Patent Description:
Continuous-flow centrifuges typically include a rotor having an input port and an output port, and stationary connections that provide the rotor with a sample to be processed, and that accept separated sample components from the rotor. Because the rotor rotates relative to these stationary connections, seal assemblies are used to couple the connections to the spinning rotor. During centrifugation, the sample flows through a stationary connection and seal assembly into the rotor, where it is separated into its component parts by density due to the g-forces generated in the rotor. Such similar device is known from <CIT>.

To reduce heat and prevent damage to the seal assembly, union seals that join the ports of the rotor to the stationary connections are cooled and lubricated by one or more operating fluids. The operating fluids are typically provided to the seal assemblies under pressure by external cooling and lubricating systems. However, because the operating fluids are under pressure, if any of the seals in the seal assembly are defective, the sample components being processed by the centrifuge may become contaminated by the operating fluids.

One way of determining if an operating fluid may be contaminating the products in the centrifuge is by detecting leaks. Leakage of an operating fluid may be detected, for example, by monitoring a reservoir of the operating fluid for the level or weight of its contents. However, even when leaks are successfully detected in this manner, detection of the leak does not prevent contamination. Rather, detection merely lets the operator know the products could be contaminated.

Thus, there is a need for improved systems, methods, and computer program products that detect and prevent contamination in continuous centrifugation systems.

The present invention overcomes the foregoing and other shortcomings and drawbacks of detecting contamination in separated products heretofore known for use in centrifugation. While the present invention will be discussed in connection with certain embodiments, it will be understood that the present invention is not limited to the specific embodiments described herein.

In an embodiment of the present invention, a control system for a centrifuge is provided. The control system includes a controller that receives a first pressure signal indicative of a first pressure of a product flowing into or out of the centrifuge, and a second pressure signal indicative of a second pressure of an operating fluid flowing into or out of the centrifuge. The controller is configured to determine a first pressure difference between the first pressure and the second pressure, and in response to the first pressure difference dropping below a first predetermined offset, output a first control signal that causes a backpressure of the product flowing out of the centrifuge to increase.

In an aspect of the present invention, the controller is configured to output a second control signal that causes the backpressure of the product flowing out of the centrifuge to decrease in response to the first pressure difference rising above a second predetermined offset.

In another aspect of the present invention, the first control signal causes the backpressure to increase by closing a valve, and the second control signal causes the backpressure to decrease by opening the valve.

In another aspect of the present invention, the first predetermined offset is less than or equal to the second predetermined offset.

In another aspect of the invention, the first pressure is of the product flowing into the centrifuge, and the controller is configured to receive a third pressure signal indicative of a third pressure of the product flowing out of the centrifuge, determine a second pressure difference between the first pressure and the third pressure, and in response to the second pressure difference dropping below a third predetermined offset, output a third control signal that causes an increase in the backpressure of the product flowing into the centrifuge.

In another aspect of the present invention, the third control signal causes the increase in the backpressure of the product flowing into the centrifuge by closing the valve.

In another aspect of the invention, the second pressure is of a lubricant, and the controller is further configured to receive a fourth pressure signal indicative of a fourth pressure of a coolant, determine a third pressure difference between the first pressure and the fourth pressure, and in response to either the first pressure difference dropping below the first predetermined offset, or the third pressure difference dropping below a fourth predetermined offset, output the first control signal.

In another aspect of the present invention, the controller is further configured to store data indicative of the first pressure, the second pressure, and an operational state of the centrifuge at each of a plurality of sample times during which the centrifuge is in operation.

In another aspect of the present invention, the controller determines that a component of the product is free of contamination based on the first pressure difference failing to drop below a fifth predetermined offset during a period of time while the centrifuge has been processing the product.

In another aspect of the present invention, the fifth predetermined offset is less than the first predetermined offset, and greater than zero.

In another embodiment of the present invention, a method of controlling a centrifuge is provided. The method includes receiving the first pressure signal indicative of the first pressure of the product flowing into or out of the centrifuge, receiving the second pressure signal indicative of the second pressure of the operating fluid flowing into or out of the centrifuge, determining the first pressure difference between the first pressure and the second pressure, and in response to the first pressure difference dropping below the first predetermined offset, increasing the backpressure of the product flowing out of the centrifuge.

In another aspect of the present invention, the method further includes decreasing the backpressure of the product flowing out of the centrifuge in response to the first pressure difference rising above the second predetermined offset.

In another aspect of the present invention, increasing the backpressure comprises closing the valve, and decreasing the backpressure comprises opening the valve.

In another aspect of the invention, the first predetermined offset is less than or equal to the second predetermined offset.

In another aspect of the invention, the first pressure is of the product flowing into the centrifuge, and the method further includes receiving the third pressure signal indicative of the third pressure of the product flowing out of the centrifuge, determining the second pressure difference between the first pressure and the third pressure, and in response to the second pressure difference dropping below a third predetermined offset, increasing the backpressure of the product flowing into the centrifuge.

In another aspect of the present invention, increasing the backpressure of the product flowing into the centrifuge comprises closing the valve.

In another aspect of the invention, the second pressure is of the lubricant, and the method further includes receiving the fourth pressure signal indicative of the fourth pressure of the coolant, determining the third pressure difference between the first pressure and the fourth pressure, and in response to either the first pressure difference dropping below the first predetermined offset, or the third pressure difference dropping below a fourth predetermined offset, increasing the backpressure of the product flowing out of the centrifuge.

In another aspect of the present invention, the method further includes storing data indicative of the first pressure, the second pressure, and the operational state of the centrifuge at each of the plurality of sample times during which the centrifuge is in operation.

In another aspect of the present invention, the method further includes determining a component of the product is free of contamination based on the first pressure difference failing to drop below the fifth predetermined offset during the period of time while the centrifuge has been processing the product.

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the present invention and, together with a general description of the present invention given above, and the detailed description given below, serve to explain the present invention.

Embodiments of the present invention are directed to methods and systems for controlling continuous flow centrifuges. A control system monitors the pressures of a sample suspension being fed into the centrifuge and one or more separated components being discharged from the centrifuge, collectively referred to as "products". The control system also monitors the pressures of operating fluids (e.g., coolant and lubricant) used to cool and lubricate the seals and bearings of the centrifuge. Based on one or more of these monitored pressures, the control system regulates the pressure of the product being discharged from the centrifuge to maintain a positive pressure cascade across the seals. This positive pressure cascade prevents the input product or any output products from being contaminate in case of seal leakage. That is, because input and output products are each maintained at a pressure that is higher than the pressure of any of the operating fluids, the operating fluids cannot penetrate into areas of the seal assembly occupied by the products.

Each of multiple operational parameters, such as the characteristics and flow rate of product and the speed of the rotor, may affect the pressure of the product flowing into the centrifuge and the product flowing out of the centrifuge. However, by maintaining a positive product pressure relative to the operating fluid pressures, the control system prevents product contamination at either the input or output of the centrifuge under all operational conditions. In addition to controlling pressure, the control system may also record operational data to document a lack of contamination risk for product validation and to facilitate problem tracing.

<FIG> depicts an operating environment <NUM> including a continuous flow centrifuge <NUM> and a centrifuge controller <NUM> in accordance with an exemplary embodiment of the present invention. The centrifuge <NUM> may include a rotor housing <NUM> and a rotor <NUM> having a rotor body <NUM> that rotates within the rotor housing <NUM>. The rotor <NUM> may further include a hollow lower shaft <NUM> having an input port <NUM>, and a hollow upper shaft <NUM> having an output port <NUM>. The rotor <NUM> may be operatively coupled to a lower seal assembly <NUM> by the lower shaft <NUM>, and an upper seal assembly <NUM> by the upper shaft <NUM>. A drive unit <NUM> may be coupled to the upper shaft <NUM> of rotor <NUM> to provide rotation to the rotor <NUM>. Each of the seal assemblies <NUM>, <NUM> may be provided with lubricant (e.g., oil) by a lubricating system <NUM> and coolant (e.g., chilled water) by a cooling system <NUM>.

The lower seal assembly <NUM> may fluidically couple the input port <NUM> of rotor <NUM> to a feed line <NUM>. The lower seal assembly <NUM> may be configured to allow the rotor <NUM> to rotate relative to the feed line <NUM>. The feed line <NUM> may provide a flow of product to the rotor <NUM> by fluidically coupling the input port <NUM> of rotor <NUM> to a product supply <NUM>, e.g., a container of a biological suspension to be separated into component parts. The product supply <NUM> may be operatively coupled to the feed line <NUM> by a pump <NUM> (e.g., a peristaltic pump) having an output port <NUM>. The pump <NUM> may provide a controlled amount or flow rate of the product to the feed line <NUM> under pressure in response to a control signal from the controller <NUM>. The output of the feed line <NUM> may be coupled to the lower seal assembly <NUM> by a product input port <NUM>.

The upper seal assembly <NUM> may fluidically couple the output port <NUM> of rotor <NUM> to an output line <NUM>, and is configured to allow the rotor <NUM> to rotate relative to the output line <NUM>. The output line <NUM> may fluidically couple a product output port <NUM> of seal assembly <NUM> to a component collection container <NUM>. A valve <NUM> operatively coupled to the output line <NUM> may regulate the flow of product between the output port <NUM> of seal assembly <NUM> and the collection container <NUM>. By way of example, the valve <NUM> may be a proportional controlled pinch valve that is used to control back pressure on the output line <NUM>. To this end, the valve <NUM> may be selectively and incrementally opened and closed by the controller <NUM> to provide a controlled amount of resistance to the flow of product from the output port <NUM> of seal assembly <NUM> into the collection container <NUM>.

The drive unit <NUM> may be configured to selectively apply torque to the rotor <NUM> through the upper shaft <NUM>, thereby causing the rotor <NUM> to rotate within the rotor housing <NUM> in response to a rotation control signal from the controller <NUM>. The drive unit <NUM> may include a high-frequency induction motor, or other suitable source of torque, that spins the rotor <NUM>, for example, at speeds up to <NUM>,<NUM> Rotations Per Minute (RPM). This rotation may allow the rotor <NUM> to generate a Relative Centrifugal Force (RCF) of, for example, up to <NUM>,<NUM>×g.

The lubricating system <NUM> may include an input port <NUM> and output port <NUM>, as well as one or more pumps, filters, heat exchangers, reservoirs, etc. (not shown) configured to provide lubricant under pressure to the seal assemblies <NUM>, <NUM>. Lubricant lines <NUM> may fluidically couple the output port <NUM> of lubricating system <NUM> to respective lubricant input ports <NUM> of each seal assembly <NUM>, <NUM>. The lubricant lines <NUM> may also fluidically couple a lubricant output port <NUM> of each seal assembly <NUM>, <NUM> to the input port <NUM> of lubricating system <NUM>. Thus, once the lubricant has circulated through the seal assemblies <NUM>, <NUM>, it may return to the lubricating system <NUM> through the input port <NUM> thereof.

The cooling system <NUM> may include an input port <NUM> and an output port <NUM>, as well as one or more pumps, filters, heat exchangers, reservoirs, etc. (not shown) configured to provide coolant under pressure to the seal assemblies <NUM>, <NUM>. In a similar manner as described above for the lubricating system <NUM>, coolant lines <NUM> may fluidically couple the output port <NUM> of cooling system <NUM> to a respective coolant input port <NUM> of each seal assembly <NUM>, <NUM>. The coolant lines <NUM> may also fluidically couple a coolant output port <NUM> of each seal assembly <NUM>, <NUM> to the input port <NUM> of cooling system <NUM>. Thus, once the coolant has circulated through the seal assemblies <NUM>, <NUM>, it may return to the cooling system <NUM> through the coolant system input port <NUM>.

It should be understood that the lubricant and coolant lines may connect the seal assemblies <NUM>, <NUM> in a series configuration (as shown), in a parallel configuration, or in any other suitable configuration. It should be further understood that the direction of flow of the operating fluids indicated by arrows <NUM>, <NUM> is exemplary only, and could be changed in alternative embodiments of the invention.

Pressure sensors <NUM>-<NUM> may be operatively coupled to one or more of the feed line <NUM>, output line <NUM>, lubricant lines <NUM>, and coolant lines <NUM>. The pressure sensors may be configured to provide the controller <NUM> with pressure signals indicative of the pressure in each of the respective lines to which the respective pressure sensors are coupled. For example, a lubricant pressure sensor <NUM> may be operatively coupled to the output port <NUM> of lubricating system <NUM>, a coolant pressure sensor <NUM> may be operatively coupled to the output port <NUM> of cooling system <NUM>, a product input pressure sensor <NUM> may be operatively coupled to the input port <NUM> of rotor <NUM>, and a product output pressure sensor <NUM> may be operatively coupled to the output port <NUM> of rotor <NUM>.

The controller <NUM> may include a processor <NUM>, a memory <NUM>, an input/output (I/O) interface <NUM>, and a Human Machine Interface (HMI) <NUM>. The processor <NUM> may include one or more devices selected from microprocessors, micro-controllers, digital signal processors, microcomputers, central processing units, field programmable gate arrays, programmable logic devices, state machines, logic circuits, analog circuits, digital circuits, or any other devices that manipulate signals (analog or digital) based on operational instructions stored in memory <NUM>. Memory <NUM> may include a single memory device or a plurality of memory devices including, but not limited to, read-only memory (ROM), random access memory (RAM), volatile memory, non-volatile memory, static random access memory (SRAM), dynamic random access memory (DRAM), flash memory, cache memory, or data storage devices such as a hard drive, optical drive, tape drive, volatile or non-volatile solid state device, or any other device capable of storing data.

The processor <NUM> may operate under the control of an operating system <NUM> that resides in memory <NUM>. The operating system <NUM> may manage controller resources so that computer program code embodied as one or more computer software applications <NUM> residing in memory <NUM> can have instructions executed by the processor <NUM>. One or more data structures <NUM> may also reside in memory <NUM>, and may be used by the processor <NUM>, operating system <NUM>, or application <NUM> to store or manipulate data.

The I/O interface <NUM> may provide a machine interface that operatively couples the processor <NUM> to one or more other devices and systems, such as the drive unit <NUM>, pump <NUM>, valve <NUM>, sensors <NUM>-<NUM>, a remote control device <NUM>, and a network <NUM>. For example, the I/O interface <NUM> may include one or more serial or parallel data ports (e.g., a Profibus port), one or more network communication ports (e.g., an Ethernet port or WiFi transceiver), as well as analog input and output ports for sending and receiving analog signals. The application <NUM> may thereby work cooperatively with the other devices and systems by communicating via the I/O interface <NUM> to provide the various features, functions, applications, processes, or modules comprising embodiments of the present invention.

The application <NUM> may have program code that is executed by one or more external resources, or otherwise rely on functions or signals provided by other system or network components external to the controller <NUM>. Indeed, given the nearly endless hardware and software configurations possible, persons having ordinary skill in the art will understand that embodiments of the present invention may include applications that are located externally to the controller <NUM>, distributed among multiple computers or other external resources, or provided by computing resources (hardware and software) that are provided as a service over the network <NUM>, such as a cloud computing service.

The HMI <NUM> may be operatively coupled to the processor <NUM> of controller <NUM> to allow a user to interact directly with the controller <NUM> The HMI <NUM> may include video or alphanumeric displays, a touch screen, a speaker, and any other suitable audio and visual indicators capable of providing data to the user. The HMI <NUM> may also include input devices and controls such as an alphanumeric keyboard, a pointing device, keypads, pushbuttons, control knobs, microphones, etc., capable of accepting commands or input from the user and transmitting the entered input to the processor <NUM>. In an embodiment of the present invention, the HMI <NUM> may include the remote control <NUM>, or otherwise operate in cooperation with the remote control <NUM>, to enable remote operation of the centrifuge <NUM>.

The controller <NUM> may be operatively coupled to one or more external resources (not shown) via the network <NUM>. External resources may include, but are not limited to, servers, databases, mass storage devices, peripheral devices, cloud-based network services, or any other resource that may be used by the controller <NUM> to implement features of embodiments of the present invention.

In an embodiment of the invention, the controller <NUM> may comprise a microcomputer, such as a Windows®-based PC controller. In this embodiment, the HMI <NUM> may include a touch-sensitive liquid-crystal-display (LCD) panel that provides a graphical user interface (GUI) for operating the centrifuge <NUM>. The controller <NUM> may also be configured to support <NUM> CFR Part <NUM> regulations for electronic records such that operational data is handled with high security and precluded from corruption or falsification. In addition, the controller <NUM> may be configured to output log data in CSV format via a Universal Serial Bus (USB) port or to a network share folder for data management and analysis by commercially available database or spreadsheet software. The controller <NUM> may also support Ethernet OPC-DA or Profibus-DP communication for monitoring real time data and remote control operation.

In an embodiment of the present invention, the controller <NUM> may be connected to an external system, such as an Integrated Process Control (IPC), having a user interface that enables programing of processes for rinsing, feeding, separating, harvesting, cleaning, and sanitizing to be programmed on site. These processes may be executed in a full-auto mode, a semi-auto mode, or a manual mode. The external system may cover the user interface of the centrifuge <NUM> and control, monitor, and record the full centrifugation process for repeatable sequences without variation. The external system may thereby simplify operator training and reduce procedural errors. The external system may also be CFR <NUM> Part <NUM> compliant with remote user management from a centralized Active Directory server, audit trail, historian SQL database, and batch data report.

The external system may communicate real time process data with a site automation system via Object Linking and Embedding (OLE) for Process Control (OPC), and integrate to site network domain and archive files on share folders for full backup. The external system may auto-stop feed when the product supply <NUM> is empty, include a pinch valve for controlling the product flow path, a tank for harvesting, tanks for feed input and feed output, and instrumentation for measuring conductivity, temperature, absorbance, concentration, density, and mass flow.

<FIG> depicts an exemplary lower seal assembly <NUM> in accordance with an embodiment of the present invention that includes a shaft seal sub-assembly <NUM> and a union seal sub-assembly <NUM>. The shaft seal subassembly <NUM> may include one or more shaft seals <NUM> that axially locate the lower shaft <NUM> of rotor <NUM> within a shaft channel <NUM> and prevent lubricant from leaking past the shaft <NUM>. The lubricant input port <NUM> and the lubricant output port <NUM> of lower seal assembly <NUM> may be fluidically coupled to the shaft seals <NUM> by respective lubricant channels <NUM>, <NUM>. The shaft seals <NUM> may thereby receive lubricant from the lubricating system <NUM> that lubricates and cools the shaft seals <NUM> during operation of the centrifuge <NUM>.

The union seal subassembly <NUM> may include a lower union bearing <NUM> located in a union bearing channel <NUM>, and an elastic member <NUM> (e.g., a spring) that urges the lower union bearing <NUM> in an upward direction within the union bearing channel <NUM>. The lower union bearing <NUM> may be configured to move within the union bearing channel <NUM> in response to axially aligned (e.g., upward and downward) forces. In operation, the elastic member <NUM> may urge the lower union bearing <NUM> in an upward axial direction and into confronting engagement with an upper union bearing <NUM>. The upper union bearing <NUM> may be operatively coupled to the lower shaft <NUM> of rotor <NUM> and configured to transfer the weight of the rotor <NUM> to the lower union bearing <NUM>.

The lower union bearing <NUM> and upper union bearing <NUM> may be configured to provide a union seal <NUM> that allows the lower shaft <NUM> to rotate relative to the lower seal assembly <NUM>. The lower union bearing <NUM> may include an axially-aligned channel <NUM> that fluidically couples the input port <NUM> of rotor <NUM> to the product input port <NUM> of lower seal assembly <NUM> through a lower portion of the union bearing channel <NUM>.

The coolant input port <NUM> and the coolant output port <NUM> may be fluidically coupled to an upper portion of the union bearing channel <NUM> by respective coolant channels <NUM>, <NUM>. Coolant from the cooling system <NUM> may circulate around the lower union bearing <NUM> during operation of the centrifuge <NUM> to remove heat generated by friction between the lower union bearing <NUM> and upper union bearing <NUM>.

<FIG> depicts an exemplary upper seal assembly <NUM> in accordance with an embodiment of the present invention. As described in more detail below, certain aspects of the upper seal subassembly <NUM> may resemble those of an inverted version of the lower seal assembly <NUM>. The upper seal assembly <NUM> may include a shaft seal sub-assembly <NUM> and a union seal sub-assembly <NUM>. The shaft seal subassembly <NUM> may include one or more shaft seals <NUM> that axially locate the upper shaft <NUM> of rotor <NUM> within a shaft channel <NUM>, and prevent lubricant from leaking past the shaft <NUM>. The lubricant input port <NUM> and the lubricant output port <NUM> of upper seal assembly <NUM> may be fluidically coupled to the shaft seals <NUM> by respective lubricant channels <NUM>, <NUM>. The shaft seals <NUM> may thereby receive lubricant from the lubricating system <NUM> that lubricates and cools the shaft seals <NUM> during operation of the centrifuge <NUM>.

The union seal subassembly <NUM> may include an upper union bearing <NUM> located in a union bearing channel <NUM>, and an elastic member <NUM> (e.g., a spring) that urges the upper union bearing <NUM> in a downward direction within the union bearing channel <NUM>. The upper union bearing <NUM> may be configured to move within the union bearing channel <NUM> in response to axially aligned (e.g. upward and downward) forces. In operation, the elastic member <NUM> may urge the upper union bearing <NUM> in a downward axial direction and into confronting engagement with a lower union bearing <NUM> that is operatively coupled to the upper shaft <NUM> of rotor <NUM>.

The upper union bearing <NUM> and lower union bearing <NUM> may be configured to provide a union seal <NUM> that allows the upper shaft <NUM> to rotate relative to the upper seal assembly <NUM>. The upper union bearing <NUM> may include an axially-aligned channel <NUM> that fluidically couples the output port <NUM> of rotor <NUM> to the product output port <NUM> of upper seal assembly <NUM> through an upper portion of the union bearing channel <NUM>.

The coolant input port <NUM> and the coolant output port <NUM> may each be fluidically coupled to an upper portion of the union bearing channel <NUM> by a respective coolant channel <NUM>, <NUM>. Coolant from the cooling system <NUM> may circulate around the upper union bearing <NUM> during operation of the centrifuge <NUM> to remove heat generated by friction between the upper union bearing <NUM> and lower union bearing <NUM>.

<FIG> depicts a control process <NUM> that may be executed by the controller <NUM>, or another suitable computing device, to control the valve <NUM>. The control process <NUM> may include an error function module <NUM> that receives a pressure signal <NUM>-<NUM> indicative of a pressure from each of the respective pressure sensors <NUM>-<NUM>, and outputs an error signal <NUM> based at least in part on the pressure signals <NUM>-<NUM>. The error signal <NUM> may be received by one or more of a proportional module <NUM>, an integral module <NUM>, and a derivative module <NUM>. Each of the modules <NUM>-<NUM> may output a respective signal <NUM>-<NUM> that is summed to generate a control signal <NUM> which is used to control the valve <NUM>. The control process <NUM> may thereby provide a proportional-integral-derivative (PID) control system that controls operation of the valve <NUM>.

The error function FERROR(t) may be configured to maintain one or more predetermined relationships between two or more of the product input pressure, product output pressure, lubricant pressure, and coolant pressure. By way of example, the error function FERROR(t) may be configured to output zero error when the product input pressure PI (as indicated by sensor <NUM>) is greater than the coolant pressure Pc (as indicated by sensor <NUM>) by a predetermined offset ΔI-C. That is, when the pressure difference (PI - PC) is equal to the predetermined offset ΔI-C. In this case, the error function FERROR(t) may be provided by: <MAT> where GI-C is a gain constant.

By way of another example, the error function FERROR(t) may be configured to output zero error when the product output pressure Po (as indicated by sensor <NUM>) is greater than the coolant pressure Pc (as indicated by sensor <NUM>) by a predetermined offset ΔO-C. That is, when the pressure difference (PO - PC) is equal to the predetermined offset ΔO-C. In this case, the error function FERROR(t) may be provided by: <MAT> where Go-c is another gain constant.

By way of yet another example, the error function FERROR(t) may be configured to output the minimum error (smallest positive error or largest negative error) between the target product input and coolant pressure difference, and the target product output and coolant pressure difference. In this case, the error function FERROR(t) may be provided by: <MAT>.

In any case, to control the pressures of the liquids flowing into and out of the seal assemblies, the error function FERROR(t) may also include additional control features, such as a dead-band, hysteresis, limiting, damping functions, etc., that are not represented in the exemplary equations.

An error signal <NUM> having a positive value may indicate that the pressure of the product is higher than it needs to be relative to one or more of the lubricant and coolant pressures. In this exemplary scenario, the modules <NUM>-<NUM> may be configured to generate signals <NUM>-<NUM> that, when summed, produce a control signal <NUM> which causes the valve <NUM> to reduce the amount of back pressure. That is, the control signal <NUM> may cause the valve <NUM> to open more fully. Opening the valve <NUM> may reduce the resistance encountered by the liquid being discharged from the centrifuge <NUM>, and thus reduce the backpressure at the product output port <NUM> of upper seal assembly <NUM>. This decreased back pressure at the upper seal assembly <NUM> may propagate through the rotor <NUM> and cause the pressure of the product at the product input port <NUM> of lower seal assembly <NUM> to decrease.

In contrast, an error signal <NUM> having a negative value may indicate that the pressure of the sample suspension is too low relative to one or more of the lubricant and coolant pressures. In this exemplary scenario, the modules <NUM>-<NUM> may be configured to generate signals <NUM>-<NUM> that, when summed, produce a control signal <NUM> which causes the valve <NUM> to increase the amount of back pressure. That is, the control signal <NUM> may cause the valve <NUM> to be less fully open, i.e., to partially close. Closing the valve <NUM> may increase the resistance encountered by the liquid being discharged from the centrifuge <NUM>, and thus increase the backpressure at the product output port <NUM> of upper seal assembly <NUM>. This increased back pressure at the upper seal assembly <NUM> may propagate through the rotor <NUM> and cause the pressure of the product at the product input port <NUM> of lower seal assembly <NUM> to increase.

The error function may be configured so that the controller <NUM> regulates the pressures of the product flowing into and out of the centrifuge, the lubricant, and the coolant so that predetermined relationships between the pressures of these fluids are maintained. For example, the error function may be configured so that the controller maintains the product input pressure at a higher level than the product output pressure, and the product output pressure at a higher level than the coolant fluid pressure. That is, the product input and output pressures PI, PO may be controlled so that: <MAT> The controller may also maintain the lubricant at a higher pressure than the coolant, i.e., PL > PC. These relationships may be maintained by controlling one or more of the lubricating system <NUM>, the cooling system <NUM>, the pump <NUM>, and the valve <NUM>. Maintaining these relationships between the different operating pressures may guarantee product integrity with no cross contamination between the product and the operating fluids of the centrifuge.

Embodiments of the present invention may provide good manufacturing practice (GMP) documentation evidence of protection against cross-contamination risk by monitoring and storing measured pressure values during centrifugation. This documentation may provide evidence of a cross-contamination free condition of the product. Coupled with the automatic backpressure adjustment feature and pressure sensor package that monitors a positive pressure across the union seals on the product line at all times, embodiments of the invention may provide sample security evidence, and stream pressure data for verification and audit traceability.

Operational data stored by the system may include batch identity, batch start date and time, an identity of who started the batch, a batch stop date and time, an identity of who stopped the batch, a report generation date, equipment information, product information, flow rates, volumes, temperatures, and pressures of the product and each operating fluid at each of one or more locations in the centrifuge system. Additional operational data stored by the system may include rotor speed, centrifugal force generated, density of the product, concentration of the product, conductivity of the product, or any other suitable data that may be used to characterize operation of the centrifuge <NUM> and processing of the product. In particular, the controller <NUM> may sample the pressure signals received from the sensors <NUM>-<NUM> at a plurality of sample times (e.g., <NUM>,<NUM> times per second) over a period of time during which the centrifuge is processing a batch of product. The indicated pressure values captured at each sample time may be stored in a database for use in generating pressure graphs and validating the resulting separated components as contamination free.

In general, the routines executed to implement the embodiments of the invention, whether implemented as part of an operating system or a specific application, component, program, object, module or sequence of instructions, or a subset thereof, may be referred to herein as "computer program code," or simply "program code. " Program code typically comprises computer-readable instructions that are resident at various times in various memory and storage devices in a computer and that, when read and executed by one or more processors in a computer, cause that computer to perform the operations necessary to execute operations or elements embodying the various aspects of the embodiments of the invention. Computer-readable program instructions for carrying out operations of the embodiments of the invention may be, for example, assembly language, source code, or object code written in any combination of one or more programming languages.

Various program code described herein may be identified based upon the application within which it is implemented in specific embodiments of the invention. However, it should be appreciated that any particular program nomenclature which follows is used merely for convenience, and thus the invention should not be limited to use solely in any specific application identified or implied by such nomenclature. Furthermore, given the generally endless number of manners in which computer programs may be organized into routines, procedures, methods, modules, objects, and the like, as well as the various manners in which program functionality may be allocated among various software layers that are resident within a typical computer (e.g., operating systems, libraries, API's, applications, applets, etc.), it should be appreciated that the embodiments of the invention are not limited to the specific organization and allocation of program functionality described herein.

The program code embodied in any of the applications/modules described herein is capable of being individually or collectively distributed as a computer program product in a variety of different forms. In particular, the program code may be distributed using a computer-readable storage medium having computer-readable program instructions thereon for causing a processor to carry out aspects of the embodiments of the invention.

Computer-readable storage media, which is inherently non-transitory, may include volatile and non-volatile, and removable and non-removable tangible media implemented in any method or technology for storage of data, such as computer-readable instructions, data structures, program modules, or other data. Computer-readable storage media may further include RAM, ROM, erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), flash memory or other solid state memory technology, portable compact disc read-only memory (CD-ROM), or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store data and which can be read by a computer. A computer-readable storage medium should not be construed as transitory signals per se (e.g., radio waves or other propagating electromagnetic waves, electromagnetic waves propagating through a transmission media such as a waveguide, or electrical signals transmitted through a wire). Computer-readable program instructions may be downloaded to a computer, another type of programmable data processing apparatus, or another device from a computer-readable storage medium or to an external computer or external storage device via a network.

Computer-readable program instructions stored in a computer-readable medium may be used to direct a computer, other types of programmable data processing apparatuses, or other devices to function in a particular manner, such that the instructions stored in the computer-readable medium produce an article of manufacture including instructions that implement the functions, acts, or operations specified in the flowcharts, sequence diagrams, or block diagrams. The computer program instructions may be provided to one or more processors of a general purpose computer, a special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the one or more processors, cause a series of computations to be performed to implement the functions, acts, or operations specified in the text of the specification, flowcharts, sequence diagrams, or block diagrams.

The flowcharts and block diagrams depicted in the figures illustrate the architecture, functionality, or operation of possible implementations of systems, methods, or computer program products according to various embodiments of the invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function or functions.

In certain alternative embodiments, the functions, acts, or operations specified in the flowcharts, sequence diagrams, or block diagrams may be reordered, processed serially, or processed concurrently consistent with embodiments of the invention. Moreover, any of the flowcharts, sequence diagrams, or block diagrams may include more or fewer blocks than those illustrated consistent with embodiments of the invention. It should also be understood that each block of the block diagrams or flowcharts, or any combination of blocks in the block diagrams or flowcharts, may be implemented by a special purpose hardware-based system configured to perform the specified functions or acts, or carried out by a combination of special purpose hardware and computer instructions.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the embodiments of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include both the singular and plural forms, and the terms "and" and "or" are each intended to include both alternative and conjunctive combinations, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" or "comprising," when used in this specification, specify the presence of stated features, integers, actions, steps, operations, elements, or components, but do not preclude the presence or addition of one or more other features, integers, actions, steps, operations, elements, components, or groups thereof. Furthermore, to the extent that the terms "includes", "having", "has", "with", "comprised of", or variants thereof are used in either the detailed description or the claims, such terms are intended to be inclusive in a manner similar to the term "comprising".

Claim 1:
A control system for a centrifuge, comprising:
a controller (<NUM>) that receives a first pressure signal indicative of a first pressure of a product flowing into or out of the centrifuge, and a second pressure signal indicative of a second pressure of an operating fluid flowing into or out of the centrifuge, the controller being configured to:
determine a first pressure difference between the first pressure and the second pressure; and
in response to the first pressure difference dropping below a first predetermined offset, output a first control signal that causes a backpressure of the product flowing out of the centrifuge to increase.