Systems and methods for fluid separation interface control using color-based optical measurement

Abstract

To provide systems and methods for fluid separation interface control using color-based optical measurement.SOLUTION: A fluid separation device comprises: a centrifugal separator configured to receive a centrifugal separation chamber of a disposable fluid flow circuit; a pump system configured to convey a fluid into the centrifugal separation chamber, and to remove a separated fluid component from the centrifugal separation chamber via an outlet; a color-based interface monitoring system configured to determine an interface position between separated fluid components flowing continuously through the centrifugal separation chamber based on dominant wavelength measurement of layers of separated fluid components during a centrifugal separation procedure; and a controller configured to measure the dominant wavelengths of the layers, calculate a duration as a color time for each measured dominant wavelength, set target color times, and calculate error signals and calculate control signals to adjust the pump system to control the flow rate and interface position.SELECTED DRAWING: Figure 5

Description

Technical Field

[0001] The present disclosure relates to the centrifugation of biological fluids. More specifically, the present disclosure relates to improved systems and methods for controlling the interface position between fluid components separated during a fluid separation procedure.

Background Art

[0002] Currently, various blood processing systems enable the collection of specific blood components rather than whole blood from a blood source such as a human donor or patient. Typically, in such systems, whole blood is drawn from the source, specific blood components or constituents are separated, removed, and collected, and the remaining blood components are returned to the source. Removing only specific components is advantageous when the blood source is a donor. This is because the time for the donor's body to return to normal or pre-donation levels may be reduced. Also, the provision of specific blood components or constituents can be done more frequently than when collecting whole blood. This increases the overall supply of blood components such as plasma and platelets, making them available for transfer and / or treatment procedures or healthcare.

[0003] Typically, whole blood is separated into its components by centrifugation. This requires that the whole blood be passed through a centrifugation assembly or centrifuge after it has been collected from the blood source and before it is returned to the blood source. To avoid the potential for contamination and infection of the source, the blood is preferably contained and processed within a disposable, sealed, sterile fluid flow circuit or fluid processing assembly throughout the entire centrifugation process. Thus, a typical blood processing system includes a permanent or reusable centrifugation assembly that includes hardware (centrifuge, drive system, pump, valve actuators, programmable control unit, etc.) that rotates the centrifuge and controls the flow via a disposable, sealed, sterile fluid flow circuit that is mounted on and interacts with the hardware. The centrifugation assembly rotates in engagement with the centrifugation chamber of a disposable fluid processing assembly during the collection procedure. However, the blood only actually comes into contact with the fluid processing assembly, which is used only once and then discarded.

[0004] Before or immediately after loading the disposable fluid flow circuit into the centrifuge assembly, the operator typically inputs the specific processing protocol to be performed by the system (e.g., the procedure for separating and collecting platelets from whole blood) and other parameters (e.g., donor weight, desired amount of separated blood component to be collected) using, for example, a touchscreen or other user interface system. Once the system is programmed, the operator performs bloodletting from the donor, and the system executes the procedure under the operator's supervision.

[0005] As the centrifuge assembly rotates the centrifuge chamber of the disposable fluid flow circuit, heavier (higher specific gravity) components of whole blood in the separation chamber, such as red blood cells, move radially outward from the center of rotation towards the outer wall or "high G" wall of the separation chamber. Lighter (lower specific gravity) components, such as plasma, move towards the inner wall or "low G" wall of the separation chamber. By including appropriately positioned channel structures and outlet ports within the separation chamber of the disposable fluid flow circuit, various components can be selectively removed from whole blood. For example, therapeutic plasmapheresis involves separating plasma from cellular blood components, collecting the plasma, and returning the cellular blood components and replacement fluid to the blood source. Alternatively, red blood cells can be collected from the separation chamber, and the remaining blood components returned to the donor. Other processes are also possible, including but not limited to platelet collection, red blood cell exchange, and plasmapheresis.

[0006] However, proper separation requires that the interface between separated components be located within a specific region between the high-G and low-G walls of the separation chamber. For example, in therapeutic plasma exchange procedures, the interface between plasma and cellular blood components affects the system's performance. If the interface is too close to the low-G wall, the collected plasma may become excessively dense or contaminated by cellular blood components. On the other hand, if the interface is too far from the low-G wall, plasma contamination may not occur, but less plasma may be collected over time, potentially reducing separation efficiency.

[0007] Various centrifuges, such as those shown and described in U.S. Patent No. 6,254,784 by Nayak et al., U.S. Patent No. 6,312,607 by Brown et al., and U.S. Patent No. 11,465,160 by Min et al. (these are incorporated herein by reference), are operable to automatically maintain the interface within a desired region when the centrifuge is in operation. Typically, the separation chamber of a fluid processing assembly is loaded between the bowl and spool of the centrifuge. A radially inclined surface is located on the radially outer wall of the separation channel within the bowl wall of the separation chamber. The interface between the overall dark and opaque erythrocyte layer and the overall bright and transparent plasma layer appears as a line on the inclined surface of the interface inclined plane. More precisely, the location where the line appears on the inclined surface is a function of the position of the interface between the high-G and low-G walls of the separation chamber. Thus, the position of the line on the inclined plane can be used to measure the position of the interface between the high-G and low-G walls.

[0008] Automatic control of the interface position has been achieved by sensing the position of the line on the inclined surface and then adjusting the centrifuge's operating parameters to position and maintain the line within the desired limits. In particular, by controlling the rate at which plasma is drawn out of the separation chamber, the line can be "moved" up (radially inward) or down (radially outward) on the inclined surface, for example by decreasing or increasing the plasma flow rate.

[0009] Optical sensor assemblies can be used to sense the position of a line on an inclined surface. Optical control systems generally operate on the principle that light penetrates optically transparent fluids such as saline or plasma (platelet-rich plasma, PRP, or platelet-poor plasma, PPP), but does not penetrate optically dense fluids such as whole blood, WB, or concentrated red blood cells (RBCs). Therefore, when using a light source and detector device as in conventional systems, the optical signal representing the thickness of the optically transparent fluid in the centrifuge can be measured and applied to calculate and maintain the position of the RBC / plasma interface or the interface location.

[0010] As the centrifuge rotates past the sensor, the sensor generates an electrical pulse with a width related to the position of the line on the inclined surface. As the line approaches the high-G wall of the separation chamber, the pulse width increases. As the line approaches the low-G wall, the pulse width narrows. By sensing the pulse width generated by the optical sensor and then using the pulse width to increase or decrease the rate at which plasma is drawn out of the separation chamber, the system attempts to maintain the line within a desired positional constraint on the inclined surface and keep the interface within a desired radial position or positional range.

[0011] At the start of the separation procedure, saline solution may be present in the centrifuge during the calibration phase, and a light source such as a laser beam penetrates the entire width of the centrifuge's inclined surface. The resulting signal is called the saline calibration signal and represents the width of the entire centrifugation gap when RBCs are not present. This signal serves as a reference for calculating the RBC / plasma interface position throughout the procedure. The RBC / plasma interface position is defined as the percentage of the saline calibration signal that is blocked by the RBCs. For example, a 40% interface position means that 40% of the original saline calibration signal is blocked by the RBCs.

[0012] The interface position indicates the thickness of the RBC bed in the centrifuge, but it is not a literal representation of the RBC bed. That is, the 40% interface position necessarily correlates with the RBC bed occupying 40% of the centrifugal gap between the high-G and low-G walls. Figure 1 shows an example of the signal generated by the photodetector for saline calibration and increasing RBC bed thickness. The pulse width PW of the voltage signal is represented as a measurement threshold by the double-headed arrow in Figure 1, measured over time, and is an important signal characteristic applied to the calculation of the interface position. PW is a measurement acquired at a given voltage threshold, such as 20% of the signal amplitude. Figure 1 shows a cross-section of the fluid gap and the optical signal PW for saline calibration (left side, e.g., PW=800μs) and increased RBC bed thickness, and the PW for plasma in PRP or PPP is shown as RBCs accumulate in the fluid gap (center, e.g., from PW=600μs to the right side, PW=400μs), decreasing the width of plasma through which light can pass.

[0013] Therefore, the system control unit can compare the PW of the measurement signal being processed with the PW generated during the saline calibration stage (which corresponds to the pulse width when light is transmitted to the photodetector across the entire width of the inclined surface). Comparing these two PWs reveals the percentage of the inclined surface occupied by the plasma layer and the RBC layer. This information can be used by the control unit to determine the position of the interface INT within the channel. In particular, the interface position can be calculated as follows:

[0014] Interface position (%) = [(saline calibration pulse width - current plasma pulse width) / saline calibration pulse width] × 100

[0015] Once the interface position is calculated, it is compared to an ideal target or target position known as the interface position setpoint. As shown in Figure 2, the difference between the calculated interface position INT and the interface position setpoint is considered an error signal (error signal = setpoint - interface position), which represents how far the interface position INT is from the ideal position.

[0016] The error signal is fed into a proportional-integral (PI) or proportional-integral-derivative (PID) based control loop in the control unit, which calculates the plasma velocity required to bring the interface position INT closer to the setpoint. For the PI control unit, this is based on how far the interface position INT is from the setpoint (proportional term, P), how long and how far the interface position INT has been from the setpoint (integral term, I), and for the PID control unit, it also includes the rate of change of the interface position (derivative term, D). An example of a control unit control loop is shown in Figure 3. Generally, slowing the PRP velocity causes the interface position to move downwards towards the high-G wall, and increasing the PRP velocity causes the interface position to move upwards towards the low-G wall.

[0017] Therefore, it is known that optical sensor systems are used to monitor the flow of blood and / or blood components through fluid flow circuits in centrifuges and to determine various characteristics of the flow. For example, U.S. Patent No. 6,899,666 (which is incorporated herein by reference) relates to an optical sensor system for observing the inside of a centrifuge chamber to detect and control the location of interfaces between separated blood components in a centrifuge. In fact, all prior art using optical sensors known to the inventors applies simple light transmission measurements for controlling interfaces and fluid layers in a centrifuge. Such systems require that light be further transmitted to a detector by means of a prism or the like, as shown in Figure 4 and described in the patent application referenced above. While such systems work well, one limitation of such systems is that the light needs to pass through the plasma layer. This can be a problem when the plasma layer is not optically transparent, such as in hyperlipidemia plasma. [Overview of the Initiative]

[0018] There are several embodiments of the subject matter that can be embodied separately or together in the apparatus and systems described and claimed below. These embodiments may be used individually or in combination with other embodiments of the subject matter described herein, and the joint description of these embodiments is not intended to preclude the use of these embodiments separately in the claims attached herein, or the claim of such embodiments separately or as a set in different combinations.

[0019] This disclosure provides a unique system and method that utilizes color measurement for controlling fluid layers in a continuous flow fluid separation centrifuge. Known prior art systems use simple light transmission measurements through the fluid at the fluid separation interface to control fluid layers in a centrifuge without determining and using the dominant wavelength of color for each layer. The system and method of this disclosure measures the dominant wavelength of the color (e.g., yellow, white, and red) of each fluid layer over time to determine the thickness of the fluid layer. Generally, the longer the time a particular dominant wavelength is measured, the thicker the fluid layer is, and vice versa. The measured duration of the fluid's color, or referred to herein as the coloring time, can be compared to a target duration or target coloring time and used to control the flow rate in and out of the centrifuge to obtain the desired fluid thickness, thereby adjusting the interface position. A key advantage over current transmission-based systems is that, as long as the plasma is colored yellow, the optical clarity of the plasma layer does not affect the interface control system. This allows the control system to successfully complete procedures involving hyperlipidemia plasma, which is currently problematic with transmission methods.

[0020] Therefore, this disclosure eliminates the need to measure light transmission through a fluid such as a plasma layer, and instead measures the color of the fluid layer by reflectance spectroscopy or by any other suitable alternative color measurement technique. This enables a color-based interface control system that depends solely on the color of the fluid layer, without regard to the optical transparency of the fluid layer. Furthermore, the color-based method can distinguish between layers that may be similar in terms of opacity, by instead relying on the color measurement of each fluid layer. This is particularly advantageous when distinguishing between different layers, as cells that obstruct light transmission may occur in more opaque layers, such as a white buffy coat layer and a red RBC layer.

[0021] In one embodiment, a fluid separation apparatus is provided, comprising a centrifuge configured to receive a centrifugal chamber of a disposable fluid flow circuit; a pump system configured to transport the fluid into the centrifugal chamber and discharge the separated fluid components from the centrifugal chamber; an outlet associated with the centrifugal chamber to remove at least a portion of the separated fluid components from the centrifugal chamber; a color-based interface monitoring system configured to determine the position of the interface between the separated fluid components flowing continuously through the centrifugal chamber during the centrifugal procedure based on color measurement of the fluid layers; and a control unit. The control unit is configured to control the pump system to transport the fluid into the centrifugal chamber; to control the centrifuge to separate the fluid in the centrifugal chamber into layers of separated fluid components and to have an interface located between the layers of separated fluid components; to measure the color of each layer of the separated fluid components via the dominant wavelength of reflected light; to calculate the duration of each dominant wavelength associated with each layer of the separated fluid components; to set a predetermined target coloring time as a set value for each layer; to calculate an error signal; and to use the error signal to calculate proportional, integral, and differential terms and control signals that change the settings of the pump system to adjust the interface position.

[0022] In another embodiment, the Disclosure provides a method for adjusting a target position of an interface between separated fluid components flowing continuously through a centrifuge, the method comprising separating a fluid in a centrifuge into layers of separated fluid components, the separated layers having an interface between them, measuring the dominant color wavelength of each layer, calculating the duration of the coloring time for each dominant wavelength measured for each layer, setting a predetermined target coloring time as a set value for a selected layer, calculating an error signal equal to the value obtained by subtracting the calculated coloring time for each layer from the target time, calculating proportional, integral, and differential terms and a control signal, and changing the flow velocity of the separated fluid components through the centrifuge using the control signal to adjust the interface position.

[0023] In yet another aspect, a blood separation system is provided, the blood separation system comprising a centrifuge configured to receive a disposable fluid flow circuit's centrifuge chamber and process blood to separate at least one cellular component from plasma, a pump system configured to move plasma within the disposable fluid flow circuit, an exit associated with the centrifuge chamber for removing at least a portion of the plasma from the centrifuge chamber, a color-based interface monitoring system configured to directly monitor the interior of the centrifuge chamber during a centrifugation procedure and determine the position of an interface between the separated components and the plasma, and a control unit. The control unit is configured to control the pump system to convey fluid into the centrifuge chamber, separate the blood in the centrifuge chamber into plasma and at least one cellular component that has been separated, control the centrifuge so that an interface is positioned between the layers, measure the color of each layer via the dominant wavelength of reflected light, calculate the duration of the dominant wavelength associated with each measured layer, set a predetermined target coloring time as a set value for each layer, calculate an error signal, and use the error signal to calculate proportional, integral, and derivative terms to change the settings of the pump system to adjust the interface position and calculate a control signal.

Brief Description of the Drawings

[0024] [Figure 1] A series of schematic views of exemplary optical signal pulse width measurements in a cross-section of a fluid gap representing saline solution, where the pulse width decreases as RBCs accumulate within the fluid gap, and thus the plasma width through which light can pass decreases.

[0025] [Figure 2] A schematic view of an example of an error signal shown as being equal to the set value - interface position.

[0026] [Figure 3] A diagram of a control loop of a system control unit attempting to calculate a control signal to change a PRP pump, then calculate an interface signal to set the set value to a higher value, then calculate an error signal, and then input the error signal into the control unit to continue to correct the process towards a higher ideal interface position.

[0027] [Figure 4] Schematic diagram of a prior art method that requires transmitting light to a photodetector through a fluid and the signal to progress as the fluid becomes optically non-transparent.

[0028] [Figure 5] Perspective view of an exemplary fluid separation apparatus including components of a fluid separation system according to one aspect of the present disclosure.

[0029] [Figure 6] Schematic diagram of an exemplary disposable fluid flow circuit that can be attached to the fluid separation apparatus of FIG. 5 to complete a fluid separation system according to one aspect of the present disclosure.

[0030] [Figure 7] Perspective view of an exemplary centrifuge of the fluid separation apparatus of FIG. 5, in which a centrifuge chamber of the fluid flow circuit is attached.

[0031] [Figure 8] Plan view of an exemplary cassette of a fluid flow circuit that can be operated to perform various different fluid treatment procedures in relation to the fluid separation apparatus of FIG. 5.

[0032] [Figure 9] Perspective view of the centrifuge of FIG. 7, with a selected portion cut away to show the optical portion of a color-based interface monitoring system.

[0033] [Figure 10] Schematic diagram of a color-based interface monitoring system having an optical fiber bundle associated with a light source and a spectroscope directed at an acute angle to the surface of the centrifuge chamber of FIGS. 7-9 and the fluid therein.

[0034] [Figure 11] Schematic diagram of the color-based interface monitoring system of FIG. 10, directed at an acute angle to the interface inclined surface of the centrifuged fluid path.

[0035] [Figure 12] This is a schematic diagram showing the distribution of light from the incident light source in a color-based interface monitoring system.

[0036] [Figure 13] This is a schematic diagram showing the reflected light delivered to the spectrometer of a color-based interface monitoring system.

[0037] [Figure 14] This is a perspective view of an exemplary centrifugal separation chamber for a fluid flow circuit.

[0038] [Figure 15] Figure 14 is a front view of the centrifugal separation chamber.

[0039] [Figure 16] Figure 14 is a bottom perspective view of the fluid flow path through the centrifugal separation chamber.

[0040] [Figure 17] Figures 14-16 are enlarged perspective views of parts of the channels in the centrifugal separation chamber, where the interfaces between the separated fluid components are (typically) located at desired positions on the inclined surfaces defined within the channels.

[0041] [Figure 18] Figure 17 is an enlarged perspective view of the channel and inclined surface, where the interface is (typically) located at an undesirable high position on the inclined surface.

[0042] [Figure 19] Figure 17 is an enlarged perspective view of the channel and inclined surface, where the interface is (typically) located at an undesirable low position on the inclined surface.

[0043] [Figure 20] This is a schematic diagram showing the measurement of different dominant wavelengths of fluid layers over time.

[0044] [Figure 21]This diagram shows the control loop of the color measurement method of the system control unit, which calculates the plasma control time, then calculates the error signal, then inputs the error signal to the PI control, then calculates the control signal, and then modifies the plasma pump.

[0045] [Figure 22] This is a logic flowchart used in conjunction with the control loop shown in Figure 21 in the color measurement method. [Modes for carrying out the invention]

[0046] The embodiments disclosed herein are intended to provide a description of the subject matter, and it should be understood that the subject matter can be embodied in various other forms and combinations not shown in detail. Accordingly, specific designs and features disclosed herein should not be construed as limiting the subject matter as defined in the appended claims.

[0047] Figures 1–22 provide background information and illustrate components of blood or fluid separation systems that embody various aspects of this subject matter. While the system can be described herein in relation to its use in separating blood into two or more components, it should be understood that the system according to this disclosure can be used to process a variety of biological fluids or body fluids, including fluids that contain both body fluids and non-body fluids (e.g., anticoagulated blood).

[0048] Generally speaking, the system comprises two main components: a durable and reusable fluid separator 10 (Figure 5) and a disposable fluid flow circuit 12 (Figure 6). The fluid separator 10 in this example includes a rotating membrane separator drive unit 14 (Figure 5), a centrifuge or centrifuge 16 (Figure 7), additional components that control the fluid flow through the disposable fluid flow circuit 12, and a control unit 18 (Figure 5). The control unit 18 manages the operation of the components of the fluid separator 10 to perform fluid processing and collection procedures selected by the operator. Many of the two main components of this disclosure are similar to those disclosed in U.S. Patent No. 10,919,235 (incorporated herein by reference). Since the interface conditioning principles described herein are not limited to specific fluid separation procedures, a complete fluid separation procedure will not be described in detail herein. However, for a description of various exemplary fluid separation procedures that can be carried out using the systems described herein and in combination with the interface conditioning principles described herein, see PCT Patent Application Publication WO2018 / 053217A1 (incorporated herein by reference).

[0049] I. Durable liquid separation equipment The fluid separation device 10 (Figure 5) is configured as a durable item for long-term use. The fluid separation device 10 in Figure 5 is merely an example of one possible configuration, and it should be understood that the fluid separation device according to this disclosure may have different configurations. For example, it is within the scope of this disclosure for the fluid separation device to omit the rotary membrane separator drive unit 14 and include only the centrifuge 16.

[0050] In the illustrated embodiment, the fluid separator 10 is enclosed in a single housing or case 20. The illustrated case 20 includes an overall horizontal section 22 (which may include inclined or angled surfaces or top surfaces to improve visibility and ergonomics) and an overall vertical section 24. The rotating membrane separator drive unit 14 and the centrifuge 16 are shown as being incorporated into the overall horizontal section 22 of the case 20, and the control unit 18 is shown as being incorporated into the overall vertical section 24. The configuration and operation of the centrifuge 16, the control unit 18, and other selected components of the fluid separator 10 will be described in more detail.

[0051] In the illustrated embodiment, the overall horizontal portion 22 is intended to be placed on a raised, overall horizontal support surface (e.g., a countertop or tabletop), but it is also within the scope of this disclosure with respect to the case 20 to include a support base that allows the case 20 to be properly positioned and oriented when placed on a floor or ground. It is also within the scope of this disclosure that the case 20 can be mounted to an overall vertical surface (e.g., a wall) by fixing the overall vertical portion 24 of the case 20 to the overall vertical surface (e.g., a wall) fixedly or removablely.

[0052] The case 20 may be configured to assume only the position or configuration shown in Figure 5, or it may be configured to move between two or more positions or configurations. For example, in one embodiment, the overall horizontal portion 22 and the vertical portion 24 may be joined by a hinge or pivot so that the case 20 can move between a functional or open configuration (Figure 5) in which the overall vertical portion 24 is oriented at an angle of about 90° relative to the overall horizontal portion 22, and a transport or closed configuration in which the overall vertical portion 24 is rotated around the hinge toward the overall horizontal portion 22. In such a reconfigurable embodiment, the overall vertical portion 24 can be considered as the lid of the case 20, and the overall horizontal portion 22 can be considered as the base. If the case 20 is reconfigurable, it may include a latch for locking the case 20 in a releaseable manner in its transport or closed configuration, and / or a handle that an operator can grasp to transport the case 20 in its closed configuration.

[0053] While it may be advantageous for the fluid separator 10 to be embodied in a compact, portable case 20, it is also within the scope of this disclosure for the fluid separator to be embodied in a larger case or fixture intended for installation in one location and long-term retention there. When the fluid separator is provided as such a fixture, more components and functions may be offered than in a more portable variant.

[0054] Rotating membrane separator driver The illustrated fluid separation device 10 includes a rotor support or a rotary membrane separator drive unit 14 (Figure 5) for housing a generally cylindrical rotary membrane separator 26 in a fluid flow circuit 12 (Figure 6). U.S. Patent No. 5,194,145 (incorporated herein by reference) describes an exemplary rotary membrane separator drive unit suitable for incorporation into the fluid separation device 10. However, it should be understood that the rotary membrane separator drive unit 14 can be configured differently without departing from the scope of this disclosure. Since the interface determination principle described herein can be carried out without a rotary membrane separator, the rotary membrane separator drive unit 14 is not described in detail herein.

[0055] Centrifuge With respect to the centrifuge or centrifugal separator 16, a centrifugal separator compartment 32 is included that can accommodate other components of the centrifugal separator 16 (Figure 7). The centrifugal separator compartment 32 may include a lid 34 that is opened to insert and remove the centrifugal separator chamber 36 of the fluid flow circuit 12. During the separation procedure, the lid 34 may be closed with the centrifugal separator chamber 36 positioned within the centrifugal separator compartment 32 as the centrifugal separator chamber 36 rotates or oscillates around the shaft 38 under the power of the electric drive motor or rotor 40 of the centrifugal separator 16.

[0056] The specific configuration and operation of the centrifuge 16 depend on the specific configuration of the centrifugal chamber 36 of the fluid flow circuit 12. In one embodiment, the centrifuge 16 is similar in structure and operation to the ALYX system manufactured by Fenwall, Incorporated, Lake Zullick, Illinois, USA, an affiliate of Fresenius Kaby AG, Bad Homburg, Germany, as described in detail in U.S. Patent No. 8,075,468, which is incorporated herein by reference.

[0057] More specifically, the centrifuge 16 may include a carriage or support 42 that holds the centrifugal chamber 36 and a yoke member 44. The yoke member 44 engages with the umbilics 46 of the fluid flow circuit 12, which extends between the centrifugal chamber 36 and the cassette 48 of the fluid flow circuit 12 (Figure 8). The yoke member 44 causes the umbilics 46 to orbit the centrifugal chamber 36 at a rotational speed of 1ω. As the umbilics 46 orbits the centrifugal chamber 36, it twists about its own axis. The twist of the umbilics 46 about its axis when it rotates with the yoke member 44 at 1ω gives the centrifugal chamber 36 a rotation of 2ω, according to known designs. The relative rotation of the yoke member 44 at a rotational speed of 1ω and the centrifugal chamber 36 at a rotational speed of 2ω keeps the umbilics 46 from twisting, eliminating the need to rotate the seal.

[0058] The fluid is introduced into the centrifuge chamber 36 through the umbilics 46, and within the centrifuge chamber 36, as a result of the centrifugal force as it rotates, the fluid is separated (for example, into a layer of less dense components such as platelet-rich plasma if the fluid is blood, and a layer of denser components such as concentrated red blood cells if the fluid is blood). Components of the interface monitoring system may be located within the centrifuge compartment 32 to monitor the separation of blood within the centrifuge chamber 36. As will be described in more detail herein with reference to Figures 9-13, a color-based interface monitoring system 50 may include a light source 52 and a spectrometer 54 connected to an optical fiber bundle 56. The optical fiber bundle 54 is positioned and oriented at an acute angle Θ with respect to the surface of the centrifuge chamber 36 to carry light from the light source 52 to the fluid F in the centrifuge chamber 36 via at least one optical fiber 58, and to carry the light directly reflected toward the light source to the spectrometer 54 via at least one optical fiber 60.

[0059] Figures 12 and 13 demonstrate the reflection and transmission characteristics of light from the light source 52. As shown in Figure 12, when light L is delivered from the light source 52 to the surface of the centrifugal chamber 36, a portion of the incident light SR is reflected from the surface by specular reflection and departs at an equivalent acute angle Θ. A portion of the light passes through the fluid across the surface as transmitted light T at a certain angle according to Snell's law, a portion of the transmitted light T is absorbed by the fluid, a portion undergoes diffuse reflection DR, and the rest undergoes diffuse reflection DT. As shown in Figure 13, a portion of the light L from the light source becomes reflected light R, which is reflected directly back towards the incident light L and delivered to the spectrometer 54 by the optical fiber 60.

[0060] Preferably, the light source 52 and the spectrometer are arranged inside the case 20, and the luminous flux 56 is connected to a fixed surface of the centrifugal separation compartment 32.

[0061] The orientation of the various components of the color-based interface monitoring system 50 depends at least in part on the specific configuration of the centrifuge chamber 36, which will be described in more detail herein. However, generally, the light source 52 emits a broadband light source (such as a Thorlabs stabilized tungsten-halogen light source, PN SLS201L, 360-2600 nm, or an equivalent provided by such a source). At a minimum, the light source will include all wavelengths in the visible range (approximately 400-700 nm), but may also include wavelengths above or below this range.

[0062] Light L is carried by at least one optical fiber 58 within the beam 56 and directed towards the separated fluid component in the centrifuge chamber 36 (which may be formed from a material that substantially transmits light or at least a specific wavelength range of light without absorbing it). The beam 56 is directed at an acute angle Θ to the surface of the centrifuge chamber 36, and some of the light is reflected back into the beam 56 and carried to the spectrometer 54 by at least one optical fiber 60. If the control unit 18 determines that the interface is in the wrong position (a position that may affect the separation efficiency of the centrifuge 16 and / or the quality of the separated blood component), it can issue commands to the appropriate components of the fluid separation unit 10 to change the operation of the fluid separation unit 10 so that the interface moves to the correct position.

[0063] Other components of a fluid separation device In addition to the rotary membrane separator drive unit 14 and the centrifuge 16, the fluid separation device 10 may include other components compactly arranged to assist in fluid processing.

[0064] The overall horizontal portion 22 of the case 20 of the illustrated fluid separator 10 includes a cassette station 62 (Figure 5) that houses a cassette 48 (Figure 8) of the fluid flow circuit 12. In one embodiment, the cassette station 62 is configured similarly to the cassette station of U.S. Patent No. 5,868,696 (incorporated herein by reference) and adapted to include additional components and functions, as shown to correspond more closely to the apparatus of U.S. Patent No. 10,919,235 (incorporated herein by reference). The illustrated cassette station 62 includes a plurality of clamps or valves V1 to V9 (Figure 5). These move between a plurality of positions (e.g., between a retracted or lowered position and an operating or raised position) to selectively contact or interact with the corresponding valve stations C1 to C9 of the cassette 48 of the fluid flow circuit 12 (Figures 6 and 8). Depending on the configuration of the fluid flow circuit 12, the cassette 48 may not include valve stations C1 to C9 for each of the valves V1 to V9 of the cassette station 62. In this case, fewer valves than all of valves V1 to V9 are used in the separation procedure.

[0065] In the operating position, valves V1-V9 engage with associated valve stations C1-C9 to prevent fluid flow through those valve stations C1-C9 (for example, by closing one or more ports associated with valve stations C1-C9, thereby preventing fluid flow through that port or more ports). In the retracted position, valves V1-V9 disengage from associated valve stations C1-C9 (or do not engage with them as strongly as when in the operating position), allowing fluid flow through those valve stations C1-C9 (for example, by opening one or more ports associated with valve stations C1-C9, thereby allowing fluid flow through that port or more ports). Additional clamps or valves V10 and V11 may be located outside the cassette station 62 and may interact with portions of the fluid flow circuit 12 or valve stations C10 and C11 (which may be along the length of the pipe) to selectively allow and prevent fluid flow through them. The valves V1 to V9 of cassette station 62 and cassette 48, and the corresponding valve stations C1 to C9, can have different configurations and operations than valves V10 and V11 located away from cassette station 62, and valve stations C10 and C11.

[0066] The cassette station 62 may be equipped with additional components such as pressure sensors A1-A4 that interact with the sensor stations S1-S4 of the cassette 48 to monitor pressure at various locations in 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 in the donor's vein during blood collection and return. Other pressure sensors A1-A4 may monitor the pressure in the rotating membrane separator 26 and the centrifuge chamber 36. The control unit 18 can receive signals from the pressure sensors A1-A4 indicating the pressure in the fluid flow circuit 12, and if the signals indicate a low or high pressure condition, the control unit 18 may initiate an alarm or error condition to warn the operator of the condition and / or attempt to bring the pressure to an acceptable level without operator intervention.

[0067] The fluid separation device 10 may also include a pump system having a plurality of pumps P1-P6 for flowing fluid through the fluid flow circuit 12. The pumps P1-P6 may be configured differently or similarly from one another and / or may function similarly or differently from one another. In the illustrated embodiment, the pumps P1-P6 are configured as peristaltic pumps, which can generally be configured as described in U.S. Patent No. 5,868,696. Each pump P1-P6 engages with different tube loops T1-T6 extending from the side of the cassette 48 (Figure 8) and can be selectively operated under the command of the control unit 18 to flow fluid through a portion of the fluid flow circuit 12. In one embodiment, all or part of the cassette station 62 is capable of translational motion in and out of the case 20, and can automatically load the tube loops T1-T6 into the associated pumps P1-P6.

[0068] The illustrated fluid separation apparatus 10 optionally includes a centrifuge outlet sensor M1 for determining one or more characteristics of the fluid flowing out of the centrifuge 16. If the fluid flowing out of the centrifuge 16 contains red blood cells, the centrifuge outlet sensor M1 may be configured to determine the hematocrit of the fluid. If the fluid flowing out of the centrifuge 16 is platelet-rich plasma, the centrifuge outlet sensor M1 may be configured to determine the platelet concentration of the platelet-rich plasma. The centrifuge outlet sensor M1 can detect one or more characteristics of the fluid by optically monitoring the fluid flowing through the tubes of the fluid flow circuit 12, or by any other suitable approach. The control unit 18 receives signals from the centrifuge outlet sensor M1 indicating one or more characteristics of the fluid flowing out of the centrifuge 16, and can use these signals to optimize the separation procedure based on those characteristics, as will be described in more detail later herein.

[0069] The illustrated fluid separation device 10 optionally further includes a rotor outlet sensor M2 that houses the piping of the fluid flow circuit 12 through which the fluid components separated from the rotating membrane separator 26 of the fluid flow circuit 12 flow.

[0070] The illustrated fluid separation device 10 also optionally includes an air detector M3 (e.g., an ultrasonic bubble detector) that houses the tube of the fluid flow circuit 12 through which the fluid flows to a recipient or container. Since it may be advantageous to prevent air from reaching the recipient or container, the air detector M3 can transmit a signal to the control unit 18 indicating the presence or absence of air in the tube. If the signal indicates the presence of air in the tube, the control unit 18 initiates an alarm or error condition to warn the operator of the condition and / or takes corrective action to prevent air from reaching the recipient or container (e.g., by reversing the fluid flow through the tube or diverting the flow to an exhaust position).

[0071] The overall vertical section 24 of case 18 may include a number of weighers W1-W6 (six are shown, but more or fewer may be provided), each of which may support one or more fluid containers F1-F8 of the fluid flow circuit 12 (Figure 6). Containers F1-F8 receive the fluid to be separated, fluid components separated during processing, or intravenous fluid or additive fluid. Each weigher W1-W6 sends a signal to the control unit 18 indicating the weight of the fluid in the associated containers F1-F8 to track the weight changes as the procedure progresses. This allows the control unit 18 to process the incremental weight changes to derive the fluid processing volume and flow rate, and subsequently generate a signal to control processing events based at least partially on the resulting processing volume. For example, the control unit 18 can diagnose leaks and obstructions in the fluid flow circuit 12 and warn the operator.

[0072] The illustrated case 20 also includes a plurality of hooks or supports H1 and H2 that can support various components of the fluid flow circuit 12 or other objects of appropriate size and configuration.

[0073] control unit The fluid separator 10 includes a control unit 18 appropriately configured and / or programmed to control the operation of the fluid separator 10. In one embodiment, the control unit 18 includes a main processing unit (MPU) which may include, for example, an Intel Corporation Pentium® type microprocessor, but other types of conventional microprocessors may also be used. In one embodiment, the control unit 18 may be mounted inside the overall vertical portion 24 of the case 20, adjacent to or integrated with an operator interface station (e.g., a touchscreen). In other embodiments, the control unit 18 and the operator interface station may be associated with the overall horizontal portion 22, or integrated into a separate device connected to the fluid separator 10 (physically, by cables, etc., or wirelessly).

[0074] The control unit 18 is configured and / or programmed to perform at least one fluid processing application, but more advantageously, it is configured and / or programmed to perform a variety of different fluid processing applications. For example, the control unit 18 may be configured and / or programmed to perform one or more of the following: double-unit erythrocyte collection procedures, plasma collection procedures, plasma / erythrocyte collection procedures, erythrocyte / platelet / plasma collection procedures, platelet collection procedures, platelet / plasma collection procedures, and mononuclear cell collection procedures. Additional or alternative procedures or applications may be included without departing from the scope of this disclosure.

[0075] More specifically, when performing any of these fluid processing procedures or applications, the control unit 18 is configured and / or programmed to control one or more of the following tasks: drawing the fluid into a fluid flow circuit 12 attached to a fluid separation device 10 at a source (such as a patient, donor, or container); transporting the fluid through the fluid flow circuit 12 to a separation location (e.g., a rotating membrane separator 26 or centrifugal chamber 36 in the fluid flow circuit 12); separating the fluid into two or more desired components; and transporting the separated components into a storage container, a second location for further separation (e.g., either the rotating membrane separator 26 and centrifugal chamber 36 not used in the first separation stage), or to a recipient (which may be the source from which the fluid was initially drawn).

[0076] This may include instructing the rotating membrane separator drive unit 14 and / or the centrifuge 16 to operate at a specific rotational speed, and instructing at least one of the pumps P1 to P6 of the pump system to transport fluid through a portion of the fluid flow circuit 12 at a specific flow velocity. Thus, while specific components of the fluid separation device 10 (e.g., the rotating membrane separator drive unit 14 or the centrifuge 16) are described as performing specific functions, it should be understood that these components are controlled by the control unit 18 to perform those functions.

[0077] In procedures requiring the use of both the centrifuge 16 and the rotary membrane separator drive unit 14, a properly programmed control unit 18 is particularly important for coordinating the operation of these two components, along with other components of the fluid separator 10, to ensure that the flow entering and leaving the centrifuge 16 and the rotary membrane separator drive unit 14 is at an appropriate level, and that the components function properly to handle the fluid circulating in the fluid flow circuit 12.

[0078] Before, during, and after the procedure, the control unit 18 can receive signals from various components of the fluid separator 10 (e.g., pressure sensors A1-A4) to monitor various aspects of the operation of the fluid separator 10 and the 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 are outside the acceptable range, the control unit 18 may initiate an alarm or error condition to warn the operator and / or take action to attempt to correct the situation. Appropriate corrective actions will vary depending on the specific error condition and may include actions to be taken with or without operator involvement.

[0079] For example, the control unit 18 may include an interface control module that receives signals from a spectrometer 54 of the interface monitoring system 50. The signals received by the control unit 18 from the spectrometer 54 indicate the position of the interface between separated blood components in the centrifuge chamber 36. If the control unit 18 determines that the interface is in the wrong position, it can issue commands to the appropriate components of the fluid separation device 10 to change their operation to move the interface to the correct position. For example, the control unit 18 can instruct one of the pumps P1 to P6 to allow blood to flow into the centrifuge chamber 36 at a different rate and / or to remove the separated blood components from the centrifuge chamber 36 at a different rate and / or to rotate the centrifuge chamber 36 by the centrifuge 16 at a different rate. Specific protocols performed by the interface control module when adjusting the position of the interface in the centrifuge chamber 36 will be described in more detail with respect to an exemplary centrifuge chamber 36.

[0080] If provided, an operator interface station associated with the control unit 18 allows the operator to view information about the system's operation (as alphanumeric characters and / or graphic images) on a screen or display unit. The operator interface station also allows the operator to select applications executed by the control unit 18, as well as to change specific functional and performance criteria of the system. If configured as a touchscreen, the screen of the operator interface station can receive input from the operator via touch activation. If the screen is not a touchscreen, the operator interface station can receive input from the operator via another input device, such as a computer mouse or keyboard. It is also within the scope of this disclosure that the operator interface station can receive input from both a touchscreen and a separate input device, such as a keypad.

[0081] II. Disposable Fluid Flow Circuits The fluid flow circuit or flow set 12 (Figure 6) is intended to be a sterile, single-use, disposable item. Before commencing a given fluid separation procedure, the operator loads the various components of the fluid flow circuit 12 into the case 20 in relation to the fluid separation device 10. The control unit 18 executes the procedure based on a pre-configured protocol, taking into account other inputs from the operator. Upon completion of the procedure, the operator disconnects the fluid flow circuit 12 from its association with the fluid separation device 10. The portion of the fluid flow circuit 12 that holds the components or multiple components of the collected fluid (e.g., collection container or bag) is removed from the case 20 and retained for storage, infusion, or further processing. The remaining portion of the fluid flow circuit 12 is removed from the case 20 and discarded.

[0082] Depending on the separation procedure performed using the system, various different disposable fluid flow circuits can be used in combination with the blood separation device 10, using appropriate fluid flow circuits. However, generally speaking, the fluid flow circuit 12 includes a cassette 48 (Figure 8) to which the other components of the fluid flow circuit 12 are connected by flexible tubes. The other components may include a plurality of fluid containers F1-F8 (e.g., for holding the fluid to be processed, separated fluid components, intravenous fluid, or additive solutions), one or more fluid source access devices (e.g., connectors for accessing blood in the fluid containers), and a rotating membrane separator 26 and / or centrifuge chamber 36 (Figures 7 and 9).

[0083] Cassette and tube Cassette 48 (Figure 8) provides a centralized, programmable, integrated platform for all the pumping and numerous valve functions required for a given fluid separation procedure. In one embodiment, Cassette 48 is configured similarly to the cassette of U.S. Patent No. 5,868,696, but is adapted to include additional components (e.g., more tube loops T1-T6) and functions.

[0084] During use, the cassette 48 is attached to the cassette station 62 of the fluid separator 10, and is positioned so that the flexible diaphragm of the cassette 48 is in contact with the cassette station 62. The flexible diaphragm covers a series of internal cavities formed by the body of the cassette 48. Different internal cavities define sensor stations S1-S4, valve stations C1-C9, and multiple flow paths. The side of the cassette 48 opposite to the flexible diaphragm is sealed by another flexible diaphragm or rigid cover, thereby sealing the fluid flow through the cassette 48 from the external environment.

[0085] Each sensor station S1-S4 is aligned with the associated pressure sensors A1-A4 of the cassette station 62, and each pressure sensor A1-A4 can monitor the pressure within the associated sensor station S1-S4. Each valve station C1-C9 is aligned with the associated valves V1-V9, and can define one or more ports that enable fluid communication between the valve stations C1-C9 and another internal cavity (e.g., a flow path) of the cassette 48. As described above, each valve V1-V9 is movable under command of the control unit 18 and moves between multiple positions (e.g., between a retracted or lowered position and an activated or raised position) to selectively contact the valve stations C1-C9 of the cassette 48. In the activated position, the valves V1-V9 engage with the associated valve stations C1-C9 to close one or more of its ports, preventing fluid flow therethrough. In the retracted position, valves V1-V9 detach from their associated valve stations C1-C9 (or contact them with less force than when in the operating position), opening one or more ports associated with valve stations C1-C9, thereby allowing fluid to flow through them.

[0086] As described, multiple tubular loops T1-T6 extend from the side of the cassette 48 and interact with the pumps P1-P6 of the fluid separator 10. In the illustrated embodiment, six tubular loops T1-T6 extend from the cassette 48 and are received by one of the six pumps P1-P6, but in other embodiments, the procedure may not require the use of all of the pumps P1-P6. In this case, the cassette 48 may contain fewer than six tubular loops. Different pumps P1-P6 can interact with the tubular loops T1-T6 of the cassette 48 to perform different tasks during the separation procedure, but in one embodiment, different pumps among the pumps P1-P6 may be configured to function as an anticoagulant pump P1, a source pump P2, a saline pump P3, a rotor pump P4, a red blood cell pump P5, and an additive pump P6. Certain procedures may require fewer than all of the sensor stations, valve stations, and / or tubular loops shown in the exemplary cassette 48 of Figure 8. Therefore, it should be understood that different cassettes of fluid flow circuits 12 can be configured differently without departing from the scope of this disclosure (e.g., using fewer sensor stations, valve stations, and / or pipe loops).

[0087] Additional tubes extend from the sides of the cassette 48 and connect to other components of the fluid flow circuit 12, such as various fluid containers F1-F8, a rotating membrane separator 26, and a centrifugal chamber 36. The number and contents of the various fluid containers F1-F8 depend on the procedure in which the fluid flow circuit 12 is used. Tubes connected to the centrifugal chamber 36 (including one inlet tube and two outlet tubes) may be assembled into the umbilics 46 (Figure 7), which are engaged by the yoke member 44 of the centrifuge 16 (as described above) to circumfer the umbilics 46 and cause the centrifugal chamber 36 to spin or rotate during the separation procedure.

[0088] Various additional components may be incorporated into the tubes leading out of the cassette 48 or into one of the cavities of the cassette 48. For example, as shown in Figure 6, a manual clamp 64 may be associated with one or more lines leading to a blood supply source and / or fluid recipient; a return line filter 66 (e.g., a microaggregate filter) may be associated with a line leading to a fluid recipient; a filter 68 may be positioned upstream of one or more fluid containers to remove substances (e.g., white blood cells) from separated components (e.g., red blood cells or platelets) flowing into the fluid containers; and / or an air trap 70 may be positioned on a line upstream of the centrifuge chamber 36.

[0089] Centrifugal separation chamber Examples of the centrifugal separation chamber 36 are shown in more detail in Figures 14 and 15, and Figure 16 shows the fluid flow path defined by the centrifugal separation chamber 36. In the illustrated embodiment, the body of the centrifugal separation chamber 36 is preformed from a rigid, biocompatible, transparent plastic material such as non-plasticized medical-grade acrylic to the desired shape and configuration (e.g., by injection molding). All contours, ports, channels, and walls that affect the fluid separation process are preformed in a single injection molding operation. Alternatively, the centrifugal separation chamber 36 can be formed by separate molded parts, either by a cup-shaped subassembly or by nesting two symmetrical halves.

[0090] The lower side of the centrifugal chamber 36 includes a molded receptacle 86 suitable for receiving the end of the umbilics 46 of the fluid flow circuit 12 (Figure 7). A suitable receptacle 86 and a method by which the umbilics 46 cooperates with the receptacle 86 to deliver fluid to the centrifugal chamber 36 and remove fluid from the centrifugal chamber 36 are described in detail in U.S. Patent No. 8,075,468.

[0091] The illustrated centrifugal separation chamber 36 has radially spaced inner (low G) wall portions 88 and outer (high G) wall portions 90, a bottom or first end wall portion 92, and a cover or second end wall portion 93. The cover 93 includes a simple flat portion that can be easily welded or otherwise fixed to the body of the centrifugal separation chamber 36. Since all functions affecting the separation process are incorporated into a single injection-molded component, tolerance differences between the cover 93 and the body of the centrifugal separation chamber 36 do not affect the separation efficiency of the centrifugal separation chamber 36. The wall portions 88 and 90, the bottom 92, and the cover 93 together define an enclosed, overall annular channel 94 (Figure 16).

[0092] An inlet 96 communicating with channel 94 is defined between opposing inner radial walls 98 and 100. One of the inner walls 98 is connected to the outer (high G) wall portion 90, separating the upstream and downstream ends of channel 94. The inner walls 98 and 100 define the inlet passage 96 of the centrifugal chamber 36, which allows fluid to flow from the umbilics 46 to the upstream end of channel 94 in one flow configuration.

[0093] The illustrated centrifugal separation chamber 36 further includes a first outlet 102 and a second outlet 104, respectively, which may be defined by opposing surfaces of the radial inner wall. Both the first outlet 102 and the second outlet 104 extend radially inward from the channel 94 and can be characterized as outlet lines. In the illustrated embodiment, the first outlet 102 extends radially inward from an opening located in the inner wall portion 88, and the second outlet 104 extends radially inward from an opening associated with the outer wall portion 90. The illustrated first outlet 102 may be located adjacent to the inlet 96 (near the upstream end of the channel 94), while the second outlet 104 may be located at the downstream end on the opposite side of the channel 94.

[0094] The centrifugal separation chamber 36 shown in Figure 14 is merely illustrative, and it should be understood that the centrifugal separation chamber 36 can be configured in different ways without departing from the scope of this disclosure. For example, there may be differences in the shape of the centrifugal separation chamber, and the positions where the inlet and outlet open into the channel. Since the position where the inlet opens into the channel can affect the separation of the fluid in the channel, it will be understood that different configurations of the centrifugal separation chamber may be preferred for use in combination with certain procedures or certain fluid separation devices.

[0095] III. Principles of Centrifugal Separation and Interface Detection As the fluid flowing into channel 94 rotates the centrifuge chamber 36 around the rotation axis 38, it separates into an optically dense layer RBC and an optically non-dense layer PLS (Figures 17-19). The optically dense layer RBC is formed as larger and / or heavier fluid particles move towards the outer (high-G) wall portion 90 under the influence of centrifugal force. If the fluid being separated is blood, the optically dense layer RBC typically contains red blood cells (hence sometimes referred to herein as the “RBC layer”), but depending on the speed at which the centrifuge chamber 36 rotates, other cellular components (e.g., larger white blood cells) may also be present in the optically dense layer RBC.

[0096] If the fluid being separated is blood, the layer with lower optical density, PLS, typically contains plasma components such as platelet-rich plasma or platelet-poor plasma (hence referred to herein as the "PLS layer"). Depending on the speed at which the centrifuge chamber 36 rotates and the length of time the blood is present in it, other components (e.g., smaller leukocytes and anticoagulants) may also be present in the layer with lower optical density, PLS.

[0097] In one embodiment, blood introduced into channel 94 via inlet 96 moves in an overall clockwise direction (orientation in Figure 14) as the optically dense layer RBCs separate from the less optically dense layer PLS. The optically dense layer RBCs continue to move in a clockwise direction as they travel the length of channel 94 along the outer wall portion 90 from the upstream end to the downstream end, where they exit channel 94 via the second outlet 104. The less optically dense layer PLS, separated from the optically dense layer RBCs, reverses direction and moves counterclockwise along the inner wall portion 88 towards the first outlet 102 adjacent to inlet 96. The inner wall portion 88 tapers inward as it approaches the second outlet 104, forcing the plasma released at the downstream end of channel 94, or at a position adjacent to the downstream end, to pull the interface back toward the upstream end of channel 94, and the hematocrit at the lower surface resuspends platelets deposited at the interface.

[0098] The transition between the optically dense layer RBC and the optically less dense layer PLS can be called the interface INT. When the fluid being separated is blood, the interface INT contains mononuclear cells and peripheral blood stem cells. The position of the interface INT within the channel 94 of the centrifuge chamber 36 can be dynamically shifted during fluid processing, as shown in Figures 17-19. If the interface INT is positioned too high (i.e., too close to the inner wall portion 88 and the first outlet 102, as in Figure 18), red blood cells may flow into the first outlet 102, potentially negatively impacting the quality of the low-density component (platelet-rich or platelet-poor plasma). On the other hand, if the interface INT is positioned too low (i.e., too far from the inner wall portion 88, as in Figure 19), the collection efficiency of the system may be impaired. The ideal or target interface position can be determined experimentally, and this may vary depending on any of several factors (e.g., the configuration of the centrifuge chamber 36, the speed at which the centrifuge chamber 36 rotates around the rotation axis 38, etc.). As described herein, it may be advantageous to adjust the position of interface INT, which is located away from the position shown in Figure 17, during the separation procedure.

[0099] Example of interface control using color-based optical measurements As described above, the fluid separation device 10 may include a color-based interface monitoring system 50 and a control unit 18 having an interface control module for monitoring the position of interface INT and adjusting or correcting it as necessary. (As previously mentioned, the system may also optionally include a centrifuge outlet sensor M1). In one embodiment, the centrifugal separation chamber 36 is formed by an inclined surface 106 extending from the high-G wall portion 90 at an angle α across at least a portion of the channel 94 (Figures 14 and 17-19). The angle α measured with respect to the rotation axis 38 is approximately 25° in one embodiment. Figures 16-18 show the orientation of the inclined surface 106 as viewed from the low-G side wall portion 88 of the centrifugal separation chamber 36. Although a flexible separation chamber is described, the general structure and function of the inclined surface 106 can be better understood by referring to U.S. Patent No. 5,632,893. The inclined surface 106 may be at different angles and may be located at any of a number of positions between the upstream and downstream ends of the channel 94, but in one embodiment, the inclined surface 106 may be located overall adjacent to the first outlet 102 in the path of fluid and / or fluid components moving from the inlet 96 to the first outlet 102.

[0100] The inclined surface 106 makes the interface INT between the optically dense layer RBC and the less optically dense layer PLS more distinguishable for detection, and displays the optically dense layer RBC, the less optically dense layer PLS, and the interface INT for viewing through the light-transmitting portion of the centrifugal chamber 36. For this purpose, the inclined path 106 and at least a portion of the centrifugal chamber 36 angularly aligned with the inclined path 106 may be formed of a light-transmitting material, but it may be advantageous for the entire centrifugal chamber 36 to be formed of the same light-transmitting material.

[0101] In the illustrated embodiment, the broadband light source 52 of the color-based interface monitoring system 50 is supported by at least one optical fiber 58 of an optical fiber bundle 56 fixed to a fixture in the centrifugal separator compartment or to the wall, and emits light directed at the surface of the centrifugal separator chamber 36 at an acute angle Θ, as shown in the schematic diagrams of Figures 10 and 11. At least one optical fiber 60 of the optical fiber bundle 56 that carries the reflected light to the spectrometer 54 is positioned at the same acute angle Θ such that the light L is reflected by the fluid in the centrifugal separator chamber 36 when it is emitted by the light source 52.

[0102] The systems and methods of this disclosure aim to eliminate the requirements for light transmission through the plasma layer and detection by prisms, etc., which can be problematic when the plasma layer is not optically transparent, such as in hyperlipidemia plasma. By measuring the color of the fluid layer by reflection spectroscopy using a spectrometer instead, or by using other acceptable color measurement techniques, this novel method allows the color-based interface control system 50 to depend solely on the color of the fluid layer, rather than on optical transparency. Current transmission-based methods cannot adequately distinguish between buffy coat and RBCs because both contain cells that obstruct light transmission. However, this color-based method can distinguish a white buffy coat layer from red RBCs, which may also be beneficial.

[0103] When light is shone on a blood sample (or any substance in general), the light is absorbed, transmitted through the sample, and typically scatters as it propagates, or the light may scatter diffusively backward. Blood and its components, including cells, which are considered a turbid medium, are characterized by low to moderate absorption and strong scattering properties. The intensity of light reflected or transmitted by a blood sample is determined by the optical properties of the fluid, particularly the scattering coefficient, absorption coefficient, and anisotropy coefficient. When a visible broadband incident light source (e.g., wavelengths of 400–700 nm) is applied, the wavelengths / colors that are not absorbed and therefore reflected or transmitted depend on the absorption coefficient of the particles in the fluid.

[0104] The wavelengths of each layer of the separated fluid components can be determined by any suitable approach without departing from the scope of this disclosure. In exemplary embodiments, the dominant wavelength of a particular layer of the separated fluid components in the centrifuge can be determined using a broadband light source 52 (Thorlabs stabilized tungsten-halogen light source, part number SLS201L, 360–2600 nm, or a suitable alternative), optical fibers 58, 60 (Thorlabs 200 μm fiber bundle reflection probes, part number RP20, or a suitable alternative), and a spectrometer 54 (Thorlabs compact CCD spectrometer, part number CCS200, 200–1000 nm, or a suitable alternative). The light source must include all wavelengths in at least the visible range (approximately 400–700 nm), but may also include wavelengths above or below this range. As previously stated, a schematic diagram of the applied setup is shown in Figure 10. It should be understood that a spectrometer 54 or other device for measuring the dominant wavelength / color of reflected light R can be configured for measuring and wavelength identification of at least a portion of the received reflected light R, or can send a signal to the control unit 18 to make such a determination.

[0105] As shown in Figure 10, the optical fiber bundle 56, which in this example has a cross-section, may include at least one optical fiber 58 for carrying light from the light source 52 and at least one optical fiber 60 for carrying reflected light R to the spectrometer 54. This bundle contains seven 200 μm fibers, six of which are optical fibers 58 arranged around the optical fiber bundle 56 to carry incident light from the broadband light source 52 to the fluid sample F, and the centrally located optical fiber 60 carries light reflected by the fluid sample F to the spectrometer 54 for wavelength / color measurement. The optical fiber 60 is centrally located relative to the ring-shaped configuration of the optical fibers 58, but it will be understood that only at least one optical fiber 58 is needed to transmit light L from the light source 52 to the fluid sample F, and only at least one optical fiber 60 is needed to transfer reflected light R from the sample fluid F to the spectrometer 54.

[0106] The fiber bundle 56 is advantageously positioned at a selected acute angle Θ with respect to the sample fluid F in the centrifuge chamber 36 to minimize the amount of specular reflection from the surface of the centrifuge chamber 36 where the color of the fluid F is measured. If Θ is equal to 90°, a considerable amount of specular reflection from the container surface is reflected directly back in the direction of the fiber bundle 56, and therefore the measured light will contain almost the spectrum of light L from the light source 52 itself, and not the spectrum reflected by the sample fluid F. If Θ is 0°, it is impossible for light to be incident on the sample fluid F. Therefore, an acute angle between 0° and 90° must be applied. While any angle from 30° to 60° appears to be acceptable, it should be noted that 45° has been experimentally determined to be the optimal angle for producing the most sensitive color measurements.

[0107] Light entering the sample fluid F is absorbed and scattered based on the sample's inherent optical properties. As shown in Figures 12 and 13, reflected light R, which is directly reflected toward the optical fiber bundle 56, is captured by the optical fiber 60 and sent to the spectrometer 54 for quantification and wavelength identification (color measurement).

[0108] The method of this disclosure utilizes the colorimetric techniques described above to measure the dominant wavelength of each layer of separated fluid components in the sample fluid F within the centrifuge chamber 36 during the operation of the centrifuge 16. The dominant wavelength measurement is combined with a duration or color time measurement used to control the position of the interface INT between layers such as the plasma layer PSL having a first color and the red blood cell layer RBC having a second color. The color-based interface monitoring system 50 utilizes a broadband light source 52 and a spectrometer 54, and the fiber optic bundle 56 is configured to be directed or aimed at the position of the inclined surface 106 of the chamber, allowing for the color measurement of each layer of the sample fluid F each time the inclined surface 106 of the chamber rotates through the fiber optic bundle 56, as shown in Figure 11.

[0109] As illustrated in Figure 20, as the ramp 106 in the centrifuge chamber 36 rotates and passes the position to which the optical fiber bundle 56 is directed, the spectrometer 54 receives the reflected light R and measures the dominant wavelengths of different colors over time. By comparing the duration for which a particular dominant wavelength is measured with a predetermined target duration, the thickness of the layers in the sample fluid F and therefore the position of the interlayer interface can be controlled. Here, the error signal of the color-based interface monitoring system 50 is the difference between the measurement time of color or duration (e.g., plasma coloring time) and the target time of color (e.g., a set value for the plasma target time). Color measurements can be performed each time the centrifuge chamber 36 rotates or at predetermined intervals.

[0110] Examples of interface detection and control In the illustrated example, during the separation of blood in channel 94, light L from the light source 50 travels through the light-transmitting portion of the outer wall portion 90 toward the inclined surface 106, intersecting with the separated blood components above it when the inclined surface 106 is rotated into the initial path of the light L. After passing through the inclined surface 106, the light continues to pass through channel 94 and the fluid within channel 94. At least a portion of the light L (i.e., the portion reflected by the fluid toward the optical fiber bundle 56) exits channel 94 and is carried to the spectrometer 54 by at least one optical fiber 60. Thus, it can be seen that the light L is exposed to the color of each fluid, such as the separated blood components, reflected from there, and then reaches the spectrometer 54. Requiring the measurement of the reflected light R by the spectrometer 54 during the rotation of the centrifuge chamber 36 can effectively sense the position of different separation layers of the fluid and improve the monitoring and correction of interface positions.

[0111] The spectrometer 54 of the color-based interface monitoring system 50 generates a signal that is transmitted to the interface control module of the control unit 18, which can determine the position of interface INT on the inclined surface 106. In one embodiment, the position of interface INT is related to distinguishing the colors of the separated component layers in the centrifugal chamber 36.

[0112] In this embodiment, as the inclined surface 106 is rotated within the path of light L from the light source 52, the light L first encounters the portion of the inclined surface 106 closest to the inner wall portion 88 (i.e., the section of the inclined surface 106 that most restricts the channel 94), as shown in Figure 14. As described above, the low optical density layer PLS having the first color is positioned adjacent to the inner wall portion 88 when separated from the high optical density layer RBC having the second color. The fluid present in the innermost radial section of the inclined surface 106 (i.e., the fluid present in the channel 94 between the inclined surface 106 and the inner wall portion 88) is the low optical density layer PLS, which tends to have the first color. Some of the light is reflected backward from the layer PLS having the first color to the optical fiber bundle 56 and then reflected back to the spectrometer 54 through at least one optical fiber 60. The spectrometer measures the dominant wavelength / color of the reflected light R to determine the color of the fluid. The spectrometer 54 then sends a signal to the control unit 18. Depending on the measured color and duration or coloring time of the fluid layer, the control unit can adjust the pump system to adjust the measured layer thickness, thereby controlling the position of the interface between layers.

[0113] As the inclined surface 106 is further rotated through the path of light L from the light source 52, the light L is exposed to portions of the inclined surface 106 that are increasingly separated from the inner wall portion 88 (i.e., the light L travels through portions of the channel 94 that are less restricted by the inclined surface 106 as the inclined surface 106 rotates through the path of light L). Until the interface INT on the inclined surface 106 rotates and enters the path of light L, the only fluid in the channel 94 through which the light L passes is the low optical density layer PLS having a first color, and the spectrometer 54 receives an overall uniform dominant wavelength or color of the reflected light R. Thus, the output of the spectrometer 54 is overall uniform while the inclined surface 106 is passing through the path of light L before being exposed to the interface INT. The control unit 18 may be programmed and / or configured to take into account signals that deviate from a particular signal level for the purpose of calculating the duration of the signal's coloration time (the duration of time during which the dominant wavelength is measured). The control unit 18 treats larger deviations of the signal as representing the end of a particular signal, for the purpose of calculating the duration of the signal's coloring time for a particular fluid layer being measured.

[0114] Immediately after the interface INT is rotated into the path of light L from the light source 52, the light L begins to encounter an optically dense layer RBC having a second color in channel 94. As described above, the optically dense layer RBC is located adjacent to the outer wall portion 90 when separated from the optically non-dense layer PLS and is not visible on the inclined surface 106 until the inclined surface 106 is positioned at a greater distance from the inner wall portion 88.

[0115] The dominant wavelength of the light reflected by the optically dense layer RBC and carried to the spectrometer by the optical fiber 60 provides a second color measurement that is different from the associated first color wavelength / color measurement of the layer PLS, generating a different signal. The control unit 18 can be programmed and / or configured to recognize this different signal as representing the presence of an optically dense layer RBC having the second color on the inclined surface 106 (and within the portion of the channel 94 through which the light L traverses), and treats this differentiated signal as the endpoint of the signal generated by the optical spectrometer 54, where the light is reflected by the less optically dense layer PLS having the first color within the channel 94.

[0116] Therefore, the duration of the coloration time of the signal from the spectrometer 54 to the control unit 18 (i.e., the time during which the reflected light R is a specific color with respect to the low-optical-density layer PLS in channel 94) is determined by the percentage of the inclined surface 106 occupied by the low-optical-density layer PLS having a first measured color and the high-optical-density layer RBC having a second measured color. Thus, a longer duration of the coloration time of the signal from the spectrometer 54 to the control unit 18 is associated with the measured color of the low-optical-density layer PLS, indicating that this layer occupies a larger portion of the inclined surface 106 and indicates a thinner optically denser layer RBC having a second measured color on the inclined surface 106 (and within channel 94). Conversely, a shorter duration of the coloration time of the signal from the optical spectrometer 54 to the control unit 18 is associated with the low-optical-density layer PLS having the first measured color occupying a smaller portion of the inclined surface 106 and indicates a thicker optically denser layer RBC having a second measured color on the inclined surface 106 (and within channel 94). In fact, it is possible to directly measure each layer and generate the duration of the colored signal representing its thickness.

[0117] By comparing the duration of the dominant wavelength measurements associated with each color of the fluid present on the inclined surface 106, the percentage of the inclined surface 106 occupied by the low optical density layer PLS having the first color and the optically high optical density layer RBC having the second color is revealed. This information can be used by the control unit 18 to determine the position of the interface INT in the channel 94.

[0118] Accordingly, a fluid separation apparatus 10 is provided, which includes a centrifuge 16 configured to receive a centrifuge chamber 36 of a disposable fluid flow circuit 12. A pump system (such as a pump system having multiple pumps P1-P6) is configured to transport the fluid F to the centrifuge chamber 36 and remove the separated fluid components (such as platelet-rich plasma) from the centrifuge chamber 36. An outlet (such as an outlet 102 or 104) is associated with the centrifuge chamber 36 to remove at least a portion of the fluid components separated from the centrifuge chamber 36. A color-based interface monitoring system is configured to determine the interface position INT between the separated fluid components flowing continuously through the centrifuge chamber 36 based on color measurements of the fluid layers during the centrifugation procedure.

[0119] System 10 further includes a control unit 18 configured to control a pump system to transport fluid F to a centrifugal chamber 36, and to control a centrifuge 16 to separate the fluid F in the centrifugal chamber 36 into layers of separated fluid components with an interface INT positioned between the layers of separated fluid components. The control unit 18 is further configured to measure the color of each layer of each separated fluid component via the dominant wavelength of reflected light R, calculate the duration as the coloring time of each dominant wavelength associated with each layer of separated fluid components, set a predetermined target coloring time as a set value for each layer, calculate an error signal, use the error signal to calculate proportional, integral, and derivative terms, and calculate a control signal to change the pump system settings to adjust the interface position.

[0120] This system for controlling the position of interface INT is merely illustrative, and it should be understood that systems with different configurations and / or functions can be used without departing from the scope of this disclosure.

[0121] Adjustment of the target interface position It will be understood that the separation procedure is dynamic and may undergo adjustments throughout the procedure to achieve enhanced results. Therefore, while the above description is useful for determining the interface INT, the interface position will be adjusted as the system and method progress through the procedure. Thus, for example, the duration of the measurement wavelength, the target coloring time as a setpoint, the error signal, and the flow velocity may change throughout the separation procedure, rather than being static.

[0122] The logic flowcharts and method control loops shown in Figures 21-22 illustrate an exemplary approach to continuous adjustment of setpoints. The separation procedure begins with fluid F being transported to a centrifuge or a centrifuge chamber 36 of a fluid flow circuit 12 located within a centrifuge 16. Fluid F is separated into at least two fluid components, which flow continuously through the centrifuge chamber 36, with an interface INT located between them. The separation procedure begins with an initial setting or target position of the interface. The initial target position may be determined experimentally based on a separation procedure selected by the operator, or it may be selected or determined by other means. For example, in a blood separation procedure in which red blood cells (as layer RBCs with a first dominant color wavelength) are separated from platelet-rich plasma (as layer PLS with a different second dominant color wavelength), the initial target position of interface INT may be a position where red blood cells do not tend to exit the centrifuge 16 with the platelet-rich plasma, and the platelet concentration of the platelet-rich plasma is sufficiently high.

[0123] The separated fluid components flow out of the centrifugal chamber 36, such as at least a portion of one of the separated fluid components passing through outlet 102 or 104. As shown in Figure 22, the system continues to operate and a method can be applied to adjust the target position of the interface INT between the separated fluid components flowing continuously through the centrifugal separator 16. This method involves separating the fluid F in the centrifugal separator 16 into layers of separated fluid components having an interface INT between the separated layers. As shown in 130, this method involves measuring the dominant color wavelength of each layer. Next, in 132, this method involves calculating the duration as the color time of each dominant wavelength measured for each layer. In 134, this method involves setting a predetermined target color time as a setpoint for the selected layer. In 136, this method continues by calculating an error signal equal to the target color time minus the color time calculated for the selected layer. In 138, this method involves calculating proportional, integral, and differential terms and a control signal. In step 140, this method further includes using a control signal to change the flow velocity of the separated fluid components passing through the centrifuge and to adjust the interface position. As shown in Figure 22, this method is intended to be repeatable to accommodate and adapt to the continuous processing and separation of fluids in the centrifuge chamber 36.

[0124] Regardless of the specific configuration of the centrifuge in this disclosure, the separation procedure begins with the delivery of a fluid to the centrifuge chamber 36 of a fluid flow circuit 12 located within the centrifuge or centrifuge 16. The fluid is separated into at least two fluid components, which flow continuously through the centrifuge chamber 36 with an interface between them. The separation procedure begins from an initial or target position of the interface.

[0125] manner Embodiment 1. A fluid separation device comprising: a centrifuge configured to receive a centrifugal chamber of a disposable fluid flow circuit; a pump system configured to transport fluid into the centrifugal chamber and remove the separated fluid components from the centrifugal chamber; an outlet associated with the centrifugal chamber for removing at least a portion of the separated fluid components from the centrifugal chamber; a color-based interface monitoring system configured to determine the position of the interface between the separated fluid components flowing continuously through the centrifugal chamber based on color measurement of the fluid layers during the centrifugal separation procedure; and a control unit, wherein the control unit is configured to control the pump system to transport the fluid into the centrifugal chamber, separate the fluid in the centrifugal chamber into layers of separated fluid components, control the centrifuge so that the interface is located between the layers of separated fluid components, measure the color of each layer of each separated fluid component via the dominant wavelength of reflected light, calculate the duration for each dominant wavelength associated with each layer of separated fluid components, set a predetermined target coloring time as a set value for each layer, calculate an error signal, and calculate a control signal that modifies proportional, integral, and differential terms and the settings of the pump system in order to adjust the position of the interface.

[0126] Embodiment 2. The fluid separation apparatus according to Embodiment 1, further comprising a color-based interface monitoring system, a broadband light source, and a spectrometer.

[0127] Embodiment 3. The fluid separation apparatus according to Embodiment 2, wherein the broadband light source includes the minimum value of all wavelengths within the visible range of approximately 400 to 700 nm.

[0128] Embodiment 4. The fluid separation apparatus according to Embodiments 2-3, wherein the broadband light source further includes at least one optical fiber.

[0129] Embodiment 5. The fluid separation apparatus according to Embodiments 2 to 4, wherein the broadband light source and the spectrometer are connected to an optical fiber bundle that includes at least one optical fiber for carrying light from the broadband light source to the fluid in the centrifugal chamber and at least one optical fiber for carrying light reflected by the fluid in the centrifugal chamber to the spectrometer.

[0130] Embodiment 6. The fluid separation apparatus according to Embodiment 5, wherein the optical fiber bundle includes a plurality of optical fibers that carry light from a broadband light source, arranged around at least one optical fiber that carries reflected light to a spectrometer.

[0131] Embodiment 7. The fluid separation apparatus according to Embodiment 5, wherein the optical fibers of the optical fiber bundle are arranged at a selected acute angle with respect to the surface of the centrifugal chamber containing the fluid to be processed.

[0132] Embodiment 8. The fluid separation apparatus according to Embodiment 7, wherein the selected acute angle is an angle between 30° and 60°.

[0133] Embodiment 9. The fluid separation apparatus according to Embodiment 7, wherein the selected acute angle is 45°.

[0134] Embodiment 10. The fluid separation apparatus according to Embodiment 1, wherein the error signal of the selected layer is equal to the target coloring time minus the coloring time calculated for the selected layer.

[0135] Embodiment 11. The fluid separation apparatus according to Embodiments 1 to 10, wherein the fluid contains anticoagulated whole blood, the interface is between red blood cells and plasma, and the separated fluid component is plasma.

[0136] Embodiment 12. The fluid separation apparatus according to embodiments 1 to 10, wherein the fluid separation apparatus is configured to process blood to separate at least one cellular component from plasma.

[0137] Embodiment 13. The fluid separation apparatus according to Embodiments 1 to 12, wherein the control unit is configured to repeatedly measure the color of each layer of each separated fluid component via the dominant wavelength of reflected light, calculate the duration as the coloring time for each measured dominant wavelength associated with each layer of the separated fluid component, set a predetermined target coloring time as a set value for the interface position, calculate an error signal, and use the error signal to calculate proportional, integral, and differential terms and a control signal to change the pump system setting in order to adjust the interface position.

[0138] Embodiment 14. The fluid separation apparatus according to Embodiments 1 to 10, wherein the fluid contains anticoagulated whole blood, the interface is between red blood cells and platelet-rich plasma, the separated fluid component is platelet-rich plasma, and the control unit is further configured to complete a routine that iteratively calculates the duration as the coloring time of the measured dominant wavelength of the platelet-rich plasma layer, calculates an error signal, utilizes the error signal to calculate proportional, integral, and differential terms to calculate a control signal, and uses the calculated control signal to change the pump system settings to adjust the interface position.

[0139] Embodiment 15. A method for adjusting the target position of an interface between separated fluid components flowing continuously through a centrifuge, comprising: separating a fluid in a centrifuge into layers of separated fluid components; the interface being between the separated layers; measuring the dominant color wavelength of each layer; calculating the duration as the coloring time of each measured dominant wavelength for each layer; setting a predetermined target coloring time as a set value for a selected layer; calculating an error signal equal to the target coloring time minus the calculated coloring time for the selected layer; calculating proportional, integral, and differential terms and a control signal; and changing the flow rate of the separated fluid components passing through the centrifuge using the control signal to adjust the interface position.

[0140] Embodiment 16. The method according to Embodiment 15, wherein the control signal further includes a signal for operating a pump system that controls the flow rate of a separated fluid component.

[0141] Embodiment 17. The method of Embodiment 15, further comprising repeatedly measuring the dominant color wavelength of each layer, calculating the duration as the coloring time of each measured dominant wavelength for each layer, setting a predetermined target coloring time as a set value for the selected layer, calculating an error signal equal to the target coloring time minus the calculated coloring time for the selected layer, calculating proportional, integral, and differential terms and a control signal, and using the control signal to change the flow rate of the separated fluid component passing through the centrifuge to adjust the interface position.

[0142] Embodiment 18. The method according to Embodiment 15, wherein the fluid contains anticoagulated whole blood, the interface is between red blood cells and platelet-rich plasma, and the separated fluid component is platelet-rich plasma.

[0143] Embodiment 19. The method according to Embodiment 18, further comprising measuring the dominant wavelength of the platelet-rich plasma layer, calculating the duration as the coloring time of the measured dominant wavelength of the platelet-rich plasma layer, setting a predetermined target coloring time for the platelet-rich plasma layer, calculating an error signal equal to the difference between the target coloring time of the platelet-rich plasma layer and the calculated coloring time of the platelet-rich plasma layer, using the error signal to calculate proportional, integral, and differential terms and calculate a control signal, and using the calculated control signal to change the flow velocity of the separated fluid component through a centrifuge to adjust the interface position.

[0144] Embodiment 20. The method according to Embodiment 19, wherein the control signal further includes a signal for operating a pump system that controls the flow rate of a separated fluid component that flows continuously through a centrifuge.

[0145] Embodiment 21. The method according to Embodiment 15, further comprising using a broadband light source and a spectrometer to measure the dominant color wavelength of each layer.

[0146] Embodiment 22. The method according to Embodiment 21, wherein the broadband light source includes the minimum value of all wavelengths within the visible range of approximately 400 to 700 nm.

[0147] Embodiment 23. The method of Embodiment 21, further comprising measuring the dominant color wavelength of each layer by carrying a broadband light source to separated fluid components via at least one optical fiber.

[0148] Embodiment 24. The method of Embodiment 21, wherein the broadband light source and spectrometer are configured to be connected to a bundle of optical fibers including at least one optical fiber that carries light from the broadband light source to the fluid in the centrifuge and at least one optical fiber that carries light reflected by the fluid in the centrifuge chamber to the spectrometer.

[0149] Embodiment 25. The method of Embodiment 24, wherein the optical fiber bundle includes a plurality of optical fibers that carry light from a broadband light source, arranged around at least one optical fiber that carries reflected light to a spectrometer.

[0150] Embodiment 26. The method of Embodiment 24, wherein the optical fibers of the optical fiber bundle are positioned at a selected acute angle with respect to the surface of the centrifugal chamber containing the fluid to be processed.

[0151] Embodiment 27. The method of Embodiment 26, wherein the selected acute angle is an angle between 30° and 60°.

[0152] Embodiment 28. The method of Embodiment 27, wherein the selected acute angle is 45°.

[0153] Embodiment 29. A blood separation system comprising: a centrifuge configured to receive a centrifugal blood separation chamber of a disposable fluid flow circuit and process blood to separate at least one cellular component from plasma; a pump system configured to move plasma within a disposable fluid flow circuit; an outlet associated with the blood separation chamber for removing at least a portion of plasma from the blood separation chamber; a color-based interface monitoring system configured to directly monitor the inside of the blood separation chamber and determine the interface position between the separated component and plasma during the centrifugal separation procedure; and a control unit, the control unit controlling the pump system to transport the fluid to the centrifugal chamber, separating the blood in the centrifugal chamber into layers of plasma and at least one cellular component separated, wherein the interface is located between the layers; measuring the color of each layer via the dominant wavelength of reflected light; calculating the duration for each measured dominant wavelength associated with each layer; and setting a predetermined target color time as a set value for the selected layer. A blood separation system configured to calculate an error signal and to use the error signal to calculate proportional, integral, and differential terms and control signals to change the pump system settings in order to adjust the interface position.

[0154] Embodiment 30. The fluid separation apparatus according to Embodiment 29, further comprising a color-based interface monitoring system, a broadband light source, and a spectrometer.

[0155] Embodiment 31. The fluid separation apparatus according to Embodiment 30, wherein the broadband light source includes the minimum value of all wavelengths within the visible range of approximately 400 to 700 nm.

[0156] Embodiment 32. The fluid separation apparatus according to Embodiments 30 to 31, wherein the broadband light source and spectrometer are configured as an optical fiber bundle including at least one optical fiber that carries light from the broadband light source to the plasma and at least one cellular component in the centrifuge chamber, and at least one optical fiber that carries the light reflected by the plasma and at least one cellular component in the centrifuge chamber to the spectrometer.

[0157] Embodiment 33. A fluid separation apparatus according to Embodiment 32, wherein the optical fiber bundle includes a plurality of optical fibers that carry light from a broadband light source, arranged around at least one optical fiber that carries reflected light to a spectrometer.

[0158] Embodiment 34. A fluid separation apparatus according to Embodiments 32-33, wherein the optical fibers of the optical fiber bundle are arranged at a selected acute angle to the surface of the centrifuge chamber containing the blood to be processed.

[0159] Embodiment 35. A fluid separation apparatus according to Embodiment 34, wherein the selected acute angle is an angle between 30° and 60°.

Claims

1. a centrifuge configured to receive a centrifuge chamber of a disposable fluid flow circuit, the centrifuge chamber having an annular channel and a sloped surface extending from a high-G wall portion toward a low-G wall portion across at least a portion of the annular channel of the centrifuge chamber; a pump system configured to transport fluid within the centrifuge chamber and remove separated fluid components from the centrifuge chamber; an outlet associated with the centrifuge chamber for removing at least a portion of the separated fluid components from the centrifuge chamber; a color-based interface monitoring system configured to determine the location of an interface between separated fluid components flowing successively through said centrifuge chamber based on color measurements of the fluid layers during a centrifugation procedure; a control unit; the color-based interface monitoring system further comprising a light source directed at the inclined surface within the centrifuge chamber and a color measurement device that measures the color of the dominant wavelength of the reflected light over time; The control unit controlling the pump system to deliver fluid into the centrifuge chamber; separating the fluid in the centrifuge chamber into layers of separated fluid components, and controlling the centrifuge so that the position of the interface is located between the layers of separated fluid components; using the light source and the color measurement device to measure the color of each layer of each separated fluid component via a dominant wavelength of reflected light; calculating a coloration time as the duration that the reflected light is present for each measured dominant wavelength associated with each layer of the separated fluid component; Set a predetermined target coloring time as the set value for each layer, Calculate the error signal; The fluid separation device is configured to utilize the error signal to calculate proportional, integral and derivative terms and control signals that modify settings of a pumping system to adjust the position of the interface.

2. The fluid separation device of claim 1 , wherein the light source comprises a broadband light source.

3. 3. The fluid separation device of claim 2, wherein the broadband light source includes all wavelength minima within the visible range of about 400 to 700 nm.

4. The fluid separation device of claim 2 , wherein the broadband light source further comprises at least one optical fiber.

5. A fluid separation device as described in claim 2, wherein the color measuring device is equipped with a spectrometer, and the broadband light source and the spectrometer are configured to be connected to an optical fiber bundle including at least one optical fiber that carries light from the broadband light source to the fluid in the centrifuge chamber and at least one optical fiber that carries light reflected by the fluid in the centrifuge chamber to the spectrometer.

6. 6. The fluid separation device of claim 5, wherein the fiber optic bundle includes a plurality of optical fibers carrying light from the broadband light source arranged around the at least one optical fiber carrying reflected light to the spectrometer.

7. 6. The fluid separation device of claim 5, wherein the optical fibers of the fiber optic bundle are positioned at a selected acute angle relative to the inclined surface of the centrifuge chamber containing the fluid to be processed.

8. 8. The fluid separation device of claim 7, wherein the selected acute angle is between 30 degrees and 60 degrees.

9. 2. The fluid separation device of claim 1, wherein the error signal for a selected layer is equal to the target coloring time minus a calculated coloring time for the selected layer.

10. 10. The fluid separation device of claim 1, wherein the fluid comprises anticoagulated whole blood, the interface is between red blood cells and plasma, and the separated fluid component is plasma.

11. 10. The fluid separation device of claim 1, wherein the fluid separation device is configured to process blood to separate at least one cellular component from plasma.

12. The control unit repeatedly using the light source and the color measurement device to measure the color of each layer of each of the separated fluid components via a dominant wavelength of reflected light; calculating a coloration time as the duration that the reflected light is present for each measured dominant wavelength associated with each of the layers of the separated fluid components; a predetermined target coloring time is set as the set value of the interface position; Calculate the error signal; 2. The fluid separation device of claim 1, configured to utilize the error signal to calculate proportional, integral and derivative terms and control signals that modify pump system settings to adjust the interface position.

13. 2. The fluid separation device of claim 1, wherein the fluid comprises anticoagulated whole blood, the interface is between red blood cells and platelet-rich plasma, and the separated fluid component is platelet-rich plasma, and the controller is further configured to iteratively complete a routine: calculate the duration as the coloration time of a measured dominant wavelength of the platelet-rich plasma layer; calculate the error signal; calculate proportional, integral, and derivative terms; utilize the error signal to calculate the control signal; and use the calculated control signal to change the pump system settings to adjust the interface location.

14. 1. A blood separation system comprising: a centrifuge configured to receive a centrifugal blood separation chamber of a disposable fluid flow circuit and process blood to separate at least one cellular component from plasma, the centrifuge chamber having an annular channel and a sloped surface extending from a high-G wall portion toward a low-G wall portion across at least a portion of the annular channel of the centrifuge chamber; a pump system configured to move the plasma within the disposable fluid flow circuit; an outlet associated with the blood separation chamber for removing at least a portion of the plasma from the blood separation chamber; a color-based interface monitoring system configured to directly monitor the interior of the blood separation chamber and determine the location of an interface between the separated components and the plasma during a centrifugation procedure; a control unit; the color-based interface monitoring system further comprising a light source directed at the inclined surface within the centrifuge chamber and a color measurement device that measures the color of the dominant wavelength of the reflected light over time; The control unit controlling the pump system to deliver fluid to the centrifuge chamber; Separating the blood in the centrifuge chamber into layers of plasma and the separated at least one cellular component, and controlling the centrifuge so that the interface is located between the layers; using said light source and said color measurement device to measure the color of each layer via the dominant wavelength of reflected light; calculating a coloration time as the duration that the reflected light is present for each measured dominant wavelength associated with each of the layers; A predetermined target coloring time is set as the setting value for the selected layer. calculating an error signal equal to the target coloring time of the selected layer minus the calculated coloring time; Calculate the proportional, integral, and derivative terms and the control signal, A blood separation system configured to utilize the error signal to calculate proportional, integral and derivative terms and control signals that modify pump system settings to adjust the interface position.

15. The fluid separation device of claim 14 , wherein the light source comprises a broadband light source.

16. 16. The fluid separation device of claim 15, wherein the broadband light source includes all wavelength minima within the visible range of about 400 to 700 nm.

17. A fluid separation device as described in claim 15, wherein the color measuring device includes a spectrometer, and the broadband light source and spectrometer are configured as an optical fiber bundle including at least one optical fiber that carries light from the broadband light source to the plasma and at least one cellular component in the centrifuge chamber, and at least one optical fiber that carries light reflected by the plasma and at least one cellular component in the centrifuge chamber to the spectrometer.

18. 1. A method for adjusting a target position of an interface between separated fluid components continuously flowing through a centrifuge, comprising: separating the fluid in the centrifuge into layers of separated fluid components, with an interface between said separated layers; Measure the dominant color wavelength of each layer, Calculate the duration as the coloration time of each dominant wavelength measured for each layer; setting a predetermined target coloring time as a setting value for the selected layer; calculating an error signal equal to the target coloring time minus the calculated coloring time for the selected layer; Calculate the proportional, integral, and derivative terms and the control signal, and varying the flow rate of the separated fluid components through the centrifuge using the control signal to adjust the interface position.

19. 20. The method of claim 18, wherein the control signals further comprise signals for operating a pump system that controls the flow rate of the separated fluid components.

20. Furthermore, repeatedly, Measure the dominant color wavelength of each layer, Calculate the duration as the coloration time of each dominant wavelength measured for each layer; setting a predetermined target coloring time as a set point for the selected layer; calculating an error signal equal to the target coloring time minus the calculated coloring time for the selected layer; Calculate the proportional, integral, and derivative terms and the control signal, 20. The method of claim 18, comprising using the control signal to vary the flow rate of the separated fluid components through the centrifuge to adjust the interface position.

21. 20. The method of claim 18, wherein the fluid comprises anticoagulated whole blood, the interface is between red blood cells and platelet-rich plasma, and the separated fluid component is platelet-rich plasma.

22. measuring the dominant wavelength of the platelet-rich plasma layer; calculating the duration as the coloration time of the measured dominant wavelength of the platelet-rich plasma layer; setting a predetermined target coloring time of the platelet-rich plasma layer; calculating an error signal equal to the target coloring time of the platelet-rich plasma layer minus the calculated coloring time of the platelet-rich plasma layer; utilizing said error signal to calculate proportional, integral and derivative terms to calculate a control signal; 22. The method of claim 21, further comprising utilizing the calculated control signal to vary the flow rate of the separated fluid components through the centrifuge to adjust the interface location.

23. 23. The method of claim 22, wherein the control signals further comprise signals for operating a pump system that controls the flow rate of the separated fluid components continuously flowing through the centrifuge.

24. 20. The method of claim 18, wherein measuring the dominant color wavelength of each layer further comprises using a broadband light source and a spectrometer.

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