Adapter device for a bioreactor flexible bag with light transmission function

Abstract

An adapter for a flexible bioreactor bag with optical transmission function is installed on a flexible bag with a through-hole at the bottom. The adapter includes an optical sensing film, an optical fiber, a lens assembly, an inner base, and an outer connector. The inner base is fixed integrally with the bottom of the flexible bag and has a central light-transmitting hole directly opposite the through-hole. The optical sensing film, carrying a fluorescent substance capable of detecting the information to be measured inside the flexible bag, is directly adhered to the light-transmitting hole. The outer connector is detachably inserted below the inner base. The lens assembly is located inside the outer connector and aligned with the light-transmitting hole and the optical sensing film. The optical fiber passes through the outer connector and connects to the lens assembly. Excitation light is input along the optical fiber and reflected by the lens assembly, then passes through the light-transmitting hole to reach the optical sensing film. Irradiating the optical sensing film generates emitted light with an intensity correlated with the information to be measured. This emitted light is output through the optical fiber via the original optical path to complete the detection. This invention achieves convenient installation and operation, stable optical signal intensity, and avoids air bubble residue. It has the advantages of wide applicability and long service life.

Description

Technical Field

[0001] This invention relates to bioreactor systems, and more particularly to a transfer device for a flexible bioreactor bag with light transmission function, belonging to the field of biotechnology. Background Technology

[0002] Bioreactors are crucial equipment in bioengineering, primarily used in cell culture, pharmaceutical production, plant and animal tissue culture, microbial fermentation, and biopharmaceutical preparation. Single-use bioreactors utilize disposable reaction bags, replacing culture containers made of stainless steel or glass. A typical single-use bioreactor consists of a disposable flexible plastic bag and a permanent rigid support structure (such as a rocking support or steel cylinder) enclosing the bag. Because the disposable flexible reaction bag is for single use and must be replaced after each experimental or production stage, it eliminates the need for cleaning, sterilization, and related process cleaning certification processes required after using permanent bioreactors. This results in reduced downtime and turnaround time, increased production changeover flexibility, and other advantages. Furthermore, single-use bioreactors have a simple structure and small footprint, reducing fixed investment and operating costs for R&D and pilot production, saving workspace, energy, and labor consumption, and shortening the time to market for new products. Therefore, in recent years, single-use bioreactors have been increasingly adopted in modern biopharmaceutical processes and are expanding into broader application areas.

[0003] To monitor the reaction environment conditions within a disposable bioreactor, such as pH and dissolved oxygen levels, sensors, including an optical sensing membrane, are typically installed in the disposable reaction bag. This membrane contains fluorescent material and is placed at the bottom of the disposable reaction bag, within the reactant environment. Light of a specific wavelength is incident from the outside and reflected off the membrane; information about the environment inside the disposable reaction bag is obtained from the analysis of the reflected light. Therefore, determining how to guide the test light into and out of the sealed bioreactor becomes a crucial technical challenge, which is particularly difficult for disposable reaction bags made of flexible materials.

[0004] The existing technology addresses the above problems by employing a sensing film fixing component integrated with a flexible bag and an optical adapter component disposed outside the flexible bag. The sensing film fixing component includes a bag attachment component welded to the flexible bag and a sensor attachment component pressed onto the bag attachment component. The optical sensing film is disposed on the sensor attachment component and in direct contact with the reactants inside the flexible bag. An optical fiber and lens assembly for conducting excitation light are fixedly connected to the optical adapter component. The optical adapter component is rotatably connected to the sensing film fixing component, and the two components are joined together by locking devices on both components, thereby enabling communication between the optical fiber and the optical sensing film. However, this technology has the following drawbacks:

[0005] First, the optical fiber and lens assembly that conduct the excitation light are all mounted on the optical adapter component. When the disposable reaction bag needs to be replaced or the optical fiber or lens assembly needs to be repaired or replaced, the optical adapter component must be rotated off the sensing film fixing component. Since the locking device has a relatively complex structure and a large locking strength, not only is the rotational installation and removal operation troublesome, but it is also easy to cause long-term damage or even breakage of the optical fiber due to rotational stress. This not only causes changes in the signal intensity between the optical sensing film and the lens, but also shortens the service life of the optical adapter component.

[0006] Secondly, the optical sensing film on the sensing film fixing component is set in the sensor attachment component, which is pressed onto the bag attachment component. Therefore, this pressure-bonded structure is very small and complex, making assembly inconvenient. Moreover, the solution inside the flexible bag may leak from the gap between the sensor attachment component and the bag attachment component and enter the light transmission hole. In addition, the optical sensing film is located in the recessed area of ​​the bag attachment component, which makes it easy for residual air bubbles to accumulate there. All these factors will affect the accuracy of the measured optical signal. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of existing technologies and provide an adapter for a flexible bioreactor bag with optical transmission function. The adapter mounts an optical fiber and lens assembly on an external connector, and fixes an internal base to the bottom of the flexible bag. The external connector is then connected to the internal base via an insert method, thereby avoiding the influence of rotational stress on the optical fiber during installation. Simultaneously, the optical sensing film is directly adhered to the light-transmitting hole of the internal base via an adhesive method, avoiding the risk of air bubble residue and leakage at the optical sensing film. This achieves the effects of convenient installation and operation, stable optical signal strength, and extended device lifespan.

[0008] Based on the above objectives, the technical solution provided by the present invention is as follows:

[0009] An adapter for a flexible bioreactor bag with light transmission function is installed at the bottom of the flexible bag, which has a through hole. The adapter comprises an optical sensing film, an optical fiber, a lens assembly, an inner base, and an outer connector. The inner base is fixedly connected to the bottom of the flexible bag and has a central light-transmitting hole facing the through hole. The optical sensing film is directly adhered to the light-transmitting hole and carries a fluorescent substance capable of detecting information to be measured inside the flexible bag. The outer connector is detachably inserted into the center below the inner base. The lens assembly is disposed inside the outer connector and aligned with the light-transmitting hole of the inner base and the optical sensing film. The optical fiber passes through the outer connector and is connected to the lens assembly.

[0010] The excitation light is input along the optical fiber and reflected by the lens assembly, and then reaches the optical sensing film through the light-transmitting hole. The excitation light irradiates the optical sensing film and generates emitted light with an intensity related to the information to be measured inside the flexible bag. The emitted light is transmitted through the original optical path and output through the optical fiber to complete the detection.

[0011] As a further improvement, the inner base includes a disc portion, a hook, and a pair of elastic clamps. The disc portion is fixedly connected to the flexible bag. The light-transmitting hole is located at the center of the disc portion. The hook protrudes downward and is connected to the lower side of the disc portion, and is symmetrically arranged at one end of the radial axis of the disc portion. The lower end of the hook is provided with a horizontal clamping plate. The pair of elastic clamps protrudes downward and is connected to the lower side of the disc portion, and is symmetrically arranged at the other end of the same radial axis. The lower end of the elastic clamps is provided with jaws that can elastically deform, and the jaws of the pair of elastic clamps form jaws.

[0012] As a further improvement, the inner base is located on the outer side of the bottom of the flexible bag, the upper side of the disc portion is plastically welded to the flexible bag, and the optical sensing film is sandwiched between the light-transmitting hole of the disc portion and the through hole of the flexible bag.

[0013] As a further improvement, the disc portion of the inner connector is located on the inner side of the bottom of the flexible bag, and the periphery of the lower side of the disc portion is welded to the flexible bag as a whole.

[0014] As a further improvement, the external connector includes a flat cylindrical portion and a retaining shaft. The retaining shaft is fixedly connected to one side of the flat cylindrical portion along its radial axis. The flat cylindrical portion has an internal cavity for placing the lens assembly, and a retaining groove is provided at the lower part of one of its outer ends. The position of the retaining groove corresponds to the retaining hook of the internal base. The retaining shaft has an optical fiber hole for inserting the optical fiber, which communicates with the internal cavity of the flat cylindrical portion. The position of the retaining shaft corresponds to the jaws of a pair of elastic clamps of the internal base. The retaining hook is engaged in the retaining groove, and the retaining shaft is pressed into the jaws and held by the two clamping feet, thereby positioning and fixing the external connector to the internal base.

[0015] As a further improvement, the hook and slot are aligned with the elastic caliper and shaft.

[0016] Compared with the prior art, the present invention achieves the following effects:

[0017] 1) The present invention mounts the optical fiber and lens assembly on a separate external connector, which is connected to the internal base by an insertion method. Therefore, the installation can be completed by simply inserting and pressing. Since the optical fiber is long and is connected to the test instrument, this insertion and pressing operation method avoids the influence of the rotational stress on the optical fiber in the prior art, reduces the risk of damage or even breakage to the optical fiber, and achieves the effect of easy operation and extended service life.

[0018] 2) The external connector can be configured as a separate component on different testing instruments, which improves the adaptability of the adapter and enhances the monitoring efficiency of the bioreactor.

[0019] 3) In this invention, the optical sensing film is directly pasted onto the light-transmitting hole of the inner base by means of an adhesive method, and is on the same plane as the bottom of the flexible bag, which completely avoids the occurrence of air bubble residue and leakage, while achieving the effect of simple and convenient installation structure and stable optical signal strength.

[0020] In summary, this invention achieves the effects of convenient installation and operation, stable optical signal intensity, avoidance of bubble residue, and improved monitoring efficiency, and has the advantages of wide applicability and long service life. Attached Figure Description

[0021] Figure 1 This is an exploded view of the structure of the present invention.

[0022] Figure 2 This is a bottom view of the present invention.

[0023] Figure 3 yes Figure 2 AA sectional view.

[0024] Figure 4 yes Figure 2 BB cross-sectional view.

[0025] Figure 5 This is a schematic diagram of the internal base.

[0026] Figure 6 This is a bottom view of the inscribed base.

[0027] Figure 7 yes Figure 6 CC section view.

[0028] Figure 8 This is a schematic diagram of the external connector.

[0029] Figure 9 This is a sectional view of the external connector.

[0030] Figure 10 This is a schematic diagram of the optical path of the present invention.

[0031] In the picture:

[0032] 01—Flexible bag, 02—Through hole, 1—Fiber optic cable, 2—External connector, 21—Flat cylindrical part, 22—Card slot, 23—Card shaft, 24—Inner cavity, 25—Fiber optic hole, 3—Lens assembly, 4—Internal base, 41—Disc part, 42—Card hook, 43—Flexible clamp, 44—Light transmission hole, 45—Clamping foot, 46—Card plate, 5—Optical sensing film. Detailed Implementation

[0033] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the following embodiments are not intended to limit the scope of protection of the present invention.

[0034] This invention is used to introduce and export excitation light and reflected light from a disposable flexible bag when monitoring reaction conditions in a bioreactor using an optical sensing membrane.

[0035] Please refer to 10. The adapter of the flexible bioreactor bag with light transmission function is installed at the bottom of the flexible bag 01. The bottom of the flexible bag 01 is provided with a through hole 02 through which light and reactants can pass.

[0036] Example 1

[0037] Please refer to the following: Figure 1 and Figure 2 The adapter in this embodiment includes an optical sensing film 5, an optical fiber 1, a lens assembly 3, an inner base 4, and an outer connector 2.

[0038] The inner base 4 is fixedly connected to the bottom of the flexible bag 01 as a whole, located on the outer side of the bottom of the flexible bag 01 and connected to the through hole 02. Please refer to the following: Figure 5, Figure 6 and Figure 7 The inner base 4 includes a disc portion 41, a hook 42, and a pair of elastic clamps 43. The upper side of the disc portion 41 is connected to the flexible bag 01. Since the flexible bag 01 and the inner base 4 are usually made of plastic, the connection method is generally plastic welding. The center of the disc portion 41 is provided with a light-transmitting hole 44, which is directly opposite the through hole 02 of the flexible bag 01 to allow detection light to pass through. The hook 42 is fixedly connected to the lower side of the disc portion 41 with a downward protrusion. The cross-section of the hook 42 is an inverted "Γ" shape, and the lower end is provided with a horizontal clamping plate 46. The pair of elastic clamps 43 are also fixedly connected to the lower side of the disc portion 41 with a downward protrusion. The lower end is provided with two opposing jaws 45 that can elastically deform. The two jaws 45 form a jaw. When the two jaws 45 are subjected to an outward force, they will bend outward and the jaw will expand. When the force is removed, the two jaws 45 spring back, and the jaw returns to its original shape. The hook 42 is symmetrically disposed at one end of the radial axis of the disc portion 41, and the pair of elastic clamps 43 are symmetrically disposed at the other end of the same radial axis.

[0039] The optical sensing film 5 is directly attached to the light-transmitting hole 44 of the inner base 4, and carries a fluorescent substance capable of detecting the information to be measured inside the flexible bag 01; please refer to [reference needed]. Figure 3 and Figure 10 The optical sensing film 5 is sandwiched between the light-transmitting hole 44 of the disc portion and the through-hole 02 of the flexible bag 01. Thus, the optical sensing film 5 contacts the reactant inside the flexible bag 01 through the through-hole 02, while simultaneously receiving the detected excitation light through the light-transmitting hole 44. Since the bottom of the optical sensing film 5 and the flexible bag 01 are on the same plane, air bubble residue and leakage are completely avoided, achieving a simple and convenient installation structure and stable optical signal intensity.

[0040] The external connector 2 is detachably inserted into the center below the internal base 4. Please refer to the following: Figure 8 and Figure 9The external connector 2 includes a flat cylindrical portion 21 and a retaining shaft 23. The flat cylindrical portion 21 has an internal cavity 24 for housing the lens assembly 3, and a retaining groove 22 at its lower outer end. This groove 22 is a side-opening groove, positioned corresponding to the position of the retaining hook 42 of the inner base 4. The retaining shaft 23 is fixedly connected to one side of the flat cylindrical portion 21 along its radial axis, positioned corresponding to the jaws of a pair of elastic clamps 43 of the inner base 4. The retaining hook 42 and the retaining groove 22 are on the same straight line as the elastic clamps 43 and the retaining shaft 23. The retaining shaft 23 has an internal fiber optic hole 25 for inserting the optical fiber 1, which communicates with the internal cavity 24 of the flat cylindrical portion 21. The cross-sectional shape of the retaining shaft 23 can be circular, square, or rectangular, etc. In this embodiment, the cross-sectional shape of the retaining shaft 23 is square. Figure 4 The shape of the gap between the two pincers 45 is also the same.

[0041] Please refer to the following: Figure 2 , Figure 3 and Figure 4 When the external connector 2 is connected to the internal base 4, the hook 42 is engaged in the slot 22, and the shaft 23 is pressed into the jaws of the elastic clamp 43 and held by the two jaws 45, thereby positioning and fixing the external connector 2 to the internal base 4. This insertion and pressing installation method avoids the influence of rotational stress on the optical fiber 1 during loading and unloading in the prior art, reducing the risk of damage or even breakage to the optical fiber 1, and achieving the effects of easy operation and extended service life. At the same time, the external connector 2 can be configured as a separate component on different detection instruments, improving the adaptability of the adapter and enhancing the monitoring efficiency of the bioreactor.

[0042] The lens assembly 3 is disposed in the inner cavity 24 of the flat cylindrical portion 21 of the outer connector 2, and is aligned with the light-transmitting hole 44 of the inner base 4 and the optical sensing film 5. The optical fiber 1 is disposed in the optical fiber hole 25 within the retaining shaft 23 of the outer connector 2, and is connected to the lens assembly 3.

[0043] The working principle of this embodiment is as follows:

[0044] Please see Figure 10 The excitation light is input along the optical fiber 1 and reflected by the lens assembly 3, and then reaches the optical sensing film 5 through the light-transmitting hole 44. The excitation light irradiates the optical sensing film 5 and generates emitted light with an intensity related to the information to be measured in the flexible bag 01. The emitted light is transmitted through the original optical path and output through the optical fiber 1 to complete the detection.

[0045] Example 2

[0046] The structure of this embodiment is basically the same as that of Embodiment 1, except that: the disc part of the inner base is located on the inner side of the bottom of the flexible bag, and the periphery of the lower side of the disc part is plastically welded to the inner side of the flexible bag, thereby fixing the inner base and the flexible bag together as one unit, while the hook and a pair of elastic clamps are located directly below the flexible bag.

[0047] During operation, the excitation light is input along the optical fiber and reflected by the lens assembly, and then reaches the optical sensing film through the light-transmitting hole of the inner base. The optical sensing film carries a fluorescent substance that can detect the information to be measured inside the flexible bag and is in direct contact with the reactant. The intensity of the emitted light generated by the excitation light irradiating the optical sensing film is correlated with the information signal to be measured inside the flexible bag. The emitted light is transmitted through the original optical path and output through the optical fiber to complete the detection.

[0048] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the invention. All equivalent changes and modifications made within the scope of the present invention should be considered within the technical scope of the present invention.

Claims

1. A transfer device for a flexible bioreactor bag with light transmission function, installed at the bottom of the flexible bag, the bottom having a through hole, characterized in that: The adapter includes an optical sensing film, an optical fiber, a lens assembly, an inner base, and an outer connector. The inner base is fixedly connected to the bottom of the flexible bag and has a light-transmitting hole in the center facing the through hole. The optical sensing film is directly pasted over the light-transmitting hole and carries a fluorescent material capable of detecting the information to be measured inside the flexible bag. The outer connector is detachably inserted into the center below the inner base in a non-rotational linear insertion manner. The lens assembly is disposed inside the outer connector and aligned with the light-transmitting hole of the inner base and the optical sensing film. The optical fiber passes through the outer connector and is connected to the lens assembly. The excitation light is input along the optical fiber and reflected by the lens assembly, and then reaches the optical sensing film through the light-transmitting hole. The excitation light irradiates the optical sensing film and generates emitted light with an intensity related to the information to be measured inside the flexible bag. The emitted light is transmitted through the original optical path and output through the optical fiber to complete the detection.

2. The adapter for the flexible bioreactor bag with light transmission function according to claim 1, characterized in that: the inner base includes a disc portion, a hook, and a pair of elastic clamps; the disc portion is fixedly connected to the flexible bag; the light-transmitting hole is located at the center of the disc portion; the hook protrudes downward and is connected to the lower side of the disc portion, and is symmetrically arranged at one end of the radial axis of the disc portion; the lower end of the hook is provided with a horizontal clamping plate; the pair of elastic clamps protrudes downward and is connected to the lower side of the disc portion, and is symmetrically arranged at the other end of the same radial axis; the lower end of the elastic clamps is provided with clamping feet capable of elastic deformation; the clamping feet of the pair of elastic clamps form clamping jaws.

3. The adapter for a flexible bioreactor bag with light transmission function according to claim 2, characterized in that: the inner base is located on the outer side of the bottom of the flexible bag, the upper side of the disc portion is plastically welded to the flexible bag, and the optical sensing film is sandwiched between the light-transmitting hole of the disc portion and the through hole of the flexible bag.

4. The adapter for the flexible bioreactor bag with light transmission function according to claim 2, characterized in that: the disc portion of the inner base is located on the inner side of the bottom of the flexible bag, and the periphery of the lower side of the disc portion is welded to the flexible bag as a whole.

5. The adapter for the flexible bioreactor bag with light transmission function according to claim 4, characterized in that: the external connector includes a flat cylindrical part and a retaining shaft, the retaining shaft is fixedly connected to one side of the flat cylindrical part along the radial axis of the flat cylindrical part, the interior of the flat cylindrical part is provided with an inner cavity for placing the lens assembly, and the lower part of one outer end is provided with a retaining groove, the position of the retaining groove corresponding to the retaining hook of the inner base, the interior of the retaining shaft is provided with an optical fiber hole for inserting the optical fiber, the optical fiber hole communicating with the inner cavity of the flat cylindrical part, the position of the retaining shaft corresponding to the jaws of a pair of elastic clamps of the inner base, the retaining hook is engaged in the retaining groove, the retaining shaft is pressed into the jaws and held by the two clamping feet, thereby positioning and fixing the external connector to the inner base.

6. The adapter for the flexible bioreactor bag with light transmission function according to claim 5, characterized in that: the hook and slot are located on the same straight line as the elastic clamp and shaft.

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