CORIOLIS flow meter and method for measuring properties of a fluid

Abstract

A Coriolis flowmeter for measuring one or more properties of a fluid is described herein, which involves a modular configuration and includes a fluid flow subsystem and a mechanical oscillator subsystem, which are functionally separated and coupled in a closed loop arrangement so that the fluid conduit is not directly vibrated and instead receives induced oscillations from the mechanical oscillator subsystem. The Coriolis flowmeter is useful for high purity applications and for bioprocessing applications. A bioprocessing system incorporating the Coriolis flowmeter is also described herein. A method for measuring one or more properties of a fluid using the disclosed Coriolis flowmeter is also described herein.

Description

Background Art

[0001] The present disclosure relates generally to Coriolis flow meters for measuring one or more properties of a fluid comprising a fluid flow, and more particularly to Coriolis flow meters in which a fluid flow subsystem is functionally separated from a mechanical oscillator system, and even more particularly to Coriolis flow meters for use in bioprocessing systems.

[0002] Coriolis flowmeters are used to measure the mass flow of fluids flowing through pipelines in different industrial process engineering environments. Coriolis flowmeters have one or more flow tubes, each with a set of natural vibration modes, which may belong to simple bending, torsion or twisting types. Each material-filled flow tube is driven to oscillate with resonance in one of these natural vibration modes. The natural vibration mode is partially defined by the combined mass of the flow tube and the material in the flow tube. In most Coriolis flowmeters, fluid flows into the Coriolis flowmeter from the connected pipeline on the inlet side. The fluid is then guided through the flow tube or multiple flow tubes and is transported to the connected pipeline on the outlet side.

[0003] Typically, electromagnetic excitation is used to cause the flow tube to oscillate. When there is no flow through a Coriolis flowmeter, all points along the flow tube oscillate with the same phase. As material begins to flow, the Coriolis acceleration causes each point along the flow tube to have a different phase relative to other points along the flow tube. Motion sensors on the flow tube produce sinusoidal signals that represent the motion of the flow tube. The phase difference between the sensor signals is proportional to the mass flow rate of the material flowing through the flow tube or multiple flow tubes.

[0004] Most Coriolis flowmeters are made of metals such as aluminum, steel, stainless steel, and titanium. It is known to use Coriolis flowmeters with different flow tube configurations. Among these configurations are single tube, double tube, straight tube, curved tube, and irregularly configured flow tubes. The flow tubes also act as mechanical oscillators.

[0005] In these prior art Coriolis flow meters, the frequency range of the oscillation modes is therefore dominated by the design and materials of the flow tube, and therefore the choice of material, geometry and thickness of the flow tube must be adapted to the composition, pressure and temperature range or other such properties of the fluid under test. Summary of the invention

[0006] In one aspect, a Coriolis flow meter for measuring one or more properties of a fluid is disclosed. A fluid flow subsystem is configured to provide a flow path for the fluid, and a mechanical oscillator subsystem is disposed proximate the fluid subsystem, wherein the mechanical oscillator subsystem and the fluid subsystem are functionally separated.

[0007] The mechanical oscillator subsystem is configured to induce oscillation in the fluid flow subsystem, and is further configured to detect the Coriolis response from the fluid. The mechanical oscillator subsystem includes a mechanical oscillator, which is connected to the fluid flow subsystem and is configured to provide a closed-loop arrangement for transmitting the oscillation to the fluid and receiving the Coriolis response from the fluid. The mechanical oscillator subsystem also includes one or more actuators for generating oscillations in the mechanical oscillator and a sensing subsystem configured to receive the Coriolis response from the fluid through the mechanical oscillator. The Coriolis flowmeter may include a flow conduit, one or more actuators and one or more sensors. One or more of these may be configured as disposable or single-use parts.

[0008] The Coriolis flow meter also includes electronic circuitry coupled to the mechanical oscillator subsystem and configured to trigger one or more actuators and a sensing subsystem, and configured to process the Coriolis responses received from the sensing subsystem to generate one or more measurements representative of one or more fluid properties of the fluid.

[0009] The disposable part subsystem may include a flow conduit, one or more actuators, one or more sensors, wherein any of these or parts or combinations of these components are configured as a disposable part. Electronic circuitry may be coupled to the disposable part subsystem and configured to trigger the one or more actuators and the one or more sensors, and configured to process the Coriolis response received from the one or more sensors to generate one or more measurements representing one or more properties of the fluid.

[0010] In another aspect, a bioprocess system for monitoring one or more fluid properties of a fluid used in a bioprocess unit is disclosed. The bioprocess system includes an inlet tubing and an outlet tubing of the bioprocess unit, wherein the inlet tubing is connected to an inlet process connection and the outlet tubing is connected to an outlet process connection. The bioprocess system includes a Coriolis flow meter as described above herein coupled to the inlet process connection and the outlet process connection and a monitoring unit configured to receive measurements representing one or more fluid properties of the fluid and configured to use the measurements to control the bioprocess.

[0011] In yet another aspect, a bioprocess system for monitoring one or more fluid properties of a fluid used in a bioprocess unit is disclosed, wherein the bioprocess unit includes a fluid flow subsystem for transferring the fluid in a bioprocess of the bioprocess unit. The fluid flow subsystem is shared with other components of the Coriolis flowmeter described above herein. In other words, the fluid flow subsystem is common to the bioprocess unit and the Coriolis flowmeter. The bioprocess system includes a monitoring unit configured to receive measurements representing one or more fluid properties of the fluid and configured to use the measurements to control the bioprocess.

[0012] In another aspect, a single use flow kit for a bioprocessing system is disclosed. The flow kit includes a fluid flow subsystem fluidly connected to a conduit as discussed above, one or more single use sensor assemblies, and one or more manifolds. It is arranged to be installed in a bioprocessing system as described above, wherein it provides a single use flow path for the system.

[0013] In yet another aspect, a method for measuring one or more fluid properties of a fluid using a Coriolis flow meter is described herein. The method includes steps for: providing a fluid flow subsystem to retain the fluid in a flow conduit; providing a mechanical oscillator subsystem as described above herein; and providing an electronic circuit coupled to the mechanical oscillator subsystem. The method includes steps for transmitting an electrical signal to trigger oscillations in the fluid through the mechanical oscillator subsystem; steps for receiving a Coriolis response from the fluid through the mechanical oscillator subsystem; and steps for processing the Coriolis response to obtain one or more measurements representing one or more fluid properties of the fluid.

[0014] In yet another aspect, a method for measuring one or more properties of a fluid using a Coriolis flow meter is described herein. The method includes the steps described herein above for providing a disposable part subsystem and providing an electronic circuit coupled to the disposable part subsystem, wherein one or more components are configured as disposable parts. The method includes the steps of transmitting an electrical signal to trigger oscillations in a fluid receiving a Coriolis response from the fluid; and the steps of processing the Coriolis response to obtain one or more measurements representing one or more fluid properties of the fluid. The Coriolis flow meter may include the disposable part subsystem described herein above, wherein one or more components are configured as disposable parts.

[0015] In yet another aspect, described herein is a method for monitoring one or more fluid properties of a fluid in a bioprocess of a biotreatment system. The method comprises coupling an inlet conduit and an outlet conduit of the bioprocess with a Coriolis flow meter described above herein using a process connection, transmitting an electrical signal to trigger oscillations in the fluid through a mechanical oscillator subsystem; receiving a Coriolis response from the fluid through the mechanical oscillator subsystem; processing the Coriolis response to obtain one or more measurements representing one or more fluid properties of the fluid; and monitoring the bioprocess using the one or more measurements. The one or more fluid properties include at least one of a mass flow rate, a density, or a temperature of the fluid. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] These and other features, aspects and advantages of the present invention will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like characters represent like parts throughout the several views, and in which:

[0017] Figure 1 is a graphical representation of an implementation of a Coriolis flow meter according to some embodiments;

[0018] Figure 2 is a block diagram representation of an implementation of a Coriolis flow meter according to some embodiments;

[0019] Figure 3-9 are graphical representations of some example implementations of Coriolis flow meters according to some embodiments;

[0020] Fig.10 According to some embodiments, the use Figure 2 A block diagram representation of an implementation of a Coriolis flowmeter for a biological processing system;

[0021] Fig.11 illustrates a flow chart showing steps of a method for measuring one or more properties of a fluid comprising a fluid flow using a Coriolis flow meter according to some embodiments;

[0022] Fig.12 A flow chart showing steps of a method for measuring one or more properties of a fluid comprising a fluid stream in a bioprocess of a bioprocessing system is illustrated according to some embodiments; and

[0023] Fig.13 FIG. 1 illustrates a method for performing a Figure 2 A block diagram representation of another embodiment of a Coriolis flow meter for a biological processing system sharing a fluid flow subsystem.

[0024] Fig.14is a block diagram representation of an implementation of a Coriolis flow meter according to some embodiments;

[0025] Fig.15 yes Fig.14 A block diagram representation of one implementation of an embodiment of;

[0026] Figure 16-19 are graphical representations of some example implementations of Coriolis flow meters according to some embodiments;

[0027] Fig. 20 is used Fig.14 A block diagram representation of an implementation of a Coriolis flowmeter for a biological processing system;

[0028] Fig.21 A single use flow kit according to the present invention is shown. DETAILED DESCRIPTION

[0029] As mentioned previously herein, Coriolis flow meters are used to measure fluid and fluid flow properties in processes in any processing system that uses fluids, such as a bioprocessing system. The various embodiments presented herein describe advantageous features of Coriolis flow meters that alleviate constraints associated with the selection of suitable materials and manufacturing processes required to manufacture Coriolis flow meters.

[0030] Those skilled in the art will appreciate that each process may have its own requirements that the Coriolis flow meter must comply with, for ensuring accurate measurement, process integrity and the life of the meter itself. For example, in a process, the contamination of the fluid is extremely undesirable, because ultra-high-grade purity must be maintained in the fluid returned to the process by the Coriolis flow meter. The embodiments presented herein solve such requirements. In some other processes, biosensitivity is important, and in some other processes, the fluid is corrosive, and some of the embodiments presented herein also solve such requirements. In some other processes, the nature of the process may require that the flow conduit is configurable in different geometries, yet in some other processes, there may be a need to allow the flow conduit to be disposable to allow only single use. The embodiments of the selection presented here also solve such requirements.

[0031] The embodiments described herein are useful for the measurement of fluid properties such as mass flow rate, density, temperature, and the like, and are particularly useful for several bioprocessing systems involving processes that are sensitive to contamination with both impurities and active biological materials, as is common in the production of drugs and in cell biology.

[0032] Figure 11 is a diagrammatic representation of an embodiment of a Coriolis flow meter 100 having a housing 120 housing a mechanical oscillator subsystem and a fluid flow subsystem; a housing 130 housing electronic circuitry used to operate the mechanical oscillator subsystem, and process connections 140 connected to inlet and outlet conduits (not shown) of a process in which fluids and fluid flows are monitored, such as a biological process in a biological treatment system. As will be appreciated by those skilled in the art, Figure 1 The embodiments are non-limiting examples of housing the various components of the Coriolis flow meter 100, and housings 120 and 130 and process connection 140 may be configured in different ways based on the end use.

[0033] Figure 2 2 is a block diagram representation of an embodiment of a Coriolis flow meter 200 that includes a mechanical oscillator subsystem 210. The mechanical oscillator subsystem 210 includes one or more actuators 220, a mechanical oscillator 230, and a sensing subsystem 240. The one or more actuators 220 are used to induce oscillations of appropriate amplitude in the mechanical oscillator 230 within the required frequency range. The one or more actuators 220 may be directly coupled to the mechanical oscillator 230 (e.g., electromagnetic coils), or may be indirectly coupled using external actuation components (e.g., mechanical couplings, ferromagnetic parts, and the like). The sensing subsystem 240 includes a pick-off sensor and associated components, such as a permanent magnet-based sensor or an optical sensor.

[0034] like Figure 2 As shown in , the Coriolis flow meter 200 includes a fluid flow subsystem 250 that is functionally separate from the mechanical oscillator subsystem 210, and eliminates the constraints of the prior art in which the fluid flow system itself is used as a mechanical oscillator, and the two are functionally integrated. Functionally separate in this article implies that the fluid flow subsystem itself is a distinct component, distinct from the mechanical oscillator subsystem.

[0035] The fluid flow subsystem 250 is configured to provide a flow path for a fluid 270 retained in the flow conduit 260. The flow conduit 260 is configured in the shape of the commonly used principles for Coriolis measurement, including but not limited to single, double or multiple loop configurations, split flow, straight pipes, counter-flow or co-flow configurations. In some implementations, the flow conduit is made of, for example, a polymer, and its effect on the oscillation mode (resonant frequency) of the mechanical oscillator is not primary. The flow conduit material in some examples adapts to the specific requirements of bioprocessing applications, such as temperature, pressure and the properties of the fluid to be measured (e.g., mass flow rate, density, corrosiveness, etc.). The material can be appropriately a polymer material that meets the requirements of USP VI (US Pharmacopoeia), specifically with respect to the level of leachables and extractables. In addition, in some examples, the material of the flow conduit has a much lower hardness than the material used for the mechanical oscillator 230.

[0036] The mechanical oscillator subsystem 210 is disposed proximate to the fluid flow subsystem 250, and the mechanical oscillator subsystem 210 is configured to induce oscillations in the fluid flow subsystem 250, and further configured to detect a Coriolis response from the fluid 270. More specifically, the mechanical oscillator 230 is coupled to the fluid flow subsystem 250 and configured to provide a closed-loop arrangement for transmission of oscillations to the fluid 270 and reception of a Coriolis response from the fluid 270.

[0037] In some implementations, the fluid flow subsystem 250 is directly coupled to the body of the mechanical oscillator 230 such that the oscillations of the mechanical oscillator are applied to the flow conduit 260 and the fluid therein. Some examples of such implementations are described in Figure 3-8 is shown in .

[0038] The Coriolis flow meter 200 also includes an electronic circuit 300 coupled to the mechanical oscillator subsystem 210 or the disposable part subsystem. The electronic circuit 300 includes a drive electronics 310 to trigger one or more actuators 220 to generate oscillations of a desired frequency and amplitude in the mechanical oscillator 230. The Coriolis flow meter 200 further includes a pick-up electronics 320 to receive the Coriolis response from the sensing subsystem 240. The electronic circuit 300 further includes a processor 330 to process the Coriolis response received from the sensing subsystem 240 to generate one or more measurements representing one or more properties of the fluid comprising the fluid flow. These measurements are displayed using a user interface 350. The electronic circuit 300 also includes a memory 340 to store the measurements for further use and communication, storing data useful to the drive electronics 310 and the pick-up electronics 320.

[0039] In operation, the electronic circuit 300 triggers one or more actuators to generate oscillations in the mechanical oscillator 230, which are transmitted to the fluid 270 in the flow conduit 260, such as by Figure 2 As a result of these oscillations, a Coriolis response (vibration amplitude and phase) is generated in the fluid and transmitted back to the mechanical oscillator 230, as shown by arrow 280, and sensed by the sensing subsystem 240. The sensed Coriolis response is transmitted to the electronic circuit 300 for further processing to obtain a measurement of one or more properties of the fluid comprising the fluid flow.

[0040] Figure 2 The configuration presented in allows for functional separation of the mechanical oscillation subsystem from the fluid flow subsystem in a Coriolis flow meter. The functional separation mitigates the effects of the material properties of the fluid flow subsystem on the resonant frequency of the oscillations used to generate the Coriolis response, which in turn is used to measure different properties of the fluid and fluid flow.

[0041] Separating the functionality of the mechanical oscillation subsystem and the fluid flow subsystem also allows separate optimization of materials for the mechanical flow subsystem and for the fluid flow subsystem to achieve better production costs and unlocks the potential for new applications that were previously unaddressable due to limitations in material selection.

[0042] The Coriolis flowmeter described above and in the embodiments described later in this article has the advantage of having a modular construction, wherein the mechanical oscillator subsystem and the fluid flow subsystem are separated in power, as well as being modular and allowing modular integration. The modular features described herein provide advantages both from a manufacturing aspect and a service aspect, and the functional separation provides a technical advantage of ensuring isolation of the fluid container portion contained in the fluid flow subsystem from the mechanical oscillation subsystem.

[0043] Fig.14 2 is a block diagram representation of an embodiment of a Coriolis flow meter 201 including a disposable parts subsystem 211. The disposable parts subsystem 211 includes one or more actuators 221, a flow conduit 231 for retaining a fluid 241, and may include one or more sensors 251. One skilled in the art will appreciate that one or more components of the disposable parts subsystem are configured as disposable parts, and others are configured as reusable resident parts.

[0044] The disposable parts subsystem 211 has the advantage that at least one of the flow conduit, one or more actuators or one or more sensors is configured as a disposable part, and the other parts are configured as reusable resident parts. Those skilled in the art will appreciate that the (one or more) disposable parts can be replaced at very low cost at intervals controlled by the needs of a specific process. In addition, in some implementations, the material of the flow conduit 231 can be changed (glass or polymer or silicone or metal) without replacing the entire Coriolis flowmeter. The disposable parts subsystem allows high accuracy measurements, reuse of parts of the Coriolis flowmeter 201, provides flexibility for single-use applications, and achieves cost and material savings.

[0045] Reference Fig.14 In some implementations, the flow conduit 231 may be coupled to a mechanical oscillator 261, or form a unitary unit with the mechanical oscillator 261, and thus take the form of a rigid, oscillating conduit. One or more actuators 221 are used to induce oscillations of appropriate amplitude in the fluid 241 within a desired frequency range through the mechanical oscillator 261 and the flow conduit 231. One or more sensors 251 are configured to receive a Coriolis response from the fluid passing through the flow conduit. The one or more sensors include, for example, electromagnetic sensors or optical sensors and associated components.

[0046] The Coriolis flow meter 201 also includes an electronic circuit 301 coupled to the or disposable part subsystem. The electronic circuit 301 includes a drive electronics 311 to trigger one or more actuators 221 to generate oscillations of a desired frequency and amplitude in the mechanical oscillator 231. The Coriolis flow meter 201 further includes a pick-up electronics 321 to receive the Coriolis response from the sensing subsystem 241. The electronic circuit 301 further includes a processor 331 to process the Coriolis response received from the sensing subsystem 241 to generate one or more measurements representing one or more properties of the fluid comprising the fluid flow. These measurements are displayed using a user interface 351. The electronic circuit 301 also includes a memory 341 to store the measurements for further use and communication, storing data useful to the drive electronics 311 and the pick-up electronics 321.

[0047] Reference Figure 3-Figure 9 Various embodiments of a Coriolis flow meter and its various components as described herein are described in more detail.

[0048] Figure 3is a diagrammatic representation of some of the components of the Coriolis flow meter 400. As shown, the mechanical oscillator 410 in this implementation is configured with an open profile 460 and provides a dual frame for a double U-shaped structure of a fluid flow subsystem 470 containing a pair of convection conduits 430. An electromagnetic coil assembly 440 (electromagnetic coil and permanent magnet) is used as an actuator, and a pair of similar assemblies 450 are used as sensors of the sensing subsystem 240, which are positioned to directly contact the mechanical oscillator 410.

[0049] Figure 4 5 is another graphical representation of some of the components of the Coriolis flow meter 500. As shown, the mechanical oscillator 510 in this implementation is configured as a paired rectangular frame having an open profile 550. In one example, the paired rectangular frame is made of polycarbonate. The paired configuration of the fluid flow subsystem 520 is provided with a corresponding flow conduit 560. In one example, the flow conduit is made of silicone. A platform 530 is used to mount the mechanical oscillator 510 and the fluid flow subsystem 520. A bracket 540 is used to secure the mechanical oscillator 510. Other components of the actuator and sensor can be provided in conjunction with the Figure 3 5. Alternatively, the platform 530 may be mounted in the same configuration as shown in FIG. 5. In this example, the platform catheter is single use and disposable.

[0050] Figure 5 Some components used to implement the Coriolis flowmeter 600 Figure 4 As shown, in this implementation, the mechanical oscillator 620 is configured as a paired rectangular frame with an open profile 610. A paired configuration of a flow conduit 650 is provided as a fluid flow subsystem, and a harness package 640 is used to attach the flow conduit 650 to the mechanical oscillator 620. In this example, the platform conduit is single-use and disposable.

[0051] Figure 6 There is still another configuration for implementing some components of the Coriolis flow meter 700. As shown, the mechanical oscillator 710 is configured as a single frame with an open profile 730. A paired configuration of flow conduits 720 is provided as a fluid flow subsystem. In this example, the mechanical oscillator 710 is made of a sheet metal substrate, the flow conduits are made of hard plastic, and the pick-up sensing has been achieved by non-contact optical methods, with the laser sensor targeting the reflective patch 740 not shown in the image.

[0052] Figure 7 is similar to Figure 2200, with the additional feature of an open profile interface 810, which in some implementations can be a separate part or component of the mechanical oscillator 230. The open profile interface advantageously couples the fluid flow subsystem to the mechanical oscillator subsystem described above herein in a closed loop arrangement.

[0053] Figure 7 All other components of the Coriolis Flow Meter 800 are as referenced Figure 2 The same is explained in the embodiment. Figure 8 and Fig. 9 are two example representations of an open profile interface 810 that may be mounted on a mechanical oscillator and secured to the flow conduits described in the previous embodiments. In some implementations, the open profile interface and the mechanical oscillator are a unitary unit, and in some implementations, they are discrete and mated to each other.

[0054] Figure 8 is a diagrammatic representation of some of the components used to implement a Coriolis flow meter 820, including a mechanical oscillator 830 providing a dual parallel linear structure that in this embodiment is a unitary unit with an open profile interface 840 configured to secure two flow conduits (not shown), and mounting features for sensors and actuators 850. It should be noted that this particular design is completely symmetrical with respect to the horizontal plane.

[0055] Fig. 9 There is yet another configuration for implementing some of the components of the Coriolis flow meter 900. In this configuration, the flow conduit 910 is inserted into an open profile interface 920, forming a single linear structure. The oscillator 930 is defined by steel inserts on either side of the flow conduit and is fully integrated into the open profile interface, which in turn contains mounting features 940 to couple the sensor 950 and actuator 960 at well-defined locations.

[0056] As will be appreciated by those skilled in the art, Figure 7-Figure 9 The open profile interface is deployed in close physical contact with the flow conduit of the Coriolis flow meter, but is not in direct contact with the fluid for which measurement of mass flow rate is to be made.

[0057] Fig.15 An embodiment is illustrated having a disposable parts subsystem 214 that includes disposable parts for one or more actuators, shown by box 222, a flow conduit 232 for retaining a fluid 242 and coupled to or coupled with a mechanical oscillator 262. In one example, the disposable parts subsystem 214 also includes disposable parts for one or more sensors, shown by box 252.

[0058] In addition, the Coriolis flow meter 212 also includes a resident sensor platform 272, which includes reusable and resident parts of the sensor shown by box 282 and reusable and resident parts of the actuator shown by box 292. One or more actuators (222 and 292) are used to induce oscillations of appropriate amplitude in the required frequency range in the fluid 242 through the mechanical oscillator 262 and the flow conduit 232. The resident part of the actuator shown by box 222 can take the form of an electromagnetic coil in one example, coupling the excitation force required to induce oscillations by means of a magnetic field to the disposable part of the actuator shown by box 222 in direct contact with the mechanical oscillator 262.

[0059] One or more sensors (disposable part 252 and permanent part 282) are configured to receive the Coriolis response from the fluid passing through the flow conduit. The one or more sensors include, for example, electromagnetic sensors or optical sensors and associated components. The disposable part of the sensor shown by box 252 is preferably but not necessarily a passive element, such as a permanent magnet for electromagnetic sensing methods or a reflective element for optical sensing methods.

[0060] The embodiments described herein above may include additional attachments, clamps and fixings such as but not limited to screws, bolts and nuts, adhesives, or may have snap-in grooves and the like to position the mechanical oscillator subsystem, fluid flow subsystem and electronic circuitry.

[0061] Those skilled in the art will appreciate that the Figure 3-Figure 9 embodiments, and other predefined shapes for the mechanical oscillator and flow conduit may be configured based on the usage environment.

[0062] Fig.16 is a pictorial representation of an implementation of a disposable part subsystem 314. As shown, the disposable part subsystem 314 includes a U-shaped flow conduit 332 in a dual flow channel configuration, which is reusable in some implementations and a disposable part in some implementations. The flow conduit is made of a polymer in one example, and of silicone in yet another example, and of glass in yet another example.

[0063] Fig.16 Other disposable parts in the configuration shown in FIG. 3 include an actuator 322, which is an electromagnetic coil in one example. Still other disposable parts include a sensor 352, which is a permanent magnet in one example. A frame 357 is used to mount the flow conduit 332 to the actuator 322, and the sensor 352 is mounted using screws or other attachment components.

[0064] Fig.174 is another pictorial representation of some of the components of the disposable parts subsystem 414. As shown, in this implementation, the disposable parts subsystem 414 includes a U-shaped mating configuration of flow conduits 432 and is reusable and acts as a mechanical oscillator. In this configuration, the disposable parts also include an actuator 422, which is an electromagnetic coil in one example. Other disposable parts include a sensor 452, which is a permanent magnet in one example. Brackets 456 are used to secure the flow conduits 432 through a frame 457 to connect to a process connection 458.

[0065] Fig.18 are graphical representations of several configurations for implementing some of the components of disposable part subsystem 214 . Fig.18 (a) illustrates a configuration 601 including a frame 621 configured as a cartridge and being reusable. The flow conduit 611 is a disposable part, and the actuators 616 and 618 and the sensors 612 and 614 are integrated into the frame 621 and are reusable parts.

[0066] Fig.18 (b) illustrates another configuration 631 containing the flow conduit 632 together with the actuator 634 as a disposable part. The sensors 636 and 638 are optical sensors and are mounted on a frame 642 and are reusable. The base 641 forms a removable but reusable part of the frame 642 for fixing the flow conduit 632.

[0067] Fig.18 (c) illustrates another configuration 644 including a flow conduit 654 that is a disposable part, while actuators and sensors (not labeled for clarity) are provided as fixed reusable parts on a base 648. The base 646 receives and fixes the flow conduit 654. A shell 646 is provided to receive the parts mounted on the base 648. The shell includes connectors 651 and 652, which in one example are mechanical connectors for allowing a snap-in configuration so that the base 648 is inserted into the shell 646. In some other implementations, the connectors 651 and 652 are electrical connectors configured in a mother-child pair, where the connector 652 is the daughter electrical connector of the mother-child pair, and the connector 651 is the mother electrical connector of the mother-child pair.

[0068] Fig.18 (d) illustrates another configuration 656 where the flow conduit 668 is mounted on the frame 666 and is a disposable part. The actuator 664 and sensors 658 and 660 are magnets, are disposable parts, and are mounted on the frame 658 which is reusable.

[0069] Those skilled in the art will appreciate that the configurations described herein above are just some non-limiting examples, and other flow channel configurations for Coriolis measurements (e.g., single, dual or multi-loop configurations, split flow, straight pipes, counter-current or co-current flow configurations) can be implemented in a similar manner.

[0070] Fig.19 (a) is a pictorial representation of another implementation showing some components of a disposable part mechanical oscillator 2001. A flow conduit 2011 made of glass is used in this implementation and is mounted on a frame 2051. Magnets 2031, 2041, and 2051, which act as actuators and sensors, are clamped onto the flow conduit 2011. In some configurations, the flow conduit 2011 is disposable.

[0071] The use of glass for the flow conduits in the above embodiments (referred to herein as glass flow conduits) has several advantages due to the thermal conductivity, electrical non-conductivity, relative corrosion safety, transparency of the glass flow conduits which enables additional optical or spectroscopic measurements.

[0072] For example, temperature compensation is often important for monitoring processes, and in prior art Coriolis flowmeters, separate temperature sensors are included to compensate for temperature changes in the fluid induced by flow conduit material properties such as hardness. The use of glass flow conduits eliminates the necessity for conventional temperature sensors because glass flow conduits allow direct optical observation and optical temperature measurement of the fluid. In addition, glass flow conduits enable measurements such as nuclear magnetic resonance-based fluid characterization measurements to be made along with conventional mass flow measurements made by the same Coriolis flowmeter.

[0073] As a further advantage, the transparency of the glass flow conduit to the visible light spectrum allows inspection of any cracks in the flow conduit by the principle of optical scattering resulting from the interaction of radiated light with small cracks.

[0074] The glass flow conduit as a disposable part meets the single-use requirement for some applications, such as in medical testing where analysis of body fluids is required to determine health-related parameters. In some of these applications, it is often desirable to perform analysis of the fluid while measuring the mass flow rate of the fluid. Likewise, it can be advantageously used in bioprocess applications to measure different properties of the bioprocess fluid in conjunction with the mass flow rate. In one embodiment, the glass flow conduit is provided by Fig.19 An insight portal, shown as reference numeral 2070 in (b), may be provided on the outer surface of the glass flow conduit 2011 to enable such analysis. The insight portal comprises one or more small areas provided as grooves in the glass flow conduit 2011, in one non-limiting example, deviating from the conventional constant outer curvature for the flow conduit, and may be located such as Fig.19The form of the flattened groove shown in (b). The inner diameter of the flow conduit is not altered, and therefore the insight portal 2070 does not cause a reduction in the flow conduit.

[0075] In some implementations, a light source (not shown) may be used to emit radiation through insight portal 2070 that impinges on the liquid within flow conduit 2011, and the reflected radiation is received by a detector (not shown) and processed to measure selected properties for analysis of the fluid, such as opacity, the presence or absence of certain elements or compounds, and the color of the fluid and other such properties. It will be appreciated by those skilled in the art that the radiation may include laser generated light, incoherent light, spectrum shaped light, microwave radiation, or gamma radiation.

[0076] In yet another embodiment, the insight portal 2070 can be used to position a coil (not shown) to generate a magnetic field using a current driver (not shown). Since the glass flow conduit is non-conductive and has negligible permeability, the current driver can generate a steady or time-varying magnetic field within the fluid. Such a magnetic field can be used in conjunction with other sensors deployed external to the glass flow conduit, including fluid characterization and analysis of the fluid complementary to and concurrent with mass flow estimation.

[0077] In some other embodiments useful for inventory management, the glass flow conduit may include a tag ( Fig.19 (a) is shown as 2061), such as an RFID (radio frequency identification) tag. In one example, the tag may include a mark printed, etched or otherwise placed on the glass flow conduit 2011. The reading from the tag can be processed by an external processor to locate the position and orientation of the glass flow conduit, or to move the glass flow conduit to a desired position using a component such as a robotic arm.

[0078] In yet another embodiment, the label 2061 is initially an invisible marking that becomes visible only after the glass flow tube 2011 is sterilized by exposure to an ultraviolet light source. As will be appreciated by those skilled in the art, an advantage of this embodiment is the added confirmation of a positive indication of completion of the sterilization regimen, which may be a requirement for certain applications.

[0079] Flow tubes made of glass offer several other advantages that allow for greater ease and accuracy in measurements, such as delayed thermodynamic interactions between the flow tubes made of glass and the fluid, expected chemical isolation between the flow tubes made of glass and the fluid, and reasonable production costs, especially considering single-use, where the flow tubes made of glass are disposable parts.

[0080] It will be appreciated by those skilled in the art that the Figure 16-Figure 19embodiments, and other predefined shapes for the flow conduit may be configured based on the usage environment.

[0081] On the other hand, Fig.10 A graphical representation of a bioprocess system 1000 is provided for monitoring one or more properties of a fluid including a fluid stream used in a bioprocess of a bioprocess unit 1010. As shown, the bioprocess unit 1010 includes an inlet conduit with an inlet process connection and an outlet conduit with an outlet process connection. Other aspects of the bioprocess unit 1010 involved in the actual process are not shown here to limit the discussion to aspects related to the monitoring of one or more properties of the fluid including the fluid stream. The bioprocess system may, for example, include a chromatography system, a filtration system, and / or a bioreactor.

[0082] like Fig.10 As shown in FIG. 1 , the Coriolis flow meter 1020 is coupled to the inlet process connection and the outlet process connection of the bioprocess unit 1010. The Coriolis flow meter 1020 mentioned herein has been previously referred to herein above. Figure 2-9 The bioprocessing system 1000 further comprises a monitoring unit 1030 configured to receive measurements representing one or more fluid properties of the fluid from the Coriolis flow meter 1020 and configured to use the measurements to control a bioprocess in the bioprocess unit 1010 . Figure 2-9 All aspects of the Coriolis flow meter are applicable in the embodiment of the bioprocessing system 1000.

[0083] In yet another aspect, Fig.11 A flow chart 2000 is illustrated showing steps of a method for measuring one or more properties of a fluid comprising a fluid flow using a Coriolis flow meter. The Coriolis flow meter referred to herein has been previously described with reference to Figure 2-9 The method includes a step 2010 for providing a Coriolis flow meter with a fluid flow subsystem that is functionally separated from a mechanical oscillator subsystem, an actuator, a sensing subsystem, and an electronic circuit. The method includes a step 2020 for transmitting an electrical signal to trigger oscillations in the fluid through the mechanical oscillator subsystem. The method includes a step 2030 for receiving a Coriolis response from the fluid through the mechanical oscillator subsystem; a step 2040 for processing the Coriolis response to obtain one or more measurements representing one or more properties of a fluid comprising the fluid flow, and a step 2050 for monitoring a biological process using the one or more measurements.

[0084] In yet another aspect, Fig.12A flow chart 3000 is illustrated showing steps of a method for measuring one or more properties of a fluid including a fluid stream in a bioprocess of a bioprocess system. The method includes step 3010 for coupling an inlet pipe and an outlet pipe of the bioprocess to a Coriolis flow meter using a process connection. The Coriolis flow meter referred to herein has been previously described with reference to Figure 2-9 The method comprises a step 3020 for transmitting an electrical signal to trigger oscillations in a fluid through a mechanical oscillator subsystem. The method comprises a step 3030 for receiving a Coriolis response from the fluid through the mechanical oscillator subsystem. The method further comprises a step 3040 for processing the Coriolis response to obtain one or more measurements representing one or more properties of a fluid comprising the fluid flow and a step 3050 for monitoring a biological process using the one or more measurements.

[0085] In still another aspect, the aforementioned functional separation further allows fluid containers of an upstream process to be used as a fluid flow subsystem in a Coriolis flow meter, for example, pre-sterilized flexible tubing. Fig.13 is another example embodiment 4000 in which the fluid flow subsystem 4040 of the Coriolis flow meter 4020 is an integral part of the bioprocess unit 4010 itself.

[0086] Reference Figure 1 , the bioprocess unit 4010 is used for the culture of cells grown in the bioreactor 4060 and contains a culture medium (media) (box 4050), which generally contains a fluid mixture of nutrients required for the growth of the cells in the bioreactor 4060. The nutrient solution is delivered to the bioreactor 4060 through a fluid flow subsystem 4040, which is a flow conduit and is part of the Coriolis flow meter 4020.

[0087] It will be appreciated by those skilled in the art that the bioprocess unit may include several other components for upstream and downstream processes that are input to or output from the bioreactor 4060. For example, along with the culture medium, which is primarily a fluid mixture of nutrients, a gas chamber containing a fluid mixture of gases such as oxygen, nitrogen, or carbon dioxide that is required for cell growth in the bioreactor 4060 may also be included. In this case, another flow conduit would be used to deliver the gas to the bioreactor, and this flow conduit would thus be part of a Coriolis flow meter, similar to Fig.13 Embodiment of the invention. Fig.13Embodiments also cover downstream processes like waste collection, cell chromatography, cell harvesting, cell clarification, cell purification, harvesting, capturing or purification of expressed biomolecules and the like, where the flow conduit (and thus the fluid flow subsystem) will be between the bioreactor and a chamber that receives the output from the bioreactor for any process used in the downstream process. The bioreactor referred to herein may be any of a stirred tank, a rocking, a single use or multiple use bioreactor or any other type used in the field of bioprocessing. Thus, due to reference to Figure 2 The modular configuration described, Fig.13 The embodiment and other embodiments above herein allow the flow conduits of the bioprocess unit to be shared as the fluid flow subsystem of the Coriolis flow meter, thereby optimizing and simplifying the process of measuring the properties of the fluid. The bioprocess system can also be a dedicated system for downstream processing, including, for example, one or more chromatography systems and / or one or more filtration systems, such as one or more cross-flow filtration systems.

[0088] The various aspects described herein allow for optimal material selection for the mechanical oscillator with respect to the frequencies of the different oscillation modes in order to achieve a high level of accuracy in the measurements. Furthermore, due to the functional separation of the mechanical oscillator system and the fluid flow subsystem in the embodiments described herein above, the design and material selection for the mechanical oscillator ensures that the influence of the material selection for the flow conduit on the oscillator behavior is limited. Thus, the oscillation characteristics are dominated by the material and geometry of the mechanical oscillator and are only slightly affected by the fluid container, which improves the measurement of the fluid.

[0089] The present invention further discloses a single-use flow kit 5000 for a bioprocessing system, such as Fig.21 . This flow kit includes a fluid flow subsystem 5001 as discussed above configured to be attached to a mechanical oscillator subsystem, which together form a Coriolis flow meter as discussed above. The flow kit also includes at least one manifold 5009 fluidly connected to the fluid flow subsystem and at least one single-use sensor assembly 5003, 5005, 5007 fluidly connected to the fluid flow subsystem. The flow kit further includes a sterile connector 5011 as is well known in the art, such as a ReadyMate TM (GE Healthcare) or KleenPak (Pall) for sterile connection to other fluid systems or units. The kit may be pre-sterilized, for example by gamma radiation, and it may be delivered in a closed package.

[0090] The single-use sensor assembly may, for example, include a flow cell 5003 with one or more transparent windows for measurement of visible or ultraviolet light absorption, which is useful, for example, for monitoring of protein concentration. Additionally or alternatively, the single-use sensor assembly may include a single-use pressure sensor 5005 as is well known in the art and available from, for example, PendoTECH. Conductivity (indicating ionic strength) may be measured by a single-use conductivity sensor 5007 as is well known in the art and available from, for example, SciLog or PendoTECH. The flow kit may further include a length of flexible tubing suitable for installation in a peristaltic pump and / or a single-use pump head for, for example, a centrifugal or diaphragm pump.

[0091] The flow kit may suitably include instructions for attachment of the fluid flow subsystem to the mechanical oscillator subsystem of the Coriolis flow meter and for connecting the flow kit to a bioprocessing system such as a chromatography or filtration system or a bioreactor. The fluid contact materials of the flow kit can suitably be of a grade meeting USP VI (US Pharmacopeia) requirements.

[0092] While only certain features of the invention have been illustrated and described herein, many modifications and changes will occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

1. A Coriolis flow meter (100; 200; 400; 500; 600; 700; 800; 820; 900; 1020； 4020), the Coriolis flow meter comprises: a fluid flow subsystem (250; 470; 520; 4040) configured to provide a flow path for the fluid; a mechanical oscillator subsystem (210) disposed proximate to the fluid flow subsystem, wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separate, and wherein the mechanical oscillator subsystem is configured to induce oscillations in the fluid flow subsystem and further configured to detect a Coriolis response from the fluid, the mechanical oscillator subsystem comprising: a mechanical oscillator (230; 410; 510; 620; 710; 830) coupled to the fluid flow subsystem, the mechanical oscillator being configured to provide a closed loop arrangement for transmission of oscillations to the fluid and reception of the Coriolis response from the fluid, one or more actuators (220; 850; 960) for generating oscillations in the mechanical oscillator, and a sensing subsystem (240) configured to receive the Coriolis response from the fluid via the mechanical oscillator; and An electronic circuit (300) is coupled to the mechanical oscillator subsystem and configured to trigger the one or more actuators and the sensing subsystem, and configured to process the Coriolis response received from the sensing subsystem to generate one or more measurements representative of one or more fluid properties of the fluid.

2. The Coriolis flow meter of claim 1, wherein the fluid flow subsystem includes a flow conduit (260; 430; 560; 650; 720; 910) to retain the fluid.

3. The Coriolis flow meter of claim 2, wherein the mechanical oscillator subsystem includes an open profile interface (810; 840; 920) to secure the flow conduit.

4. The Coriolis flow meter of claim 3, wherein the open profile interface includes a plurality of sockets to secure the flow conduit.

5. The Coriolis flow meter of claim 3, wherein the open profile interface (840) and the mechanical oscillator (830) are a unitary unit.

6. The Coriolis flow meter of claim 2, wherein the flow conduit is disposable.

7. The Coriolis flow meter of claim 1 or 2, further comprising a platform (530) to receive the mechanical oscillator subsystem and the fluid flow subsystem.

8. The Coriolis flow meter of claim 1 or 2, wherein the mechanical oscillator subsystem, the fluid flow subsystem, and the electronic circuit are modular and allow for modular integration.

9. The Coriolis flow meter of claim 2, wherein the flow conduit is made of at least one of a polymer, a metal, a silicone, or a glass.

10. The Coriolis flow meter of claim 1 or 2, wherein the mechanical oscillator subsystem provides a linear structure to which the fluid flow subsystem is mechanically attached.

11. A Coriolis flow meter as claimed in claim 1 or 2, wherein the mechanical oscillator subsystem provides a U-shaped structure to which the fluid flow subsystem is mechanically attached.

12. The Coriolis flow meter of claim 1 or 2, wherein the one or more measurements are used to monitor a biological process.

13. The Coriolis flow meter of claim 1 or 2, wherein the one or more properties include at least one of mass flow rate, density, or temperature of the fluid.

14. A Coriolis flow meter for measuring one or more fluid properties of a fluid, the Coriolis flow meter comprising: a fluid flow subsystem configured to provide a flow path for the fluid; a mechanical oscillator subsystem disposed proximate the fluid flow subsystem, wherein the mechanical oscillator subsystem is configured to induce oscillations in the fluid flow subsystem and detect a Coriolis response generated in the fluid, the mechanical oscillator subsystem comprising: an open profile interface coupled to the fluid flow subsystem to provide a closed loop arrangement for transmission of oscillations to the fluid flow subsystem and reception of the Coriolis response from the fluid flow subsystem, one or more actuators for generating oscillations in the open profile interface, and a sensing subsystem configured to receive the Coriolis response from the fluid flow subsystem through the open profile interface; as well as an electronic circuit coupled to the mechanical oscillator subsystem and configured to trigger the one or more actuators and the sensing subsystem, and configured to process the Coriolis responses received from the sensing subsystem to generate one or more measurements representative of one or more fluid properties of the fluid, Wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separated.

15. The Coriolis flow meter of claim 14, wherein the fluid flow subsystem includes a flow conduit to retain the fluid.

16. The Coriolis flow meter of claim 15, wherein the open profile interface secures the flow conduit.

17. A Coriolis flow meter as claimed in claim 14 or 15, wherein the one or more fluid properties include at least one of mass flow rate, density or temperature of the fluid.

18. A bioprocessing system for monitoring one or more fluid properties of a fluid used in a bioprocess unit, the bioprocessing system comprising: an inlet conduit and an outlet conduit of the bioprocess unit, wherein the inlet conduit is connected to an inlet process connection and the outlet conduit is connected to an outlet process connection; A Coriolis flow meter coupled to the inlet process connection and the outlet process connection, wherein the Coriolis flow meter comprises: a fluid flow subsystem to receive and retain said fluid in a flow conduit, A mechanical oscillator subsystem, the mechanical oscillator subsystem comprising: a mechanical oscillator coupled to the fluid flow subsystem in a closed-loop arrangement for transmission of oscillations to the fluid and reception of a Coriolis response from the fluid, one or more actuators for generating oscillations in the mechanical oscillator, and a sensing subsystem for receiving the Coriolis response from the fluid through the mechanical oscillator, wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separate, and electronic circuitry coupled to the mechanical oscillator subsystem and configured to obtain one or more measurements representative of the one or more fluid properties of the fluid; and A monitoring unit is configured to receive the measurements representing the one or more fluid properties of the fluid and to use the measurements to control the biological process.

19. The bioprocessing system of claim 18, wherein the mechanical oscillator subsystem, the fluid flow subsystem, and the electronic circuit are modular and allow for modular integration.

20. The bioprocessing system of claim 18 or 19, wherein the fluid flow subsystem comprises a flow conduit to retain the fluid.

21. The bioprocessing system of claim 20, wherein the mechanical oscillator subsystem includes an open profile interface to secure the flow conduit.

22. The bioprocessing system of claim 21, wherein the open profile interface includes a plurality of receptacles to secure the flow conduit.

23. The bioprocessing system of claim 21, wherein the open profile interface and the mechanical oscillator are a unitary unit.

24. The bioprocessing system of claim 18 or 19, wherein the one or more fluid properties include at least one of mass flow rate, density, or temperature of the fluid.

25. The bioprocessing system of claim 18 or 19, wherein the mechanical oscillator subsystem provides a linear structure or a U-shaped structure to which the fluid flow subsystem is mechanically attached.

26. A method for measuring one or more fluid properties of a fluid using a Coriolis flow meter, the method comprising: providing a fluid flow subsystem to retain fluid in the flow conduit; A mechanical oscillator subsystem is provided, the mechanical oscillator subsystem comprising: a mechanical oscillator coupled to the fluid flow subsystem in a closed loop arrangement for transmission of oscillations to the fluid and reception of a Coriolis response from the fluid, one or more actuators for generating oscillations in the mechanical oscillator, and a sensing subsystem for receiving the Coriolis response from the fluid through the mechanical oscillator, wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separate; providing an electronic circuit coupled to the mechanical oscillator subsystem; transmitting an electrical signal to trigger oscillations in the fluid via the mechanical oscillator subsystem; receiving the Coriolis response from the fluid via the mechanical oscillator; and The Coriolis response is processed to obtain one or more measurements representative of the one or more fluid properties of the fluid.

27. The method of claim 26, further comprising monitoring a biological process using the one or more measurements.

28. The method of claim 26 or 27, wherein the mechanical oscillator subsystem includes an open profile interface for securing the flow conduit.

29. The method of claim 26 or 27, wherein the one or more fluid properties include at least one of mass flow rate, density, or temperature of the fluid.

30. A method for monitoring one or more fluid properties of a fluid in a bioprocess of a bioprocessing system, the method comprising: The inlet and outlet pipes of the bioprocess are coupled to a Coriolis flow meter using a process connection, wherein the Coriolis flow meter comprises: Fluid flow subsystem to retain the fluid in the flow conduit, A mechanical oscillator subsystem, the mechanical oscillator subsystem comprising: a mechanical oscillator coupled to the fluid flow subsystem in a closed-loop arrangement for transmission of oscillations to the fluid and reception of a Coriolis response from the fluid, one or more actuators for generating oscillations in the mechanical oscillator, and a sensing subsystem for receiving the Coriolis response from the fluid through the mechanical oscillator, wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separate, and an electronic circuit coupled to the mechanical oscillator subsystem; transmitting an electrical signal to trigger oscillations in the fluid via the mechanical oscillator subsystem; receiving the Coriolis response from the fluid via the mechanical oscillator; processing the Coriolis response to obtain one or more measurements representative of the one or more fluid properties of the fluid; and monitoring the biological process using the one or more measurements, The one or more fluid properties include at least one of mass flow rate, density or temperature of the fluid.

31. The method of claim 30, wherein the mechanical oscillator subsystem includes an open profile interface for securing the flow conduit.

32. The method of claim 30 or 31, wherein the mechanical oscillator subsystem provides a linear structure or a U-shaped structure to which the fluid flow subsystem is mechanically attached.

33. A bioprocessing system for monitoring one or more fluid properties of a fluid used in a bioprocess unit, the bioprocessing system comprising: a fluid flow subsystem for transferring fluids using flow conduits in a bioprocess in said bioprocess unit; A mechanical oscillator subsystem, the mechanical oscillator subsystem comprising: a mechanical oscillator coupled to the fluid flow subsystem in a closed-loop arrangement for transmission of oscillations to the fluid and reception of a Coriolis response from the fluid, one or more actuators for generating oscillations in the mechanical oscillator, and a sensing subsystem for receiving the Coriolis response from the fluid through the mechanical oscillator, wherein the mechanical oscillator subsystem and the fluid flow subsystem are functionally separate, and an electronic circuit coupled to the mechanical oscillator subsystem and configured to obtain one or more measurements representative of the one or more fluid properties of the fluid, and wherein the fluid flow subsystem and the mechanical oscillator subsystem form a Coriolis flow meter; as well as A monitoring unit is configured to receive the measurements representing the one or more fluid properties of the fluid and to use the measurements to control the biological process.

34. The bioprocessing system of claim 33, wherein the mechanical oscillator subsystem provides a linear structure or a U-shaped structure to which the fluid flow subsystem is mechanically attached.

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