Bioreactor for biomanufacturing

Abstract

A bioreactor for cultivating and manufacturing three-dimensional biomaterials. The system comprises a housing that defines a controlled internal environment; one or more sensors for monitoring parameters such as temperature, humidity, pH, and light; and a mould support structure that is height-adjustable and rotatable, enabling multiple growth configurations. The bioreactor includes an internal and / or external liquid container, pumps, tubing, and a heater for fluid circulation and conditioning. An internal pump may provide agitation or directional flow. A processor regulates environmental and operational parameters to enable internal, external, or tidal growth modes. The bioreactor supports direct growth of biomaterials, such as bacterial cellulose, into pre-defined three-dimensional geometries, reducing post-processing and material waste.

Description

[0001] BIOREACTOR FOR BIOMANUFACTURING

[0002] The invention relates generally to a bioreactor which combines growth and manufacturing capabilities. More particularly, but not exclusively, the invention relates to a modular bioreactor which can be arranged in several ways to combines growth and 3D manufacturing capabilities.

[0003] Background

[0004] Bioreactors have become critical tools in biotechnology for the cultivation of a wide range of biological materials (referred to as “biomaterials”). Traditional bioreactors are typically designed to facilitate the growth of microbial or cellular cultures on flat or loosely configured surfaces, which work well for biochemical production or cell harvesting.

[0005] However, traditional bioreactors present limitations when it comes to producing structured biomaterials. For biomaterials that require a specific form factor - such as bacterial cellulose or Kombucha SCOBY (Symbiotic Culture of Bacteria and Yeast) -current bioreactor systems fall short. Growing biomaterials on flat surfaces leads to significant limitations, as it requires extensive post-processing to shape the material into forms suitable for industrial applications, including packaging, textiles, and biomedical devices. Biomaterials grown on flat surfaces are also limited in size, and form, as they are restricted to a flat form.

[0006] In conventional bioreactor systems, post-processing of flat-grown biomaterials is often labour-intensive and can compromise material properties, as reshaping may require cutting, folding, or bonding. This approach therefore limits scalability, introduces variations in material consistency, and often results in waste, all of which reduce the economic viability and environmental benefits of biomaterials. For applications that demand specific structural qualities or custom shapes these limitations are significant. The inability of flat-surface bioreactors to produce pre-shaped biomaterials directly in the desired forms restricts both the design possibilities and the sustainability of biomaterial production.

[0007] The present invention was devised with the foregoing in mind. Summary of Invention

[0008] According to a first aspect of the invention, there is provided a bioreactor.

[0009] The bioreactor may comprise a housing. The housing may define an internal environment of the bioreactor. The interior of the housing may be defined as the internal environment of the bioreactor. The housing may be at least partially transparent. The housing may comprise transparent walls.

[0010] Defining an internal environment via a housing provides a closed space in which the environment can be controlled and optimised for biomaterial growth. Having a transparent housing enables a user to monitor progress of the manufacturing process.

[0011] The bioreactor may comprise one or more environmental sensors. The environmental sensors may be configured to monitor the internal environment of the bioreactor. The one or more environmental sensor may comprise one or more of: a temperature sensor; a humidity sensor; a pH sensor; and a light sensor.

[0012] Having environmental sensors enables a user to monitor the internal environment to ensure it is suitable and / or optimal for biomaterial growth.

[0013] The temperature sensor may be configured to measure the air temperature within the bioreactor. The temperature sensor may be configured to measure the temperature of a mould within the bioreactor. The temperature sensor may be configured to measure the temperature of a liquid within the bioreactor. The temperature sensor may be configured to measure the temperature of a biomaterial as it is forming within the bioreactor.

[0014] The light sensor may be configured to measure the intensity of light within the bioreactor. The light sensor may be configured to measure the intensity of light falling on a mould within the bioreactor. The light sensor may be configured to measure the intensity of light falling on a biomaterial as it is forming within the bioreactor.

[0015] The bioreactor may comprise a mould support structure connectable to a mould. The mould support structure may be configured to suspend the mould within the bioreactor. The mould support structure may be configured to suspend a plurality of moulds within the bioreactor. The mould support structure may be universal such that any mould shape can be connected to the mould support structure.

[0016] Having a mould support structure enables a mould to be suspended within the bioreactor. This enables a biomaterial to be grown on an inner or outer surface of the mould.

[0017] The mould support structure may be height adjustable. The mould support structure may comprise a rotatable bearing system which is connectable to a mould. The rotatable bearing system may be height adjustable. The mould support structure may comprise one or more vertical rods with a horizontal rod connected thereto. The mould support structure may comprise a rotatable axle. The rotatable axle may be connected to the bearing system. The rotatable axle may be connected to the horizontal rod.

[0018] Having a height adjustable mould support structure enables moulds of different sizes to be used in the bioreactor. Having a height adjustable mould support structure enables mould to be positioned appropriately within the bioreactor.

[0019] The bioreactor may comprise a device to drive rotation, such as a motor. The motor may be configured to drive rotation of at least part of the mould support structure. The motor may be configured to drive rotation of at least part of the mould support structure such that, when a mould is connected to the mould support structure, the motor drives rotation of the mould. The motor may be connected to the axle and configured to drive rotation of the axle. The motor may be connected to the horizontal bar of the mould support structure, and the axle may be connected to motor.

[0020] Having a rotational device, such as motor, enables a mould to be rotated. Rotating a mould ensures that nutrients are temporarily supplied to all of the surface upon which the biomaterial is to be grown. Rotating a mould also ensures the entire surface upon which the biomaterial is to be grown is supplied with oxygen.

[0021] The bioreactor may comprise an internal container configured to retain a liquid therein. The internal container may be removable from the bioreactor. Having a container with a liquid therein may enable the supply of nutrients to a biomaterial forming on the mould. Having an internal container may enable a mould to be partially submerged within the liquid within the container.

[0022] The housing may comprise one or more openings. The openings may be configured to enable part of the mould support structure to pass through the housing. Having part of the mould support structure outside of the housing enables user adjustment of the mould support structure without interfering and potentially contaminating the internal environment of the bioreactor.

[0023] The openings may be elongated openings. The elongated openings may be configured to enable height adjustment of the mould support structure. The elongated opening may be at least partially restricted to reduce contamination. The elongated openings may be at least partially restricted using silicone projections.

[0024] The bioreactor may comprise an external liquid container. The external liquid container may be configured to store a liquid for supply to the internal container.

[0025] The bioreactor may comprise a tubing. The tubing may be configured to convey liquid in and / or out of the bioreactor. The bioreactor may comprise a pump. The pump may be configured to convey liquid through the tubing. The pump may be a temperature-controlled pump configured to control the temperature of a liquid passing therethrough.

[0026] The tubing may be configurable to connect to:

[0027] (i) the external liquid container;

[0028] (ii) the internal container; and / or

[0029] (iii) a mould.

[0030] The bioreactor may comprise a processor. The processor may be configured to receive environmental data from the one or more environmental sensors. The processor may be configured to display environmental data to a user. The processor may be configured to transfer environmental data (wired or wirelessly) to an external device.

[0031] The processor may be configured to control one or more environmental controls. The one or more environmental controls may comprise one or more of: a temperature control;

[0032] a humidity control;

[0033] a pH control; and

[0034] a light control.

[0035] The temperature control may comprise a heating element. The temperature control may comprise a cooling element.

[0036] The humidity control may comprise one or more valves to provide and / or remove humid air. The humidity control may comprise the temperature control.

[0037] The pH control may comprise one or more sources with a predetermined pH. The pH control may be configured to release the one or more sources into the internal environment of the bioreactor.

[0038] The light control may comprise one or more lights sources with adjustable brightness.

[0039] The bioreactor may comprise a UV sterilisation system.

[0040] The bioreactor may comprise one or more filters. The filters may be micron-graded filters.

[0041] The device may be operable in one or more manufacturing modes. The device may be modular and allow for user configuration between a plurality of manufacturing modes. Switching between manufacturing modes may comprise changing the components of the bioreactor and / or providing instructions to the processor.

[0042] The one or more manufacturing modes may comprise an external rotational growth mode. In the external rotational growth mode, the mould support structure may be configured to partially submerge a mould within a liquid retained within the internal container and rotate the mould within the liquid.

[0043] The one or more manufacturing modes may comprise an internal rotational growth mode. In the internal rotational growth mode, the mould support structure may be configured to rotate a sealed mould with a liquid retained within the sealed mould. The one or more manufacturing modes may comprise an external tidal growth mode. In the external tidal growth mode, the mould support structure may be configured to at least partially submerge a mould within the container, and the processor may be configured to repeatedly raise and lower the liquid level in the container by conveying liquid via the tubing from the external container into the internal container. The liquid may be conveyed through the tubing via the pump.

[0044] The one or more manufacturing modes may comprise an internal tidal growth mode. In the internal tidal growth mode, the processor may be configured to repeatedly raise and lower a liquid level within a sealed mould by conveying liquid via the tubing from the external container into the mould. The liquid may be conveyed through the tubing via the pump.

[0045] According to a second aspect of the invention, there is provided a kit of parts comprising:

[0046] the bioreactor of the first aspect of the invention; and

[0047] one or more moulds connectable to the mould support system.

[0048] The moulds may be three-dimensional moulds.

[0049] The moulds may comprise surface detail on an interior and / or exterior surface.

[0050] According to a third aspect of the invention, there is provided a method of forming a biomaterial.

[0051] The method may comprise providing a bioreactor as defined in the first aspect of the invention. The method may comprise providing a mould. The method may comprise connecting the mould to a mould support structure of the bioreactor. The method may comprise configuring the bioreactor for a desired manufacturing mode. The method may comprise providing a liquid configured to provide nutrients for growth of the biomaterial. The method may comprise operating the bioreactor according to one of the manufacturing modes. Optional features of any of the above aspects may be combined with the features of any other aspect, in any combination. Features which are described in the context or separate aspects and embodiments of the invention may be used together and / or be interchangeable wherever possible. Similarly, where features are, for brevity, described in the context of a single embodiment, those features may also be provided separately or in any suitable sub-combination.

[0052] Brief description of the drawings

[0053] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0054] Figure 1 shows a schematic of a bioreactor according to an example of the invention;

[0055] Figure 2 shows a schematic of another bioreactor according to an example of the invention;

[0056] Figure 3 shows a front view of a bioreactor according to an example of the invention;

[0057] Figure 4 shows a side view of a bioreactor according to an example of the invention;

[0058] Figure 5 shows a rear view of a bioreactor according to an example of the invention;

[0059] Figure 6 shows an enlarged view of part of a mould support system used in some bioreactors of the present invention;

[0060] Figure 7 shows a schematic of a bioreactor of the present invention operating in one of the possible manufacturing modes;

[0061] Figure 8 shows a schematic of a bioreactor of the present invention operating in another one of the possible manufacturing modes;

[0062] Figure 9 shows a schematic of a bioreactor of the present invention operating in another one of the possible manufacturing modes; and Figure 10 shows a schematic of a bioreactor of the present invention operating in another one of the possible manufacturing modes.

[0063] Detailed description

[0064] The present invention can harness microbial biotechnology to create eco-friendly, multifunctional materials and products from bacteria and other microorganisms. The pioneering approach of the present invention can use biofabrication and advanced manufacturing to convert resources, such as food or agricultural waste, into more valuable resources, setting new standards for sustainability across sectors like healthcare, automotive, and fashion.

[0065] Figure 1 shows a schematic of a bioreactor 10.

[0066] The bioreactor 10 can be used to grow and / or cultivate complex three-dimensional biomaterials. The bioreactor 10 can be used to grow three-dimensional biomaterials using bacteria, such as microbial bacteria, or other microorganisms. In some examples, the bioreactor 10 can be used to grow three-dimensional biomaterials using food or agricultural waste as a source of nutrients for microbial bacteria and / or other microorganisms.

[0067] The bioreactor 10 comprises a housing 12. The space enclosed by the housing 12 is defined as an internal environment of the bioreactor 10.

[0068] The bioreactor 10 comprises an environmental sensor 14. The environmental sensor 14 is configured to monitor the internal environment of the bioreactor 10. In other examples, the bioreactor 10 can comprise a plurality of environmental sensors 14. In other examples, the environmental sensor 14 can be omitted.

[0069] The environmental sensor(s) 14 can comprise one or more of: a temperature sensor; a humidity sensor; a pH sensor; and a light sensor.

[0070] In the example of Figure 1, the environmental sensor 14 is disposed on an internal surface of the housing 12. In other examples, the environmental sensor(s) 14 can be disposed on an external surface of the housing 12, or in any other position inside or outside of the housing 12 from which the environmental sensor(s) 14 can monitor the internal environment of the bioreactor 10.

[0071] The bioreactor 10 comprises a mould support structure 16. The mould support structure 16 is connectable to a mould. The mould support structure 16 is configured to suspend a mould connected to the mould support structure 16 within the bioreactor 10.

[0072] In the example of Figure 1, the mould support structure 16 is disposed entirely within the housing 12. In other examples, the mould support structure 16 can be disposed at least partially outside of the housing 12.

[0073] The mould support structure 16 can be universal, meaning any mould, or a wide range of moulds, can be connected to the mould support structure 16. In some examples, a mould is provided as part of the bioreactor 10.

[0074] The bioreactor 10 can be configured such that biomaterials are grown onto, or inside, a mould connected to the mould support structure 16. For example, the bioreactor 10 can be configured such that a biomaterial grows onto the external surface of a mould or the internal surface of a mould.

[0075] In some examples, the biomaterial grown onto, or inside, the mould is one of: bacterial cellulose, or Kombucha SCOBY. However, bioreactors of the present invention are not limited to production of a specific biomaterial. For example, bacteria are being engineered with enhanced properties. These “future materials” have no platform to be explored, researched, and developed. The bioreactors of the present invention provide this platform. The bioreactors of the present invention are universal for all types of bacteria and / or microorganism because the internal environment of bioreactor can be controlled to meet the required growing conditions of each organism.

[0076] To grow biomaterials onto, or inside, a mould, the mould is exposed to oxygen and a source of nutrients for the bacteria and / or microorganisms via a liquid. The mechanisms for ensuring the supply of oxygen and nutrients is discussed in detail later in the description. The liquid used to provide nutrients to the bacteria and / or microorganisms can comprise waste, such as food or agricultural waste, retained within a mesh (e.g., similar to a tea bag). In other examples, the liquid can comprise raw materials such as sugars dissolved and / or dispersed therein. The liquid used to provide the nutrients will depend on the biomaterials being formed and the bacteria and / or microorganisms used to produce the biomaterial.

[0077] It is to be appreciated that the bioreactors of the present invention are scalable dependent on the required conditions for the bacteria and / or microorganisms to grow, and dependent on the amount and / or size of the biomaterial being produced.

[0078] It also to be appreciated that the bioreactors of the present invention can be modular, such various components can be swapped in and / or out depending on a manufacturing mode of the bioreactor. This is discussed is greater detail later on.

[0079] Figure 2 shows a schematic of a bioreactor 10’.

[0080] The bioreactor 10’ of Figure 2 is similar to the bioreactor 10 of Figure 1 in that it comprises a housing 12’, an environmental sensor 14’, and a mould support structure 16’.

[0081] The mould support structure 16’ is disposed partially outside of the housing 12’. The mould support structure 16’ is configured to stand upon a surface outside of the housing 12’ and extend through a wall of the housing 12’ into the internal environment of the bioreactor 10’. The portion of the mould support structure 16’ to which the mould 20’ is connectable is within the bioreactor 10’, because the biomaterials are to be grown on the mould 20’ .

[0082] The bioreactor 10’ comprises a mould 20’ connected to the mould support structure 16’. In the example of Figure 2, the mould 20’ is cylindrical but, in other examples, the mould 20’ can comprise any three-dimensional shape. In the example of Figure 3 discussed later in the description, a mould is shown in the shape of a hand. In some examples, the mould can be hollow.

[0083] The bioreactor 20’ comprises a motor 18’. The motor 18’ is configured to drive rotation of at least part of the mould support structure 16’ such that, when the mould 20’ is connected to the mould support structure 16’, the motor 18’ drives rotation of the mould 20’. In the example of Figure 2, the mould support structure 16’ comprise an axle 16-1’ which is rotatable and the motor 18’ is configured to drive rotation of the axle 16-1’.

[0084] In the example of Figure 2, the motor 18’ is connected to the mould support structure 16’. In other examples, however, the motor 18’ can be connected to any other part of the bioreactor 10’ or can be freestanding.

[0085] The bioreactor 10’ comprises an internal container 22’. The container 22’ is described as “internal” as it is disposed within the housing 12’. The internal container 22’ is configured to retain a liquid therein.

[0086] In some examples, the internal container 22’ is placed within the housing 12’ and is moveable within, and removable from, the bioreactor 10’. In other examples, the container 22’ is fixed to, or relative to, the housing 12’.

[0087] The internal container 22’ is an open container such that there is no upper surface to the container 22’. The internal container 22’ is open such that liquid can be conveyed (for example, poured) into and out of the container 22’.

[0088] The mould support structure 16’ is height adjustable. The mould support structure 16’ is height adjustable such that the height of a mould 20’ connected to the mould support structure 16’ can be adjusted. The motor 18’ can be connected to a rail of the mould support system 16’ such that the height of the motor 18’ can be adjusted together with the mould 20’. This can reduce vertical load on the motor 18’.

[0089] The mould support structure 16’ is height adjustable such that the height of a mould 20’ connected to the mould support structure 16’ can be lowered to partially, or fully, submerge the mould 20’ within a liquid retained in the internal container 22’. At least partially submerging the mould 20’ within a liquid in the container 22’ and rotating the mould 20’ via the motor 18’ can ensure that an entire outer surface of the mould 20’ is exposed to (i.e., at least temporarily brought into contact with) the liquid whilst also providing a supply of oxygen via the air.

[0090] Figures 3, 4, and 5 respectively show front, side, and rear views of a bioreactor 100 according to an example of the invention. The bioreactor 100 can comprise any of the features described in relation to the bioreactors 10, 10’ of Figures 1 and 2, and vice versa.

[0091] The bioreactor 100 comprises a mould support structure 116 comprising two portions 116a, b. Each portion 116a, b is connectable to a mould. In some examples, both portions 116a, b can be connected to a single mould when in use, or only one of the portions 116a, b can be connected to a mould.

[0092] In the example of Figure 3, one portion 116a of the mould support structure 116 is connected to a mould 120 and the other portion 116b of the mould support structure 116 is not connected to a mould. The mould 120 is in the shape of a hand and, in this example, the bioreactor 100 is configured to grow a biomaterial on the outer surface of the mould 120 in the shape of the outer surface of a hand.

[0093] The bioreactor 100 comprises a housing 112. The housing 112 is shaped as a cube and is formed of an aluminium frame with transparent walls disposed between edges of the frame. The walls are made of glass. In other examples, the housing can be any other shape, and different materials can be used for the frame and / or walls of the housing 112.

[0094] One wall of the housing 112 is formed from two transparent doors instead of single piece of transparent material. The doors comprise magnetic handles and are configured to enable a user to access the inside of the bioreactor 100 when they are open. In other examples, there can be doors and / or other openings on additional walls of the housing 112, or the doors can be omitted entirely.

[0095] Each portion 116a, b of the mould support structure 116 is connected to a respective side of the housing 112. In other examples, one or more portions of the support structure 116 can be freestanding.

[0096] As shown most clearly in Figures 3 and 4, each portion 116a, b of the mould support structure 116 comprises a pair of vertical rods 116-3 with a horizontal rod 116-4 extending between the pair of vertical rods 116-3. The vertical rods 116-3 act as a rail such that the height of the horizontal rod 116-4 is adjustable along the vertical rods 116- 3. A motor 118 is connected to the horizontal rod 116-4. The motor 118 is connected to an axle 116-1, which can be connected to a mould.

[0097] The support structure 116 of the present example also comprise a bearing system 116-2. An enlarged perspective view of the bearing system 116-2 is shown in Figure 6. The bearing system 116-2 is a height adjustable rod with a rotatable ring attached to it. In use, the axle 116-1 is connected to one side of the bearing system 116-2 such that, as the axle 116-1 rotates, the rotatable ring rotates with it. The mould 120 can be connected to the other side of the rotatable ring of the bearing system 116-2 such that the mould 120 also rotates with the axle 116-1.

[0098] The motor 118 is configured to drive rotation of the axle 116-1. In the example shown, the motor is a geared 12V DC motor with a rotation speed of up to lOrpm. In other examples including a motor, any other motor can be used.

[0099] In other examples, any other structure can be used to secure the mould within the bioreactor 100.

[0100] The housing comprises a pair of elongated openings 126, as shown most clearly in Figure 4. In other examples, the housing 112 can comprise no elongated openings, one elongated opening, or any plurality of elongated openings. The openings 126 are provided in sidewalls of the housing 112. The elongated openings 126 are configured to enable adjustment of the mould support structure 116. For example, the mould support structure 116 is height adjustable in the example of Figures 3-5, and the elongated openings 126 enable the sections of the mould support structure 116 extending through the side walls of the housing to be height adjustable. The axle 116-1 extends through the elongated openings 126.

[0101] The elongated openings 126 are partially restricted in order to reduce contamination of the internal environment of the bioreactor 100. As shown in the example of Figure 4, the elongated openings 126 comprises a plurality of projections which partially restrict the openings 126 to prevent conveyance of contaminants through the openings 126. In the example of Figures 3 and 4, the projections are formed of, or comprise, silicone. In other examples wherein the mould support structure 116 is not height-adjustable, the openings 126 are not elongated and be, for example circular.

[0102] A roof (i.e., top surface) of the housing 112 comprises a UV lighting system 113. The UV lighting system 113 is configured to sterilise the internal environment of the bioreactor 100 before use, and / or after use. In other examples, the UV lighting system 113 can be part of any other surface of the housing 112.

[0103] The roof (i.e., top surface) of the housing 112 also comprises an LED lighting system 115 configured to illuminate the bioreactor 100. In other examples, the LED lighting system can be disposed on a different surface of the housing. In other examples, any other lighting system can be used for illumination (e.g., a filament bulb).

[0104] The bottom surface of the housing 112 is provided with a tray 123. The tray 123 is an anti-drip and anti-leak tray. The tray 123 comprises openings in an upper surface such that any liquid which pours or drips onto the upper surface passes through said openings and is trapped within the tray 123.

[0105] As shown most clearly in Figure 5, the bioreactor 100 comprises an external liquid container 128. In the example of Figure 5, the external liquid container is a bag but, in other examples, the external liquid container 128 can be any container suitable for retaining a liquid therein. The liquid container 128 is “external” in the sense that it is disposed outside of the housing 112.

[0106] The bioreactor 100 comprises a tubing 130 configured to convey liquid in and / or out of the bioreactor 100. In the examples of Figures 3-5, the tubing 130 is configured to convey liquid between the external liquid container 128 and an internal liquid container 122. In some examples, the conveyance of liquid between the external liquid container 128 and the internal liquid container 122 is controlled via a pump 132 configured to convey liquid through the tubing. In other examples, alternatives to pump can be used.

[0107] In the example of Figures 3-5, the pump 132 is a temperature-controlled pump such that liquid conveyed via the pump 132 is heated or cooled to a desired temperature. In the present example, the pump is a 12V DC 4.8W centrifugal pump. In other examples, any other type of pump can be used. The tubing 130 can be connectable to, or permanently connected to, the external liquid container 128. The tubing 130 can be connectable to, or permanently connected to, the internal liquid container 122. The tubing 130 can be connectable to, or permanently connected to, a mould 120. The possible configuration for the tubing 130 are explained in greater detail later in the description in relation to various operating modes.

[0108] The bioreactor comprises a processor 124. In the present example, the processor 124 is an Arduino board and riley controller. In other examples, alternative processors can be used.

[0109] In some examples, the processor 124 is configured to receive environmental data from one or more environmental sensors (not shown in Figures 3-5).

[0110] In some examples, the processor 124 is configured to display the environmental data from one or more environmental sensors to a user.

[0111] In some examples, the processor 124 can be configured to control one or more environmental controls. In some examples, the processor 124 can be configured to control one or more environmental controls based on environmental data received from the one or more environmental sensors. In some examples, the processor is configured to control one or more manufacturing parameters, including motor speed, pump speed, pump temperature, and pH of liquid being used in the bioreactor 100.

[0112] For example, if the processor 124 receives temperature data from a temperature sensor indicating that the temperature of the internal environment of the bioreactor is below a desired value, the processor 124 can instruct the heat-pump to increase the temperature of liquid conveyed into the internal container 122, and / or the processor 124 can activate a heater within the bioreactor 100.

[0113] In some examples, the processor 124 is configured to maintain an internal environment which is suitable for growth of the bacteria (in this case bacterial cellulose). This may comprise: an acidic environment with a pH around 4.5 to 5.5; a temperature range of around 25°C to 30°C; and a relative humidity between 70-90%. In other examples, the processor 124 can be configured to maintain alternative internal environment conditions, which may be suitable and / or optimal for growth of alternative biomaterials.

[0114] In some examples, the bioreactor 100 comprises one or more filters (not shown) to prevent contaminants entering the bioreactor 100. The one or more filters can be micron-graded filters.

[0115] In some examples, the bioreactor can be operable in one or more manufacturing modes. To switch between manufacturing modes, the processor can receive instructions to operate in a desired manufacturing mode and the user can configure the bioreactor 100 as required for the desired manufacturing mode. For example, the bioreactor 100 can be modular such that components (e.g., the container 122, and the tubing 130) can be inserted and / or removed by a user in order to configure the bioreactor 100 for use in a desired manufacturing mode. To instruct the processor to operate in a specific manufacturing mode, a user may be able to select a predetermined manufacturing mode via a user interface, or they may be able to adjust each of the environmental controls and pump / motor settings individually.

[0116] Various manufacturing modes are discussed below with reference to particular examples of the invention. For each of Figures 7-10 discussed below, the bioreactors 200, 300, 400, 500 are similar to the bioreactors described elsewhere in this description and corresponding reference numbers are used to refer to corresponding features. Not all features are labelled and / or shown in Figures 6-9, but this does not prevent them from being included.

[0117] Figure 7 shows a schematic of a bioreactor 200 in a first manufacturing mode, which may be referred to as an external rotational growth mode.

[0118] The bioreactor 200 comprises a mould support structure 216 configured to support a pair of moulds 220-1, 2. The bioreactor 200 comprises a motor 218 configured to drive rotation of the moulds 220-1, 2. In other examples, a single mould can be used.

[0119] The bioreactor 200 comprises an internal container 222 which retains a liquid from which the biomaterial is to be formed. The mould support structure 216 is configured to partially submerge the moulds 220-1, 2 within the liquid retained within the internal container 222. As the moulds 220-1, 2 rotate, the outer surfaces of the moulds 220-1, 2 are exposed to the liquid in the internal container 222.

[0120] The internal environment defined within the housing 212 of the bioreactor 200 is configured to promote and / or optimise the biomaterial growth. The continuous rotation of the moulds 220-1, 2 enables the biomaterial to grow across the entire outer surfaces of the moulds 220-1, 2. As such, moulds can be selected with particular shapes to provide biomaterials with desired structures.

[0121] For the external rotational growth mode, a user may be required to configure the bioreactor 200 to provide the container 222 with the relevant liquid retained therein, and to adjust the height of the mould support structure 216 so as the partially submerge the one or more moulds within the liquid. In some examples, the user is required to provide instructions to a processor (for example, via a user interface) to indicate that the bioreactor 200 is to operate in an external rotational growth mode. The processor may be configured to activate the motors 218 to drive rotation of the moulds 220-1, 2 when in an external rotational growth mode.

[0122] The external rotational growth mode can be particularly effective for creating biomaterials with intricate external textures and shapes, as the rotation ensures even coverage and development of the material.

[0123] Figure 8 shows a schematic of a bioreactor 300 in a second manufacturing mode, which may be referred to as an internal rotational growth mode. The bioreactor 300 can be the bioreactor 200 of Figure 7 but with various components adjusted and swapped in or out.

[0124] The bioreactor 300 comprises a mould support structure 316 configured to support a mould 320. The bioreactor 300 comprises a motor 318 configured to drive rotation of the mould 320.

[0125] The mould 320 in the bioreactor 300 is hollow such that there is an empty internal space within the mould 320. When in use in the internal rotational growth mode of Figure 8, the internal space is filled, or at least partially filled, with a liquid from which a biomaterial is to be grown. The mould 320 can be sealable so as to prevent the liquid from exiting the mould 320.

[0126] The internal environment defined within the housing 312 of the bioreactor 300 is configured to promote and / or optimise the biomaterial growth. The continuous rotation of the mould 320 enables the biomaterial to grow across the entire interior surface of the mould 320. As such, a mould 320 can be selected with particular shapes to provide biomaterials with desired structures.

[0127] For the internal rotational growth mode, a user may be required to configure the bioreactor 300 to provide the mould 320 with the relevant liquid retained therein. In some examples, the user is required to provide instructions to a processor (for example, via a user interface) to indicate that the bioreactor 300 is to operate in an internal rotational growth mode. The processor may be configured to activate the motors 318 to drive rotation of the moulds 320 when in an internal rotational growth mode.

[0128] The internal rotational growth mode can be suited for creating hollow or concave items. Smaller moulds can be used in this mode and may allow air access within the mould to ensure the bacteria can absorb sufficient oxygen for growth.

[0129] Figure 9 shows a schematic of a bioreactor 400 in a third manufacturing mode, which may be referred to as an external tidal growth mode. The bioreactor 400 can be the bioreactor 200 of Figure 7 and / or the bioreactor 300 of Figure 8, but with various components adjusted and swapped in or out.

[0130] The bioreactor 400 comprises a mould support structure 416 configured to support a mould 420. The bioreactor 400 comprises a motor 418. However, in the external tidal growth mode, the motor 418 is not active, and the mould 420 is not rotated.

[0131] The bioreactor 400 comprises an internal container 422 which retains a liquid from which the biomaterial is to be formed.

[0132] The mould support structure 416 is configured to partially submerge the mould 420 within the liquid retained within the internal container 422. The bioreactor 400 comprises tubing 430 configured to convey liquid into and out of the internal container 422. In some examples, liquid is conveyed into and out of the internal container 422 so as to periodically raise and lower the liquid level within the internal container 422. As the liquid level raises and lowers, the entire outer surface of the mould 420 is exposed to the liquid and oxygen.

[0133] The internal environment defined within the housing 412 of the bioreactor 200 is configured to promote and / or optimise the biomaterial growth. The adjustment of the liquid level within the internal container 422 enables the biomaterial to grow across the entire outer surfaces of the moulds 420. As such, moulds can be selected with particular shapes to provide biomaterials with desired structures.

[0134] For the external tidal growth mode, a user may be required to configure the bioreactor 400 to provide the container 422 with the relevant liquid retained therein, and to adjust the height of the mould support structure 216 so as the partially submerge the one or more moulds within the liquid. The user may also be required to connect the tubing 430 to the internal container 422. In some examples, the user is required to provide instructions to a processor (for example, via a user interface) to indicate that the bioreactor 400 is to operate in an external tidal growth mode. The processor may be configured to activate a pump to convey liquid through the tubing to raise and lower the liquid level within the internal container 422 when in an external tidal growth mode.

[0135] The external tidal growth mode can be ideal for non-uniform mould shapes that lack a central axis for rotation. This mode can ensure uniform access to nutrients and oxygen, maintaining stability, which is vital during the early stages of growth, and prevent the detachment of the developing biomaterial.

[0136] Figure 10 shows a schematic of a bioreactor 500 in a fourth manufacturing mode, which may be referred to as an internal tidal growth mode. The bioreactor 500 can be the bioreactor 200 of Figure 7, the bioreactor 300 of Figure 8, and / or the bioreactor 400 of Figure 9, but with various components adjusted and swapped in or out.

[0137] The bioreactor 500 comprises a mould support structure 516 configured to support a mould 520. The bioreactor 300 comprises a motor 518. However, in the internal tidal growth mode, the motor is not active, and the mould 520 is not rotated. The mould 520 in the bioreactor 500 is hollow such that there is an empty internal space within the mould 520. When in use in the internal tidal growth mode of Figure 9, the internal space is filled, or at least partially filled, with a liquid from which a biomaterial is to be grown. The mould 520 can be sealable so as to prevent the liquid from exiting the mould 520.

[0138] The internal environment defined within the housing 512 of the bioreactor 500 is configured to promote and / or optimise the biomaterial growth.

[0139] The bioreactor 500 comprises tubing 530-1, 2 configured to convey liquid into and out of the mould 520. In some examples, liquid is conveyed into and out of the mould 520 so as to periodically raise and lower the liquid level within the mould 520. As the liquid levels raises and lowers, the entire internal surface of the mould 420 is exposed to the liquid. In the example of Figure 9 the tubing is formed of an input tubing 530-1 configured to convey liquid into the mould 520 and an output tubing 530-2 configured to convey liquid out of the mould 520. However, in other examples, a single piece of tubing can be used to convey liquid both into and out of the mould 520.

[0140] For the internal tidal growth mode, a user may be required to configure the bioreactor 500 to the mould 520 with the relevant liquid retained therein and to connect the tubing 530-1, 2 to the mould 520. In some examples, the user is required to provide instructions to a processor (for example, via a user interface) to indicate that the bioreactor 500 is to operate in an internal tidal growth mode. The processor may be configured to activate a pump to liquid into and out of the mould 520 via the tubing 530-1, 2 when in an internal tidal growth mode.

[0141] The internal tidal growth mode can be suitable for achieving a clean, detailed finish on the exterior of the produced biomaterial, making it suitable for designs requiring high precision and aesthetic clarity.

[0142] Following formation of biomaterials using the bioreactor, bacterial welding can be used to combine a plurality of manufactured biomaterials. This can be used for multi-part assemblies requiring a smooth, cohesive appearance. For bacterial welding, two or more separately cultivated parts are brought before they dry. By bringing the components together, they naturally bond due to the bacteria's ability to share nutrients across the contact points.

[0143] In some examples, the system enables three-dimensional formation of bio-fabricated material both around and within a mould. In an external moulding configuration, biological material such as a microbial cellulose-based material is grown along an outer surface of a mould to form a continuous shell or cover having a controlled thickness and geometry. In an internal moulding configuration, growth occurs on an inner surface of a hollow or sealed mould so that a lining or internal structure is formed within the mould itself. Internal and external moulding may be driven by the rotational and / or tidal manufacturing modes described above.

[0144] In some examples, three-dimensional growth of material is promoted throughout the thickness of the growing structure by cyclically modifying one or more environmental conditions, for example oxygenation, nutrient flow, temperature, humidity, pH and / or shear exposure. This cyclic modulation of the environment may be controlled by the processor (for example processor 124) on the basis of data from one or more environmental sensors. By dynamically adjusting these conditions, material can be formed not only at an air-liquid interface but also through the depth of a liquid medium or within a mould cavity, providing a controlled three-dimensional form rather than only a surface coating.

[0145] In some examples, the mould (for example the mould 20, 20', 120) is rigid, flexible, inflatable and / or dissolvable. Suitable materials for the mould may include silicone, wax, hydrogel or polyvinyl alcohol (PVA), among others. A flexible or inflatable mould can deform or expand as biological material accretes, and a dissolvable mould can gradually disintegrate or merge with the developing material during growth. In some examples, the dissolvable mould contributes nutrients or mechanical support during growth and becomes partially or fully integrated into the resulting component. This approach can enable near-net-shape manufacture of complex three-dimensional parts whilst reducing or eliminating a subsequent core-removal step.

[0146] In some examples, the surface of the mould may include patterned or textured features configured to influence cell adhesion, oxygen access and / or orientation of fibres during growth. Such texturing can be used to direct the formation of ridges, channels or reinforcement regions in the resulting biomaterial, improving structural performance or functional fit.

[0147] In some examples, the housing (for example housing 12, 12', 112) defines a substantially enclosed internal environment which maintains controlled conditions for growth without requiring a separate external incubator. The housing may include transparent or translucent panels (for example glass panels supported by an aluminium frame) and internal lighting to permit continuous visual monitoring of the growth process whilst reducing contamination risk. The system can therefore combine, within a single machine, the functions typically provided by an incubator, a bioreactor and a manufacturing platform, enabling direct access and active control during fabrication.

[0148] In some examples, one or more sealed or partially sealed feedthroughs (for example the elongated openings 126 with silicone projections) allow actuators, sensors or light sources to operate within the bioreactor whilst maintaining a substantially closed internal environment. Such feedthroughs may be positioned above or below the main chamber to support dilferent manufacturing modes whilst minimising the size of any gaps and hence limiting contamination.

[0149] In some examples, the structural frame of the housing (for example the aluminium frame of housing 112) comprises extruded profiles and / or universal connection features that enable modules such as pumps (for example pump 132), liquid reservoirs (for example the external liquid container 128 and / or internal liquid container 122), control electronics (for example processor 124) and sensors (for example sensor 14) to be repositioned, replaced or added. This modularity allows the same core system to be reconfigured or up-scaled for dilferent manufacturing modes (for example external rotational, internal rotational, external tidal and internal tidal modes) or for dilferent output scales without requiring a complete redesign of the machine.

[0150] In some examples, the modularity and low-energy requirements of the system allow the bioreactor to be transported, assembled and operated in remote or resource-limited locations. For example, the system can be deployed in post-crisis or olf-grid environments to produce materials on demand without large-scale industrial infrastructure. In these examples, the same core architecture can be used for distributed manufacturing, field repair or rapid fabrication of functional shells, linings or structural components.

[0151] Although many examples described herein refer to bacterial cellulose growth, the bioreactor can be operated with other organisms or biological processes including fungi, micro-algae and mineral-precipitating microorganisms (for example microbial induced calcite precipitation). In such examples, the processor may regulate temperature, humidity, nutrient composition, pH, gas composition and / or liquid-level cycling to support the particular organism and direct the resulting biomaterial. This can enable production of composite, mineralised or hybrid structures beyond cellulose-only materials.

[0152] From reading the present disclosure, other variations and modifications will be apparent to the skilled person. Such variations and modifications may involve equivalent and other features which are already known in the art, and which may be used instead of, or in addition to, features already described herein.

[0153] Although the appended claims are directed to particular combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel feature or any novel combination of features disclosed herein either explicitly or implicitly or any generalisation thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention.

[0154] Features which are described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

[0155] For the sake of completeness it is also stated that the term "comprising" does not exclude other elements or steps, the term "a" or "an" does not exclude a plurality, and any reference signs in the claims shall not be construed as limiting the scope of the claims.

Claims

24Claims1. A bioreactor, comprising:a housing defining an internal environment of the bioreactor;one or more environmental sensors configured to monitor the internal environment of the bioreactor; anda mould support structure connectable to a mould, wherein the mould support structure is configured to suspend the mould within the bioreactor.

2. The bioreactor of claim 1, further comprising a motor configured to drive rotation of at least part of the mould support structure such that, when a mould is connected to the mould support structure, the motor drives rotation of the mould.

3. The bioreactor of any preceding claim, further comprising an internal container configured to retain a liquid therein.

4. The bioreactor of any preceding claim, wherein the mould support structure is height adjustable.

5. The bioreactor of any preceding claim, wherein the housing comprises an elongated opening configured to enable height adjustment of the mould support structure.

6. The bioreactor of claim 5, wherein the elongated opening is at least partially restricted to reduce contamination, optionally using silicone projections.

7. The bioreactor of any preceding claim, further compromising an external liquid container8. The bioreactor of any preceding claim, further comprising a tubing configured to convey liquid in and / or out of the bioreactor.

9. The bioreactor of claim 8, further comprising a pump configured to convey liquid through the tubing.

10. The bioreactor of claim 8 or claim 9, wherein the tubing is configurable to connect to:(iv) the external liquid container;(v) the internal container; and / or(vi) a mould.

11. The bioreactor of any preceding claim, further comprising a processor.

12. The bioreactor of claim 11, wherein the processor is configured to receive environmental data from the one or more environmental sensors.

13. The bioreactor of any preceding claim, wherein the one or more environmental sensors comprise one or more of:a temperature sensor;a humidity sensor;a pH sensor; anda light sensor.

14. The bioreactor of claim 13, wherein the processor is configured to control one or more environmental controls, wherein the one or more environmental controls comprise one or more of:a temperature control;a humidity control;a pH control; anda light control.

15. The bioreactor of any preceding claim, further comprising a UV sterilisation system.

16. The bioreactor of any preceding claim, further comprising one or more filters.

17. The bioreactor of any preceding claim, wherein the device is operable in one or more manufacturing modes.

18. The bioreactor of claim 17, wherein the one or more manufacturing modes comprises an external rotational growth mode, wherein the mould support structure is configured to partially submerge a mould within a liquid retained within the container and rotate the mould.

19. The bioreactor of claim 17 or claim 18, wherein the one or more manufacturing modes comprises an internal rotational growth mode, wherein the mould support structure is configured to rotate a sealed mould with a liquid retained therein;20. The bioreactor of any of claims 17-19, wherein the one or more manufacturing modes comprises an external tidal growth mode, wherein the mould support structure is configured to at least partially submerge a mould within the container, and the processor is configured to repeatedly raise and lower the liquid level in the container by conveying liquid via the tubing from the external container.

21. The bioreactor of any of claims 17-20, wherein the one or more manufacturing modes comprises an internal tidal growth mode, wherein the processor is configured to repeatedly raise and lower a liquid level within a sealed mould by conveying liquid via the tubing from the external container.

22. The bioreactor of any preceding claim, wherein the bioreactor is configured for both external moulding and internal moulding, such that biological material is grown (i) on an outer surface of a mould to form a shell and / or (ii) on an inner surface of a hollow or sealed mould to form a lining or internal structure.

23. The bioreactor of any preceding claim, wherein three-dimensional growth of material is promoted throughout the thickness of the grown structure by cyclic modulation of one or more environmental parameters including oxygenation, nutrient flow, temperature, humidity, pH and / or shear exposure under control of the processor, wherein such modulation is dynamically regulated through feedback from one or more environmental sensors monitoring conditions within the bioreactor, thereby enabling adaptive adjustment of the growth environment to optimise material formation.

24. The bioreactor of any preceding claim, wherein the mould is rigid, flexible, inflatable and / or dissolvable, and includes patterned or textured surfaces configured to27influence biological adhesion or structural orientation of a grown material, and wherein a dissolvable mould is configured to at least partially disintegrate or merge with the growing material and / or release nutrients during fabrication.

25. The bioreactor of claim 24, wherein the patterned or textured surface of the mould is configured to induce directional fibre alignment, controlled porosity, or gradient density within the grown material, thereby providing tailored mechanical anisotropy or fluid-flow pathways in the resulting biostructure.

26. The bioreactor of claim 24 or 25, wherein the dissolvable mould contributes nutrients or mineral precursors during growth and becomes structurally integrated into the resulting biocomposite material.

27. The bioreactor of any preceding claim, wherein the housing defines a substantially enclosed internal environment configured to maintain controlled conditions for growth without requiring an external incubator, and wherein the housing comprises one or more transparent or translucent panels formed of acrylic, glass, polycarbonate, borosilicate glass, or another transparent polymeric or composite material, together with internal illumination arranged to permit continuous visual monitoring of the growth process while reducing contamination.

28. The bioreactor of any preceding claim, wherein the structural frame of the housing comprises extruded profiles and / or universal connection interfaces configured to enable repositioning, replacement or scaling of modules including one or more of: a pump, a liquid reservoir, a processor and an environmental sensor, and wherein the modules are mechanically and electronically connectable so as to permit functional reconfiguration and scalable expansion of the bioreactor for dilferent manufacturing modes or environmental control schemes, such that the system is adaptable for distributed or deployable manufacturing in remote or resource-limited environments.

29. The bioreactor of any preceding claim, wherein the biological process comprises cultivation of one or more microorganisms selected from bacteria, fungi, microalgae or mineral precipitating species, including but not limited to cellulose-producing and polyhydroxyalkanoateproducing (PHA-producing) bacteria, and wherein the processor is configured to regulate temperature, humidity, nutrient composition, pH, gascomposition and / or liquid cycling to support growth of the selected microorganisms, and wherein two or more microorganisms may be sequentially or simultaneously cultivated to form composite or layered biomaterials, including hybrid structures that combine organic, polymeric and / or mineral phases.

30. A kit of parts comprising:the bioreactor of any of claims 1-29; andone or more moulds connectable to the mould support system.

Images