CN206244792U

CN206244792U - Disposable bioreactor sensor interface

Info

Publication number: CN206244792U
Application number: CN201621346492.0U
Authority: CN
Inventors: 冯昌东
Original assignee: Rosemount Analytical Inc
Current assignee: Rosemount Inc
Priority date: 2016-09-28
Filing date: 2016-12-08
Publication date: 2017-06-13
Anticipated expiration: 2026-12-08
Also published as: CN107868756A

Abstract

Propose a kind of bioreactor sensing system.Bioreactor sensing system includes biological reaction container.Biological reaction container includes being configured to provide the hole at the interface for monitoring the content in biological reaction container.Biological reaction container is additionally included at the neighbouring hole port for being connected to biological reaction container.Bioreactor sensing system also includes the sensing device further being at least partially disposed in port so that sensing element is exposed to content.Bioreactor sensing system also includes being configured to be applied to the outer seal in a part for a part for sensing device further and port.

Description

Disposable bioreactor sensor interface

Cross-Reference to Related Applications

The application is based on and requires the U.S. Provisional Patent Application Serial No. 62/265 submitted on December 10th, 2015, 819 rights and interests, its content is incorporated herein by reference in their entirety.

Technical field

The utility model is related to a kind of disposable bioreactor sensor interface and the sealing for bioreactor Formula sensor interface system.

Background technology

Bioreactor supports the biological respinse for many important applications, including cell culture, fermentation etc..Biological respinse The influence of temperature, pressure, pH and other changes may easily be received.In addition, with the carrying out of biological respinse, reaction in itself may Change the various parameters in biological reaction container, such as dissolved oxygen content and/or pH.Therefore, one is monitored over time Or multiple process variables are probably important to track the progress of biological respinse.

Life science industry away from by stainless steel making, with the big of large-scale cleaning in place (CIP) infrastructure Type, capital-intensive equipment, and towards by the use of the small-sized of the bag as disposable bioreactor based on polymer or container Equipment development.Disposable bioreactor bag can be only used once and be abandoned afterwards.Can using disposable bioreactor With the capital cost needed for significant reduction factory.For example, in the existing equipment using stainless steel CIP infrastructure, up to 90% running cost is probably related to CIP infrastructure, including is designed to bear the high-end of steam clearing cycle Instrument.By using disposable disposable bioreactor bag, the CIP parts of capital cost can be eliminated, equipment can be with Flexible and much smaller, this then allows the production of more small lot, for example for more targeted drug therapy and its Required for its small-scale application.

Utility model content

Propose a kind of bioreactor sensing system.Bioreactor sensing system includes biological reaction container.It is biological Reaction vessel includes being configured to provide the interface for monitoring the content in biological reaction container or interface (interface) Hole.Biological reaction container is additionally included at adjacent bores the port for being connected to biological reaction container.Bioreactor sensing system Also include the sensing device further being at least partially disposed in port so that sensing element is exposed to content.Bioreactor sense Examining system also includes being configured to be applied to the outer seal in a part for a part for sensing device further and port.

Brief description of the drawings

Fig. 1 is embodiment of the present utility model to its particularly useful disposable bioreactor (single-use Bioreactor schematic diagram).

Fig. 2A and Fig. 2 B are the schematic diagram of the sensor for being connected to disposable bioreactor bag (bag)；

Fig. 3 is the connection of the sealing between sensor and bioreactor port according to one embodiment of the present utility model The schematic diagram for connecing；

Fig. 4 A-4D are the sensor for being connected to the port on bioreactor according to one embodiment of the present utility model Schematic diagram；

Fig. 5 is the flow of the method sealed sensor according to embodiment of the present utility model to bioreactor port Figure.

Specific embodiment

Disposable bioreactor can have one or more interfaces or interface or joint interface (interface), its Being configured to attachment can be carried out and the sensor device of monitoring process variable with reaction.Promote disposable, disposable Using and using and provide the reliable tool interface system for sealing between instrument and bioreactor simultaneously for bioreaction technology will It is the significant benefit for life sciences industry.

Fig. 1 is schematic diagram of the embodiment of the present utility model to its particularly useful disposable bioreactor.Sensor Device 30 for measurement disposable bioreactor 20 in biological specimen characteristic, such as pressure, temperature, pH, dissolved oxygen etc. It is useful.Sensor 30 can be installed to disposable bioreactor 20 and be arranged to offer relative to being pointed to biology The electricity instruction of sample 22 in reactor 20 parameter interested.Sensor 30 is connected to suitable analyzer, and the analyzer is carried Reading and/or other suitable instructions for the parameter interested for sample 22.

In the application of disposable bioreactor, various sensor devices (such as sensor 30) be desirably integrated into or with Other modes are connected to bioreactor bag.According to embodiment as herein described, set between sensor and bioreactor Mechanical interface.Mechanical interface can be easy to be arranged on sensor in port.Mechanical interface can also provide the one of high reliability Property.In one embodiment, mechanical interface can include seal, its prevent bioreactor fluids leak into environment and Pollution of the environment to biological reaction material.In one embodiment, main body of the mechanical interface at least in part with sensor is Chong Die And/or it is Chong Die with the sensor receiving port on bioreactor at least in part.The use of outer seal can be than relying on Extra benefit is provided in the current system of inner sealing mechanism.

Fig. 2A and 2B are to show that current sensor device is connected to one kind of disposable bioreactor bag by port 40 The schematic diagram of mode.As shown in Figure 2 A, disposable bioreactor bag generally has so-called " port with barb ".Band barb Port 40 generally include the round flange 42 intersected with cylindrical side wall 44 with approximate right angle 46.Hose barb 49 is arranged on circle The distal end 48 of cylindrical side wall 44, hose barb 49 is configured to interfere with the deformable side wall of flexible pipe (such as rubber or elastic hose) (interfere).Port 40 with barb is common on disposable bioreactor, and biological respinse is connected to receive The flexible pipe of device.

Flange 42 can be attached in any suitable manner bioreactor bag in hole, such as ultrasonic bonding, or By using any other suitable method.Flange 42 can be arranged in bioreactor so as to wall 44 passes through bioreactor Hole in bag.Flange 42 can also be connected to the outer surface of bioreactor bag, so that cylindrical side wall 44 is not passed through biology instead Answer the hole in device bag.Therefore, the port 40 with barb is highly useful, and for pipe provides spirit to disposable bioreactor Connection selection living.Therefore, it is desirable to any outside sealing mechanism and the existing port compatible with barb.

At present, the sensor device of such as sensor device 50 is designed to be located at the barb of disposable bioreactor bag In the such as port 40 of port.The external diameter of sensor 50 is sized such that it can be coupled to the internal diameter of cylindrical side wall 44 51 Within.O-ring 52 is configured to combine the internal diameter 51 of cylindrical side wall 44, to cause that sensor device 50 is sealed in band barb Port 40 in.

Sensor 50 can include any suitable sensing device further, and the sensing device further is configured to provide relative to biology The electricity instruction of the parameter interested of the biological sample in reactor bag.Such sensor can include temperature sensor, pressure Force snesor, dissolved oxygen sensor, carbon dioxide sensor, conductivity sensor, pH sensors, visual sensor (colorimetric sensors) or it is configured to any other suitable sensor of detection parameter interested.Work as sensing Device 50 is correctly mounted when in cylindrical side wall 44, and component can be as shown in Figure 2 B.However, it has been found that cylindrical side The inner surface of wall 44 may not have appropriate quality control, to be reliably formed sealing using O-ring 52.End with barb The critical design aspect of mouth 40 is to be connected to one section of pipe, and allows fluid to flow through wherein.In order that with cylindrical side wall 44 Seal sensor 50 is carried out on surface, possibly cannot be realized for the suitable strong fluid of all applications using only O-ring 52 and/or Mechanical seal.If installed therein in sensor device 50 for example, there is cut on the internal diameter 51 of cylindrical side wall 44 There is the risk that fluid is leaked by cut afterwards.Outer seal can provide more reliable and more strong sealing.

In one embodiment, sensor draw bail may include the use of outer seal to avoid fluid through sensing Any one of device 50 or cylindrical side wall 44.This outer seal may be utilized independently and be sealed to life with by sensor mechanism Thing reactor, or made in addition to the inner sealing mechanism as described by Fig. 2A and 2B in the case of needing redundant seal part With.

Fig. 3 is the connection of the sealing between sensor and bioreactor port according to one embodiment of the present utility model The schematic diagram for connecing.In one embodiment, outer seal can provide the connection knot for current sensor-bioreactor The extra protection of structure.For example, outer seal can be placed on the upper of the sensor-port assembly shown in Fig. 2 B.Another In individual embodiment, outer seal is used in the case of not having additional sealing mechanism between sensor and port.

Outer seal can support the use of the structure of many a variety of biosensor organism reactor bags.Outside sealing Part can also provide O-ring between ratio such as sensor and port more reliable and more strong sealing.Can expect will be biological anti- The reactant mixture in device 102 is answered to isolate with the environment 100 outside bioreactor 102.In one embodiment, seal 110 can be placed on interface or connection place between sensor 104 and sensor port 106, to strengthen or generating in reaction Barrier between mixture and environment 100.

In one embodiment, sensor 104 has the external diameter of the internal diameter less than the sensor port 106 for receiving, and The external diameter is configured to mate in the internal diameter in the port 106 for receiving sensor.Sensor port 106 can be by with one The material of fixed elasticity is formed so that it can more easily receive sensor 104, without significant gap.In an implementation In example, at least a portion of sensor 104 is configured to fit within sensor port 106.Port coupling part 116 is constructed Sensor coupling part 114 is connected in parallel into being received at joint 120.Port section 116 and Sensor section 114 are constructed To be for example assembled together with corresponding shape.

In one embodiment, seal 110 is configured to at least a portion of sensor 104 and port 106 Partly overlap so that it crosses over joint 120.Sensor section 114 physically connects with port section 116 at joint 120 Close (interface with).In one embodiment, Sensor section 114 for example by the interlocking of individual features physically It is connected to port section 116.In one embodiment, joint 120 extends substantially along the whole circumference of sensor 104. Along joint 120, sensor coupling part 114 and port coupling part 116 can have different possibility shape and structure. In one embodiment, the shape of the form fit port section 116 of Sensor section 114.

Fig. 4 A-4D show the sensing for being connected to the port on bioreactor according to embodiment of the present utility model Device.As shown in Figure 4 A, in one embodiment, the port 140 with barb includes that one extended along the circumference of port 140 is fallen Hook 149.In one embodiment, barb 149 is located substantially on the edge of port 140.However, port 140 can include multiple Barb 149, or including along port 140 length extend barb 149 part, and the circumference including port 140 one Individual or some.In one embodiment, barb 149 is hose barb.In one embodiment, port 140 is configured to Sensing device further 160 is received along the direction shown in arrow 150, as shown in Figure 4 B.Therefore, at least some embodiments shown in this article The port with barb of disposable bioreactor need not be changed.This is probably useful, so as in sensor 160 and market The more firmly sealing of (substantial) is provided between upper existing existing bioreactor.

Fig. 4 B show the sensing device further 160 with sensing end 168, and sensing end 168 is configured to sensing and biological respinse One or more parameters that reactant mixture in device is associated.In one embodiment, sensor 160 be cylinder form simultaneously And be configured to mate in the inside diameter 151 of the port 140 with barb.In one embodiment, sensor 160 includes edge The hose barb 164 of the length positioning of the outer surface of sensor 160.In one embodiment, barb 164 is located at from sensing end At a certain distance from 168.Sensing the distance between end 168 and barb 164 allow when can be chosen in fully-inserted port 140 Sensing end 168 is exposed to reactant mixture.

In one embodiment, sensor barb 164 is configured to be cooperated with the barb 149 on port 140 so that for example The outer seal 162 for showing in figure 4 c forms strong mechanical seal between sensor 160 and port 140.At one In embodiment, the strong material including flexible of seal 162.In one embodiment, seal 162 includes elastic tube.When When sensing device further 160 is installed to barb port 140, elastic tube or artificial rubber pipe 162 (elastomerictubing) are generally Slided on the external diameter of sensor device 160, the square upward sliding for preferably being indicated in arrow 166.In one embodiment, it is close Sealing 162 can be attached to sensor 160 before port 140 is inserted.In another embodiment, seal 162 can passed Sensor 160 is attached after being connected to port 140.

In one embodiment, it is once elastic tube 162 is located so that it extends above and below barb 164, then whole The component of 160/ seal of individual sensor 162 is connected to port 140.In one embodiment, the component of 160/ seal of sensor 162 It is configurable to be connected to port 140 so that barb 164 abuts (abuts) barb 149, for example as shown in Figure 4 D.Therefore, exist In one embodiment, hose barb 164 sets sensing end 168 one relative to the position at the sensing end 168 of sensing device further 160 Relative depth in secondary property bioreactor.In the embodiment shown in Fig. 4 A-4D, sensing end 168 substantially with barb The inner wall section of port 40 is flushed.It is envisaged, however, that other desired depths at sensing end 168.For example, in some embodiments In, sensing end 168 substantially extends possible to be interacted with reactant mixture therein in disposable bioreactor It is beneficial.

In at least one embodiment, for example as shown in Figure 4 D, there is barb 164 direction opposite with barb 149 to orient. This opposite directionality cause the component of 160/ seal of sensor 162 along shown in arrow 150 direction slide when will with Stop when barb 149 is contacted.In one embodiment, when in place, 160/ seal of sensor 162 is produced and port 140 Firm machinery and Fluid Sealing.However, it is expressly contemplated that, wherein barb 149 and 164 has substantially the same directionality Embodiment can implement.Although in addition, the single barb that the implementation being illustrated in figures 4A and 4 B is illustrated on port 140 The Barb portion 164 divided on 149 and sensor 160, in other embodiments, each Barb portion can include multiple barb Point.Additionally, pipe 160 can include any suitable polymeric material, it can fully deform and its own bias flexible pipe is fallen Hook portion 149 and 164, to produce the sealing of high reliability between the port with barb and sensor device.

Fig. 5 is one kind side that sensor is sealed to bioreactor port according to one embodiment of the present utility model The flow chart of method.Method 200, shows for placing strong between bioreactor port and external environment condition as shown in Figure 5 One illustrative methods of seal.In one embodiment, bioreactor is disposable with one or more ports Bioreactor, one or more ports are configured to receive one or more sensors monitor the change of one or more processes Amount.In one embodiment, bioreactor bag has the sensor port with barb, such as shown in Fig. 4 A-4D.However, It is expected that other port organizations that can couple with sensor.For example, in one embodiment, it is possible to use different ports Structure, it can fully receive sensing element and potted component.

In block 210, sensing element is obtained.Sensing element can be pressure sensor, temperature sensor or any other Appropriate sensor, to detect any appropriate parameter to monitor ongoing reaction in bioreactor.In an implementation In example, the sensor for obtaining in block 210 includes being configured to allow for the connection with the port mechanical attachment on bioreactor bag Binding structure.In one embodiment, bioreactor bag includes the port with barb, and sensor also includes falling accordingly Hook.Barb on sensor and port can be oriented in the same direction or in opposite directions.

In frame 220, port is positioned for being connected with sensing device further.Bioreactor bag can include one or more Port, and based on monitoring various process variable the need for, different sensors can more advantageously be placed on different ports In.In frame 220, port is positioned for being connected to sensing element.Port is positioned such that it has and is configured to machinery Be connected to the structure of selected sensing element.

In frame 230, sensing element is positioned in the port of bioreactor bag.This can include insert the sensors into or In sliding into port.In addition, sensor can include the sealing mechanism of its own.In such an embodiment, as indicated at block 234, May need to place sealing mechanism as needed.For example, in one embodiment, the sensing element with O-ring packing can It is placed in port as second seal.However, in another embodiment, sensing element does not include potted component, such as Shown in frame 232, and sensing element positioning is included sensing element was moved to the position in port before potted component is placed Put.In one embodiment, this may include to slide sensing element until sensing element along the internal edge of selected port It is exposed to reactant mixture.In one embodiment, when the structure of the external margin along sensor is connected to or adjacent When the corresponding structure of (abuts) along the edge of port, sensor is in place.For example, in one embodiment, sensor and Both port includes barb element.

In frame 240, outer seal is set.As shown in figure 5, during sensor moves to the position in seal first, And it is connected to port after seal/sensor cluster.However, it is expressly contemplated that, seal can be in sensor quilt It is actuated into setting afterwards in port.In one embodiment, seal be configured to it is Chong Die with port at least in part, such as in frame It is shown in 242 and/or a part of Chong Die with sensor at least in part, as shown in frame 244.In one embodiment, Seal is configured to substantially cover the equal part of sensor and port.

Although describing the utility model with reference to preferred embodiment, it will be recognized to those skilled in the art that In the case of not departing from spirit and scope of the present utility model, can be changed in form and details.

Claims

1. a kind of bioreactor sensing system, including：

Biological reaction container, the biological reaction container includes：

Hole, the hole is configured to provide the interface for monitoring the content in the reaction vessel；And

Port, the port is connected to the biological reaction container at the neighbouring hole；

Sensing device further, the sensing device further is at least partially disposed in the port so that sensing element is exposed to described interior It is tolerant；And

Outer seal, the outer seal be configured to be applied to the sensing device further a part and the port one On part.

2. bioreactor sensing system according to claim 1, wherein the outer seal includes elastic tube.

3. bioreactor sensing system according to claim 1, wherein the sensing device further includes sensor construction, institute Stating port includes port organization, and wherein described sensor construction and the port organization include interface, and wherein described Outer seal fluidly seals the interface.

4. bioreactor sensing system according to claim 3, wherein the sensing element falls including sensor flexible pipe Hook.

5. bioreactor sensing system according to claim 4, wherein the port organization includes port hose barb, And wherein described port hose barb and the sensor hose barb have opposite directionality.

6. a kind of hermetic sensor interface system for bioreactor, the hermetic sensor interface system includes：

Seal, the seal includes：

Sensor receiving portion, the sensor receiving portion is configured to couple to sensing device further；

Port receiving portion, the port receiving portion is configured to couple to the port on bioreactor；And

Wherein described seal provides mechanical interface and causes that the mixture in the bioreactor is sealed to exempt to be exposed to External environment condition.

7. hermetic sensor interface system according to claim 6, wherein the sensing device further and the port are in institute State and engaged at mechanical interface.

8. hermetic sensor interface system according to claim 6, wherein the seal is pipe.

9. hermetic sensor interface system according to claim 8, wherein the pipe is elastic tube.

10. hermetic sensor interface system according to claim 8, wherein the seal is polymer pipe.

11. hermetic sensor interface systems according to claim 6, wherein the sensor receiving portion is configured to The sensor construction on the outer surface of the sensing device further is received, and wherein described port receiving portion is configured to receive Port organization on the outer surface of the port on the bioreactor.