Flow measurement system for disposable containers

Abstract

A venturi flow meter for connection to a disposable container is provided. The venturi flow meter includes a meter body formed of a polymer and configured for allowing fluid flow therethrough. A first annular diaphragm is mounted adjacent an inner surface of the meter body and has a first inner diameter. A second annular diaphragm is mounted adjacent the inner surface of the meter body and has a second inner diameter different than the first inner diameter.

Description

[0001] This application is a divisional application of the patent application filed by Rosemount Corporation on November 9, 2016, with application number 201611035233.0, entitled "Flow Measurement System for Disposable Containers". Background Technology

[0002] Single-use containers, such as bioreactors, are used to generate and support biological reactions for a variety of purposes. The life sciences industry has progressed from large, capital-intensive facilities made of stainless steel with extensive in-situ cleaning (CIP) infrastructure to smaller facilities using polymer bags or containers as bioreactors. Bioreactor bags are used once and then discarded. Single-use bioreactor technology significantly reduces plant costs. For example, in existing facilities using stainless steel CIP infrastructure, up to 90% of the cost of operating the equipment can be due to the in-situ cleaning infrastructure, which includes very high-end instruments designed to withstand steam cleaning cycles. By progressing to manageable single-use bioreactor bags, the capital-intensive CIP portion can be eliminated, and the equipment can be more flexible and smaller, which in turn allows for smaller batch production for more targeted drug therapies and other small-scale applications.

[0003] As pharmaceutical manufacturers shift from larger stainless steel process containers to smaller, pre-sterilized, single-use plastic bag systems, there is a need to measure process variables within these systems to control growth environments and subsequent processes. Typically, pharmaceutical manufacturers and the life sciences industry have used relatively inexpensive sensors and relatively natural methods derived from fluid isolation, such as silica gels. These methods can lead to inaccurate measurements, which is unacceptable for the life sciences industry, which uses these materials to support a wide range of biological reactions. Summary of the Invention

[0004] A Venturi tube flow meter for connection to a disposable container is provided. The Venturi tube flow meter includes an instrument body formed of a polymer and configured to allow fluid flow through it. A first annular diaphragm is mounted near the inner surface of the instrument body and has a first inner diameter. A second annular diaphragm is mounted near the inner surface of the instrument body and has a second inner diameter different from the first inner diameter. Attached Figure Description

[0005] Figure 1 This is a schematic view of a stainless steel durable support device used in conjunction with a bioreactor bag, and embodiments of the present invention are particularly applicable to this stainless steel durable support device.

[0006] Figure 2 This is a schematic view of a disposable container system with a sterilization flow measurement system according to an embodiment of the present invention.

[0007] Figure 3 This is a sectional view of a Venturi tube flow meter using an annular seal according to an embodiment of the present invention.

[0008] Figure 4 This is a flowchart of a method for generating flow rate values ​​for fluid flow from or to a disposable container according to an embodiment of the present invention. Detailed Implementation

[0009] Users of disposable containers, such as bioreactors, expect a relatively inexpensive and relatively accurate range of instruments for these containers. A key motivation for using these disposable plastic containers is significantly reduced capital costs, as mentioned above, due to the elimination of in-situ cleaning infrastructure, faster batch turnaround times, and smaller and more flexible process capabilities. While some new products have been developed to provide higher-quality pressure and level measurements for disposable containers, currently no solution is available for measuring fluid flow to or from these containers.

[0010] Embodiments of the present invention generally provide an efficient solution for measuring flow rates in disposable containers, such as bioreactors. According to embodiments of the invention, a polymer-based venturi flow meter is used in conjunction with a relatively high-quality differential pressure measuring device. The portion of the venturi flow meter in contact with the flowing fluid is constructed using a relatively low-cost polymer, such as a plastic, and may be pre-sterilized. In one embodiment, the venturi flow meter is then fluidly connected to the relatively high-quality differential pressure measuring device. It should be noted that although embodiments of the invention have been described with respect to a single differential pressure measuring device associated with the venturi flow meter, embodiments of the invention can be practiced using this measurement performed by a separate device.

[0011] For disposable containers such as bioreactors, fluid flow measurement presents particular challenges. In particular, these containers often contain living cells or organisms. As these cells or organisms flow through the system, they are often particularly susceptible to sudden stresses or other significant forces. Therefore, to effectively measure flow parameters for liquids that may contain living cells or organisms, it is important to do so with minimal disturbance to the flow distribution. For example, living cells conveyed in and / or from a bioreactor in tubes must be handled carefully to prevent rupture or other undesirable effects. Accordingly, some embodiments of the invention typically provide polymeric venturi tubes with suitably large chokes to minimize disturbance to fluid flow.

[0012] Figure 1This is a schematic view of a bioreactor, which is particularly applicable to this embodiment. The bioreactor 100 includes a rigid support 102, which includes a polymer bag 104 and a plurality of tubes 106, 108. Multiple sensors and / or tubes of the bioreactor are connected to an analyzer 110, which is capable of measuring or otherwise determining multiple aspects of the bioreaction and / or the biofluid therein, and providing information about the bioreaction and / or the biofluid. The polymer flow measurement system according to an embodiment of the invention would typically be attached to one or more of the tubes 106, 108 connected to the polymer bag 104.

[0013] Figure 2 This is a schematic view of a polymer bioreactor bag 104 disposed within a rigid container 102. A biofluid, such as cell culture or fermentation paste 112, is disposed within the bioreactor bag 104 and undergoes the biological reaction of interest. Tubes or hoses 114 are connected to the interior of the polymer bag 104 via ports 116. Accordingly, any suitable fluid can flow into or from the bioreactor bag 104 via the tubing 114, as indicated by the bidirectional arrows 115.

[0014] like Figure 2 As shown, a pressure measuring device, such as a differential pressure transmitter 130, is fluidly connected to a Venturi flow meter 132 via liquid-filled pulse lines 134, 136. In one embodiment, the liquid in the liquid-filled pulse lines 134, 136 is substantially incompressible, such as that via a pair of annular diaphragms ( Figure 3 (As shown) The bioreactive fluid flowing through pipe 114 is isolated from water or silicone oil. Alternatively, any fluid that is substantially incompressible at the pressure of the fluid flowing through venturi flow meter 132 can be used. Thus, if the venturi flow meter is suitable for relatively low-pressure applications, then the fluid in lines 134, 136 can be slightly compressible, provided that the fluid is substantially incompressible relative to the pressure flowing through venturi flow meter 132.

[0015] The Venturi flow meter 132 is connected to the cooperating fittings 138 and 140 via any suitable connector, such as the known three-clamp couplings 142 and 144. (See also:) Figure 3 and Figure 4More specifically, as fluid flows through the Venturi tube flowmeter 132, the fluid flow rate generates different pressures via liquid-filled pulse lines 134, 136. In one embodiment, the pressure in lines 134, 136 is sensed by a differential pressure measurement transmitter 130, and the value of the measured differential pressure is converted into a flow-related value, such as flow rate or mass flow rate, via hardware, software, or a combination thereof. Furthermore, the pressure of the fluid itself can also be measured and indicated via any suitable technology. Once the differential pressure measurement transmitter 130 has measured or otherwise determined the flow-related value, the flow-related value can be displayed locally at the bioreactor and / or transmitted to a remote device. Further, in some embodiments, instrument 130 can also perform diagnostics and / or bioreactoring regarding the device itself to provide additional information beyond simply reporting the pressure in the disposable bioreactor bag 104. Even further, instrument 130 can also be configured to transmit flow-related information to one or more additional devices via a process communication loop or segment, such as a high-speed channel addressable remote converter. These are process communication loops or segments of protocols such as the FOUNDATION™ fieldbus protocol. However, other suitable wired and / or wireless process communication protocols according to embodiments of the invention may be used. Furthermore, the embodiments described herein may also include wirelessly transmitting the flow-related information to any suitable device via antenna 120 according to a wireless process communication protocol such as IEC 62591. In one embodiment, instrument 130 is a commercially available clean pressure transmitter sold under the trade name model 3051, obtained from Emerson Process Management, Shakopee, Minnesota.

[0016] Figure 3 This is a sectional view of a Venturi tube flow meter according to an embodiment of the present invention. In one embodiment, the Venturi tube flow meter 132 is formed of plastic, which is sterilized by radiation, such as by using gamma radiation. The Venturi tube flow meter 132 includes a pair of annular diaphragms 146, 148 fluidly connected to corresponding liquid-filled pulse lines 134, 136. Each annular diaphragm is formed generally of a rectangular portion of a flexible polymer, the longer side of which is aligned transversely to the axis of the instrument body 152, thereby forming a ring, or at least a partial ring, around the inner diameter of the instrument body 152.

[0017] Although embodiments of the invention can be practiced in which the annular diaphragms 146 and 148 do not extend completely around the inner diameter of the instrument body 152, at least one embodiment includes an annular diaphragm that extends completely around the inner diameter of the instrument body 152. Additionally, as Figure 3As shown, annular diaphragms 146 and 148 are arranged around the inner diameter of the instrument body 152 at locations with different diameters. As shown, annular diaphragm 146 is located at a portion of the relatively larger diameter of the inner diameter of the instrument body 152, while annular diaphragm 148 is located at a necked region 150 having a relatively smaller diameter compared to the portion connecting to annular diaphragm 146. In one embodiment, annular diaphragms 146 and 148 are made of plastic and formed to the inner surface of the instrument body 152, and plastically welded in place. Accordingly, each annular diaphragm 146 and 148 moves in response to pressure changes in the instrument body 152. This movement is then transmitted via liquid-filled pulse lines 134 and 136 to another diaphragm, such as the sensing diaphragm in the differential pressure transmitter 130. The Venturi tube flowmeter 132 provides an effective differential pressure generator with satisfactory range capability, high pressure recovery, and strong signal generation. By using an annular seal upstream of the venturi tube and another annular seal downstream of the venturi tube, the differential pressure signal transmitted to the differential pressure transmitter 130 can be easily converted by the differential pressure transmitter 130 into a flow-related value such as flow rate or mass flow rate, and transmitted to any suitable device and / or indicated locally by the differential pressure transmitter 130.

[0018] According to embodiments of the invention, the instrument body 152 and sealing system can be formed from sufficiently low-cost materials, such that, apart from the differential pressure transmitter 130, the entire system can be considered for single use. In one embodiment, the venturi / sealing system is delivered to the end user under pre-sterilization conditions and is ready to be connected to a single-use container. Conversely, the differential pressure transmitter, such as transmitter 130, is a durable component of the infrastructure supporting the bioreactor process. This method utilizes a high-performance differential pressure transmitter 130 and allows the user to maintain all supporting infrastructure, including possible FDA traceability.

[0019] Figure 4This is a flowchart of a method for measuring the flow rate of fluid flowing into or from a disposable container according to an embodiment of the present invention. Method 200 begins at block 202, where a flow rate with respect to the disposable container is generated. This flow rate can enter or exit the container. Then, at block 204, a first venturi pressure is transmitted to a pressure measuring device via a fluid-filled isolation system. An example of block 204 is that the pressure is transmitted from instrument body 152 to differential pressure transmitter 130 via fluid-filled pulse line 134. At block 206, a second venturi pressure is transmitted to the pressure measuring device via a second fluid-filled system. An example of block 206 is that the pressure is transmitted from an annular diaphragm 148 to differential pressure transmitter 130 via fluid-filled pulse line 136. However, those skilled in the art will recognize that blocks 204 and 206 can be performed using two different pressure measuring devices. Furthermore, the description of the first and second pressures is not intended to indicate that one occurs after the other. Instead, "first" and "second" are provided only as labels to increase clarity. Then, at block 208, the pressure difference between the pressures provided by the first fluid filling system and the second fluid filling system is measured. In one embodiment, this is achieved by directly measuring the pressure difference between the pressures delivered by the fluid filling pulse lines 134 and 136. However, embodiments of the invention can be practiced where each pressure is measured separately and the difference is calculated. Furthermore, each individual pressure measurement can be performed using separate devices, and the difference can be calculated using yet another device.

[0020] Then, at block 210, the flow rate value is determined based on the measured differential pressure. In one embodiment, the flow rate value may be a flow velocity 212, while in another embodiment, the flow rate value may be a mass flow rate 214. Finally, at block 216, the flow rate value is provided as an output. This output may be provided locally to the process controller via a device such as the differential pressure measuring transmitter 130, or remotely to the process controller, or via process communication to a monitoring device, as described above.

[0021] Embodiments of the present invention provide a low-cost solution for flow measurement of disposable containers, such as bioreactors. Devices constructed according to embodiments of the invention can be easily sterilized in the field and / or during manufacturing. When sterilized during manufacturing, the device can be housed in aseptic packaging, eliminating the need for end-users to perform any sterilization prior to use. Furthermore, the system can be provided with pre-filled liquid-filled pulse lines, allowing end-users to simply remove the shipping cap from each line and place the diaphragm or flexible diaphragm of each pulse line against the corresponding isolating diaphragm of the differential pressure transmitter. Of course, the embodiments can also be implemented during commissioning with the liquid-filled pulse lines pre-filled at the user's location.

[0022] Although the invention has been described with reference to preferred embodiments, those skilled in the art will recognize that changes in form and detail may be made without departing from the spirit and scope of the invention.

Claims

1. A Venturi tube flow meter for connection to a disposable container, the Venturi tube flow meter comprising: An instrument body, the instrument body being formed of a polymer and configured to allow fluid flow through it; A first annular diaphragm is mounted near the inner surface of the instrument body and has a first inner diameter; A second annular diaphragm is installed near the inner surface of the instrument body and has a second inner diameter different from the first inner diameter; and A first pulse line connected to a first annular diaphragm, wherein the first pulse line contains an incompressible fluid; A second pulse line connected to a second annular diaphragm, wherein the second pulse line contains an incompressible fluid; Each of the first and second annular diaphragms is constructed of plastic; and Among them, the Venturi tube flow meter is sterilized and placed in aseptic packaging.

2. The Venturi tube flow meter according to claim 1, wherein: The instrument body is made of plastic.

3. The Venturi tube flow meter according to claim 1, wherein: At least one of the first and second annular diaphragms extends completely around the inner diameter of the instrument body.

4. The Venturi tube flow meter according to claim 1, wherein: Each of the first and second pulse lines is filled with water.

5. The Venturi tube flow meter according to claim 1, wherein: The instrument body, the first pulse line, and the second pulse line are housed in sterile packaging.

6. The Venturi tube flow meter according to claim 1, wherein: Each of the first and second pulse lines is fluidly connected to the pressure measuring instrument.

7. The Venturi tube flow meter according to claim 6, wherein: Each of the first and second pulse lines is fluidly connected to the same pressure measuring instrument.

8. The Venturi tube flow meter according to claim 7, wherein: The pressure measuring instrument is a differential pressure transmitter.

9. The Venturi tube flow meter according to claim 8, wherein: The differential pressure transmitter is configured to measure the pressure difference between the pressure in the first pulse line and the second pulse line and to determine the flow-related value output.

10. The Venturi tube flow meter according to claim 9, wherein: The output of flow-related values ​​is transmitted according to the process communication protocol.

11. The Venturi tube flow meter according to claim 10, wherein: The process communication protocol is a wireless process communication protocol.

12. A method for measuring the flow rate of a bioreaction fluid, the method comprising the following steps: Provides a venturi tube instrument body formed of polymer; The flow rate of the generated bioreaction fluid through the main body of the Venturi tube instrument; The difference between a first venturi pressure at a first position in the instrument body and a second venturi pressure at a second position in the instrument body is measured, the second position having a diameter different from that of the first position in the instrument body; The flow-related values ​​of the bioreaction fluid are determined based on the measured difference between the pressure in the first and second venturi tubes. and Provide traffic-related values ​​as output. The pressure of the first venturi tube is measured by connecting an annular diaphragm located at the first position to a pressure measuring instrument. Each of the first and second annular diaphragms is constructed of plastic.

13. The method according to claim 12, wherein: The pressure of the second venturi tube is measured by connecting the annular diaphragm located at the second position to a pressure measuring instrument.

14. The method according to claim 12, wherein: The flow rate-related values ​​are determined by using a differential pressure transmitter.

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