fluid. For example, it may be determined that platelets are present in the plasma. Accordingly, the amplitude and / or frequency of the light transmission intensity signal may be used to detect the presence of cellular material inthe plasma by comparing measured frequencies and / or amplitudes to empirically predetermined thresholds indicative of cell content in a fluid.

[0083] As noted above, in one example, the light transmission intensity being monitored may be a maximum light transmission intensity, as described in U.S. Patent Application No. 18 / 101 ,275, over time. For example, the maximum transmitted light intensity measurement may be the maximum light intensity received at one light detector 104 of the plurality of among a plurality of light intensities detected by respective light detectors 104. That is, the maximum transmitted light intensity may be the highest light intensity measurement from among a plurality of light transmission intensity measurements a light detector 104 among all light intensity measurements by corresponding light detectors overpowered by each time the transmitted light intensities are detected.

[0084] Fig. 9 is a block diagram illustrating an example of a method 1100 for determining the presence of cellular material in a fluid using an optical detection assembly 100 of the type described herein. The method includes at 1 110, measuring light transmission intensity over a predetermined time interval and at 1120, calculating the light transmission intensity signal frequency and amplitude. At 1130, the calculated transmission intensity signal frequency may be compared to a stored threshold frequency. If the calculated transmission intensity signal frequency is greater than that stored threshold frequency, then the method includes at 1200, determining that cellular material is present in the fluid. If the calculated transmission intensity signal frequency is less than the stored threshold frequency, then the method may return to measuring the light transmission intensity over the predetermined time at 11 10. Thus, at 1130 and 1200, determining that cellular material is present in the fluid is based on a comparison of transmission intensity signal frequency to the stored threshold frequency, which may be referred to generally as the frequency method.

[0085] At 1 140, the method includes comparing the calculated transmission intensity signal frequency to the stored threshold frequency and comparing a calculated transmission intensity signal amplitude to a stored threshold amplitude. If the calculated transmission intensity signal frequency and calculated intensity signal amplitude are greater than a respective threshold frequency and threshold amplitude, then the methodincludes, at 1 00, determining that cellular material is present in the fluid. If the calculated frequency and / or calculated amplitude are less than a respective threshold frequency and / or threshold amplitude, then the method may return to measuring the light transmission intensity over the predetermined time at 11 10. The method at 1140 and 1200 may be referred to as the combined method.

[0086] At 1 150, the calculated transmission intensity signal amplitude may be compared to a stored threshold amplitude. If the calculated transmission intensity signal amplitude is greater than that stored threshold amplitude, then the method includes at 1200, determining that cellular material is present in the fluid. If the calculated transmission intensity signal amplitude is less than the stored threshold amplitude then the method may return to measuring the light transmission intensity over the predetermined time at 1110. The method at 1150 and 1200 may be referred to as the amplitude method.

[0087] The various measurements, calculations, comparisons and determinations of the method 1100 may be performed by a controller, such as controller 18, based on signals produced by the light detector 104 indicative of the light transmission intensity over a predetermined time. In addition, the controller may access information stored in a memory or storage device including, for example, threshold frequency information, threshold amplitude information, and time information. The controller may store in the memory or storage device information received in the signals indicative of the light transmission intensity.

[0088] Fig. 10 is a block diagram illustrating another method 2100 for determining the presence of cellular material in a fluid according to the present disclosure. The method 2100 may include at 2110, emitting light from light source 102 into a fluid in a vessel, and at 2120 receiving at least a portion of the light exiting the vessel with a plurality of light detectors of a light detector array 104 over a predetermined time interval. At 2130, the method includes measuring, by the controller, light transmission intensity over a predetermined time interval. The measuring may be based on one or more light transmission intensity signals provided by the light detector array 104 indicative of the intensity of transmitted light received at the light detector 104. At 2140,the method includes calculating, by the controller, a frequency and / or an amplitude of the light transmission intensity signal.

[0089] At 2150, the method may further include comparing, by the controller, the calculated frequency to a stored threshold frequency and / or the calculated amplitude to a stored threshold amplitude, and at 2160, determining, by the controller, whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude. For example, the controller may determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency and / or the calculated amplitude is greater than the threshold amplitude. Conversely, the controller may determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and / or the calculated amplitude is less than the threshold amplitude.

[0090] In various examples, the controller may determine whether cellular material is present in the fluid based only on a comparison of the calculated frequency to the threshold frequency, or a comparison of the calculated amplitude to the threshold amplitude. In further examples, the controller may compare both the calculated frequency and calculated amplitude to a respective threshold frequency and threshold amplitude, and may determine that cellular material is present in the fluid if one or both of the calculated frequency and calculated amplitude are greater than the threshold frequency or threshold amplitude.

[0091] In the examples above, the optical detection assembly 100 may detect the presence of a cellular material, such as platelets, in a fluid, such as plasma, in a biological fluid processing procedure. The presence of the platelets in the plasma may be determined based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0092] The signals generated by the spinner inlet sensor M1 and the spinner outlet sensor M2 are received by the controller 18, which compares the signals from the spinner inlet sensor M1 (which are indicative of the composition of the platelet-rich plasma) to the signals from the spinner outlet sensor M2 (which are indicative of the composition of the platelet-poor plasma or supernatant) in order to more accuratelydetermine the platelet concentration of the platelet-rich plasma. This improvement is on account of the signals from the two sensors M1 and M2 being representative of two fluids that are identical (including any non-cellular components of the plasma that affect an optical analysis, such as lipids) except for their cellular composition, which is the fluid characteristic of interest. Otherwise, if the controller 18 were to use only the signals from the spinner inlet sensor M1 to determine the platelet concentration of the plateletrich plasma, the result may be incorrect due to the effects of the presence of the various non-cellular components within the platelet-rich plasma on the optical analysis.V. Aspects

[0093] Aspect 1 . An optical detection assembly for monitoring a fluid in a vessel, comprising: a light source configured and oriented to emit a light into a fluid in a vessel; a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors; and a controller programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0094] Aspect 2. The optical detection assembly of Aspect 1 , wherein the controller calculates the frequency of the light transmission intensity signals and is programmed to determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency.

[0095] Aspect 3. The optical detection assembly of Aspect 1 , wherein the controller calculates the frequency of the light transmission intensity signals and isprogrammed to determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

[0096] Aspect 4. The optical detection assembly of Aspect 1 , wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude.

[0097] Aspect 5. The optical detection assembly of Aspect 1 , wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

[0098] Aspect 6. The optical detection assembly of Aspect 1 , wherein the controller calculates both the frequency and the amplitude of the light transmission intensity signals.

[0099] Aspect 7. The optical detection assembly of Aspect 6, wherein the controller is programmed to determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude.

[0100] Aspect 8. The optical detection assembly of Aspect 6, wherein the controller is programmed to determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

[0101] Aspect 9. The optical detection assembly of any one of Aspects 1 -8, wherein the controller is configured to determine whether platelets are present in plasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0102] Aspect 10. A biological fluid processing device comprising: a pump system; a valve system; a controller programmed to control the operation of the pump system and the valve system to execute a biological fluid processing procedure; and an optical detection assembly comprising a light source configured and oriented to emit a light into a fluid in a vessel, and a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel andoutput light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors, wherein the controller is further programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0103] Aspect 1 1 . The biological fluid processing device of Aspect 10, the controller calculates the frequency of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

[0104] Aspect 12. The biological fluid processing device of Aspect 10, wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

[0105] Aspect 13. The biological fluid processing device of Aspect 10, wherein the controller calculates the frequency and the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

[0106] Aspect 14. The biological fluid processing device of any one of Aspects 10-13, wherein the controller is configured to determine whether platelets are present inplasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0107] Aspect 15. A method of determining the presence of cellular material in a fluid in a vessel comprising: emitting a light into a fluid in a vessel; receiving at least a portion of the light exiting the vessel with a plurality of light detectors of a light detector array and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors over a predetermined time interval; measuring light transmission intensity over the predetermined time interval based on the light transmission intensity signals; calculating a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval; comparing the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude; and determining whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0108] Aspect 16. The method of Aspect 15, the controller calculates the frequency of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

[0109] Aspect 17. The method of Aspect 15, wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

[0110] Aspect 18. The method of Aspect 15, wherein the controller calculates the frequency and the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

[0111] Aspect 19. The method of any one of Aspects 15-18, wherein the controller is configured to determine whether platelets are present in plasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0112] Aspect 20. A method of determining presence of cellular material in a fluid using an optical detection assembly comprising a light source, a light detector array, and a controller, the method comprising: measuring, by the controller, light transmission intensity over a predetermined time interval based on light transmission intensity signals received from the light detector array; calculating, by the controller, a frequency and an amplitude of the light transmission intensity signals; comparing, by the controller, the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude; and determining, by the controller, whether cellular content is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

[0113] It will be understood that the embodiments 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.

Claims

CLAIMS1 . An optical detection assembly for monitoring a fluid in a vessel, comprising: a light source configured and oriented to emit a light into a fluid in a vessel; a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors; and a controller programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

2. The optical detection assembly of claim 1 , wherein the controller calculates the frequency of the light transmission intensity signals and is programmed to determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency.

3. The optical detection assembly of claim 1 , wherein the controller calculates the frequency of the light transmission intensity signals and is programmed to determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

4. The optical detection assembly of claim 1 , wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude.

5. The optical detection assembly of claim 1 , wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

6. The optical detection assembly of claim 1 , wherein the controller calculates both the frequency and the amplitude of the light transmission intensity signals.

7. The optical detection assembly of claim 6, wherein the controller is programmed to determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude.

8. The optical detection assembly of claim 6, wherein the controller is programmed to determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

9. The optical detection assembly of any one of claims 1 -8, wherein the controller is configured to determine whether platelets are present in plasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

10. A biological fluid processing device comprising: a pump system; a valve system;a controller programmed to control the operation of the pump system and the valve system to execute a biological fluid processing procedure; and an optical detection assembly comprising a light source configured and oriented to emit a light into a fluid in a vessel, and a light detector array comprising a plurality of light detectors and configured to receive at least a portion of the light exiting the vessel and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors, wherein the controller is further programmed to receive the light transmission intensity signals from the light detector array over a predetermined time interval, measure light transmission intensity over the predetermined time interval based on the light transmission intensity signals, calculate a frequency and / or amplitude of the light transmission intensity signals over the predetermined time interval, compare the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude, and determine whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.1 1 . The biological fluid processing device of claim 10, the controller calculates the frequency of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

12. The biological fluid processing device of claim 10, wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to:determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

13. The biological fluid processing device of claim 10, wherein the controller calculates the frequency and the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

14. The biological fluid processing device of any one of claims 10-13, wherein the controller is configured to determine whether platelets are present in plasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

15. A method of determining the presence of cellular material in a fluid in a vessel comprising: emitting a light into a fluid in a vessel; receiving at least a portion of the light exiting the vessel with a plurality of light detectors of a light detector array and output light transmission intensity signals indicative of an intensity of transmitted light received by the light detectors over a predetermined time interval; measuring light transmission intensity over the predetermined time interval based on the light transmission intensity signals; calculating a frequency and / or an amplitude of the light transmission intensity signals over the predetermined time interval;comparing the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude; and determining whether cellular material is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

16. The method of claim 15, the controller calculates the frequency of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated frequency is greater than the threshold frequency, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency.

17. The method of claim 15, wherein the controller calculates the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated amplitude is less than the threshold amplitude.

18. The method of claim 15, wherein the controller calculates the frequency and the amplitude of the light transmission intensity signals and is programmed to: determine cellular material is present in the fluid if one or both of the calculated frequency is greater than the threshold frequency and the calculated amplitude is greater than the threshold amplitude, and determine cellular material is not present in the fluid if the calculated frequency is less than the threshold frequency and the calculated amplitude is less than the threshold amplitude.

19. The method of any one of claims 15-18, wherein the controller is configured to determine whether platelets are present in plasma based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

20. A method of determining presence of cellular material in a fluid using an optical detection assembly comprising a light source, a light detector array, and a controller, the method comprising: measuring, by the controller, light transmission intensity over a predetermined time interval based on light transmission intensity signals received from the light detector array; calculating, by the controller, a frequency and an amplitude of the light transmission intensity signals; comparing, by the controller, the calculated frequency to a threshold frequency and / or the calculated amplitude to a threshold amplitude; and determining, by the controller, whether cellular content is present in the fluid based on the comparison of the calculated frequency to the threshold frequency and / or the calculated amplitude to the threshold amplitude.

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