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GB2629183A - A modular biological processing cartridge and container - Google Patents

A modular biological processing cartridge and container Download PDF

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Publication number
GB2629183A
GB2629183A GB2305807.6A GB202305807A GB2629183A GB 2629183 A GB2629183 A GB 2629183A GB 202305807 A GB202305807 A GB 202305807A GB 2629183 A GB2629183 A GB 2629183A
Authority
GB
United Kingdom
Prior art keywords
fluid
container
biological processing
housing
processing cartridge
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
GB2305807.6A
Other versions
GB202305807D0 (en
Inventor
Keating Tim
Jepps Gary
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TTP PLC
Original Assignee
TTP PLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by TTP PLC filed Critical TTP PLC
Priority to GB2305807.6A priority Critical patent/GB2629183A/en
Publication of GB202305807D0 publication Critical patent/GB202305807D0/en
Priority to PCT/GB2024/051035 priority patent/WO2024218519A1/en
Publication of GB2629183A publication Critical patent/GB2629183A/en
Pending legal-status Critical Current

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50855Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using modular assemblies of strips or of individual wells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/505Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • B01L3/523Containers specially adapted for storing or dispensing a reagent with means for closing or opening
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/028Modular arrangements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/04Exchange or ejection of cartridges, containers or reservoirs
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0605Metering of fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0684Venting, avoiding backpressure, avoid gas bubbles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0689Sealing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/141Preventing contamination, tampering
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/021Identification, e.g. bar codes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0803Disc shape
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877Flow chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/0289Apparatus for withdrawing or distributing predetermined quantities of fluid
    • B01L3/0293Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • External Artificial Organs (AREA)

Abstract

A modular container 200 for biological processing arranged to be retained, in use, within a slot in a biological processing cartridge, the container comprising a bottom housing 250 comprising an internal cavity, a top housing 220 attached to the bottom housing with a fluid opening 240 to provide a fluid connection from the top housing to the cavity of the bottom housing and one or more engagement 230, 231, 232 components configured to releasably retain the container within the slot. The engagement components maybe a rear wall for abutting against a frame of the cartridge when fully inserted into the cartridge slot, a front edge 231 to engage with a snap fit connector of the cartridge or grooves 232 to engage with guide rails of the cartridge. The top housing may be connected to the bottom housing by welding or a push fit connection. The opening may connect with a fluid conduit positioned inside the bottom housing.

Description

A MODULAR BIOLOGICAL PROCESSING CARTRIDGE AND CONTAINER
FIELD OF THE INVENTION
The present invention relates to a cartridges and containers for performing biological processing.
BACKGROUND
Biological processing includes a wide range of workflows and thus a wide range of specialist equipment is required. As one specific example, in the field of diagnostics there has been a growing need to provide sample preparation devices that can be used in the analysis of a sample from a patient. In particular, there has been a growing need for 'point-of-care' diagnostic devices that enable a sample to be analysed at the location of a patient to ensure rapid analysis and to improve overall care for the patient.
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, such as molecular diagnostics, chemical analysis, immunoassays, polymerase chain reaction (PCR) and flow cytometry. Other types of biological processing may require many other processes to be performed.
It has been considered to provide biological processing cartridges that are capable of particular types of analysis approaches. However, each cartridge must be designed and manufactured with a specific type of analysis in mind, with the required reagents pre-installed into the cartridge. This means that the reagents are not necessarily stored in optimum conditions within the cartridge, and limits flexibility of the system.
Therefore, it is an object of the present invention to address the problems identified above.
SUMMARY OF INVENTION
According to an aspect of the present invention, there is provided a biological processing cartridge, comprising: a frame; a plurality of slots arranged on the frame, wherein each slot comprises one or more engagement components configured to releasably retain a container for biological processing within the slot; and a fluid manipulation device configured to transfer fluid to and from a fluid opening provided on each container.
By providing engagement components within each slot, each modular container is always inserted correctly into the slot. The container may comprise corresponding engagement components to those in each slot.
As used herein the term "biological processing" may refer to any biological and/or synthetic biological processes, including chemical processes. For example, the biological processing cartridge may be used for sample analysis, and/or diagnostics such as in vitro diagnostics, among other things. However, it will be appreciated that the biological processing cartridge may be used for other purposes and within other industries. During use, the biological processing cartridge may be mounted on or in a biological processing instrument. The instrument may comprise one or more processing tools (e.g. analysis tools).
Preferably, the frame comprises a cylindrical wall with the plurality of slots being arranged around the circumference of the cylindrical wall, thereby providing a cylindrical biological processing cartridge.
As an alternative to the cylindrical frame with slots around its circumference, the plurality of slots may be arranged along a (substantially straight) length of the frame, thereby providing a linear biological processing cartridge. Advantageously, a linear arrangement may allow for the cartridge to have any suitable number of slots simply by increasing the length of the frame. Any of the optional features described herein in relation to a cylindrical biological processing cartridge may also be provided in relation to a linear biological processing cartridge or any other shape of cartridge.
The fluid manipulation device may comprise a pipetting nozzle and/or a sealing member. The fluid manipulation device may be mounted at a centre of the cylindrical biological processing cartridge, and the pipetting nozzle and/or the sealing member may be radially offset from the centre of the biological processing cartridge, whereby rotation of the fluid manipulation device about the centre locates the pipetting nozzle and/or the sealing member adjacent to the fluid opening (and/or one or more vent openings) on each of the containers. In other words, the pipetting nozzle and/or the sealing member of the fluid manipulation device are located on an arm of the fluid manipulation device that extends from the centre of the biological processing cartridge in a cantilever arrangement. In this way, rotation of the fluid manipulation device about the centre may locate the pipetting nozzle over any of the openings of the containers when they are retained in each of the slots on the cylindrical wall, thereby allowing fluid to be transferred between the openings in the containers. The fluid manipulation device may extend through a mounting aperture in a base of the frame, thereby allowing the fluid manipulation device to be rotated within the frame. Alternatively, the fluid manipulation device may be mounted on a set of rails that run around the inside of the biological processing cartridge.
The sealing member may be configured to be located over (e.g., pressed on) the opening and/or one or more vents provided on each container. In this way, the contents of each container may be (temporarily) sealed to prevent evaporation, thereby increasing fluid recovery. Especially where fluid in each container is heated, the sealing member may increase the amount of fluid that is retained in the container and/or reduce heat flow out of the container. Furthermore, the sealing member may allow the container to be pressurised. Preferably, the sealing member is arranged on a separate arm of the fluid manipulation device, and preferably extends in an opposite direction to the arm that provides the pipetting nozzle. Alternatively, the sealing member may be arranged on the same arm of the fluid manipulation device as the pipetting nozzle. The sealing member may comprise a compressible gasket.
Where a linear biological processing cartridge is used, the fluid manipulation device may be movable along the length of the frame to locate the pipetting nozzle and/or the sealing member adjacent to the fluid opening on each of the containers. As described above, this allows any of the containers to be accessed by the fluid manipulation device. The slots may be provided on a base of the frame, or may be located on an outer wall. For example, the fluid manipulation device may be mounted on a set of rails that run parallel to the slots, or the fluid manipulation device may have a housing that wraps around the base to allow sliding of the base through the housing.
Preferably, the plurality of slots is arranged on the frame to form a first row of slots, and a second row of slots that is offset from the first row. Where a cylindrical cartridge is used, the rows may be radially offset to provide concentric rings of slots. Where a linear cartridge is used, the rows may be straight and parallel. It will be appreciated that where other shapes of cartridges are used, the rows may be offset in other ways. Optionally, three or more rows of slots may be provided, with each row being offset from adjacent rows.
The biological processing cartridge may further comprise a transfer element arranged to provide a fluidic path between the first row of slots and the second row of slots. The transfer element may be referred to as a "flow cell". In this way, fluid may be transferred between the rows. This is advantageous since in many biological processing operations, the volumes of fluid being transferred and stored in the containers may initially be small, but as more fluid is added and mixed, there is a need to transfer and store larger volumes of fluid. By providing two rows of slots, the first row may be configured to handle smaller volumes (e.g., with smaller containers), and the second row may be configured to handle larger volumes (e.g., with larger containers). The flow cell allows for the fluid to be transferred from containers in the first row to containers in the second row during the process.
The flow cell may be configured to provide other functions as well as transfer of fluid. For example, the flow cell may allow for fluid to be heated when passing therethrough; the flow cell may itself comprise a heater, or may be arranged adjacent to a separate heater, during use. Alternatively or additionally, one or more sensors may be located adjacent to the flow cell during a transfer, thereby allowing for measurements of the fluid to be made. The flow cell may comprise a detector to confirm that fluid is flowing and/or to measure the flow rate of the fluid. The flow cell may comprise a splitter to divide the fluid from the container in the first row into two (or more) containers in the second row.
Preferably, the fluid manipulation device is a first fluid manipulation device, and the cartridge further comprises a second fluid manipulation device. This may allow for more than one container to be manipulated at the same time. For example, the fluid manipulation devices may be used to transfer fluid from a first container in the first row to a second container in the second row; to do this, the first fluid manipulation device may raise the pressure at an opening on one side of the flow cell, and the second fluid manipulation device may lower the pressure at an opening on an opposite side of the flow cell, thereby inducing a flow of the fluid through the flow cell.
Preferably, the first and second fluid manipulation devices are configured to handle different volumes of fluid. As mentioned above, during many biological processes, the volume of fluids being transferred may be initially small before becoming larger towards the end of a particular workflow. Therefore, it may be difficult to maintain accurate metering of fluid throughout the workflow. In order to address this the first fluid manipulation device may be configured to handle small volumes with high precision and the second fluid manipulation device may be configured to handle larger volumes (or vice versa). It will be appreciated that the cartridge may comprise more than two fluid manipulation devices, such as three or more. Each fluid manipulation device may correspond to a row of slots.
The biological processing cartridge may comprise a locking arrangement, wherein: when the fluid manipulation device is at a first height, the locking arrangement engages with the frame, such that movement (e.g. rotation) of the fluid manipulation device relative to the frame is inhibited; and when the fluid manipulation device is at a second height that is preferably greater than the first height, the locking arrangement disengages with the frame, such that the fluid manipulation device and the frame are movable (e.g. rotatable) separately to each other. Preferably, the locking arrangement is provided on the fluid manipulation device, though it will be appreciated that the locking arrangement may be a separate component, such as a separate actuator to inhibit movement of the fluid manipulation device relative to the frame. In this way, the relative positions of the fluid manipulation device, the frame (which retains the containers), and the one or more processing tools may all be controlled only by manipulation (e.g., raising, lowering and rotation) of the fluid manipulation device relative to the frame. This may be by manipulation (rotation) of the fluid manipulation device, the frame, or a combination of both. For example, the locking arrangement may comprise a rib located on the fluid manipulation device, such that the rib engages in a notch in the frame at a first height and disengages from the slot when at the second height. A plurality of notches may be provided in the frame to correspond to each slot that may hold a container. Alternatively, the locking arrangement may comprise gears that may be engaged and disengaged when the fluid manipulation device moves between the first height and the second height.
The biological processing cartridge may further comprise a removable lid with a top portion arranged to cover an upper opening in the frame. In this way, when each of the slots in the frame retains a corresponding container, the contents of the biological processing cartridge may be sealed from the surroundings, thereby inhibiting cross-contamination.
The lid may further comprise a side wall extending from the top portion, the side wall overlapping at least a portion of the frame, wherein the lid is movable between: a collapsed configuration where the lid inhibits movement of the fluid manipulation device relative to the frame; and an expanded configuration where the fluid manipulation device and the frame may move relative to each other. For example, the collapsed configuration may retain the fluid manipulation device at its first height, where rotation of the fluid manipulation device relative to the frame is prevented.
In this way, during transport and/or storage of the biological processing cartridge, movement of the components of the biological processing cartridge is prevented by moving the lid into the collapsed configuration. Furthermore, the collapsed configuration may save space during transport and/or storage. The frame may comprise a mark which is concealed by the side wall of the lid in the collapsed configuration and revealed in the expanded configuration, thereby indicating whether the biological processing cartridge has yet been used. Optionally, the frame and/or side wall of the lid may have a ratchet mechanism to prevent the lid from being fully removed from the frame, and to prevent the lid from being moved from the expanded configuration to the collapsed configuration. In this way, accidental reuse of the biological processing cartridge is prevented.
According to a further aspect of the present invention, there is provided a biological processing instrument for manipulating the biological processing cartridge as described above and herein, the instrument comprising: a base configured to support a frame of the cartridge, the base comprising one or more processing tools arranged to analyse a container retained within a slot of the frame; an actuator arranged to engage with a fluid manipulation device of the cartridge, wherein the actuator is operable to both move both the fluid manipulation device relative to the frame, and to move the cartridge as a whole relative to the base.
In this way, any of the containers that may be provided in each of the slots in the frame may be moved to be adjacent to any one of the processing tools. This allows any of the containers to undergo any process that involves any of the processing tools.
Preferably, the one or more processing tools comprise at least one of: a temperature control device, a magnetic device, and an identification device.
The temperature control device may adjust the temperature of a container retained in one of the slots. The temperature control device may comprise a heater and/or a cooler. The heater may be a separate component to the cooler and located adjacent to a different slot, or both the heater and cooler may be provided as a single temperature control device adjacent the same slot. The magnetic device may be configured to agitate one or more magnetic elements (e.g. beads) that are present within a cavity of the container. This may be for mixing of the fluid within the container, or may be for separation of target substances from the remainder of the fluid. The processing tools may comprise a shaker for agitating fluid in the container. The identification device may be configured to identify a mark on a container retained within one of the slots, such as a barcode, QR code, or RFID tag.
The actuator may be movable relative to the base between: a first height where the actuator moves the fluid manipulation device together with the frame upon the base; and a second height where the actuator moves the fluid manipulation device relative to the frame.
At the first height, a locking arrangement of the biological processing cartridge may engage the fluid manipulation of the device with the frame, so that (e.e.g rotational or lateral) movement of the fluid manipulation device using the actuator also moves the frame, thereby moving the biological processing cartridge as a whole on the base. At the second height, the locking arrangement may disengage, thereby allowing control of the fluid manipulation device while the frame rests upon the base.
According to another aspect of the present invention, there is provided a modular container for biological processing arranged to be retained, in use, within a slot in a biological processing cartridge, the container comprising: a bottom housing comprising an internal cavity; a top housing attached to the bottom housing, the top housing comprising a fluid opening, thereby to provide a fluid connection from the top housing to the cavity of the base portion; and one or more engagement components configured to releasably retain the container within the slot.
By providing engagement components, the modular container is always inserted correctly into the slot. The slot in the biological processing cartridge may comprise corresponding engagement components to those on the container. The top housing may be attached to the bottom housing by welding and/or a push fit operation. The top housing may be detachable from the bottom housing, thereby allowing the top housing and/or bottom housing to be repaired or replaced.
Preferably, the one or more engagement components are provided on the top housing. By having a common top housing that is attached to a bottom housing, different bottom housings may be provided such that the container may perform different functions, while still ensuring that the container is correctly inserted into the slot.
The cavity of the bottom housing may comprise chambers, reservoirs and/or pathways, which may be configured to contain fluids and/or (dry) solid material. For example, different bottom housings may be configured to have a cavity with a particular size in order to contain a particular amount of fluid. The fluid opening in the top housing may allow fluid to be added and removed from the modular container, such as by using a pipetting nozzle of a fluid manipulation device. As used herein, the term "fluid" may refer to liquids, gasses, and/or vapour. The container may be referred to as a "pot".
Preferably, the one or more engagement components comprise at least one of: a joining element, a datum reference, and a guide or groove that corresponds to a complementary guide or groove in the slot of the biological processing cartridge. The joining element may comprise a snap connector. The joining element may comprise a weld.
The modular container may further comprise a fluid conduit connected to the fluid opening in the top housing, the fluid conduit arranged to extend into the cavity of the bottom housing in order to provide the connection to the cavity.
The fluid conduit may be push-fit onto the top housing. The fluid conduit may be detachable from the top housing, thereby allowing the fluid conduit to be repaired or replaced. The fluid conduit may have a predetermined bore size, which may be selected depending on the purpose of a particular container.
An end of the fluid conduit that extends into the cavity may be tapered and/or flared. In this way, shearing forces may be reduced. Alternatively, the fluid conduit may have a slanted end, thereby providing a fluid conduit in the form of a needle.
The fluid conduit comprises one or more holes along a length of the fluid conduit.
In this way, fluid passing through the fluid conduit may be more efficiently mixed by passing through the one or more holes, such as with fluid already present within the bottom housing.
The fluid conduit may be configured to retain a volume of fluid therein. In this configuration, the fluid conduit may be referred to as a "flow cell". For example, the fluid may be retained by freezing it inside the fluid conduit prior to use. Alternatively or additionally, the flow cell may be sealed with a membrane such as welded foil. The retained volume of fluid may be washed into the cavity of the bottom housing by passing another fluid (such as a buffer) through the fluid conduit. In this way, small amounts of fluid do not need to be pumped or transferred through long tubes from elsewhere, which may lead to fluid becoming trapped within the tubes. Therefore, since wasted fluid is reduced, the overall amount of fluid required may be reduced. Particularly due to the substantial expense of some fluids required in certain tests, this may reduce the operating cost. The volume of fluid retained by the fluid conduit may be less than 10 pl, such as about 7 pl.
The cavity of the bottom housing may contain one or more magnetic elements. In this way, a magnetic device (e.g., located in a biological processing instrument) may move the one or more magnetic elements, thereby agitating (i.e. mixing) a fluid contained within the cavity, or for separation of target substances from the remainder of the fluid (e.g. elution of proteins, lipids, DNA, RNA).
The top housing further may further comprise a sample opening on a top surface of the top housing, the sample opening configured to receive a fluid sample. In this way, the container may be partially removed from its slot, during use, to move it to a "loading position" in which the sample opening is exposed. Subsequently, a sample fluid may be deposited into the sample opening before the container is re-inserted into the slot to a "loaded position". Preferably, a seal is maintained between the container and the slot throughout movement between the loading position and its fully inserted (loaded) position, thereby allowing samples to be added to the container and/or the biological processing cartridge, during a biological processing operation. Optionally, a top surface of the bottom housing may seal the sample opening. Alternatively, the sample opening may provide a fluid connection into the bottom housing in a similar manner to the fluid opening.
The top housing may further comprise one or more vent openings connected to the cavity of the bottom housing. In this way, when fluid is added or removed from the cavity via the fluid opening during use (such as by using a pipetting nozzle on a fluid manipulation device), the vent openings allow for pressure equalisation in the cavity such that fluid flow is not inhibited. The one or more vent openings and/or the fluid opening may be arranged to be sealed by pressing a sealing member on the top of the top housing, which may allow the bottom housing to be pressurised. For example, the sealing member may be provided by a compressible gasket. The sealing member may be provided on the fluid manipulation device. The one or more vent openings and/or the fluid opening may be arranged within a common region on a top surface of the top housing thereby facilitating sealing using the sealing member. For example, the vent openings may be located around or adjacent to the fluid opening.
The cavity of the bottom housing may provide a pathway that connects the fluid opening in the top housing to the one or more vent openings in the top housing.
In other words, a first end of the pathway connects to the fluid opening in the top housing, and a second end of the pathway connects to the one or more vent openings in the top housing.
The pathway may comprise a chamber arranged adjacent to a portion of an outer surface of the bottom housing, whereby the chamber is locatable adjacent to a temperature control device when the container is retained in the slot of the biological processing cartridge. In this way, it may be possible to adjust the temperature of fluid contained within the bottom housing. Preferably, the portion of the outer surface that is adjacent to the chamber is located on a base of the bottom housing.
The portion of the outer surface that is adjacent to the chamber may be provided by a conductive film, whereby to conduct heat between fluid located in the chamber and the temperature control device.
The modular container may further comprise an air chamber in fluid connection with the pathway, whereby to provide an air spring within the bottom housing. In this way, when the openings in the top housing are sealed, pressure changes within the pathway may be accommodated by the air chamber, thereby preventing damage to the bottom housing. For example, the temperature control device may comprise a heater for raising the temperature of fluid and/or gas in the bottom housing, with the air spring accommodating for expansion of the fluid and/or gas.
The modular container may further comprise a membrane disposed over the fluid opening of the top housing, and preferably the one or more vent openings of the top housing, thereby sealing the cavity in the bottom housing. In this way, the contents of the container may be isolated from the surroundings in order to prevent contamination. By providing the seal using a membrane, the seal may be broken after the container is installed into the slot within the biological processing cartridge, such as by a pipetting nozzle for transferring fluid into or out of the container. In other words, the contents of the container remain within a sterile environment up until the point of use.
The modular container may further comprise an identification mark. The identification mark may be a barcode, QR code, RFID tag, or any other suitable identification marker. In this way, it may be possible to uniquely identify the container. For example, it may be possible to identify the contents of the container such as fluid contained within the cavity, to check an expiry date, assess whether the container is compatible with a particular test protocol, and/or to confirm the presence of the container within a particular slot in the biological processing cartridge.
According to another aspect of the present invention, there is provided an apparatus comprising the biological processing cartridge as described above and herein, and one or more of the modular containers as described above and herein.
In summary, the apparatus, the modular containers, and the biological processing cartridge described above and herein have the following benefits: Firstly, storage may be improved. Since each of the modular containers may be stored separately in their optimal storage conditions, the shelf-life is extended, and reliability is improved. Furthermore, since each container may have a different shelf-life, the lifetime of the cartridge is not limited by individual reagents within a particular container Secondly, testing may be more flexible. For example, since all the containers are interchangeable (with common engagement components on the top housing), a greater variety tests may be performed using the same frame and/or biological processing instrument. The user may also remove the containers from the remainder of the cartridge after use, in order to perform specific further processing.
Furthermore, a user may add their own types of containers before use of the cartridge, which may be specifically tailored to their testing requirements.
Thirdly, manufacturing and assembly is more efficient. For example, the containers may be manufactured and/or filled in separate locations, which removes the need for manufacturing, assembly, and shipping from a common location. In addition, the containers may be stored at test locations/facilities, so that a particular cartridge can be easily assembled on-site. Different containers can also be made from different materials in order to suit the lifetime and properties of the intended contents. Since the containers are manufactured separately to the biological processing cartridge, they may be more easily and efficiently filled with a particular fluid during a single manufacturing step; for example, an array of containers may be configured to fit on a 96 well plate (with a 9mm pitch), which may enable them to be filled with fluid using a standardised apparatus. I.e., each container may have dimensions corresponding to a position within a filling device such as a 96 well plate. This allows for custom filling of the containers.
Fourthly, the components are more reusable. Since many of the components are removable from each other (e.g., frame, container, lid, fluid manipulation device), they may be detached from each other after use, and may be recycled or reused. For example, since only the containers and the fluid manipulation device contact any of the fluids (reagents), the other components may be reused in other biological processing cartridges. Accordingly, the apparatus is more sustainable than prior approaches where the entire biological processing cartridge must be carefully disposed of.
It will be understood by a skilled person that any apparatus feature described herein may be provided as a method feature. 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.
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.
BRIEF DESCRIPTION OF DRAWINGS
One or more embodiments of the present invention will now be described with reference to the accompanying figures, in which: Figures 1A to 1D show perspective, side, top and exploded view of an embodiment of an apparatus comprising a biological processing cartridge and one or more modular containers inserted into slots of the biological processing cartridge; Figures 2A and 2B show perspective views of a frame that forms part of the biological processing cartridge; Figures 3A to 3B show one or more engagement components that releasably retain the modular containers within the slots of the biological processing cartridge; Figures 4A and 4B show a fluid manipulation device that forms part of the biological processing cartridge; Figures 5A to 5C show the fluid manipulation device being movable between a first height and second height relative to the frame; Figures 6A and 6B show a lid of the biological processing cartridge that is movable between a respective collapsed configuration and an expanded configuration; Figures 7A shows an alternative position for the fluid manipulation device, and 7B shows a biological processing cartridge having two fluid manipulation devices; Figure 8 depicts a schematic top down an instrument upon which the apparatus may be located, during use; Figures 9A and 9B show an example of a linear biological processing cartridge; Figures 10A and 10B show an example of a linear biological processing cartridge, where the slots are arranged in two parallel rows; Figure 11 shows the biological processing cartridge of Figure 10 located on a biological processing instrument; Figures 12A and 12B show a perspective, and exploded view of an embodiment of a container with a top housing, a bottom housing, and a fluid conduit therebetween; Figures 13A and 13B show an example of the top housing; Figures 14A to 14C show fluid openings and vent openings arranged on a top surface of the top housing; Figures 15A to 15E show various examples of the fluid conduit that may provide a fluid connection from the top housing to the bottom housing; Figures 16A to 16C show a further example of a fluid conduit that is configured to retain a volume of fluid therein; Figure 17 shows an example of the bottom housing; Figures 18A and 18B show a perspective and an exploded view of a first embodiment of a container where the bottom housing is configured to hold a first volume of fluid; Figures 19A and 19B show a perspective and an exploded view of a second embodiment of a container where the bottom housing is configured to hold a second, smaller volume of fluid; Figures 20A and 20B show a perspective and an exploded view of a third embodiment of a container where the bottom housing is configured to hold a third, even smaller volume of fluid; Figures 21A to 21 D show a further embodiment of a container where the bottom housing is configured to allow heating of fluid inside the bottom housing; Figures 22A to 22E show an embodiment of a sample container where a fluid sample may be added to the bottom housing through a sample opening in the top housing; Figures 23A and 23B show identification marks located on each container; and Figure 24 shows a plurality of containers for use in the linear biological processing cartridges of Figures 9 to 11.
DETAILED DESCRIPTION
Figures 1A to 1D show perspective, side, top and exploded views of an apparatus 1 according to the present invention. The apparatus 1 comprises a biological processing cartridge 100 and one or more modular containers 200 (or "pots"), which are releasably retained within respective slots 125 of the biological processing cartridge 100. As will be described later in more detail, the biological processing cartridge 100 and/or the modular containers 200 comprise one or more engagement components to releasably retain each container 200 within one of the slots 125.
More specifically, the biological processing cartridge 100 comprises a cartridge frame 120 with a plurality of slots 125 arranged on the frame 120. The frame 120 is preferably formed form a single piece of material, and thus may be described as a monolithic frame 120. Each slot 125 has one or more engagement components configured to releasably retain a modular container 200 for biological processing within the slot 125. The biological processing cartridge 100 also comprises a fluid manipulation device 140 configured to transfer fluid to and from each container 200 when they are installed in the biological processing cartridge 100. The biological processing cartridge 100 may also comprise a lid 160 to provide a sealed internal cavity within the biological processing cartridge 100 so that the fluid manipulation device 140 may transfer fluid between the container 200 without cross contamination with the surroundings of the biological processing cartridge 100.
The modular containers 200 will be described in detail in relation to Figures 12 to 24 but as a brief summary, each of the modular containers 200 comprises an internal cavity for holding fluid, and a fluid opening 242 to allow the fluid to be added and removed from the internal cavity of the container 200. The modular container 200 may also comprise one or more vents openings 244 to allow air to flow into and out of the container 200. When a plurality of containers 200 are installed into the biological processing cartridge 100, each of the containers 200 may perform a specific purpose and/or may contain a different reagent for a particular test, thereby allowing different combinations of containers 200 to be used for different tests. As used herein, the term "fluid" or "fluid connection" may refer to liquids, vapour, and/or gasses, though it will be appreciated that solid material may be stored in any of the containers 200 described herein. For example, a "cake" of solid (e.g., freeze-dried) material may be stored in the containers 200.
By having a modular apparatus 1 where the containers 200 are interchangeable in the biological processing cartridge 100, each of the containers 200 may be stored separately before the apparatus 1 is assembled before use; this may allow the containers 200 to be stored in optimum conditions and allows all containers to be stored up to their full shelf-life before use (rather than discarding the entirety of a pre-assembled apparatus). This also simplifies manufacturing since, the containers 200 and the biological processing cartridge 100 may be manufactured and/or filled in different places before being assembled later. Testing is also more flexible since, different combinations of containers 200 may be retained in the biological processing cartridge 100 depending on the particular test, and individual containers 200 may be removed afterward for further testing individually. Furthermore, since the containers 200 are removable, they may be disposed of separately to the components of the biological processing cartridge 100, which may be recycled or reused.
The frame 120 will now be described with particular reference to Figures 2A and 2B. The frame 120 comprises an outer wall 122, which is preferably cylindrical with the plurality of slots 125 arranged around the circumference of the outer wall 122, thereby providing a cylindrical biological processing cartridge 100. The cylindrical biological processing cartridge 100 may have a diameter of about 65 mm, and/or may have a height of about 35 mm, though it will be appreciated that these dimensions are purely exemplary. While the biological processing cartridge described herein is cylindrical, it will be appreciated that other shapes of biological processing cartridge 100 may be used. Furthermore, while twelve slots 125 are present in this example, it will be appreciated that more or fewer slots 125 may be provided in order to releasably retain a different number of containers 200.
The frame 120 has an upper opening defined by a rim 122a of the outer wall 122. The lid 160 may be mounted over the rim 122a to cover the upper opening, thereby enclosing an internal cavity of the biological processing cartridge 100.
The frame 120 also comprises a base 130 arranged within the outer wall 122 of the frame 120. In the case of a cylindrical biological processing cartridge 100, the base 130 is preferably circular. The base 130 has a plurality of apertures 132 arranged through the base 130. A mounting aperture 132a is arranged at the centre of the base 130 to facilitate mounting of the fluid manipulation device 140 onto the frame 120. A plurality of slot apertures 132b are also provided in the base 130, with each one corresponding to one of the slots 125. The slot apertures 132b are arranged such that when a container 200 is retained within one of the slots 125, an upper surface of the container 200 that includes its fluid opening 242 is exposed to the internal cavity of the biological processing cartridge 100. In other words, each container 200 is mounted generally below the base 130 of the frame 120. Preferably a seal is formed between each container 200 and its corresponding slot aperture 132b thereby maintaining closure of the internal cavity of the biological processing cartridge 100 when the lid 160 also covers the upper opening of the frame 120.
A plurality of support elements 134 extend from a lower surface of the base 130. The support elements 124 preferably extend a distance from the base 130 that is greater than the height of any of the containers 200. In this way, the apparatus 1 may be placed consistently upon a flat surface (or on a biological processing instrument 300) upon its support elements 124 regardless of the size and shape of the containers 200 retained in the slots 125. Preferably, the outer wall 122, the base 130 and the support elements 134 are formed from a single piece of material. Alternatively, the frame 120 may be formed from separate components that are connected together.
The one or more engagement components will now be described in relation to Figures 3A to 3D. Figure 3A depicts the apparatus 1 where one of the containers 200 has been partially removed from its corresponding slot 125 in the frame 120 of the biological processing cartridge 100. Figures 3B and 3C depict the container when fully inserted into the slot 125 in the frame 120. As shown, the container 200 comprises a rear wall 230 which abuts against the outer wall 122 of the frame 120 when the container 200 is fully inserted into the slot 125. The outer wall 122 of the frame 120 may comprise an indentation 126 that has a shape corresponding to the rear wall 230 of the container 200. In this way, an outer surface of the apparatus 1 is substantially continuous when the container 200 is correctly positioned in the slot 125. Accordingly, the rear wall 230 of the container 200 and the outer wall 122 of the frame 120 may be considered to be one of the engagement components, and may be referred to as a "bump stop", or "datum reference".
Additionally, as shown in Figure 4C, the one or more engagement components may comprise a joining element such as a snap connector 127 to retain the container 200 in the slot 125. In this example, a snap connector 127 is positioned on a radially inward edge of the slot aperture 132b and may be arranged to snap over a front edge 231 of the container 200. Therefore, when the container 200 is fully inserted into the slot 125, the snap connector 127 prevents the container 200 from coming loose from the slot 125 which may lead to cross contamination between the internal cavity of the biological processing cartridge 100 and the surroundings. The snap connector 127 preferably prevents removal of the container 200 from the cartridge 100 by a user, thereby preventing unsafe reuse of containers 200. The snap connector 127 may allow for removal of the container 200 using specialist equipment, so that the containers may nevertheless be disposed of. Alternatively, the joining element may be provided by a weld.
As shown in Figure 3D, the one or more engagement components may comprise guide rails 128 on the frame 120 to maintain alignment of the container 200 when it is inserted into the slot 125. While not shown in Figure 3D, the container 200 preferably comprises a groove 232 that corresponds to the guide rail 128, such as a groove that runs along a side surface of the container 200. I.e., the guide rails 128 and the groove 232 are complementary to each other. In this way, motion of the container 200 is constrained by the guide rails 128 only to the axis along which the container 200 is inserted, thereby inhibiting incorrect insertion of the container into each of the slots 125. While one specific arrangement of guide rails 128 is shown in this embodiment, it will be appreciated that other configurations of guides and/or grooves may be provided for both the frame 120 and each container 200 so that the containers 200 are always correctly inserted into the slots 125 in the frame 120. For example, guide rails may be provided on the container 200 and grooves may be provided on the frame 120, or a combination of both.
An example of a fluid manipulation device 140 will now be described in relation to Figures 4A and 4B. The fluid manipulation device 140 is preferably mounted at the centre of the cylindrical biological processing cartridge 100. The fluid manipulation device 140 comprises a mounting column 142. The mounting column 142 has a first (bottom) end 142a extending along a vertical axis to a second (top) end 142b. The mounting column 142 may be tubular; in this way, a protrusion 165 of the lid 160 may extend at least partially into the top end 142b of the mounting column 142 to maintain it in a vertical position when the biological processing cartridge 100 is fully assembled. The bottom end 142a of the mounting column is configured to inserted into the mounting aperture 132a in the base 130 of the frame 120. Preferably, a seal is maintained between the mounting column 142 and the mounting aperture 132a so that the internal cavity of the biological processing cartridge 100 is isolated from the surroundings during use. As will be described later in relation to Figures 5A to 5C, the fluid manipulation device 140 may be able to translate along the vertical axis, while maintaining the seal between the fluid manipulation device 140 and the frame 120.
Extending from the mounting column 142, preferably in a direction perpendicular to the vertical axis (i.e. radially), is a pipetting arm 144. In other words, the pipetting arm 144 extends from the mounting column 142 in a cantilever arrangement. The pipetting arm 144 includes a pipette 145 with a pipetting nozzle 146 that may transfer fluid between the fluid openings 242 of the containers 200 when installed in the slots 125. Therefore, the pipetting nozzle 146 is radially offset from the mounting column 142 and thus the centre of the biological processing cartridge 100 by a distance that aligns the pipetting nozzle 146 with each of the fluid openings 242 of the containers 200. In this way, rotation of the fluid manipulation device 140 about the centre of the biological processing cartridge 100 (i.e. rotation of the mounting column 142 in the mounting aperture 132a) may locate the pipetting nozzle 146 adjacent to any of the fluid openings 242 of any of the containers 200. The pipette 145 is configured to accurately transfer small volumes of fluid between each of the containers 200.
The fluid manipulation device 140 may further comprising a sealing member 152. The sealing member 152 may be provided on a sealing arm 150 that also extends from the mounting column 142, and preferably in a direction that is perpendicular to the vertical axis. Preferably, the sealing arm 150 extends from the mounting column 142 in an opposite direction to the pipetting arm 144, as shown in Figures 4A and 4B. Advantageously, this maintains balance of the fluid manipulation device 140, which may help it remain aligned inside the internal cavity of the biological processing cartridge 100. Alternatively, the sealing arm 150 may be movable independently to the pipetting arm 144, or the sealing member 152 may also be provided on the pipetting arm 144. The sealing member 152 is radially offset from the mounting column 142 and thus the centre of the biological processing cartridge 100 by a distance that aligns the sealing member 152 with each of the fluid openings 242 and vent openings 244 of the containers 200.
Therefore, by rotation of the fluid manipulation device 140 about the centre of the biological processing cartridge 100 (i.e. rotation of the mounting column 142 in the mounting aperture 132a), the sealing member 152 may be located over (and pressed on) the fluid opening 242 and/or vent openings 244 on the containers 200. This may allow the contents of each container 200 to be (temporarily) sealed to prevent evaporation of the contents, and/or to allow the contents to be pressurised. Preferably, the height of the pipetting nozzle 146 (e.g. as measured from the base 130 of the frame 120 during use) is substantially equal to the height of the sealing member 152. Therefore, both the pipetting nozzle 146 and the sealing member 152 may be used simultaneously on different containers 200. The sealing member 152 may be a ring of compressible material such as rubber; in this way the sealing member 152 may be pressed over a region 241 containing the fluid opening 242 and vent openings 244 to provide the seal. Alternatively, the sealing member 152 may be overmoulded onto the sealing arm 150.
As will now be described in relation to Figures 5A to 5C, the fluid manipulation device 140 may be movable relative to the frame 120 along the vertical axis. I.e., the fluid manipulation device 140 may both rotate about the vertical axis and move along the vertical axis. The fluid manipulation device 140 may comprise a locking arrangement, wherein: when the fluid manipulation device 140 is at a first height (e.g. with the pipetting nozzle 146 closer to the base 130 of the frame 120), the locking arrangement engages with the frame 120, and when the fluid manipulation device 140 is at a second height (e.g. with the pipetting nozzle 146 further from the base 130 of the frame 120) the locking arrangement disengages with the frame 120. The locking arrangement may comprise a locking rib 148 arranged on an outer surface of the mounting column 142 along a vertical direction. The base of the frame may comprise a plurality of notches 138, such as a notch 138 corresponding to each of the slots 125. The first height of the fluid manipulation device 140 is shown in Figures 5A and 5C, where the locking rib 148 is engaged within one of the notches 138. When in this position, rotation of the fluid manipulation device 140 relative to the frame 120 is inhibited. The second height of the fluid manipulation device 140 is shown in Figure 5B, where the locking rib 148 has been raised out of the notch 138. Therefore, the fluid manipulation device 140 may rotate relative to the frame 120 such as to move the pipetting nozzle 146 adjacent to the fluid opening 242 of a different container 200.
As an alternative to the locking arrangement depicted in Figures 5A to 5C, gears may be provided on both the fluid manipulation device 140 and the frame 120 such that teeth on the gears are engaged when the fluid manipulation device 140 is lowered, and the teeth on the gears are disengaged when the fluid manipulation device 140 is raised. As a further alternative, the locking arrangement may prevent relative movement when in the raised position, and allow relative movement when in the lowered position; this may be achieved by providing notches or gears on the lid 160 that engage with the fluid manipulation device 140.
The locking arrangement has several advantages. Firstly, during storage and/or transport of the biological processing cartridge 100, restricting movement of the fluid manipulation device 140 may prevent damage or wear to the biological processing cartridge 100. Secondly, during use, rotation of the fluid manipulation device 140 when at the first height may also be used to rotate both the frame 120 and the fluid manipulation device 140. As will be described further in relation to Figure 8, this may be advantageous when the biological processing cartridge 100 is located in a biological processing instrument 300, which may include heaters, magnetic devices, and/or identification devices. Therefore, the biological processing cartridge 100 as a whole may be rotated relative to the instrument 300 only by manipulation of the fluid manipulation device 140.
Referring now to Figures 6A and 6B, the lid 160 comprises a top portion 162 arranged to cover the upper opening of the frame 120. The lid 160 preferably comprises a side wall 164 extending from the top portion 162 at its perimeter. The side wall 164 overlaps at least a portion of the outer wall 122 of the frame 120 (preferably over its exterior) thereby sealing the internal cavity of the biological processing cartridge 100 during use. The outer wall 122 of the frame 120 may comprise one or more clips 129 so that the lid 160 may be retained over the upper opening of the frame 120. The lid 160 may be free to rotate relative to the frame 120, such as to remain fixed when mounted on a biological processing instrument 300. In order to reduce friction between the lid 160 and the frame 120, a small number (less than five, preferably three) clips 129 may be provided.
As mentioned above, the lid 160 may comprise a protrusion 165 that extends into the mounting column 142 of the fluid manipulation device 140; in this way, rotation of the fluid manipulation device 140 is constrained about the vertical axis.
The lid 160 may be movable between a collapsed configuration (shown in Figure 6A) and an expanded configuration (shown in Figure 6B). In the collapsed configuration, the lid 160 inhibits movement of the fluid manipulation device 140 relative to the frame 120 by retaining the fluid manipulation device 140 in its first (lowered) position. Therefore, the collapsed configuration is intended to prevent usage of the apparatus 1. In the collapsed configuration, the biological processing cartridge 100 may take up less space during storage and/or transport, and by inhibiting motion of the fluid manipulation device 140, the risk of damage to components of the biological processing cartridge 100 is reduced, such as due to unwanted relative movement between the frame 120 and the fluid manipulation device 140.
In the expanded configuration, the fluid manipulation device 140 is movable between both its first (lowered) position and its second (raised) position, thereby allowing the fluid manipulation device 140 to be rotated relative to the frame 120 and for the fluid manipulation device 140 and the frame 120 to be rotated together.
Therefore, the expanded configuration is intended for use of the apparatus 1.
The outer wall 122 of the frame 120 may comprise a mark 169 which is concealed in the collapsed configuration and revealed in the expanded configuration, thereby indicating whether the biological processing cartridge 100 has yet been used. The outer wall 122 of the frame 120 and/or side wall 164 of the lid 160 may have a ratchet mechanism 166 to prevent the lid 160 from being fully removed from the frame 120, and to prevent the lid 160 from being moved from the expanded configuration to the collapsed configuration. In this way, accidental reuse of the biological processing cartridge 100 is prevented. The clips 129 of the frame 120 may be part of the ratchet mechanism 166 or the ratchet mechanism 166 may be provided by separate features on the lid 160 and/or the frame 120.
While the fluid manipulation device 140 has been described above as being mounted at the centre of the cylindrical biological processing cartridge 100, it will be appreciated the fluid manipulation device 140 may be mounted in other positions. For example, as shown in Figure 7A, the fluid manipulation device 140 is mounted on (or adjacent to) the outer wall 122 of the frame 120 and extends radially inwards in order to align the pipetting nozzle 146 (or the sealing member 152) with any of the fluid openings 242 of any of the containers 200. Additionally, as shown in Figure 7B, the biological processing cartridge 100 may comprise two fluid manipulation devices 140-1, 140-2. In this example, a first fluid manipulation device 140-1 is mounted at the centre of the biological processing cartridge 100, and a second fluid manipulation device 140-2 is mounted from the outer wall 122 of the frame 120. In other examples, both of the fluid manipulation devices 140 may be mounted from the centre, or both may be mounted from the outer wall 122. It will be appreciated that three or more fluid manipulation devices 140 may also be present, which may be provided in any appropriate position. By providing more than one fluid manipulation device 140, it may be possible to perform different steps of a biological processing operation simultaneously, such as simultaneous transfers between different pairs of containers 200.
The apparatus 1 may be located on a biological processing instrument 300 during use. A top-down view of such an instrument 300 is shown in Figure 8. The instrument 300 comprises a base 301 upon which the support elements 134 of the biological processing cartridge 100 rest. The instrument 300 also comprises a fluid manipulation connector 305, which engages with the first end 142a of the mounting column 142 of the fluid manipulation device 140 during use. The fluid manipulation connector 305 may rotate relative to the base 301 during use and may move vertically so that the fluid manipulation device 140 moves between its raised and lowered positions (relative to the biological processing cartridge 100). This may be achieved either by moving the base 301, by moving the fluid manipulation connector 305, or a combination of both. In this way, it is possible to rotate the fluid manipulation device 140 in isolation (when raised relative to the biological processing cartridge 100) or rotate the biological processing cartridge together with the fluid manipulation device 140 (when in the lowered position). During movement of both the cartridge 100 and the fluid manipulation device 140, the support elements 134 may slide over the base 301.
The instrument 300 may comprise one or more processing tools (e.g. analysis tools). The one or more processing tools may comprise a temperature control device 310. The temperature control device 310 may comprise a heater and/or a cooler. When a container 200 is positioned over the temperature control device 310 (e.g. by rotation of the biological processing cartridge 100 as a whole) it may be possible to adjust the temperature of the contents of the container 200.
The one or more processing tools may comprise a magnetic device 320. When a container 200 is positioned over the magnetic device 320 (e.g. by rotation of the biological processing cartridge 100 as a whole), the magnetic device 320 may be configured to agitate magnetic elements such as magnetic beads located in the container 200. This may allow for remote mixing of the contents of the container 200 and/or may be used to separate target substances from the remainder of the fluid in the container 200 (e.g. for elution of proteins, lipids, DNA, RNA).
The one or more processing tools may comprise an identification device 330. The identification device 330 is configured to identify each of the containers 200 using an identification mark 235 on each of them such as a barcode, QR code, or RFID tag. Prior to a particular analysis method being performed on the apparatus 1 with the instrument 300, the identification device 330 may scan each of the containers 200 to verify that the correct ones have been inserted into the biological processing cartridge 100.
Since the biological processing cartridge 100 is rotatable relative to the base 301, any of the containers 200 releasably retained within any of the slots 125 may be located next to any of the processing tools such as the temperature control device 310, the magnetic device 320 and/or the identification device 330. I.e. any container 200 may undergo any process. It will be appreciated that the instrument 300 may comprise other processing tools as well as, or instead of those described above.
While the above description has generally related to a cylindrical biological processing cartridge 100, it will be appreciated that other shapes are possible. By way of example, Figures 9A and 9B show an example of a linear biological processing cartridge 100' containing a plurality of containers 200' within a plurality of slots 125'. The cartridge 100' has a frame 120' comprising a base 130'. However, the slots 125' are arranged along the length of the base 130', thereby providing a linear biological processing cartridge 100'. Alternatively, the slots 125' may be provided in outer wall of the frame 120'. As shown, there are 15 slots 125' along the length of the base 130'. An advantage of the linear cartridge 100' is that the length may simply be increased to allow the cartridge 100' to have any suitable number of slots 125'.
The biological processing cartridge 100' also comprises a fluid manipulation device 140'. The fluid manipulation device 140' is similar to the device 140 previously described but is instead movable along the length of the base 130' to locate the pipetting nozzle 146' and/or the sealing member 152' adjacent to the fluid opening 242' on each of the containers 200'. As shown in Figures 9A and 9B, the fluid manipulation device 140' has a housing 149' that wraps around the base 130' thereby attaching the fluid manipulation device 140' to the base 130' while allowing sliding of the base 130' through the housing 149'. Alternatively, the fluid manipulation device 140' may be mounted on a set of rails so that it is movable along the length of the base 130'. While not shown in Figures 9A and 9B, the linear biological processing cartridge 100' may have other components corresponding to those previously described, such as a lid.
Preferably, the slots 125' are arranged on the frame 120' to form a first row of slots 125-1' and a second row of slots 125-2' that is offset from the first row 125-1'. As shown in Figures 10A, the rows 125-1', 125-2' are straight and parallel to each other. By providing the slots 125' in two rows it is possible to increase the total number of slots 125' without increasing the length of the biological processing cartridge 100'. Therefore, in other examples three or more rows of slots 125' may be provided, with each row being offset from adjacent rows. Furthermore, while the presence of multiple rows is described in relation to the linear cartridge 100', it will be appreciated that the cylindrical cartridge 100 described previously may also have two or more rows of slots 125 that are radially offset to provide concentric rings of slots 125.
While a single fluid manipulation device 140' may be used to access all of the slots 125' in both of the rows, preferably the biological processing cartridge 100' comprises a first fluid manipulation device 140-1' and a second fluid manipulation device 140-2'. In this example, the first fluid manipulation device 140-1' accesses the slots 125' in the first row 125-1' and the second fluid manipulation device 140-2' accesses the slots 125' in the second row 125-2'. By configuring the fluid manipulation devices 140' in this way, all the containers 200' in any of the slots 125' may be accessed by one of the fluid manipulation devices 140' by sliding of the fluid manipulation devices 140' relative to the frame 120'. The fluid manipulation devices 140' may be slidable together, or may be individually movable. The fluid manipulation devices 140' need not be identical to each other. For example, the first and second fluid manipulation devices 140-1', 140-2' may be configured to handle different volumes of fluid. In many biological processing operations, the volumes of fluid being transferred and stored in the containers 200' may initially be small, but as more fluid is added and mixed there is a need to transfer and store larger volumes of fluid. Therefore, it may be difficult to maintain accurate metering of fluid throughout a biological processing workflow. In order to address this, the first fluid manipulation device 140-1' may be configured to handle small volumes with high precision and the second fluid manipulation device 140-2' may be configured to handle larger volumes (or vice versa).
It may be advantageous to transfer fluid from containers 200' in the first row 125-1' of slots 125' to containers 200' in the second row 125-2' of slots 125' (or vice versa). Therefore, the biological processing cartridge 100' may comprise a transfer element 190' arranged to provide a fluidic path between the first row of slots 125-1' and the second row of slots 125-2'. The transfer element 190' may be referred to as a "flow cell". By providing two rows of slots 125-1', 125-2', the first row 125-1' may be configured to handle smaller volumes (e.g., with smaller containers 200'), and the second row 125-2' may be configured to handle larger volumes (e.g., with larger containers 200'). The transfer element 190' allows for the fluid to be transferred between the rows 125-1', 125-2' and therefore between containers 200' in different rows 125-1', 125-2' during the process.
A cross section through the transfer element 190' is shown in Figure 10B. The fluid transfer element 190' has a first fluid opening 192-1' connected to a second fluid opening 192-2' by a fluid pathway 194'. In this example, a transfer from the first row 125-1', 125-2' is performed using both fluid manipulation devices 140-1', 140-2' described above. Before the transfer, the first fluid manipulation device 140-1' may take fluid from a container 200' in the first row of slots 125-1'. Subsequently, the pipetting nozzle 146-1' of the first fluid manipulation device 140-1' may make sealing contact with a first fluid opening 192-1' of the transfer element 190'. Likewise, the pipetting nozzle 146-2' of the second fluid manipulation device 140-2' may make sealing contact with a second fluid opening 192-2' of the transfer element 190'. Then the first fluid manipulation device 140-1' outputs the fluid into the first fluid opening 192-1' (using an increased internal pressure), and the second fluid manipulation device 140-2' uses a decreased internal pressure, which draws the fluid through the fluid pathway 194', out of the second fluid opening 192-2' and into the second fluid manipulation device 140-2'. Subsequently, the second fluid manipulation device 140-2' may transfer the fluid to a container 200' in the second row of slots 125-2'.
While the example above uses two fluid manipulation devices 140' to transfer fluid through the flow cell 190', it will be appreciated that such a transfer may be performed using only a single fluid manipulation device 140'. For example, the flow cell 190' may have an internal volume (rather than a direct pathway) for intermediate storage of fluid, whereby fluid is added to the internal volume from the first row 125-1' in a first stage, and removed from the internal volume to the second row 125-2' in a second stage. However, preferably, the flow cell 190' has no internal storage in order to provide more reliable metering of the transferred fluid, and to reduce the amount of fluid that may be left behind in the flow cell 190' after a transfer.
The flow cell 190' may be configured to perform other functions as well as transfer of fluid. For example, the flow cell 190' may allow for fluid to be heated when passing therethrough. The flow cell 190' may itself comprise a heater (not shown), or may be arranged to be adjacent to a separate heater, during use. One or more sensors may be located adjacent to the fluid pathway 194' during a transfer, thereby allowing for measurements of the fluid to be made. The flow cell 190' may comprise a detector to confirm that fluid is flowing and/or to measure the flow rate of the fluid. The flow cell 190' may comprise a splitter to divide the fluid from a container 200' in the first row of slots 125-1' into two (or more) containers 200' in the second row of slots 125-2'.
Figure 11 shows the linear biological processing cartridge 100' located on a biological processing instrument 300'. The biological processing instrument 300' comprises one or more processing tools such as a temperature control device 310', a magnetic device 320', an identification device 330'. These processing tools correspond to those described previously in relation to the instrument 300 and thus will not be described again in detail.
The biological processing cartridge 100' moves relative to the processing tools, so that any of the containers 200' in any of the slots 125' may be located adjacent to any of the processing tools. Furthermore, the fluid manipulation device(s) 140' are also movable relative to the frame 120'. While not shown in Figure 11, the instrument 300' may comprise a base 301' to support the biological processing cartridge 100', and may comprise a fluid manipulation connector 305' to actuate the sliding of the cartridge 100' on the base 301' and/or to actuate motion of the fluid manipulation device(s) 140' within the cartridge 100'. It will be appreciated that any features described in relation to the cylindrical biological processing cartridge 100 may be applied to the linear biological processing cartridge 100'. For example, the cartridge 100' may comprise a locking arrangement, and/or a (movable) lid to provide an internal cavity, among other things.
The container 200 will now be described in detail in relation to Figures 12 to 24. As shown in Figures 12A and 12B, the container 200 comprises a top housing 220 and a bottom housing 250. The bottom housing 250 has an internal cavity 251 which may contain fluid during use. The top housing 220 is attached to the bottom housing 250 such as by welding and/or a push fit operation. A fluid connection may be formed between the top housing 220 and the bottom housing 250 with a fluid conduit 280. The containers 200 may have dimensions that allow them to be arranged together on a 96-well plate (with a pitch of 9 mm), so that many containers 200 may be filled simultaneously using standard equipment.
The top housing is shown in Figures 13A and 13B. The top housing 220 is preferably formed from moulded plastic. The top housing 220 comprises one or more engagement components configured to releasably retain the container 200 within the slot 125 of the biological processing cartridge 100. Preferably, the one or more engagement components on the top housing 220 correspond (i.e. complement) to those on the biological processing cartridge 100. More specifically, the top housing 220 has a rear wall 230 that abuts against the outer wall 122 of the frame 120 when fully inserted into a slot 125 of the frame 120, in order to provide a bump stop or datum reference. Additionally, the top housing 220 may have a front edge 231 that is arranged to engage with a snap connector 127 of the frame 120. It will be appreciated that a snap connector 127 may engage with other parts of the container 200. The terms "front" and "rear" as used in relation to the container 200 refer to the direction that the container 200 is inserted into one of the slots 125. Additionally, the top housing 220 may comprise grooves 232 that correspond to the guide rails 128 of the frame 120; in this way, motion of the container 200 is constrained along a particular axis when it is inserted into one of the slots 125. As shown in Figures 12A and 12B, the grooves 232 are located on a side surface of the top housing 220 and thus engage with the guide rails 128 of the frame 120 that extend inward from the sides of each slot 125. It will be appreciated that the top housing 220 may instead have guide rails, and that the frame 120 may instead have grooves, or a combination of both.
The top housing 220 has a top surface 222, with at least one opening 240 arranged on the top surface 222. The at least one opening 240 may comprise a fluid opening 242 to allow fluid to be added and removed from the internal cavity 251 of the bottom housing 250, such as through the fluid conduit 280. The at least one opening 240 may comprise one or more vent openings 244 which allow air to flow into and out of the internal cavity 251 of the bottom housing 250. The at least one opening 240 may comprise a sample opening 246, which will be described later in relation to Figures 22A to 22E.
The arrangement of the fluid opening 242 and the vent openings 244 will now be described further in relation to Figures 14A to 14C. The fluid opening 242 and the vent openings 244 are preferably arranged within a common region 241 on the top surface 222 of the top housing 220, thereby allowing both the fluid opening 242 and the vent openings 244 to be covered simultaneously with the sealing member 152. The top surface 222 of the top housing 220 preferably comprises an indentation 242a, with the fluid opening 242 being located at a base 242b of the indentation 242a. In this way, fluid flows towards the fluid opening 242 by gravity, and fluid is less likely to spill elsewhere on the container 200 or the biological processing cartridge 100. Preferably, the indentation 242a has a shape that corresponds to the shape of the pipetting nozzle 146 of the fluid manipulation device 140. For example, the pipetting nozzle 146 may be cylindrical and/or may have a taper, with the indentation 242a having a corresponding cylindrical shape and/or corresponding taper. In this way, the pipetting nozzle 146 may be lowered into the indentation 242a and form a seal with the indentation 242a. Subsequently, fluid may be added or removed by the pipetting nozzle 146 through the fluid opening 242 while maintaining said seal; this allows fluid to be removed using a suction force through the pipetting nozzle 146 and ensures that the fluid does not spill elsewhere on the container 200 or in the biological processing cartridge 100.
A side wall 242c may extend from a bottom surface of the base 242b of the indentation 242a. As shown particularly in Figure 14C, the fluid conduit 280 may be press fit within the side wall 242c in order to connect the fluid conduit 280 to the fluid opening 242. The side wall 242c may be referred to as a "tube extension interface".
Preferably a plurality of vent openings 244 are provided, such as around or adjacent to the fluid opening 242. When the top housing 220 is connected to the bottom housing 250, the vent openings 244 connect to the internal cavity 251 of the bottom housing 250 via an upper opening 254. As shown in Figure 14A, five vent openings 244 are present on the top surface 222 of the top housing 220, which are arranged equidistantly around the indentation 242a. It will be appreciated that a different number of vent openings 244 may be provided, which may have a different spacing or a different location relative to the fluid opening 242. The vent openings 244 are arranged so that when the pipetting nozzle 146 is lowered into the indentation 242a, the vent openings 244 are not fully obscured by the pipetting nozzle 146. Therefore, when fluid is added or removed from the internal cavity 251 of the bottom housing 250 using the pipetting nozzle 146, air may flow into or out of the internal cavity 251 to equalise the pressure.
Preferably, a seal (not shown) such as a foil seal is provided that covers both the fluid opening 242 and the vent openings 244 prior to use. In this way, once the top housing 220 is attached to the bottom housing 250, the container 200 may be transported and stored with the seal preventing cross-contamination of the contents of the bottom housing 250 with the environment. When the container 200 is inserted into the biological processing cartridge 100 for a particular testing process, the seal may be broken within the sealed internal cavity of the biological processing cartridge, thereby maintaining the barrier between the contents of the bottom housing 250 and the surroundings. For example, the seal may be broken by pressing the pipetting nozzle 146 against the (foil) seal. The vent openings 244 may be at least partially provided inside the indentation 242a; in this way, when the seal is broken by the pipetting nozzle 146, the seal is less likely to block the vent openings 244. Additionally, by providing the vent openings 244 inside the indentation 242a (i.e. not on a top horizontal surface), there is a reduced chance that fluid may fall through the vent openings 244 into the bottom housing 250. Preferably, several vent openings 244 are provided to reduce the chance that all the vent openings 244 are obscured by the broken seal. In this example, there are five vent openings 244 but it will be appreciated that more or fewer may be provided.
Various configurations of fluid conduit 280 will now be described with reference to Figures 15A to 15E. Generally, the fluid conduit 280 may have a tubular wall 282 with top end 282a and a bottom end 282b. The tubular wall 282 surrounds a central bore 284, through which fluid flows during use. The fluid conduit 280 may be rigid (e.g. plastic or metal) or may be flexible (e.g. rubber). The top end 282a may have a standardised size (e.g. diameter), so that any fluid conduit 280 may be attached to the top housing 220 in the same way, such as by being press fit into the side wall 242c.
In the fluid conduit 280-1 shown in Figure 15A, the tubular wall 282 is cylindrical. In this way, it may be easy to cut the fluid conduit 280-1 to any particular length from an off-the-shelf piece of tube (e.g., to suit a particular size of bottom housing 250).
In Figure 15B, the fluid conduit 280-2 has a tubular wall 282 which is tapered from a first size (e.g. diameter) at its top end 282a to a second larger size (e.g. diameter) at its bottom end 282b. In Figure 15C, the fluid conduit 280-3 has a flared bottom end 282b. By providing a fluid conduit 280-3 with a flare and/or a taper, the shearing forces may be reduced. For example, where long polymers or strands of DNA are moved through the fluid conduit 280-3, having a wider portion of the tubular wall 282 may reduce the chance that such strands may break.
In Figure 15D, the fluid conduit 280-4 has a slanted end, thereby providing a fluid conduit 280-4 in the form of a needle. In Figure 15E, the fluid conduit 280-5 comprises one or more holes 285 along its length. In this way, fluid passing through the fluid conduit 280-5 may be more efficiently mixed by passing through the one or more holes 285, such as with fluid already present within the internal cavity 251 of the bottom housing 250.
As shown in Figures 16A to 16C, the fluid conduit 280-6 may be configured to retain a volume of fluid therein. In this configuration the fluid conduit 280-6 may be referred to as a flow cell 280-6. The outer wall 282 of the flow cell 280-6 widens between its top end 282a and its bottom end 282b to provide a storage cavity 286. Prior to use, a small volume of fluid may be frozen inside the storage cavity 286, where the volume of fluid may be melted and/or washed out of the flow cell 280-6 and into the bottom housing 250, such as using a buffer solution. Alternatively or additionally, the flow cell 280-6 may be sealed with a membrane (not shown), such as welded foil. In this way, small amounts of fluid do not need to be pumped or transferred through long tubes from elsewhere or from other containers 200 using the fluid manipulation device 140, which may lead to fluid becoming trapped within the tubes. Therefore, since wasted fluid is reduced, the overall amount of fluid required may be reduced. Particularly due to the substantial expense of some fluids required in certain tests, this may reduce the operating cost. The volume of fluid retained by the storage cavity 286 of the flow cell 280-6 may be less than 10 pl, such as about 7 pl. The volume of fluid may be as low as 2 pl, or even lower. Different sizes of flow cell 280-6 may be provided to contain different volumes, which may be interchangeable depending on the size of the bottom housing 250. Alternatively, the flow cell 280-6 may contain a solid material, which may be dissolved when fluid passes through the flow cell 280-6.
Various configurations of bottom housing 250 will now be described in relation to Figures 17 to 22E. Figure 17 shows a simple example of a bottom housing 250, that may be used for storing fluid. The bottom housing 250 may be substantially cup shaped with a base 252, and a rim 253 surrounding an upper opening 254. Preferably, the bottom housing 250 is tapered towards the base 252 so that fluid within the bottom housing 250 flows towards the base 252. In this way, when the bottom end 282b of the fluid conduit 280 is located at the base 252, it may be possible to remove substantially all of the fluid inside the bottom housing 250. The bottom housing 250 is preferably formed from a moulded piece of plastic.
Alternatively, the bottom housing 250 may be vacuum formed.
The upper opening 254 is preferably sealed when the bottom housing 250 is attached to the top housing 220, thereby providing an internal cavity 251 of the bottom housing 250. More specifically, the rim 253 abuts against a lower surface of the top housing 220 so that fluid (including air) is prevented from leaking out therebetween. However, as discussed above in relation to Figures 14A to 14C, a fluid opening and one or more vent openings 244 may be provided to allow fluid and/or air to move into or out of the internal cavity 251 through the top housing 220. In this example, the rim 253 extends in a rearward direction to provide an upper surface 256, which when assembled is arranged to seal the sample opening 246 of the top housing 220. Alternatively, the upper opening 254 of the bottom housing 250 may have a seal, such as a foil seal, that blocks the sample opening 246 of the top housing 220. In other examples, such as the one described in relation to Figures 22A to 22E the bottom housing 250 may not seal the sample opening 246. The bottom housing 250 may be attached to the top housing 220 by welding and/or a push fit operation. The top housing 220 and the bottom housing 250 may be detachable from each other, thereby allowing either to be repaired or replaced.
As well as storing fluid, the bottom housing 250 of the container 200 may contain magnetic elements such as magnetic beads. These magnetic beads may be agitated using a magnetic device 320 on the instrument 300. This may allow for remote mixing of fluid inside the container 200 and/or may be used to separate target substances from the remainder of the fluid in the container 200 (e.g. for elution of proteins, lipids, DNA, RNA).
The internal cavity 251 may have a predetermined volume for storing a predetermined amount of fluid. Figures 18 to 20 show examples of containers where the bottom housing 250 is configured to hold a different volume of fluid. It will be appreciated that other sizes of bottom housing 250 may also be used in addition to those described herein. In each case a corresponding fluid conduit 280 is provided which has a length that preferably extends to the base 252 of the bottom housing 250.
More specifically, in the container 200-1 shown in Figures 18A and 18B, the bottom housing 250-1 is configured to hold a first volume of fluid, which may be about 800 pl. In the container 200-2 shown in Figures 19A and 19B, the bottom housing 250-2 is configured to hold a second volume of fluid, which is smaller than the first volume of fluid. For example, the bottom housing 250-2 may be configured to hold about 200 pl. In the container 200-3 shown in Figures 20A and 20B, the bottom housing 250-3 is configured to hold a third volume of fluid, which is smaller than the second volume of fluid. For example, the bottom housing 250-3 may be configured to hold about 50 pl.
In the examples described above and herein, the same design of top housing 220 may be used for any of the containers 200. This allows manufacturing to be simplified, since only one type of top housing 220 needs to be manufactured, which can then be attached to different types of bottom housing 250 during a separate manufacturing stage or by an end user. While it is preferred that only a single design of top housing 220 is used, it will be appreciated that variations of top housing 220 may nevertheless by used for certain applications.
A further configuration of bottom housing 250-4 will now be described in relation to Figures 21A to 21D. In this example, the bottom housing 250-4 is configured to allow heating of fluid inside the bottom housing 250-4, which may be particularly useful for PCR tests. A container 200 using this bottom housing 250-4 may be referred to as a PCR container 200-4. More specifically, the bottom housing 250-4 comprises a pathway 260 that connects the fluid opening 242 to the vent openings 244 of the top housing 220. For example, the bottom housing 250-4 may have a top surface 261 with a first aperture 261a that is arranged to press fit onto the side wall 242c on the top housing 220. Therefore, in this example no fluid conduit is required, but in other examples, a fluid conduit may be used. Additionally, the bottom housing 250-4 may be laser welded to the top housing 220 in order to provide a strong seal therebetween. The pathway 260 connects from the first aperture 261a through the bottom housing 250-4 via a heating chamber 262 and then to a second aperture 261b on the top surface 261 of the bottom housing 2504 that is arranged to connect to the vent openings 244 of the top housing 220. Preferably, the heating chamber 262 is located next to a portion of a portion of an outer surface of the bottom housing 250-4, such as a side or edge of the bottom housing 250-4. This allows fluid in the heating chamber 262 to be heated or cooled using an external temperature control device 310 located adjacent to said outer surface of the bottom housing 250-4.
In this example, the bottom housing 250-4 comprises a cuvette segment 267 attached to a base 268. The cuvette segment 267 may be made of moulded plastic in a similar manner to the bottom housings 250 already described above.
The base 268 is provided by a thermally conductive membrane, such as a thin film of foil 268. The foil 268 may be heat welded to the cuvette segment 267. The foil 268 provides the bottom surface of the heating chamber 262, such that heat may be efficiently transferred to or from the heating chamber 262 by a heater or cooler located below the container 200-4, such as by using the temperature control device 310 on the instrument 300.
When the container 200-4 is heated during a particular test, the heater is pressed against the foil 268 at a region 268a that provides a base of the heating chamber 262, thereby heating fluid contained within the heating chamber 262. Preferably, the sealing member 152 is also used to seal the fluid opening 242 and the vent openings 244, as shown in Figure 21D. In this way, the contents of the heating chamber 262 may also be pressurised. Furthermore, evaporation of the fluid from the bottom housing 250-4 may also be inhibited thereby improving recovery of fluid from the container 200-4.
Preferably the pathway 260 also connects to an air chamber 264 which may act as an air spring during pressurisation of the heating chamber 262. This allows the contents of the heating chamber 262 to be pressurised during heating, without damage to components of the bottom housing 250-4 such as the foil 268. Furthermore, external pressure may be applied to the foil 268 at a region 268b that provides a base of the air chamber 264, thereby allowing the pressure in the heating chamber 262 to be externally controlled. For example, pressure may be applied using an actuator (not shown) on the base 301 of the instrument 300.
Accordingly, as well as allowing heating of fluid inside the bottom housing 250-4, the fluid may still be accessed afterward. This may be particularly advantageous since in typical PCR devices, it is not always possible to re-access the fluid for further testing.
A further configuration of bottom housing 250-5 will now be described in relation to Figures 22A to 22E. In this configuration, the container 200 may be referred to as a sample container 200-5. As already discussed above, the one or more openings 240 of the top housing may include a sample opening 246, as shown again in Figure 22A. While the other bottom housings 250 described above have an upper surface 256 that seals the sample opening 246, the upper opening of bottom housing 250-5 extends beneath the sample opening 246, when attached to the top housing 220. Therefore, fluid can be added and removed from the sample container 200-5 using the sample opening 246 as well as the fluid opening 242 already discussed. Two views of the sample container 200-5 are shown in Figures 22B and 22C. Preferably the sample container 200-5 is free standing, with a bottom support 272 that is substantially flat.
Figure 22D shows a loaded position where the sample container 200-5 fully inserted into a slot 125 of the biological processing cartridge 100. Figures 22E shows a loading position where the container 200-5 is only partially inserted into the slot 125 in the biological processing cartridge 100. In this position, a user may add a sample into the bottom housing 250-5 using the sample opening 246 in the top housing 246. Preferably, when in the loading position, a seal is still maintained between the sample container 200-5 and the slot 125, thereby allowing samples to be added to the sample container 200-5 while minimising cross-contamination with the surroundings. Once the sample container 200-5 is subsequently moved to the loaded position, the pipetting nozzle 146 may remove the sample from the sample container 200-5 using the fluid opening 242, as previously described. The sample container 200-5 may be provided to the user in the loading position for the sample to be added. The sample container 200-5 may have a modified top housing 220 so that the snap connector does not prevent the sample container 200-5 from being moved from the loaded position to the loading position. In this way, a user is not prevented from adding a sample to the sample container 200-5, even once the biological processing cartridge 100 is fully assembled.
As shown in Figures 23A and 23B, each of the containers 200 may comprise an identification mark 235 to allow the container to be uniquely identified. The identification mark 235 may indicate the contents of a particular container 200 and preferably the expiry date of the contents. The identification mark 235 may be a QR code, a barcode, an RFID tag, or any other suitable mark. In this example, the identification mark 235 is located on the rear wall 230 of the top housing 220; in this way, the identification mark 235 always appears in the same position relative to the biological processing cartridge 100 so that the identification mark 235 may be quickly and consistently identified. Alternatively, the identification mark 235 may be located elsewhere on the top housing 220 or may be located on the bottom housing 250.
Figure 24 shows a plurality of containers 200' that may be particularly suitable for use with the biological processing cartridge 100' described in relation to Figures 9 to 11, thereby forming an apparatus 1'. In particular, Figure 24 shows a first "large" container 200-1', a second "medium" container 200-2', and a third "small" container 200-3', corresponding to the containers 200-1, 200-2, 200-3 already described in relation to Figures 18 to 20. A PCR container 200-4' is also shown, which corresponds to the PCR container 200-4 described in relation to Figure 21.
While not shown in Figure 24, a sample container corresponding to the sample container 200-5 described in relation to Figure 22 may also be used with the linear biological processing cartridge 100'. Also shown is the transfer element 190' that was already described above, which may also be considered as a type of container 200' that fits into the slots 125' in the frame 120'. It will be appreciated that any of the features of the containers 200 described above for the cylindrical biological processing cartridge 100 may be incorporated into the containers 200' for the linear biological processing cartridge 100'. Therefore, features such as the engagement components, vent openings, fluid conduits, foil seal, and identification marks (among others) may also be incorporated into the containers 200'.
Advantageously, since the apparatus 1, 1' described herein is modular, the containers 200 may be stored separately up until their individual expiry date (as indicated by the identification mark 235). More specifically, each container 200 may be stored separately (in their individual optimum storage conditions) up until the expiry date is reached. For previous approaches where the containers were part of the cartridge already, the whole cartridge would need to be discarded when any individual part of the cartridge reached its expiry date. Therefore, the present invention reduces waste of both the fluids and the physical components such as the containers and/or cartridge.
For example, the identification device 330 on the instrument 300 may be configured to identify identification marks 235 on each of the containers 200. This may occur when the apparatus 1 is first installed in the instrument 300, with a computer system checking the combination of identification marks 235 on all of the containers 200 in order to provide a predetermined test protocol. The identification mark 235 may also allow the location of each container 200 within the slots 125 of the biological processing cartridge 100 to be tracked during a test protocol.
While various examples of bottoms housings 250 and fluid conduits 280 have been described above in isolation, it will be appreciated that these examples may be combined in any suitable way in order to form a container. For example, the flow cell 280-6 may be used in any of the containers 200 discussed above. The sample opening may allow for fluid samples to be added to any of the containers 200 not just the sample container 200 described above. Furthermore, while a common top housing 220 is preferred, variations of the top housing may be used in order to provide certain functions within certain biological processing operations.
The apparatus 1, cartridge 100 and containers 200 described above have the following advantages.
Firstly, each container 200 may be stored separately in their optimal storage conditions (e.g. temperature, humidity), which means that individual containers 200 may have an extended shelf life as compared to all containers being stored together when pre-installed into a cartridge 100. For example, each container 200 may be stored within a machine with separate sections for each type of container 200. For example, there may be separate sections for storage at -80 degrees, -20 degrees, ambient temperature, dry storage, PCR containers, and/or sample containers. The machine may be further configured to assemble an apparatus 1 via input of a particular design by a user. This may further reduce user errors when assembling the apparatus 1 with a plurality of separate containers 200.
Secondly, the apparatus 1 has flexibility to provide a large variety of uses. Since many different types of containers 200 may be combined in the cartridge 100 in many different combinations (via the common engagement components), there are a large number of uses for the apparatus 1 within a range of industries such as bioprocessing, synthetic biologic, diagnostics, among others. In some applications, custom containers 200 may be manufactured in addition to those described above. Accordingly, the apparatus 1 may be considered to be a flexible lab assistant. Since some or all of the containers 200 may be removable from the cartridge 100 after use, the apparatus 1 permits further testing as required for a user's specific purpose.
Thirdly, manufacturing and assembly of the apparatus 1 is more efficient. For example, particular container 200 containing particular reagents may be manufactured and assembled in different parts of the world. Subsequently, they may be transported (in their corresponding optimum storage conditions) to the point of use for assembly, which reduces the total transport volume. Furthermore, this may allow different types of container 200 to be manufactured from materials that suit their contents.
Fourthly, since the apparatus 1 is formed from several components, each may be disposed of individually. For example, some components such as the frame 120 and the lid 160 do not contact any of the fluids at all, and thus may be reused in a further apparatus 1 (optionally after a disinfection process such as by using an autoclave). Alternatively, such components may be recycled, and may be made from specific materials that enable easier recycling (e.g. bamboo). Therefore, the apparatus 1 is more sustainable than previous approaches where the entire cartridge (including waste fluids) needed to be disposed of as a whole.
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. Furthermore, one skilled in the art will understand that the present invention may not be limited by the embodiments disclosed herein, or to any details shown in the accompanying figures that are not described in detail herein or defined in the claims. Indeed, such superfluous features may be removed from the figures without prejudice to the present 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 devise without departing from the basic scope thereof, which is determined by the claims that follow.

Claims (17)

  1. CLAIMS1. A modular container for biological processing arranged to be retained, in use, within a slot in a biological processing cartridge, the container comprising: a bottom housing comprising an internal cavity; a top housing attached to the bottom housing, the top housing comprising a fluid opening, thereby to provide a fluid connection from the top housing to the cavity of the base portion; and one or more engagement components configured to releasably retain the container within the slot.
  2. 2. The modular container of claim 1, wherein the one or more engagement components are provided on the top housing.
  3. 3. The modular container of claim 1 or claim 2, wherein the one or more engagement components comprise at least one of: a joining element, a datum reference, and a guide or groove that corresponds to a complementary guide or groove in the slot of the biological processing cartridge.
  4. 4. The modular container of any preceding claim, further comprising a fluid conduit connected to the fluid opening in the top housing, the fluid conduit arranged to extend into the cavity of the bottom housing in order to provide the connection to the cavity.
  5. 5. The modular container of claim 4, wherein an end of the fluid conduit that extends into the cavity is tapered and/or flared.
  6. 6. The modular container of claim 4 or 5, wherein the fluid conduit comprises one or more holes along a length of the fluid conduit.
  7. 7. The modular container of any of claims 4 to 6, wherein the fluid conduit is configured to retain a volume of fluid therein.
  8. 8. The modular container of any preceding claim, wherein the cavity of the bottom housing contains one or more magnetic elements.
  9. 9. The modular container of any preceding claim, wherein the top housing further comprises a sample opening on a top surface of the top housing, the sample opening configured to receive a fluid sample.
  10. 10. The modular container of any preceding claim, wherein the top housing further comprises one or more vent openings connected to the cavity of the bottom 10 housing.
  11. 11. The modular container of claim 10, wherein the cavity of the bottom housing provides a pathway that connects the fluid opening in the top housing to the one or more vent openings in the top housing.
  12. 12. The modular container of claim 11, wherein the pathway comprises a chamber arranged adjacent to a portion of an outer surface of the bottom housing, whereby the chamber is locatable adjacent to a temperature control device when the container is retained in the slot of the biological processing cartridge.
  13. 13. The modular container of claim 12, wherein the portion of the outer surface that is adjacent to the chamber is provided by a conductive film, whereby to conduct heat between fluid located in the chamber and the temperature control device.
  14. 14. The modular container of any of claims 11 to 13, further comprising an air chamber in fluid connection with the pathway, whereby to provide an air spring within the bottom housing.
  15. 15. The modular container of any preceding claim, further comprising a membrane disposed over the fluid opening of the top housing, and preferably the one or more vent openings of the top housing, thereby sealing the cavity in the bottom housing.
  16. 16. The modular container of any preceding claim, further comprising an identification mark.
  17. 17. An apparatus comprising a biological processing cartridge and one or more of the modular containers of any of claims 1 to 16.
GB2305807.6A 2023-04-20 2023-04-20 A modular biological processing cartridge and container Pending GB2629183A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
GB2305807.6A GB2629183A (en) 2023-04-20 2023-04-20 A modular biological processing cartridge and container
PCT/GB2024/051035 WO2024218519A1 (en) 2023-04-20 2024-04-22 A modular biological processing cartridge and container

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB2305807.6A GB2629183A (en) 2023-04-20 2023-04-20 A modular biological processing cartridge and container

Publications (2)

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GB202305807D0 GB202305807D0 (en) 2023-06-07
GB2629183A true GB2629183A (en) 2024-10-23

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GB (1) GB2629183A (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4310488A (en) * 1980-05-19 1982-01-12 Hoffmann-La Roche Inc. Sample or reagent container for analyzers
US20140269158A1 (en) * 2013-03-13 2014-09-18 II Robert Paul Luoma Methods and apparatus to agitate a liquid
WO2016132018A1 (en) * 2015-02-19 2016-08-25 Thermo Fisher Scientific Oy Sample vessel
US20170102316A1 (en) * 2010-11-03 2017-04-13 Pocared Diagnostics Ltd. Optical Cup
WO2018115928A1 (en) * 2016-12-20 2018-06-28 Diapath S.P.A. Disposable container for stains or reagents for staining machines of biological material and staining system comprising said container
US20190270086A1 (en) * 2015-12-04 2019-09-05 Ttp Plc Sample preparation system and cartridge
WO2022043228A1 (en) * 2020-08-24 2022-03-03 F. Hoffmann-La Roche Ag Reagent container cap, reagent container unit and reagent kit

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4310488A (en) * 1980-05-19 1982-01-12 Hoffmann-La Roche Inc. Sample or reagent container for analyzers
US20170102316A1 (en) * 2010-11-03 2017-04-13 Pocared Diagnostics Ltd. Optical Cup
US20140269158A1 (en) * 2013-03-13 2014-09-18 II Robert Paul Luoma Methods and apparatus to agitate a liquid
WO2016132018A1 (en) * 2015-02-19 2016-08-25 Thermo Fisher Scientific Oy Sample vessel
US20190270086A1 (en) * 2015-12-04 2019-09-05 Ttp Plc Sample preparation system and cartridge
WO2018115928A1 (en) * 2016-12-20 2018-06-28 Diapath S.P.A. Disposable container for stains or reagents for staining machines of biological material and staining system comprising said container
WO2022043228A1 (en) * 2020-08-24 2022-03-03 F. Hoffmann-La Roche Ag Reagent container cap, reagent container unit and reagent kit

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Publication number Publication date
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