Bioprocessing apparatus

Abstract

A biological processing apparatus, comprising: a housing; a carousel located within the housing, the carousel comprising a plurality of containers. The housing comprises a transfer port at a fixed position with respect to the housing, and the transfer port is connected to at least one control port through a fluidic system thereby enabling a pump to control a flow of fluid through the fluidic system and transfer port via the at least one control port, during use. The carousel is rotatable within the housing to align each of the plurality of containers with the transfer port, and wherein the carousel is movable parallel to its axis of rotation to move the transfer port into fluid communication with each of the containers.

Description

[0001] BIOPROCESSING APPARATUS

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a bioprocessing apparatus, such as a bioprocessing apparatus for performing diagnostic tests.

[0004] BACKGROUND

[0005] Bioprocessing apparatuses can be used for various bioprocessing operations, such as diagnostics. The point-of-care diagnostics market has been growing for several years with the ultimate goal of fulfilling the promise of personalised medicine and providing the right therapy at the right time for the right patient. Many analytical approaches can be applied to samples in such apparatuses such as molecular diagnostics, chemical analysis, immunoassays, polymerase chain reaction (PCR) and flow cytometry.

[0006] Typical apparatuses and systems that perform such operations include a plurality of containers (known as “pots”) which each contain fluid and / or allow for a particular reaction of manipulation to be performed on the fluid. The systems have a moving pipette that can transfer fluid between each of the plurality of containers as required for a particular bioprocessing operation. In addition, the containers may be heated during certain processes, and magnetic beads may be manipulated with one of the containers with an external magnet to perform DNA separation. Since beads can bind to DNA within the sample, when the beads are immobilised with an external magnetic device, they are washed several times with a buffer solution to remove other substances within the sample. When the magnetic device is removed, the beads are released together with the purified DNA.

[0007] However, these apparatuses have a number of problems. Firstly, they are typically very bulky with several complex components that all need to work together at the same time. For example, existing systems require a separate movable pipette device (often mounted on an x-y robot) that allows for access to all the plurality of containers. This type of system is very expensive to manufacture and difficult to operate.

[0008] Secondly, existing apparatuses often require large volumes of fluid to be transferred around the system. Since there always needs to be sufficient reagents and fluid to perform a particular bioprocessing operation, typically additional volumes of redundant fluid are included, which further increases the expense of operating the apparatus.

[0009] One reason that larger volumes of fluid is required is due to inaccurate metering within the movable pipette device. Usually, the pipettes include complicated internal sensors to determine the volumes of fluid being transferred, but these internal sensors frequently give erroneous measurements (e.g., due to pressure fluctuations or air-springs within the apparatus). Furthermore, the complexity of the internal sensors further increases the size and expense of the apparatus. In some examples, the pipette and associated sensors can be a third of the total cost of the apparatus.

[0010] Another reason is due to the size of existing apparatuses, which means there are usually large dead volumes (e.g., within tubing) thereby leading to fluid being wasted. Due to the need for complicated sensors, it has been found difficult to reduce the size of the apparatus without worsening the issue of inaccurate metering.

[0011] A third problem with existing apparatuses also stems from the size of the apparatus. Where volumes of fluid are heated, it is often difficult to ensure that the fluid is uniformly heated. Due to the large volume within the containers, it is necessary to rely upon local convection to evenly heat fluid, which is slower and less reliable. Similarly, magnetic bead separation is inefficient when performed within pots, since a large amount of buffer is required to sufficiently wash the sample. This is because in a larger container there is no way to direct the flow of the buffer directly over the magnetic beads, so the container would need to be filled and emptied three or more times with buffer solution to perform adequate separation. It is an object of the present invention to address the problems discussed above.

[0012] SUMMARY OF INVENTION

[0013] According to a first aspect of the present invention there is provided a biological processing apparatus, comprising: a housing; a carousel located within the housing, the carousel comprising a plurality of containers; wherein the housing comprises a transfer port at a fixed position with respect to the housing, and the transfer port is connected to at least one control port through a fluidic system thereby enabling a pump to control a flow of fluid through the fluidic system and transfer port via the at least one control port, during use; and wherein the carousel is rotatable within the housing to align each of the plurality of containers with the transfer port, and wherein the carousel is movable parallel to its axis of rotation to move the transfer port into fluid communication with each of the containers.

[0014] Advantageously, by allowing fluid communication with each of the containers using a transfer port provided fixedly in the housing, fluid transfer to and from the containers can be done more reliably and the apparatus can be provided in a more compact form. Furthermore, since the transfer port is operated using a pump (e.g., an external pump) via the one or more control ports, having a fixed transfer port means that there is no relative motion between the transfer port and the control ports, so the transfer port does not need to be connected to the control ports via complicated valving that allows relative movement. The carousel can be rotated to align any of the containers with the transfer port, and then axial movement of the carousel can be used to bring the transfer port into fluid communication with the aligned container. As a result, the connection with any of the containers can be controlled only via movement of the carousel. Once in fluid communication, pressure can be applied to the at least one control port to drive fluid between the container and the transfer port.

[0015] The transfer port may be provided by a pipette at a fixed position with respect to the housing, and the carousel may be movable parallel to its axis of rotation to move the pipette into each of the containers. In this way, the movement of the pipette parallel to the rotation axis can place the transfer port (e.g., provided by a tip of the pipette) into fluid communication with each of the containers. The “at least one control port” may simply be referred to herein as “at least one port” and vice versa.

[0016] Alternatively or additionally, at least one of the containers may comprise a pipette, and the carousel may be movable parallel to its axis of rotation to form a seal between the transfer port and the pipette. For example, the apparatus may include a sealing element for forming the seal between the transfer port and the pipette. Preferably, the sealing element is provided around the transfer port. The sealing element may comprise a ring of material, preferably elastic or elastomeric material. Following axial motion of the carousel, the sealing element may seal around an upper opening of the pipette, thereby enabling fluid to be transferred through the pipette by operating the pump to pressurise (or depressurise) the at least one control port. Advantageously the transfer port can be brought into fluid communication with the pipette with only a small movement of the carousel parallel to its axis.

[0017] Each of the plurality of containers may be substantially sealed during use. The internal volume of each container may be alignable with a pressure port on the housing, thereby enabling the pressure within the container to be controlled. The housing may comprise a pressure port configured to control a pressure in each of the containers, wherein movement of the carousel parallel to its axis of rotation places both the pressure port and the transfer port into fluid communication with each of the containers. The pressure port may be located adjacent to the transfer port so that both ports may be brought into simultaneous fluid communication with one of the containers (e.g., by movement of the carousel parallel to its axis of rotation). This pressure port allows for “headspace control” within the apparatus. Therefore, the pressure port may be referred to as a “control port”. The term “headspace pressure” may refer to a pressure experienced within each of the containers. During use, a pressure difference may be applied (e.g., using one or more pumps) between the transfer port and the pressure port, thereby driving flow of fluid into or out of the pipette. According to an aspect of the present invention there is provided a biological processing apparatus, comprising: a housing; a carousel located within the housing, the carousel comprising a plurality of containers; wherein the housing comprises a pipette at a fixed position with respect to the housing, and the pipette is connected to at least one port through a fluidic system thereby enabling a pump to control operation of the pipette via the at least one port, during use; and wherein the carousel is rotatable within the housing to align each of the plurality of containers with the pipette, and wherein the carousel is movable parallel to its axis of rotation to move the pipette into each of the containers.

[0018] Advantageously, by having the pipette fixed with respect to the housing, its functionality may be enhanced, since it no longer needs to be a smaller component located within the housing itself. Furthermore, since the pipette is operated using a pump (e.g., an external pump) via the one or more (e.g., control) ports, having a fixed pipette means that there is no relative motion between the pipette and the ports, so the pipette does not need to be connected to the (e.g., control) ports via complicated valving that allows relative movement.

[0019] The containers may be integrally formed with housing. Alternatively, the carousel may have a plurality of slots each configured to receive a respective container. The fluidic system may comprise one or more fluid channels.

[0020] The fluidic system may be arranged adjacent to an external surface of the housing, thereby enabling fluid within the fluidic system to be manipulated by an external processing instrument. For example, a heater may be located adjacent the fluidic system to heat fluid passing through the fluidic system. By performing heating of fluid when it passes through the fluidic system, it is possible to heat the fluid to a much more uniform temperature (as compared to heating a volume of fluid within a container and relying upon local convection to bring the fluid to a uniform temperature). Alternatively or additionally, a magnetic device may be located adjacent to the fluidic system. By providing a fluidic system adjacent to an external surface of the housing, the magnetic separation can be performed within the fluidic system instead of a container. This means that when the beads are washed in a fluidic channel of the fluidic system, only a small amount of buffer is needed, since the fluid is forced to flow directly over the magnetic beads during washing.

[0021] The external surface is preferably an upper surface of the housing. However, it will be appreciated that other surfaces, such as a lower surface may be used for at least part of the fluidic system. For example, the fluidic system may be arranged on both an upper and a lower external surface of the housing to allow for manipulation of the fluid from different sides.

[0022] Preferably, the external surface of the housing is a substantially planar surface. This particularly enables the apparatus to be manipulated by an external processing instrument, since all parts of the fluidic system are arranged upon a consistent predetermined surface.

[0023] The fluidic system may comprise a plurality of channels arranged within a single layer on the external surface of the housing. This means that all parts of the fluidic system are accessible on the external surface (i.e., without any tubing being concealed within a second layer below the first layer). This further helps with manipulation of the apparatus by an external processing instrument

[0024] Preferably, the plurality of channels is formed by slots and / or grooves in the housing, over which a sealing film is secured. For example, the housing may be a piece of material (e.g., plastic) with grooves along its surface. When the sealing film is secured (e.g., glued or welded), over the grooves, channels are formed. Alternatively or additionally, at least some of the channels may be formed by slots that go all the way through the plastic and two sealing films may be used on opposite sides. This means that some channels of the fluidic system can be provided on different sides of the apparatus (which may enable the fluid within the channels to be manipulated by different processing tools of an external processing instrument).

[0025] Preferably, the sealing film is configured to facilitate manipulation of the fluid through the film by a processing tool, during use. For example, where optical actuators or sensors are used, the sealing film may be transparent. Where heaters are used to heat fluid within the channels, the sealing film may be a thin layer of plastic (with low thermal resistance), or a metal foil layer (with high heat conductivity). Where magnetic devices are used to manipulate the fluid, it may be desirable not to use a metallic sealing film. For example, a plastic film may be used. The sealing film may be thin (e.g., 1 mm or less) to allow the processing tools to more effectively manipulate the fluid within the channels.

[0026] The at least one (e.g., control) port may comprise a metering port, and the fluidic system may comprise a metering channel that connects the pipette (e.g., either of the housing or of the container) to the metering port, and wherein the metering channel includes one or more fluid sensing locations at predetermined positions along the channel that correspond to predetermined volumes of fluid retained in the metering channel between each sensing location and a tip of the pipette.

[0027] During use, a corresponding fluid sensor may be arranged to detect fluid within the metering channel at each of the fluid sensing locations. The fluid sensors may be part of the apparatus. Preferably, the fluid sensors are part of the external processing instrument into which the apparatus is inserted during use. The fluid sensors may be optical sensors.

[0028] In this way, fluid can be drawn into the metering channel through the pipette (e.g., pipetting device) (e.g., by applying negative pressure to the metering port with the pump) until the fluid sensor detects presence of fluid at one of the predetermined positions. This means that a precisely known volume of fluid is contained within the metering channel. Since the metering channel can be very narrow, it is possible to measure small volumes (e.g., 10pL) with very high accuracy (e.g., to the nearest 0.1 pL). Having a more accurate way of metering fluid is several advantages.

[0029] Firstly, by using fluid sensors on the metering channel for metering of fluid, the cost of the apparatus can be substantially reduced since the pump does not require its own dedicated metering system. In existing apparatuses, about a third of the costs could be attributed to the pipette and pump, since it required its own dedicated internal sensors to detect the volumes being pumped. However, by using sensors to monitor the presence at fluid at fluid sensing locations in the metering channel, the pump does not need its own metering and can be significantly less expensive.

[0030] Secondly, the metering is more accurate than existing apparatuses (i.e. , ones that use sensors within the pump). Such existing apparatuses are often inaccurate due to the presence of air springs (and other pressure fluctuations) within the containers. Even if the pump or pipette has highly accurate (and expensive) internal sensors, it is not always possible to account for such pressure fluctuations. However, with metering in the metering channel, the sensors directly measure the volume of fluid, so there can be no variation due to pressure fluctuations.

[0031] Thirdly, as a result of the inaccuracy discussed above, existing systems require redundant fluid to be provided. Since some of the fluids can be very costly in certain bioprocessing operations (e.g., the “master mix” used in PCR operations), having more accurate metering means that additional redundant fluid is not required, thereby reducing the costs associated with each bioprocessing operation.

[0032] Preferably, the metering channel is arranged in a serpentine pathway, and wherein each of the fluid sensing locations is provided at a straight section in the pathway. In this way, the metering channel can be relatively long (and therefore measure a large volume of fluid), while still occupying a small area on the housing. By having straight sections for the fluid sensing locations, the sensors are more able to reliably detect the presence of fluid. Each of the straight sections may be labelled with a marker to identify the volume of fluid between the corresponding fluid sensing location and the tip of the pipette. The serpentine pathway may comprise a plurality of bends or zigzags.

[0033] A surface of the housing may comprise one or more slots or grooves, and a sealing film is secured over the one or more slots or grooves to provide the fluidic system. In this way, the channels of the fluidic system may be particularly easy to manufacture, e.g., by etching or machining a slot or groove within a piece of plastic. Furthermore, since the (e.g., plastic) film is the only component separating the fluid from the surrounding environment, the fluid may be particularly easy to manipulate with a processing instrument (such as a heater or magnetic device). In other words, due to the limited separation between the processing instrument, the fluid will be more responsive to changes in temperature or magnetic field. Alternatively, a tube may be used to provide channels in the fluidic system.

[0034] At least one (e.g., control) port may comprise a cuvette port, and the fluidic system may further comprise a cuvette channel that connects the pipette (e.g., of the housing or of the container) to the cuvette port. For example, the fluidic system may have a junction where fluid can be diverted from the pipette into the metering channel (e.g., where a pump applies negative pressure to the metering port), or into the cuvette channel (e.g., where the pump applies negative pressure to the cuvette port).

[0035] This allows fluid to be pumped into a separate part of the fluidic system for measurement in the cuvette channel. The apparatus may include valving so that air pressure can be applied by a pump to either of the ports to select whether fluid flows from the pipette into the metering channel or the cuvette channel. Where the apparatus includes more than one port, valving may be used to allow any of the ports to be operated with a single pump.

[0036] The cuvette channel may have a cuvette segment that may be optically excited by an external light source with fluorescence being detected on the opposite side of the cuvette segment to the light source. The cuvette channel may have a larger cross-sectional area than the metering channel. Advantageously this minimises the surface area exposed to eluate during cuvette filling. The cuvette channel may allow for aspiration and / or dispensing of fluid for mixing of lyo reagents.

[0037] The apparatus may comprise an air spring connected to the cuvette channel. The air spring may be connected to the cuvette channel on the same side of the cuvette segment as the cuvette port (i.e., downstream of the cuvette segment). Alternatively, the air spring may be upstream of the cuvette segment. A surface of the housing may comprise an indentation, and a sealing film may be secured over the indentation to provide the air spring. Advantageously, an operator or actuator can apply pressure to the sealing film to adjust the pressure within the cuvette segment. The sealing film may be a metal film to improve thermal conduction to the fluid from an external heater. The sealing film may be the same sealing film as described above for sealing one or more grooves. Alternatively, separate films may be used (e.g., with different materials).

[0038] The apparatus may further comprise: a sample input chamber accessible via an opening in the housing, and a sample input pipette arranged in the sample input chamber, wherein the sample input pipette is also connected to the at least one port through the fluidic system. In this way, a user may input their sample into the apparatus without needing to remove the carousel from the housing. Instead, the user simply puts their sample into the sample input chamber, operates a pump via the at least one port (e.g., the metering port) to draw the fluid out of the sample input chamber through the sample input pipette (e.g., into the metering channel). Subsequently, the pump can be operated to transfer the sample into one of the containers in the carousel (e.g., from the metering channel), as required for a bioprocessing operation.

[0039] A cap may be provided to cover the opening in the housing when it is not required for inputting a sample into the chamber. A headspace inlet (or valve) may be provided to allow air to flow into the sample input chamber to replace the fluid that is extracted through the sample input pipette (including when the cap is closed).

[0040] Alternatively or additionally, the apparatus may further comprise a sample access container in the carousel, the sample access container comprising a sample access opening, wherein the housing is configured to expose at least a portion of the carousel to facilitate access to the sample access container via the sample access opening. The provides a flexible way of incorporating a sample access container. Furthermore, it may also allow a simplified system (for example, since there is no need for extra valving, junctions and / or fluidic channels in the apparatus). Also, a user may input their sample into the apparatus without needing to remove the carousel from the housing.

[0041] The fluidic system may be a first fluidic system, the transfer port (e.g., pipette) may be a first transfer port (e.g., first pipette), and the housing may further comprise a second transfer port (e.g., second pipette) at a fixed location with respect to the housing, and the second transfer port (e.g., second pipette) is connected to at least one (e.g., control) port through a second fluidic system thereby enabling the pump to control operation of the second transfer port (e.g., pipette) via the at least one (e.g., control) port. Advantageously, this allows to completely separate processes to be performed within the apparatus without the fluids ever passing through the same fluidic system or the same pipette. This ensures that separate bioprocessing operations remain completely separate to each other and the risk of cross contamination between processes is reduced. For example, a single user sample can be split into two (or more) parts using different master-mixes, and then amplified in separate amplification chambers. This multiplies the number of tests that can be performed using the same sample without increasing the risk of crosscontamination.

[0042] The second fluidic system may contain features corresponding to the first fluidic system. For example, the second fluidic system may include a (second) metering channel connected to a (second) metering port. The second fluidic system may include a (second) cuvette channel connected to a (second) cuvette port. Any features described above and herein in relation to the first fluidic system can also be present in the second fluidic system. Furthermore, it will be appreciated that more than two fluidic systems can also provided, such as three, four, five or more.

[0043] The first transfer port (e.g., first pipette) may be arranged on the housing to align with a first subset of the plurality of containers, and the second transfer port (e.g., second pipette) may be arranged on the housing to align with a second subset of the plurality of containers that is different from the first subset. Advantageously, different pipettes can be used for different biological processing operations, thereby reducing the chance of cross contamination of the processes. The first subset and second subset may be non-overlapping (e.g., mutually exclusive) subsets. Alternatively, the containers may include a container that is accessible by both pipettes, thereby allowing fluid to be passed between the first fluidic system and the second fluidic system, if desired.

[0044] Preferably, the first and second subset of containers are each provided as a ring of containers on the carousel at a different distance from the axis of rotation to each other. In this way, the pipettes can remain fixed, and rotation of the carousel allows the pipettes to access any of the containers in their respective subset.

[0045] Preferably, the sample input pipette is a first sample input pipette, and the apparatus further comprises a second sample input pipette arranged in the sample input chamber, wherein the first sample input pipette is connected to the first fluidic system and the second sample input pipette is connected to the second fluidic system.

[0046] Advantageously, this allows the user to input a single sample into the sample input chamber, and this sample can be easily divided into completely separate fluidic systems within the apparatus through separate sample input pipettes. This may allow several different diagnostic tests to be performed on the same sample without any possibility for cross contamination. It will be appreciated that there may be more than two fluidic systems (each with corresponding sample input pipettes).

[0047] Alternatively, samples may be split elsewhere in the apparatus. For example, a splitting chamber may be provided elsewhere in the cartridge, into which two (or more) pipettes extend to allow fluid to be separately extracted into respective fluidic systems. In this way, initial cleaning or preparatory steps can be performed to the input sample within the cartridge prior to separating into two (or more) separate fluidic systems for different bioprocessing operations to be performed.

[0048] Respective cuvette channels of the first and second fluidic system may be arranged adjacent to each other on an external surface of the housing so that they can be sealed simultaneously to lock fluid within the respective cuvette segments. Advantageously, sealing the cuvette channels enables to the cuvette segments to be pressurised, which may be beneficial within a PCR operation. By placing the cuvette channels adjacent to each other, they can be sealed simultaneously with a single sealing device.

[0049] Preferably, the carousel is movable parallel to its axis of rotation between a collapsed configuration where the carousel is clipped onto the housing for storage, and an expanded configuration where the carousel is movable relative to the housing to align the transfer port (e.g., pipette or pipettes). Advantageously, the apparatus can be kept in its collapsed configuration during storage and transport. This reduces the size of the apparatus, thereby increasing the storage density. In the collapsed configuration, a total height of the apparatus may be 15mm or less. Furthermore, the apparatus may be easier to deliver, since it can fit into smaller packaging and be posted to a user through a post-box or letterbox. In the collapsed configuration, movement of the carousel is inhibited. When in the collapsed configuration, the pipette(s) may extend into one or more support slots within the carousel (e.g., at a location on the carousel where there are no containers), thereby supporting them during storage and transport, and reducing the risk of breakage. In the expanded operation, the carousel can rotate relative to the housing for alignment of the pipette with the plurality of containers, and the carousel can move parallel to its axis of rotation (e.g., in an expansion direction) to move the pipette into each of the containers.

[0050] Preferably, the carousel and the housing have complementary sealing features that seal the interior of the housing from the surroundings when in the collapsed configuration. In this way, after a user has input their sample into the apparatus, it can be sealed, thereby preventing unwanted leakage post-use. The complementary sealing features may comprise interlocking lips, such as lips located around a circumference of the housing and the carousel. The lips provide a convoluted path around the carousel circumference that safeguards against leakage.

[0051] Preferably, each of the plurality of containers comprises a sealing film that is pierceable by the pipettes (e.g., one or more of the pipettes that are part of the housing) during use. Advantageously, this ensures that the contents of the containers remain isolated from the surroundings up until the point of use. Furthermore, when the sealing film is pierced, air can enter the containers to replace any fluid that is removed by the pipette.

[0052] According to a second aspect of the present invention there is provided a method of performing bioprocessing using the biological processing apparatus as described above and herein, the method comprising: connecting the apparatus to a processing instrument; and operating the processing instrument to: rotate the carousel relative to the housing to align the transfer port on the housing with a different container of the plurality of containers, and manipulate air pressure at the at least one control port to control movement of fluid through the fluidic system.

[0053] According to another aspect of the present invention there is provided a method of performing bioprocessing using the biological processing apparatus as described above and herein, the method comprising: connecting the apparatus to a processing instrument; and operating the processing instrument to: rotate the carousel relative to the housing to align the pipette on the housing with a different container of the plurality of containers, and manipulate air pressure at the ports to control movement of fluid through the fluidic system.

[0054] Advantageously, this allows fluid to be transferred between separate containers with very few moving parts and a simple connection to the external processing instrument. The processing instrument only needs to move the carousel (e.g., rotationally and parallel to its rotational axis) to align and facilitate transfer of fluid with the pipette, and operate a pump to apply (positive or negative) pressure at one of the ports to move fluid through the fluidic system.

[0055] The fluidic system may be arranged adjacent to an external surface of the housing and the method may further comprise operating a processing tool of the biological processing instrument adjacent the external surface to manipulate fluid within the fluidic system.

[0056] Advantageously, by providing the fluidic system adjacent to the external surface (and particularly where the external surface is planar and / or arranged in a single 2D layer), it is easy to manipulate the fluid with processing tools in easy-to-access and repeatable locations. The processing tool may comprise one or more of: a heater, a magnetic device, and a light source. The processing tool may comprise a sensor (e.g., an optical sensor). The instrument may have a combination of processing tools, as required.

[0057] The fluidic system may be arranged adjacent to an external surface of the housing and the method further may further comprise operating one or more sensors of the biological processing instrument adjacent the external surface of the housing to determine a volume of fluid retained in a metering channel of the fluidic system. For example, the metering channel may have predetermined locations where sensors can monitor for the presence of fluid, thereby indicating that a particular volume of fluid is retained in the metering channel between the predetermined location and the transfer port (e.g., the tip of the pipette). For the reasons already discussed above in relation to the first aspect, this allows for improved accuracy of the metering, reduced size of the apparatus, and reduced operational complexity.

[0058] Preferably, the instrument retains the housing at a fixed position (e.g., relative to the surroundings) and rotates the carousel. Advantageously, this prevents any tangling of the connections (e.g., tubes) between the ports and the instrument. Alternatively, the carousel may remain fixed (e.g., relative to the surroundings), and the instrument may rotate the housing.

[0059] It will be understood by a skilled person that any apparatus feature described herein may be provided as a method feature, and vice versa. It will also be understood that particular combinations of the various features described and defined in any aspects described herein can be implemented and / or supplied and / or used independently.

[0060] Moreover, it will be understood that the present invention is described herein purely by way of example, and modifications of detail can be made within the scope of the invention.

[0061] BRIEF DESCRIPTION OF DRAWINGS

[0062] One or more embodiments will now be described, purely by way of example, with reference to the accompanying figures, in which:

[0063] Figure 1 shows an exploded view of an embodiment of a bioprocessing apparatus having a housing and a carousel;

[0064] Figures 2A and 2B show cross sections through the apparatus to show operation of transfer pipettes of the housing and relative movement of the housing and carousel;

[0065] Figures 3A and 3B show further details of an input chamber and input pipettes on the housing;

[0066] Figures 4A and 4B show channels formed on the housing that form fluidic systems connected to the transfer pipettes and input pipettes; Figure 5 shows ports that allow pumps to control the flow of fluid through the fluidic systems and pipettes;

[0067] Figures 6A and 6B show further details of a metering channel that forms part of each of the fluidic systems;

[0068] Figures 7A and 7B show further details of a cuvette channel that forms part of each of the fluidic systems;

[0069] Figures 8A and 8B show how external instruments may manipulate fluid flowing through a processing portion of the cuvette channel;

[0070] Figures 9A to 9C depict relative movement of the housing and carousel between an expanded configuration, an intermediate position, and a collapsed configuration;

[0071] Figure 9D shows complementary sealing features on the housing and carousel;

[0072] Figures 10A and 10B show examples of containers that may form part of the carousel;

[0073] Figure 11 shows an alternative embodiment of a bioprocessing apparatus having a housing and a carousel, where pipettes are provided within the containers in the carousel;

[0074] Figure 12 shows an exploded view of the alternative embodiment of Figure 11 ;

[0075] Figures 13A and 13B show a cross section through the bioprocessing apparatus to illustrate how a transfer port on the housing may be brought into fluid communication with one of the pipettes by axial movement of the carousel; and Figures 14A and 14B show a cross section through the bioprocessing apparatus to illustrate operation of a sample access container in the carousel.

[0076] DETAILED DESCRIPTION

[0077] Figure 1 shows an exploded view of a bioprocessing apparatus 10 (which may be referred to as a biological processing apparatus 10). The apparatus 10 includes a housing 100 and a carousel 200 that (once assembled) is located within the housing 100.

[0078] As shown in Figure 1 , the carousel 200 is substantially cylindrical and has a plurality of slots 205 (only some labelled) concentrically arranged about its central axis. Each of the slots 205 is arranged to receive a respective container 210 (only some labelled). Different combinations of containers 210 can be placed within the slots 205 in order to allow a particular bioprocessing operation to be performed by the apparatus 10. For example, different containers 210 can contain different liquids, reagents, or samples that may be used at different times during a particular process.

[0079] The housing 100 includes a frame 105 within which the carousel 200 is located. The frame 105 may be made of a rigid material such as plastic. The frame 105 may be injection moulded. The frame 105 may have a cylindrical cavity arranged to receive the carousel 200 and to allow movement of the carousel 200 relative to the frame 105. The housing 100 includes several pipettes (as described in detail later), which allow fluid to be transferred between the containers 210 in the carousel 200.

[0080] Since many bioprocessing operations being performed with the apparatus 10 require a patient sample (e.g., a sample for a diagnostic test), an external surface 114 of the housing 100 has an opening 132 that allows a user to input a sample into an input chamber 130 of the apparatus 10. The opening 132 may be closed by a cover 134 to prevent the sample leaking from the apparatus 10 during use.

[0081] The external surface 114 of the housing includes a plurality of slots or grooves 116, over which an upper sealing film 118 and a lower sealing film 178 are secured to define closed fluidic channels through the housing 100. These films 118, 178 may be welded or bonded onto the external surface 115 of the housing 100. As discussed later, these closed fluidic channels form part of different fluidic systems of the apparatus 10, where different bioprocessing operations can be performed separately in different fluidic systems. The plurality of slots or grooves are injection moulded; alternatively, they may be machined onto the external surface 114 in a separate manufacturing step. A label 119 may be attached to the top of the housing 100 to identify the apparatus 10.

[0082] As can be appreciated from Figure 1 , the apparatus 10 only contains a small number of components that can be manufactured and assembled using low-cost methods (such as injection moulding and heat-staking). While Figure 1 shows the containers 210 as being separate to the carousel 200 (thereby enabling more flexible combinations to be achieved), in other designs, the containers 210 are integrally formed as part of the carousel (thereby further reducing the assembly time and cost).

[0083] As shown in Figures 2A and 2B, the housing 100 of the apparatus 10 includes a first transfer pipette 110a and a second transfer pipette 110b. The first transfer pipette 110a is connected to a first fluidic system 150a on the external surface 114 of the housing 100. The second transfer pipette 110b is connected to a second fluidic system 150b on the external surface 114 of the housing 100. The first transfer pipette 110a is arranged on the housing 100 to align with a first subset 210a of the plurality of containers 210 arranged in an outer ring of the carousel 200. The second transfer pipette 110b is arranged on the housing 100 to align with a second subset 210b of the plurality of containers 210 arranged in an inner ring of the carousel 200.

[0084] During use of the apparatus 10, the carousel 200 can be moved vertically (i.e., parallel to its axis) so that the transfer pipettes 110a, 110b can be moved into the containers (to the position shown in Fig 2A) and out of the containers 210 (to the position shown in Fig 2B). In addition, when the transfer pipettes 110a, 110b are moved outside the containers 210, the carousel 200 can be rotated about its axis to align any of the containers in the first subset 210a with the first transfer pipette 110a and any of the containers in the second subset 210b with the second transfer pipette 110b. In this way, the housing 100 can remain entirely fixed (e.g., when mounted and connected to an external processing instrument), with all the movement required to transfer fluid between containers 210 being performed via movement of the carousel 200. The subsets 210a, 210b of the containers can be mutually exclusive and non-overlapping subsets; alternatively, some containers 210 may be provided in both subsets to allow fluid to be transferred between the fluidic systems 150a, 150b if desired.

[0085] The input chamber 130 will now be described in more detail with reference to Figures 3A and 3B. Figure 3A shows the opening 132 and cover 134 on the external surface 114 of the housing 100. The cover 134 can slide along the external surface 114 of the housing in order to prevent access to the opening 132. Figure 3B shows a cross section through the input chamber 130. Extending into the input chamber 130 is a first input pipette 120a and a second input pipette 120b. As described later, the first input pipette 120a is connected to the first fluidic system 150a, and the second input pipette 120b is connected to the second fluidic system 150b. In this way, the user can input a single sample into the apparatus 10 via the opening 132. The sample can be either a liquid sample or a swap. The user can then close the cover 134 to seal the input chamber 130 from the atmosphere. Subsequently, the sample can be drawn through both of the input pipettes 120a, 120b into separate fluidic systems 150a, 150b where separate bioprocessing operations can be performed in parallel. Since the cover 134 is closed during operation of the input pipettes 120a, 120b, a headspace inlet 136 may be provided into the input chamber 130 so that air can flow into it to replace fluid that is removed by the input pipettes 120a, 120b. The headspace inlet 136 may be connected to a corresponding venting port 137 within the housing 100, such as by a channel on the external surface 114 of the housing 100. The venting port 137 may be controlled by a valve (in the external processing instrument), so that the sample can only be drawn from the input chamber 130 when required.

[0086] The fluidic systems 150a, 150b will now be described in more detail with reference to Figures 4A and 4B. The first fluidic system 150a is located on the right-hand side of Figures 4A and 4B and the second fluidic system 150b is located on the left-hand side. The first fluidic system 150a is connected to the first transfer pipette 110a and the first input pipette 120a. These “first” pipettes 110a, 120a are connected to a first metering port 162a by a first metering channel 160a. The second fluidic system 150b is connected to the second transfer pipette 110ba and the second input pipette 120b. These “second” pipettes 110b, 120b are connected to a second metering port 162b by a second metering channel 160b. The metering channels 160a, 160b will be discussed further in relation to Figure 6A and 6B.

[0087] The first pipettes 110a, 120a are also connected to a first cuvette port 172a by a first cuvette channel 170a. The second pipettes 110b, 120b are also connected to a second cuvette port 172b by a second cuvette channel 170b. The cuvette channels 170a, 170b will be discussed further in relation to Figures 7A and 7B.

[0088] Figure 5 depicts the underside of the housing 100 (without the carousel 200 present), so that the ports 162, 172 can be more easily seen. The ports 162a, 172a connected to the first fluidic system 150a may be operated by a first pump. The ports 162b, 172b connected to the second fluidic system may be operated by a second pump. In this way, the apparatus 10 may be mounted into an external processing instrument during use, with each of the ports 162, 172 connected to pumps in the processing instrument. This allows the pumps to apply (positive or negative) pressure to the ports, which causes fluid to move through the pipettes 110, 120 and through the metering channels 160 and / or cuvette channels 170. Valves may be used within the external processing instrument so that the first pump and second pump can supply pressure (either negative or positive) to either of their respective ports. In other words, the first pump can control the pressure at either the first metering port 162a or the first cuvette port 172a, and the second pump can control the pressure at either the second metering port 162b or the second cuvette port 172b. While all of these ports could be connected to a single pump (e.g., with a four-way valve system), having two pumps enables the fluidic systems 150a, 150b to operate substantially independently. The venting port 137 may also be connected to the instrument to selectively allow for equalisation of the input chamber 130 with atmospheric pressure.

[0089] Figures 6A and 6B show further details of the first metering channel 160a, though it will be appreciated that the second metering channel 160b has corresponding features. The metering channel 160a follows a serpentine pathway on the housing 100. The serpentine pathway has straight sections at predetermined positions along the metering channel. As shown in Figures 6A and 6B, these predetermined positions are marked with volumes “1 Opl”, “30pl” and “70pl”, which indicate the volume contained within the metering channel 160a between the location marked with the respective arrow and the tip of the transfer pipette 110a (and the tip of the input pipette 120a). While the apparatus 10 in Figures 6A and 6B has predetermined positions at 10 l, 30pl and 70pl, it will be appreciated that the predetermined positions may be located elsewhere to enable different volumes of fluid to be precisely measured as required for a particular process. During use, sensors (e.g., in the external processing instrument) can be positioned at the straight sections to monitor for presence of fluid within the metering channel 160a. This means that when fluid is detected by one of the sensors, a precisely known volume of fluid has been extracted from one of the containers 210 (or the input chamber 130) by the pipette 110a (or input pipette 120a). For example, as shown in Figure 6B, the fluid extends from the tip of the first transfer pipette 110a to the first predetermined position on the metering channel 160a (marked as 10pl) indicating that 10pl of fluid has been extracted from the container 210 by the transfer pipette 110a. This precisely known volume of fluid can then be dispensed into a different container 210 within the carousel 200, as required for a particular bioprocessing operation. Since the metering channel 160a is narrow, the sensor allows for precise volumes of fluid to be measured, such as with a precision of 0.1 pl. Furthermore, since the accuracy of the metering is not dependent upon sensors within the pumps (as may be the case in existing apparatuses), the pumps used with the apparatus 10 can be less complex and expensive since they do not need dedicated fluid sensors.

[0090] The cuvette channels 170 will now be described in more detail with reference to Figures 7A and 7B. Cuvette channels 170 may be particularly beneficial for certain bioprocessing operations, such as PCR operations. As discussed below, the cuvette channels 170 can be filled with fluid, sealed, clamped and thermally treated for the amplification of nucleic acid. The resulting fluid can then be externally observed. For PCR operations, a “master mix” may be used, which is a pre-mixed, and often freeze dried, solution of reagents. Typically, it includes the primer and probes used in PCR for a given assay target (e.g., influenza A, Covid- 19, etc.)

[0091] Fig 7A shows the second cuvette channel 170b, though it will be appreciated that the first cuvette channel 170a has corresponding features. The cuvette channel 170b includes a processing portion 171 b with a larger diameter (as discussed further in relation to Figures 8A and 8B). The cuvette channel 170b also includes a cuvette segment 174b downstream of the processing portion 171 b. The cuvette segment 174b allows properties of the fluid to be measured in a separate part of the fluidic system 150b to the metering channel 160b. For example, the cuvette segment 174b may be optically excited from below by an external light source where the light enters via a polished flat on the cuvette edge with fluorescence being measured from above by a sensor (e.g., in the external processing instrument). Downstream of the cuvette segment 174b, an air-spring 176b is connected to the cuvette channel 170b. The air-spring 176b is formed by an indentation on the lower surface of the housing 100, over which a (lower) sealing film 178 is secured (as shown in Fig 1). This means that an operator (or an actuator) can apply pressure to the sealing film 178 during use, thereby allowing pressure within the cuvette segment 174b to be controlled. By maintaining a higher pressure within the cuvette segment 174b, bubble formation is prevented. The sealing film 178 may be a metal film which may allow for better conduction of heat from an external heater into the fluid in the cuvette segment 174b.

[0092] As shown in Figure 7B, the cuvette channel 170b is formed in part by grooves and indentations on the underside of the housing 100, with the lower sealing film 178 enclosing the grooves and indentations to form the cuvette channel 170b. In addition, the cuvette channels 170a, 170b of both fluidic systems 150a, 150b have a portion upstream of their respective cuvette segments 174a, 174b that are adjacent to each other on the housing 100. This means that once fluid is pumped into the cuvette segments 174a, 174b, the fluid can be sealed within the cuvette segments 174a, 174b with a single sealing operation. A welding head may achieve this by accessing the metal sealing film 178 on the underside of the housing 100 and heating the housing to locally melt the cuvette channels 170a, 170b so that the melt shut. This prevents fluid from escaping from the cuvette segments 174a, 174b during subsequent thermal treatment or pressurisation by applying a force to the air springs 176a, 176b.

[0093] The processing portion 171 b will now be described with reference to the cross sections in Figures 8A and 8B. While this discussion will refer to the processing portion in the second cuvette channel 170b, it will be appreciated that this discussion is equally applicable to the processing portion 171a in the first cuvette channel 170a. The processing portion 171 b is formed by a groove on the external surface 114 of the housing 100 over which an (upper) sealing film 118 is secured (see Figure 1). Since the sealing film 118 may be made from a thin material such as plastic, it allows the fluid within the processing portion 171 b to be manipulated by an external processing instrument. For example, the processing instrument may include a heater block 310 (as shown in Fig 8A) and a magnetic device 320 (as shown in Fig 8B).

[0094] As shown in Fig 8A, the heater block 310 may be located adjacent to the processing portion 171 b during use. Since the processing portion 171 b has a reasonably small cross section, and the sealing film 118 provides minimal thermal resistance, the heater block 310 can more directly apply heat to fluid as it passes through the processing portion 171 b, which allows the fluid to be brought up to a more precise and uniform temperature when required. This is an improvement upon existing methods, where the fluid needs to be gradually heated within a larger processing pot. Due to the large volume of the pot (and distance between fluid in the centre of the pot and the heater), it is necessary to rely upon internal convection within the pot to bring the fluid up to temperature. This takes much longer and there is less certainty as to the resulting temperature reached by the fluid. In the apparatus 10, since all of the fluid has to pass directly underthe heater block 310 (e.g., on the way to the cuvette segment 174b), all of the fluid can reach the required temperature without relying upon convection.

[0095] As shown in Fig 8B, the magnetic device 320 includes three magnets 322a, 322b, 322c that are movable towards and away from the processing portion 171 b so as to control the strength of the magnetic field that is applied to fluid in the processing portion 171 b. The magnetic device 320 may be used for magnetic separation of DNA within a sample. More specifically, the sample may include magnetic beads. When the sample is brought into the processing portion 171 b (via application of negative pressure to the cuvette port 172b), the magnetic device 320 may be located adjacent to the processing portion 171 b thereby locking the magnetic beads in place within the channel 170b. Subsequently, the beads can be washed by drawing a buffer solution into the processing portion 171 b and over the magnetic beads. Once the magnetic device 320 is removed, the beads are freed, together with purified DNA. The DNA can then be pumped into the cuvette segment 174b for further processing. Since the processing portion 171 b is relatively narrow, only a small amount of buffer is needed to wash the magnetic beads. This is an improvement upon existing methods that use the beads within larger pots; as a result of the large volume of the pot, three washing steps are required in order to sufficiently wash the beads, and each washing step requires the pot to be fully filled, which uses a large quantity of buffer. Since the processing portion 171 b requires the buffer to pass directly over the beads, they can be washed with only a small amount of buffer.

[0096] The cuvette channels 170 (and especially the processing portions 171) have a larger channel size than the metering channels 160. This is advantageous, since the reagents in the master mix often bind to plastic surfaces, so having a larger channel proportionally reduces the surface area of fluid in contact the plastic, thereby reducing the proportion of the master-mix that may be affected. Furthermore, due the compact design of the housing 100 the cuvette channels 170 are also shorter, which further reduces this problem.

[0097] The relative movement of the housing 100 and carousel 200 will now be discussed further with reference to Figures 9A to 9D. Figure 9A shows the expanded configuration of the carousel 200, where it can rotate about its axis to align the containers 210 with the transfer pipettes 210.

[0098] Figure 9B shows an intermediate position of the carousel 200, where the transfer pipettes 110 extend into respective containers 210 in the carousel 200 to allow for fluid to be added or removed from the containers 210.

[0099] Figure 9C shows a collapsed configuration of the apparatus 10, where the carousel 200 is clipped into the housing 100 for storage and transport. In this collapsed configuration, relative movement between the housing 100 and the carousel 200 is inhibited. Additionally, in order to protect the transfer pipettes 110a, 110b, their tips are clipped into respective holders 280a, 280b on the carousel 200. As well as protecting internal components of the apparatus 10, by having a collapsed configuration, the size of the apparatus 10 may be substantially reduced during storage and transport. The total height of the apparatus 10 in this configuration is about 10mm. This increases the storage density and may also allow the apparatus 10 to be posted to and from a user through a post-box or letterbox to input their sample.

[0100] Furthermore, the housing 100 and the carousel 200 include complementary sealing features that seal the interior of the housing 100 from the surroundings in the collapsed configuration. As shown particularly in Figure 9D, these sealing features include a rim 190 on the housing 100 that extends into a corresponding slot 290 on the carousel 200 in the collapsed configuration. The rim 190 extends all the way around the circumference of the housing 100 and the slot 290 extends all the way around the circumference of the carousel 200. This forms a convoluted pathway between the carousel 200 and the housing 100 which inhibits leakage from the apparatus 10 during transport or storage.

[0101] The external processing instrument is configured to move the apparatus 10 between each of the configurations discussed above. For example, the instrument may initially move the carousel 200 from the collapsed configuration, perform a particular test by manipulating the position of the carousel 200, and then return the carousel 200 to the collapsed configuration at the end.

[0102] Further details of the containers 210 will now be described with reference to Figures 10A and 10B. Figure 10A shows a first example of a container 210-1 which may be referred to as a high-volume wet reagent pot. Figure 10B shows a second example of a container 210-2 which may be referred to as a low-volume dry reagent pot. In both cases, the containers 210 have an upper opening 212 over which a sealing film 214 is secured. The sealing film 214 ensures that the containers 210 do not leak during storage or transport. The sealing film 214 can be pierced by the transfer pipettes 110a, 110b of the housing 100 during use of the apparatus 10. This means that the contents of the containers 210 remain completely sealed until required, thereby further minimising the possibility for any cross contamination and / or reagent expiration. In the apparatus 10, the containers 210 can be located within different slots 205 in the carousel 200. This allows flexibility to adapt the apparatus 10 for different applications (e.g., by changing out individual containers 210). Furthermore, if different volumes are required, containers 210 can be swapped accordingly. This also allows the containers 210 to be produced in different locations, and to be filled and sealed using conventional methods, such as 96 well pipetting robots and plate sealers. The containers 210 can also be made from different materials if required and can be stored in different environments before being snapped into the slots 205 in the carousel 200 prior to a particular bioprocessing operation being performed.

[0103] Alternatively, the carousel 200 can be provided as a monolithic carousel 200 with the containers 210 integrally formed. As a further alternative, some of the containers 210 may be integrally formed, with other containers being interchangeable.

[0104] It will be appreciated that many modifications can be made to the apparatus 10. For example, while the apparatus 10 has two fluidic systems 150a, 150b, further fluidic systems can be provided, for example with corresponding input pipettes, transfer pipettes and subsets of the containers. Additionally, while the fluidic systems 150a, 150b are mostly shown as being located on the upper surface of the housing 100, it will be appreciated that any surfaces of the housing 100 may be used in any combination to provide the fluidic systems. While the user sample is split within the input chamber 130, the user sample could alternatively be split elsewhere in the apparatus 10, such as within a dedicated splitting chamber or container, into which two (or more) pipettes may be inserted; for example, initial clean-up of the sample can be performed prior to splitting extracted RNA / DNA later in the process (e.g., only for the master-mix step).

[0105] While fluid volume sensors are described above as being located on the metering channels, it will be appreciated that the cuvette channels may also include predetermined positions for external sensors. This may reduce the quantity of fluid needed to fill the cuvette segment (PCR chamber). A further embodiment of a biological processing apparatus 10’ will now be described with reference to Figures 11 to 14. Figure 11 shows the apparatus 10’ when assembled and Figure 12 shows an exploded view so that internal components are visible. Unless otherwise stated, the apparatus 10’ corresponds to the apparatus 10 already described above. To avoid the need to describe the apparatus 10’ in detail again, any common features in the apparatus 10’ should be assumed as being similar to those in the apparatus 10, and corresponding reference numbers have been used where possible.

[0106] The apparatus 10’ is the same in that it has a housing 100’ and a carousel 200’ that is located within the housing 100’. The carousel 200’ is substantially cylindrical. The housing 100’ includes a frame 105’ with a cylindrical cavity arranged to receive the carousel 200’. The carousel 200’ rotates within the cylindrical cavity around an axis. The carousel 200’ is also movable parallel to this rotational axis.

[0107] An external surface 114’ of the housing 100’ includes a plurality of slots or grooves 116’ over which an upper sealing film 118’ and a lower sealing film 178’ are secured to define closed fluidic channels through the housing 100’. Similar to the previous apparatus 10, these closed fluidic channels 116’ form fluidic systems of the apparatus 10’. A label 119’ is attached to the top of the housing 100 to identify the apparatus 10’.

[0108] The carousel 200’ is formed from a lower portion 20T and an upper portion 202’. These are attached together to enclose a plurality of containers 210’. In this example, the containers 210’ are integral with the carousel 200’ but in other examples there may be a plurality of slots into which different types of containers may be inserted. The upper portion 202’ may be covered by a sealing film 214’ so that the contents of the containers 210’ remains enclosed until the point of use.

[0109] The apparatus 10’ differs from the one described previously in that the housing 100’ does not itself include a pipette for accessing each of the containers 210’. Instead, the upper portion 202’ of the carousel 200’ has a plurality of openings 240’ (only some labelled) to enable fluid to be added and removed from each of the containers 210’. A plurality of pipettes 218’ (only some labelled) are individually provided in each container 210’, with each pipette 218’ in communication with one of the openings 240’.

[0110] Figures 13A and 13B show cross-sections through one of the containers 210’ to illustrate how fluid may be transferred using pipettes 218’ and the openings 240’. In Figure 13A the carousel 200’ has been moved in a downward direction along its rotational axis so that the upper portion 202’ is spaced from the housing 100’. In Figure 13B, the carousel 200’ has been moved in an upward direction along its rotational axis so that the upper portion 202’ contacts the housing 100’.

[0111] The upper portion 202’ of the carousel 200’ includes a first opening 240-1’ and a second opening 240-2’ that correspond to the container210’. It will be appreciated that similar openings are provided for the other containers 210’ on the carousel 200’. For this particular container 210’ (but not necessarily for the others), a sample transfer opening 240-3’ is also provided on the upper portion 202’ but this will be discussed in more detail later in relation to Figures 14A and 14B. The pipette 218’ is attached to the first opening 240-1’ so that the pipette 218’ extends downward into the bottom of the container 210’.

[0112] The housing 100’ includes a transfer port 141’ that can be aligned with the first opening 240-1’ of each container 210’ (e.g., by rotation of the carousel 200’). In this example, the housing 100’ includes several transfer ports 141’ (only some of which labelled in Figure 11) connected to different parts of the fluidic system (or to different fluidic systems) so that different operations (e.g., metering, processing or measurement) can be carried out. The carousel 200’ may be rotated so that the first opening 240-1 of any of the containers 210’ can be aligned with any of the transfer ports 141’. This means that the operations can be carried out on any of the containers 210’. While Figures 13A and 13B only show cross-sections corresponding to one of the transfer ports 141’, it will be appreciated that this description also applies to the other transfer ports 141’.

[0113] The upward movement of the carousel 200’ into the position shown in Figure 13B (i.e., parallel to its rotational axis), places the transfer port 141’ in fluid communication with the first opening 240-1’ (and therefore with the pipette 218’). The transfer port 14T may be connected to a control port (not shown) by the fluidic system, so that pressure (either positive or negative) can be applied at the control port (e.g., by a pump on an external processing instrument) to move fluid into or out of the container 210’.

[0114] To further enable precise control of fluid transfers, the apparatus 10’ also differs from the apparatus 10 previously described in that it uses “headspace control”, where the pressure within each of the containers 210’ can also be controlled by the external processing instrument. To achieve this, the housing 100’ also includes a pressure port 142’ that can be aligned with the second opening 240-2’ of each container 210’ (e.g., by rotation of the carousel 200’). The housing 100’ may include several pressure ports 142’, each paired with a respective transfer port 14T. During use, a pressure difference can be applied between the transfer port 14T and the pressure port 142’, which drives movement of fluid through the pipette 218’ (either into or out of the container 210’).

[0115] The transfer ports 14T and pressure ports 142’ each comprise a sealing element 141a’, 142a’. The sealing elements 141a’, 142a’ are provided by rings of elastomeric material. In this way, when the carousel 200’ is moved into contact with the housing 100’, a fluid tight (and air-tight) seal is formed therebetween.

[0116] Another way in which the apparatus 10’ differs from the apparatus 10 described previously in that the carousel 200’ includes a sample access chamber 230’ that can be access through an opening 232’ in the side of the carousel 200’ rather than an input chamber 130 within the housing 100. This is particularly visible in Figure 11 , where the housing 100’ is configured to expose a portion of the carousel 200’. The opening 232’ of the sample access container 230’ may have a cover 234’ to prevent the sample leaking from the apparatus 10’ during use.

[0117] Figures 14A and 14B show a cross-section through the apparatus 10’ that passes through the sample access container 230’. Figure 14A shows the carousel 200’ moved away from the housing 100’ (similar to Figure 13A). Figure 14B shows the carousel 200’ moved into contact with the housing 100’ (similar to Figure 13B). The sample access container 230’ slopes downward towards the centre of the carousel 200’. In this way, any fluid entering the sample access container 230’ (e.g., through the opening 232’) collects at a predetermined position. A sample conduit 233’ connects the lowermost point of the sample access container 230’ to the sample transfer opening 240-3’ discussed above in relation to Figure 13. The sample access container 230’ is also connected to a sample pressure opening 240-4’ in the upper portion 202’ which allows the sample access container 230’ to be pressurised when fluid is transferred.

[0118] In a similar manner to the first opening 240-1’ and second opening 240-2’ discussed above, the sample transfer opening 240-3’ can be aligned with a sample transfer port 143’ on the housing 100’. Likewise, the sample pressure opening 240-4’ can be aligned with a sample pressure port 144’ on the housing 100’. To facilitate sealing when moved to the position in Figure 14B, the sample transfer port 143’ has a corresponding sealing element 143a’ and the sample pressure port 144’ has a corresponding sealing element 144a’. As shown in Figures 13A and 13B, the transfer port 14T is connected to the sample transfer port 143’ through one of the fluidic channels 116’.

[0119] When the apparatus 10’ is moved to the position shown in Figure 14B pressure can be applied to the ports 242’, 244’ to drive flow of fluid between the sample access container 230’ and the container 210’.

[0120] For example, to move a sample from the container 210’ into the sample access container 230’, positive pressure may be applied at the pressure port 142’ and negative pressure may be applied at the pressure port 144’. In this way, as shown by the arrows in Figure 14B, fluid is driven upward through the pipette 218’, out of the first opening 240-1’ and through the transfer port 141’, through the fluidic channel 116’, through the sample transfer port 143’ and the sample transfer opening 240-3, down the sample conduit 233 and into the sample access container 230’. As a result, fluid can be easily transferred from the container 210’ to the sample access container 230’ simply by applying pressure at two ports. Therefore, one or both of the pressure ports 142’, 144’ may be referred to as “control ports”. Once in the sample access container 230’ the sample could be removed from the sample access opening 232’. For this to occur, the positive pressure is instead applied at pressure port 144’ and negative pressure is instead applied at pressure port 142’.

[0121] Although the discussion above generally relates to operation of the transfer ports I pressure ports for moving fluid between a container 210’ and the sample access container 230’, it will be appreciated that other transfer ports 141’ and / or pressure ports 142’ can be operated in a similar way to move samples into other parts of the apparatus 10’. For example, a different transfer port 141’ may be connected to a control port through a metering channel; by applying negative pressure at the control port and positive pressure at the pressure port 142’ a sample can be extracted from the container into the metering channel. A similar process can be carried out to move a sample into a cuvette channel for processing. These transfer ports 14T may be located at different locations on the housing 100’ so that rotation of the carousel 200 within the housing 100’ can bring the first opening 240-1’ of any of the containers 210’ into fluid communication with any of the transfer ports 14T (and similarly any of second openings 240-2’ into communication with any of the pressure ports 142’).

[0122] The apparatus 10’ is advantageous in that is enables connection with the fluidic system to be controlled with only a small amount of axial movement of the carousel 200’. In the previous apparatus 10, to enable rotation of the carousel 200, the carousel 200 needs to be moved downward sufficiently far for the pipettes 110a, 110b to be completely removed from the container 210. However, in the apparatus 10’ in Figures 11 to 14, only a small axial movement is required to place the ports 14T, 142’, 143’, 144’ in communication with the openings 240-1’, 240- 2’, 240-3’, 240-4’. This means that the apparatus 10’ can be more compact.

[0123] While the foregoing is directed to exemplary embodiments of the present invention, it will be understood that the present invention is described herein purely by way of example, and modifications of detail can be made within the scope of the invention. Moreover, other and further embodiments of the invention will be apparent to those skilled in the art from consideration of the specification, and may be devised without departing from the basic scope thereof, which is determined by the claims that follow.

Claims

CLAIMS1 . A biological processing apparatus, comprising: a housing; a carousel located within the housing, the carousel comprising a plurality of containers; wherein the housing comprises a transfer port at a fixed position with respect to the housing, and the transfer port is connected to at least one control port through a fluidic system thereby enabling a pump to control a flow of fluid through the fluidic system and transfer port via the at least one control port, during use; and wherein the carousel is rotatable within the housing to align each of the plurality of containers with the transfer port, and wherein the carousel is movable parallel to its axis of rotation to move the transfer port into fluid communication with each of the containers.

2. The biological processing apparatus of claim 1 , wherein the fluidic system is arranged adjacent to an external surface of the housing, thereby enabling fluid within the fluidic system to be manipulated by an external processing instrument.

3. The biological processing apparatus of claim 2, wherein the external surface of the housing is a planar surface.

4. The biological processing apparatus of claim 2 or 3, wherein the fluidic system comprises a plurality of channels arranged within a single layer on the external surface of the housing.

5. The biological processing apparatus of claim 4, wherein the plurality of channels is formed by slots and / or grooves in the housing, over which a sealing film is secured.

6. The biological processing apparatus of claim 5, wherein the sealing film is configured to facilitate manipulation of the fluid through the film by a processing tool, during use.

7. The biological processing apparatus of any preceding claim, wherein the housing comprises a pressure port configured to control a pressure in each of the containers, wherein movement of the carousel parallel to its axis of rotation places both the pressure port and the transfer port into fluid communication with each of the containers.

8. The biological processing apparatus of any preceding claim, wherein the transfer port is provided by a pipette at a fixed position with respect to the housing, and the carousel is movable parallel to its axis of rotation to move the pipette into each of the containers.

9. The biological processing apparatus of any of claims 1 to 7, wherein at least one of the containers comprises a pipette, and the carousel is movable parallel to its axis of rotation to form a seal between the transfer port and the pipette.

10. The biological processing apparatus of claim 9, further comprising a sealing element for forming the seal between the transfer port and the pipette, preferably wherein the sealing element is provided by a ring of elastomeric material.11 . The biological processing apparatus of any of claims 8 to 10, wherein the at least one control port comprises a metering port, and the fluidic system comprises a metering channel that connects the pipette to the metering port, and wherein the metering channel includes one or more fluid sensing locations at predetermined positions along the channel that correspond to predetermined volumes of fluid retained in the metering channel between each sensing location and a tip of the pipette.

12. The biological processing apparatus of claim 11 , wherein the metering channel is arranged in a serpentine pathway, and wherein each of the fluid sensing locations is provided at a straight section in the pathway.

13. The biological processing apparatus of any of claims 8 to 12, wherein the at least one control port comprises a cuvette port, and the fluidic system further comprises a cuvette channel that connects the pipette to the cuvette port.

14. The biological processing apparatus of claim 13, further comprising an air spring connected to the cuvette channel.

15. The biological processing apparatus of claim 14, wherein a surface of the housing comprises an indentation, and a sealing film is secured over the indentation to provide the air spring.

16. The biological processing apparatus of any preceding claim, further comprising: a sample input chamber accessible via an opening in the housing, and a sample input pipette arranged in the sample input chamber, wherein the sample input pipette is also connected to the at least one port through the fluidic system.

17. The biological processing apparatus of any of claims 1 to 15, further comprising a sample access container in the carousel, the sample access container comprising a sample access opening, wherein the housing is configured to expose at least a portion of the carousel to facilitate access to the sample access container via the sample access opening.

18. The biological processing apparatus of any preceding claim, wherein: the fluidic system is a first fluidic system, the transfer port is a first transfer port, and the housing further comprises a second transfer port at a fixed location with respect to the housing, and the second transfer port is connected to at leastone control port through a second fluidic system thereby enabling the pump to control operation of the second transfer port via the at least one control port.

19. The biological processing apparatus of claim 18, wherein the first transfer port is arranged on the housing to align with a first subset of the plurality of containers, and the second transfer port is arranged on the housing to align with a second subset of the plurality of containers that is different from the first subset.

20. The biological processing apparatus of claim 19, wherein the first and second subset of containers are each provided as a ring of containers on the carousel at a different distance from the axis of rotation to each other.

21. The biological processing apparatus of any of claims 18 to 20, when dependent upon claim 14, wherein the sample input pipette is a first sample input pipette, and the apparatus further comprises a second sample input pipette arranged in the sample input chamber, wherein the first sample input pipette is connected to the first fluidic system and the second sample input pipette is connected to the second fluidic system.

22. The biological processing apparatus of any of claims 18 to 21 , when dependent upon claim 11 , wherein respective cuvette channels of the first and second fluidic system are arranged adjacent to each other on an external surface of the housing so that they can be sealed simultaneously to lock fluid within the respective cuvette segments.

23. The biological processing apparatus of any preceding claim, wherein the carousel is movable parallel to its axis of rotation between a collapsed configuration where the carousel is clipped onto the housing for storage, and an expanded configuration where the carousel is movable relative to the housing to align the transfer port.

24. The biological processing apparatus of claim 23, wherein the carousel and the housing have complementary sealing features that seal the interior of the housing from the surroundings when in the collapsed configuration.

25. The biological processing apparatus of any preceding claim when dependent on claim 8, wherein each of the plurality of containers comprises a sealing film that is pierceable by the pipette during use.

26. A method of performing bioprocessing using the biological processing apparatus of any preceding claim, the method comprising: connecting the apparatus to a processing instrument; and operating the processing instrument to: rotate the carousel relative to the housing to align the transfer port on the housing with a different container of the plurality of containers, and manipulate air pressure at the at least one control port to control movement of fluid through the fluidic system.

27. The method of claim 26, wherein the fluidic system is arranged adjacent to an external surface of the housing and the method further comprises operating a processing tool of the biological processing instrument adjacent the external surface to manipulate fluid within the fluidic system.

28. The method of claim 27, wherein the processing tool comprises one or more of: a heater, a magnetic device, and a light source.

29. The method of any of claims 26 to 28, wherein the fluidic system is arranged adjacent to an external surface of the housing and the method further comprises operating one or more sensors of the biological processing instrument adjacent the external surface of the housing to determine a volume of fluid retained in a metering channel of the fluidic system.

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