WO2022251515A2 - Dispositif de traitement de cartouche de réaction - Google Patents

Dispositif de traitement de cartouche de réaction Download PDF

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Publication number
WO2022251515A2
WO2022251515A2 PCT/US2022/031156 US2022031156W WO2022251515A2 WO 2022251515 A2 WO2022251515 A2 WO 2022251515A2 US 2022031156 W US2022031156 W US 2022031156W WO 2022251515 A2 WO2022251515 A2 WO 2022251515A2
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WO
WIPO (PCT)
Prior art keywords
cartridge
interface
fluid
chamber
emission
Prior art date
Application number
PCT/US2022/031156
Other languages
English (en)
Other versions
WO2022251515A9 (fr
WO2022251515A3 (fr
Inventor
Nathan Andrew Ray
Drew FOSTER
David Luke MCDONALD
James SAMMUT
Johnny Steve RACHELE
Mirsaeed SAFARI
Ben Druce
Vincent KHAU
Mark James Fisher
Original Assignee
Proof Diagnostics
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 Proof Diagnostics filed Critical Proof Diagnostics
Publication of WO2022251515A2 publication Critical patent/WO2022251515A2/fr
Publication of WO2022251515A3 publication Critical patent/WO2022251515A3/fr
Publication of WO2022251515A9 publication Critical patent/WO2022251515A9/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/043—Hinged closures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers

Definitions

  • This disclosure relates to a device for processing a reaction cartridge for performing a closed reaction on a sample and obtaining a diagnostic result from the reaction.
  • sample to answer platform that requires minimal sample handling and preparation and minimal requirements for trained clinical lab personnel.
  • aspects of the present disclosure provide such an integrated system along with associated processes, disposable sample collection and processing components, and disposable reaction components.
  • aspects of the disclosure include a device for processing a fluid reaction cartridge including one or more fluid chambers, one or more pressure ports, and a plurality of fluid flow channels.
  • the device may include a housing having an opening for receiving a fluid reaction cartridge, a lid for closing the opening, a cartridge interface, and a cartridge interface linkage assembly.
  • the cartridge interface may include one or more pressure tubes, and the cartridge interface is movable between a first position in which the pressure tubes are not operatively engaged with pressure ports of a cartridge disposed within the housing and a second position in which the pressure tubes are operatively engaged with pressure ports of the cartridge disposed within the housing.
  • the cartridge interface linkage assembly couples the lid to the cartridge interface so that the cartridge interface in its first position when the lid is in an open position and the cartridge interface moves from its first position to its second position as the lid is moved from the open position to a closed position.
  • the cartridge includes one or more frangible seals, wherein the cartridge interface includes one or more frangible seal pins, and wherein the frangible seal pins are not operatively engaged with the frangible seals of a cartridge disposed within the housing when the cartridge interface is in its first position and the frangible seal pins are operatively engaged with the frangible seals of the cartridge disposed within the housing when the cartridge interface is in its second position.
  • the cartridge interface linkage assembly may include first interface links attached to the cartridge interface and movable with the cartridge interface between its first and second positions, a second interface link pivotably coupled to the housing at a first fixed pivot and including coupling arms coupled to the first interface links, a third interface link pivotably coupled to the second interface link at a first floating pivot, and a fourth interface link pivotably coupled to the third interface link at a second floating pivot and pivotably coupled to the housing at a second fixed pivot, wherein the lid is attached to the fourth interface link.
  • each coupling arm of the second interface link is coupled to an associated one of the first interface links by a coupling pin extending from the coupling arm into a coupling slot formed in the associated first interface link, and the coupling slot is oriented transversely to a direction of movement of the cartridge interface between its first and second positions.
  • the device may include a thermal module that includes a thermal block and a motor operative coupled to the thermal block.
  • the thermal block is configured to be movable between a first position not engaged with any fluid chamber of the fluid reaction cartridge and a second position engaged with a fluid chamber of the fluid reaction cartridge so as to enable thermal energy transmission from the thermal block to the contents of the engaged fluid chamber when the thermal block is in its second position.
  • the motor is operatively coupled to the thermal block so as to effect powered movement of the thermal block between its first and second positions.
  • the device may include a thermal interface recess formed in the thermal block and configured to receive the engaged chamber when the thermal block is in its second position.
  • the device may include a magnet module including a magnet carrier including one or more magnets carried thereby, and the magnet carrier is configured to be movable between a first position not engaged with any fluid chamber of the fluid reaction cartridge and a second position engaged with a fluid chamber of the fluid reaction cartridge so as to expose to the contents of the engaged fluid chamber to a magnetic force when the magnet carrier is in its second position.
  • the device may include a motor operatively coupled to the magnet carrier so as to effect powered movement of the magnet carrier between its first and second positions.
  • the device may include a thermal/magnetic module including a thermal block configured to be movable between a first position not engaged with any fluid chamber of the fluid reaction cartridge and a second position engaged with a fluid chamber of the fluid reaction cartridge so as to enable thermal energy transmission from the thermal block to the contents of the engaged fluid chamber when the thermal block is in its second position.
  • the thermal block may include one or more magnets carried thereby so as to expose to the contents of the engaged fluid chamber to a magnetic force when the thermal block is in its second position.
  • the device may include a motor operatively coupled to the thermal block so as to effect powered movement of the thermal block between its first and second positions.
  • the device may include a switch operatively coupled to the lid, and the motor is activated to effect powered movement of the thermal block from its first position to its second position when the switch generates a signal indicating the lid has been closed.
  • the device may include a thermal interface recess formed in the thermal block and configured to receive the engaged chamber when the thermal block is in its second position.
  • one of the one or more fluid chambers of the fluid reaction cartridge is a detection chamber having a wall that is optically transparent or translucent.
  • the device may include an optics module that may include a first excitation channel including a first excitation source for generating a first excitation optic signal and one or more excitation optic elements defining a first excitation optic path configured to direct the first excitation optic signal generated by the first excitation source toward the contents of the detection chamber through the transparent or translucent wall.
  • the optics module may include an emission channel that may include a photodetector and one or more emission optic elements defining an emission optic path configured to direct an emission optic signal emitted by the contents of the detection chamber through the transparent or translucent wall to the photodetector.
  • the optics module may include a second excitation channel that may include a second excitation source for generating a second excitation optic signal different from the first excitation optic signal and one or more excitation optic elements defining a second excitation optic path configured to direct the second excitation optic signal generated by the second excitation source toward the contents of the detection chamber through the transparent or translucent wall.
  • the first excitation optic path and the second excitation optic path are oriented at an angle with respect to each other, and the emission optic path is oriented at an angle that bisects the angle between the first excitation optic path and the second excitation optic path.
  • the one or more excitation optic elements defining the first excitation optic path comprise a collimating lens, a spectral bandpass filter, and an illumination condenser
  • the one or more emission optic elements defining the emission optic path comprise an objective lens, a dual band emission filter, and a detector focusing lens.
  • the device may include a cartridge marking module comprise one or more cartridge marking mechanisms configured to effect a mark on the fluid reaction cartridge.
  • Each cartridge marking mechanism may include a motor and a marking pin operatively coupled to the motor, and the motor is configured and controlled to actuate the pin to selectively mark the fluid reaction cartridge by punching a hole in a label of the fluid reaction cartridge.
  • the one or more cartridge marking mechanisms may include a first cartridge marking mechanism positioned to punch a hole in a first location on the label of the fluid reaction cartridge, a second cartridge marking mechanism positioned to punch a hole in a second location on the label of the fluid reaction cartridge, and a third cartridge marking mechanism positioned to punch a hole in a third location on the label of the fluid reaction cartridge.
  • one of the one or more fluid chambers of the fluid reaction cartridge is a detection chamber having a wall that is optically transparent or translucent.
  • the device may include an optics module configured to detect an emission optic signal emitted by the contents of the detection chamber and to determine if the detected emission optic signal exceeds a predetermined threshold and a cartridge marking module that may include a first cartridge marking mechanism configured to punch a hole in a first location on a label of the fluid reaction cartridge if the emission optic signal detected by the optics module exceeds the predetermined threshold and a second cartridge marking mechanism configured to punch a hole in a second location on the label of the fluid reaction cartridge if the emission optic signal detected by the optics module does not exceed the predetermined threshold.
  • the one or more fluid chambers of the fluid reaction cartridge is a detection chamber having a wall that is optically transparent or translucent.
  • the device may include an optics module and a cartridge marking device.
  • the optics module may be configured to detect a first emission optic signal emitted by the contents of the detection chamber and a second emission optic signal emitted by the contents of the detection chamber and to determine if the first emission optic signal exceeds a first predetermined threshold and if the second emission optic signal exceeds a second predetermined threshold.
  • the cartridge marking module may include a first cartridge marking mechanism configured to punch a hole in a first location on a label of the fluid reaction cartridge if the first emission optic signal detected by the optics module does not exceed the first predetermined threshold, a second cartridge marking mechanism configured to punch a hole in a second location on the label of the fluid reaction cartridge if the first emission optic signal detected by the optics module exceeds the first predetermined threshold and the second emission optic signal detected by the optics module exceeds the second predetermined threshold, and a third cartridge marking mechanism configured to punch a hole in a third location on the label of the fluid reaction cartridge if the first emission optic signal detected by the optics module exceeds the first predetermined threshold and the second emission optic signal detected by the optics module does not exceed the second predetermined threshold.
  • aspects of the disclosure include a device for processing a fluid reaction cartridge including a detection chamber having a wall that is optically transparent or translucent.
  • the device may include an optics module and a cartridge marking module.
  • the optics module may be configured to detect an emission optic signal emitted by the contents of the detection chamber and to determine if the detected emission optic signal exceeds a predetermined threshold.
  • the cartridge marking module may include a first cartridge marking mechanism configured to punch a hole in a first location on a label of the fluid reaction cartridge if the emission optic signal detected by the optics module exceeds the predetermined threshold and a second cartridge marking mechanism configured to punch a hole in a second location on the label of the fluid reaction cartridge if the emission optic signal detected by the optics module does not exceed the predetermined threshold.
  • aspects of the disclosure include a device for processing a fluid reaction cartridge including a detection chamber having a wall that is optically transparent or translucent.
  • the device may include an optics module and a cartridge marking module.
  • the optics module may be configured to detect a first emission optic signal emitted by the contents of the detection chamber and a second emission optic signal emitted by the contents of the detection chamber and to determine if the first emission optic signal exceeds a first predetermined threshold and if the second emission optic signal exceeds a second predetermined threshold.
  • the cartridge marking module may include a first cartridge marking mechanism configured to punch a hole in a first location on a label of the fluid reaction cartridge if the first emission optic signal detected by the optics module does not exceed the first predetermined threshold, a second cartridge marking mechanism configured to punch a hole in a second location on the label of the fluid reaction cartridge if the first emission optic signal detected by the optics module exceeds the first predetermined threshold and the second emission optic signal detected by the optics module exceeds the second predetermined threshold, and a third cartridge marking mechanism configured to punch a hole in a third location on the label of the fluid reaction cartridge if the first emission optic signal detected by the optics module exceeds the first predetermined threshold and the second emission optic signal detected by the optics module does not exceed the second predetermined threshold.
  • the device may include a thermal/magnetic module that includes a thermal block and a motor operatively coupled to the thermal block.
  • the thermal block may be configured to be movable between a first position not engaged with the reaction chamber of the fluid reaction cartridge and a second position engaged with the reaction chamber of the fluid reaction cartridge so as to enable thermal energy transmission from the thermal block to the contents of the engaged reaction chamber when the thermal block is in its second position.
  • the thermal block may include one or more magnets carried thereby so as to expose to the contents of the engaged reaction chamber to a magnetic force when the thermal block is in its second position.
  • the motor is operatively coupled to the thermal block so as to effect powered movement of the thermal block between its first and second positions.
  • the device may include a housing having an opening for receiving a fluid reaction cartridge, a lid for closing the opening, and a switch operatively coupled to the lid.
  • the motor is activated to effect powered movement of the thermal block from its first position to its second position when the switch generates a signal indicating the lid has been closed.
  • the device may include a thermal interface recess formed in the thermal block and configured to receive the engaged chamber when the thermal block is in its second position.
  • FIG. l is a perspective view of a processing device having a lid shown in an open configuration with a reaction cartridge inserted into the device.
  • FIG. 2 is a front view of a cartridge holder frame of the processing device with a reaction cartridge supported therein.
  • FIG. 3 is a rear view of the cartridge holder frame and reaction cartridge.
  • FIG. 4 is a partial side view of the lid, a cartridge interface block, and a cartridge interface linkage assembly of the processing device operatively coupling the lid to the cartridge interface block.
  • FIG. 5 is a perspective view of the cartridge interface block and cartridge interface linkage assembly.
  • FIG. 6 is an exploded perspective view of the cartridge interface block and the cartridge interface linkage assembly.
  • FIG. 7 is a perspective view of the cartridge interface block and first interface links of the cartridge interface linkage assembly.
  • FIG. 8 is a cross-sectional view in the direction A-A in FIG. 7.
  • FIG. 9 is a partial transverse cross-sectional view of the cartridge interface block pressed against the reaction cartridge held in the cartridge holder frame.
  • FIG. 10 is a partial transverse cross-sectional view of the reaction cartridge and the processing device showing a left hand side of the cartridge interface block, the cartridge interface linkage assembly, and the lid in a fully open position.
  • FIG. 11 is a partial transverse cross-sectional view of the reaction cartridge and the processing device showing a left hand side of the cartridge interface block, the cartridge interface linkage assembly, and the lid in a partially closed position.
  • FIG. 12 is a partial transverse cross-sectional view of the reaction cartridge and the processing device showing a left hand side of the cartridge interface block, the cartridge interface linkage assembly, and the lid in a nearly fully closed, over-center position.
  • FIG. 13 is a partial side view of the reaction cartridge and the processing device showing the cartridge interface block, the cartridge interface linkage assembly, and the lid in a fully closed position.
  • FIG. 14 is a partial side view in the direction of line B-B in FIG. 13 of the first interface links and reaction cartridge, with the cartridge interface block omitted.
  • FIG. 15 is a partial side view of the cartridge holder frame and cartridge, the cartridge interface block, the cartridge interface linkage assembly, and cartridge lid sealer gantry operatively coupled to the cartridge holder frame and the cartridge interface linkage assembly, with the lid in an open position.
  • FIG. 16 is a perspective view of the cartridge lid sealer gantry.
  • FIG. 17 is a perspective view of a thermal/magnetic module.
  • FIG. 18 is a partial side view of the thermal/magnetic module, the cartridge holder frame, and a reaction cartridge, showing the thermal/magnetic module not engaged with the reaction chamber of the reaction cartridge.
  • FIG. 19 is a partial side view of the thermal/magnetic module, the cartridge holder frame, and a reaction cartridge, showing the thermal/magnetic module engaged with the reaction chamber of the reaction cartridge.
  • FIG. 20 is a perspective view of the cartridge holder frame and a reaction cartridge and a cartridge marking module.
  • FIG. 21 is a cross-sectional view of the cartridge marking module in the direction C-
  • FIG. 22 is a perspective view of a single marking mechanism of the cartridge marking module.
  • FIG. 23 is a side view of the cartridge holder frame and a reaction cartridge and an optics module.
  • FIG. 24 is a cross-sectional view of the optics module in the direction D-D in FIG.
  • FIG. 25 is a block diagram that schematically illustrates a control architecture for the processing device.
  • FIG. 26 is a back view of the cartridge.
  • FIG. 27 is a flowchart showing a process for performing an assay on the cartridge.
  • This description may use various terms describing relative spatial arrangements and/or orientations or directions in describing the position and/or orientation of a component, apparatus, location, feature, or a portion thereof or direction of movement, force, or other dynamic action.
  • such terms including, without limitation, top, bottom, above, below, under, on top of, upper, lower, left of, right of, in front of, behind, next to, adjacent, between, horizontal, vertical, diagonal, longitudinal, transverse, radial, axial, clockwise, counter-clockwise, etc., are used for convenience in referring to such component, apparatus, location, feature, or a portion thereof or movement, force, or other dynamic action in the drawings and are not intended to be limiting.
  • terms used herein to describe a physical and/or spatial relationship between a first component, structure, or portion thereof and a second component, structure, or portion thereof such as, attached, connected, fixed, joined, linked, coupled, or similar terms or variations of such terms, shall encompass both a direct relationship in which the first component, structure, or portion thereof is in direct contact with the second component, structure, or portion thereof and an indirect relationship in which there are one or more intervening components, structures, or portions thereof between the first component, structure, or portion thereof and the second component, structure, or portion thereof.
  • the term “about” applies to all numeric values and terms indicating specific physical conditions, orientations, or relationships, such as, rough, smooth, straight, horizontal, vertical, parallel, perpendicular, concentric, or similar terms, specified herein, whether or not explicitly indicated. This term generally refers to a range of numbers, conditions, orientations, and relationships that one of ordinary skill in the art would consider as a reasonable amount of deviation to the recited numeric values, conditions, orientations, and relationships (i.e., having the equivalent function or result) in the context of the present disclosure.
  • this term can be construed as including a deviation of ⁇ 10 percent of the given numeric value, condition, orientation, or relationship, provided such a deviation does not alter the end function or result of the stated value, condition, orientation, or relationship. Therefore, under some circumstances as would be appreciated by one of ordinary skill in the art a value of about 1% can be construed to be a range from 0.9% to 1.1%.
  • adjacent refers to being near or adjoining. Adjacent objects can be spaced apart from one another or can be in actual or direct contact with one another. In some instances, adjacent objects can be coupled to one another or can be formed integrally with one another.
  • the terms “substantially” and “substantial” refer to a considerable degree or extent.
  • the terms can refer to instances in which the event, circumstance, characteristic, or property occurs precisely as well as instances in which the event, circumstance, characteristic, or property occurs to a close approximation, such as accounting for typical tolerance levels or variability of the embodiments described herein.
  • the terms “optional” and “optionally” mean that the subsequently described, component, structure, element, event, circumstance, characteristic, property, etc. may or may not be included or occur and that the description includes instances where the component, structure, element, event, circumstance, characteristic, property, etc. is included or occurs and instances in which it is not or does not.
  • FIG. 1 shows a perspective view of a processing device 200 as disclosed herein.
  • Processing device 200 includes a housing 202 and may include a control and/or display panel 204.
  • An opening at the top of the housing 202 receives a reaction cartridge 10 inserted therein and a hinged lid 208 that maybe moved between an open position, as shown in FIG. 1, and a closed position by rotating the lid 208 (counter-clockwise in the illustrated example).
  • FIGS. 2 and 3 show front and back views, respectively, of a cartridge holder frame
  • Cartridge holder frame 210 that is located within the housing 202 and fixed to side mounting components (not shown) disposed within the housing.
  • Cartridge holder frame 210 is configured to receive and hold a reaction cartridge inserted into the device 200 in a vertical, operative orientation, as shown.
  • Cartridge holder frame 210 may include asymmetric features that cooperate with complementary asymmetric features of the reaction cartridge 10 to ensure the reaction cartridge can only be inserted into the device in one direction and in one orientation.
  • reaction cartridge 10 is shown held in the cartridge holder frame 210.
  • Reaction cartridge 10 provides a point-of-care, sample-to-answer platform for performing a diagnostic test on a sample material.
  • reaction cartridge 10 may include a handle 14 at one end for grasping the reaction cartridge when inserting it into or removing it from the processing device 200 and one or more registration features that are engaged by and cooperate with cooperating features within processing device 200 to position the reaction cartridge 10.
  • engagement features may comprise notches 18 formed in opposed edges of the reaction cartridge 10 that may be engaged by one or more spring-biased ball detents or similar mechanisms within processing device 200 as described below.
  • reaction cartridge 10 includes four notches 18 - two on opposite sides of a top end of the reaction cartridge 10 (see FIG. 2) and two on opposite sides of a middle portion of the reaction cartridge 10 (see FIG. 3).
  • Reaction cartridge 10 may include a first pneumatic port (or pressure port) 42, a second pneumatic port (or pressure port) 44, and a third pneumatic port (or pressure port) 46 for cooperatively interfacing with pneumatic elements (e.g., nozzles or tubes) of processing device 200.
  • Reaction cartridge 10 may further include a first flow control element 48, a second flow control element 52, a third flow control element 56, a fourth flow control element 60, and a fifth flow control element 66.
  • Each of flow control elements 48, 52, 56, 60, 66 may comprise an alterable flow-blocking feature that is altered, e.g., melted, dissolved, punctured, delaminated, etc., by a cooperating component of processing device 200 to change the flow control device from a flow- blocking status to a flow-permitting status.
  • each of flow control elements 48, 52, 56, 60, 66 comprises a frangible seal opening, or valve, that is opened by a non-puncturing pin of the processing device 200 pressing on the valve to cause sufficient deflection of the material to open the valve.
  • flow control elements 48, 52, 56, 60, 66 may comprise a via formed through a base of the reaction cartridge, whereby a portion of a film applied to a back surface of the reaction cartridge and surrounding each via separates from the back surface of the reaction cartridge in the region surrounding the via when pushed by a non-puncturing pin extending through the via to permit fluid flow.
  • a label or front surface of the reaction cartridge 10 may include a result marking area providing locations to be punched or otherwise altered for indicating a test result. For example, a punch through the label, a printed mark, or other alteration at location 36 may indicate a positive test result, at location 38 may indicate a negative test result, and at location 34 may indicate an invalid test.
  • Reaction cartridge 10 may further include a hinged cap 20 for closing a sample inlet port of a sample chamber.
  • Hinged cap 20 may include an opening in which a sealing membrane 21 is secured. Sealing membrane 21 pliably contacts a perimeter edge of the sample inlet port when the hinge is closed to provide a secure seal.
  • processing device 200 may include a pressing mechanism that presses the sealing membrane 21 against the perimeter of the sample inlet port to enhance the seal provided by the membrane 21.
  • the sample chamber which may also constitute a reaction chamber and a detection chamber, includes a portion 92 that is exposed so that an outer wall thereof is accessible by the processing device 200. An opposed surface of portion 92 may comprise a translucent or transparent material to enable optical signals to pass into and out of portion 92.
  • Cartridge holder frame 210 may further include an optical detection window 214 that is aligned with a back side of the portion 92 of the sample/reaction chamber of reaction cartridge 10.
  • FIG. 26 is a back view of the cartridge 10 (i.e., the side of the cartridge 10 opposite that shown in FIG. 2) illustrating additional features of the cartridge 10.
  • Cartridge 10 may include a rehydration buffer storage reservoir 70.
  • One or more reagents may be provided in one or more chambers, channels, or reservoirs.
  • dried or lyophilized reagents are contained within a reagent chamber 76.
  • a first dried or lyophilized reagent pellet, or plug, 78 and a second dried or lyophilized reagent pellet, or plug, 80 may be heat-staked within receiving openings formed in reagent chamber 76.
  • Cartridge 10 may further include a waste chamber 84 and a sample reaction chamber 88.
  • Sample reaction chamber 88 includes an upper portion 90 and a lower portion 92 when cartridge 10 is in a vertical, operative orientation as shown in FIG. 26 having a smaller volumetric capacity than the upper portion 90. Because lower portion 92 is volumetrically smaller than upper portion 90 and has smaller transverse dimensions (width and depth) than upper portion 90, lower portion 92 functions as a funnel to concentrate the contents of chamber 88. The smaller dimensions of lower portion 92 also facilitate efficient application of magnetic forces to the contents, heating of the contents, and excitation and measurement of optical signals from the contents by efficient interfacing with thermal/magnetic components and optics components (i.e., minimize length of optical pathway). Lower portion 92 is a bead collection chamber as well as a reaction and detection zone and magnet and heater interface. A sample inlet 86 is open to the upper portion 90 of the sample reaction chamber 88 and is covered by cap 20 described above.
  • a first conduit 50 extends between a bottom end of lower portion 92 of sample reaction chamber 88 and waste chamber 84, passing through first flow control element 48.
  • sample reaction chamber 88 is directly connected the to the waste chamber 84 by first conduit 50.
  • a second conduit 54 extends between second pneumatic port 44 and fourth flow control element 60, passing through second flow control element 52 and rehydration buffer storage reservoir 70.
  • a third conduit 58 extends between third pneumatic port 46 and a top end of upper portion 90 of sample reaction chamber 88, passing through third flow control element 56.
  • a first serpentine conduit 62 extends between fourth flow control element 60 and reagent chamber 76.
  • rehydration buffer storage reservoir 70 is directly connected to reagent chamber 76 by first serpentine conduit 62 and a portion of second conduit 54.
  • a second serpentine conduit 68 extends between fifth flow control element 66 and reagent chamber 76.
  • a fourth conduit 64 extends between fifth flow control element 66 and a top end of lower portion 92 of sample reaction chamber 88.
  • reagent chamber 76 is directly connected to sample reaction chamber 88 by second serpentine conduit 68 and fourth conduit 64.
  • a fifth conduit 65 extends between first pneumatic port 42 and a top end of waste chamber 84. Numerical designations of components, e.g., first, second, third, etc., are for distinguishing one component from another and are not intended to be limiting or to have any implied connotation.
  • processing device 200 is configured to process reaction cartridge 10 by selectively applying pressure to, closing, or venting any of the first, second, and third pneumatic ports 42, 44, 46 and by opening the flow control elements 48, 52, 56, 60, 66, to selectively effect fluid movement within the reaction cartridge from one chamber to another via fluid flow channels within the reaction cartridge 10, to apply heat to one or more selected chambers, or chamber portions, of the reaction cartridge, such as portion 92 of the sample/reaction chamber, to incubate the contents of the chamber, and to detect the results of a reaction performed on the contents of the sample/reaction chamber by measurement of optical emissions from the reaction chamber within the reaction cartridge, such as portion 92 of the sample/reaction chamber.
  • Processing device 200 is also configured to physically mark or alter the reaction cartridge at one of locations 34, 38, 36 to provide a result indication on the reaction cartridge.
  • Cartridge holder frame 210 provides a cradle to receive and hold the reaction cartridge 10 inserted into the processing device 200.
  • detent devices such as spring-biased ball plungers 212a, 212b, may be provided on one or both opposed sides of the cradle of cartridge holder frame 210 to extend into and engage the middle notches 18 formed on opposed sides of the reaction cartridge 10 when the reaction cartridge is inserted into the cartridge holder frame 210.
  • the spring-biased ball plunger 212a and/or 212b engaged with notches 18 urges the reaction cartridge 10 laterally into a repeatable datum position (X-direction) within the cartridge holder frame 210 and locates the reaction cartridge in the Z-direction within the device 200.
  • processing device 200 includes a cartridge interface block 222 operatively coupled to the lid 208 and supporting pressure tubes 224a, 224b, 224c and frangible seal pins 228a, 228b, 228c, 228d, 228e.
  • the cartridge interface block 222 is retracted away from cartridge holder frame 210 to permit a reaction cartridge 10 to be inserted into or removed from the processing device 200 without interference from the cartridge interface block 222.
  • Lid 208 is operatively coupled to the cartridge interface block 222 so that as the lid 208 is closed after a reaction cartridge 10 is inserted into the processing device 200, the cartridge interface block 222 moves laterally to engage the reaction cartridge 10, whereby pressure tubes 224a, 224b, 224c (pressure tubes may be referred to herein generically with number 224, without a letter suffix) engage the first pneumatic port 42, second pneumatic port 44, and third pneumatic port 46, respectively, and frangible seal pins 228a, 228b, 228c, 228d, 228e (frangible seal pins may be referred to herein generically with number 228, without a letter suffix), engage flow control elements 48, 52, 56, 60, 66, respectively, of reaction cartridge 10 to push on the film forming the flow control element and deflect the film sufficiently to separate the film from the perimeter of the via of the flow control element.
  • pressure tubes 224a, 224b, 224c pressure tubes may be referred to herein generically with number 224
  • lid 208 is operatively coupled to the cartridge interface block 222 by a cartridge interface linkage assembly 220 comprising opposed (i.e., left and right) first interface links 232a, 232b, a second interface link 260, a third interface link 268, and a fourth interface link 274.
  • Fourth interface link 274 constitutes a hinge mechanism of the lid 208.
  • First interface links 232a, 232b are secured to opposed sides of the cartridge interface block 222 and are mounted within the housing 202 for lateral movement in the direction of double-headed arrow “A” in FIG. 4 (i.e., the “Y” direction).
  • Second interface link 260 is pivotably secured with respect to housing 202 at first fixed pivots 262a, 262b. It should be noted that most features of the cartridge interface linkage assembly present an identical left and right mirror image. Therefore, reference to such features may be specifically to the left and right counterparts by a number followed by a letter, such as left, right first fixed pivots 262a, 262b, or simply by a number without a letter, such as first fixed pivot 262, which will be understood as referring to the left and/or right counterpart.
  • illustration of a pivot in this disclosure may be by a drawing showing a pivot pin, or rod, as shown in FIG. 5, or showing a circular hole, or boss, that receives the pin, as in FIG. 6.
  • Second interface link 260 is operatively coupled to the first interface links 232a, 232b by coupling pins 266a, 266b extending laterally from circular bosses (also labeled 266a, 266b in FIG. 6) at the ends of coupling arms 261a, 261b of second interface link 260 into coupling slots 234a, 234b of the first interface links 232a, 232b.
  • Third interface link 268 is pivotably coupled to second interface link 260 by pins extending through bores at first floating pivots 264a, 264b of second interface link 260 and into bores 270a, 270b in third interface link 268.
  • Fourth interface link 274 is pivotably coupled to third interface link 268 by pins extending through bores at second floating pivots 276a, 276b of fourth interface link 274 and into bores 272a, 272b in third interface link 268, and fourth interface link 274 is pivotably secured with respect to housing 202 at second fixed pivots 278a, 278b.
  • First and second fixed pivots 262, 278 are fixed to the housing 202 in the Y direction and permit only rotational movement.
  • First and second floating pivots 264, 272 permit both rotational movement and lateral (Y- and Z-direction) movement.
  • FIG. 10 is a partial transverse cross-sectional view of the processing device 200 showing the left hand side of the cartridge interface linkage assembly 220, the cartridge interface block 222, reaction cartridge 10, and lid 208, with lid 208 in a fully open position. With the lid 208 in the fully open position, the cartridge interface block 222 is retracted from the reaction cartridge 10 so that the pressure tubes 224 and the frangible seal pins 228 are not engaged with reaction cartridge 10.
  • FIG. 11 is a partial transverse cross-sectional view of the processing device 200 showing the left hand side of the cartridge interface linkage assembly 220, the cartridge interface block 222, reaction cartridge 10, and lid 208, with lid 208 in a partially closed position.
  • fourth interface link 274 pivots counter-clockwise about the second fixed pivot 278, and second floating pivot 276 moves in a radial arc with respect to fixed pivot 278, the arc having components in the positive Y-direction and the negative Z-direction.
  • Lateral translation of the second floating pivot 276 causes third interface link 268 to pivot clockwise.
  • the clockwise rotation of the coupling arm 261 moves the coupling pin 266 in an arc having components in the positive Y-direction and the positive Z direction.
  • Coupling pin 266 extends into the vertically-oriented coupling slot 234 of the first interface link 232 (left-hand coupling slot 234a of left-hand first interface link 232a shown in FIG.
  • the vertical (Z-direction) orientation of the coupling slot 234 - which is transverse to the Y- direction movement of the cartridge interface block 222 and first interface links 232 - allows the coupling pins 266 to move in the Z direction without applying a Z-direction force to the first interface links 232 but transmits the Y-direction movement of the coupling pins 266 to a corresponding Y-direction movement of the first interface links 232 and the cartridge interface block 222
  • FIG. 12 is a partial transverse cross-sectional view of the processing device 200 showing the left hand side of the cartridge interface linkage assembly 220, the cartridge interface block 222, reaction cartridge 10, and lid 208, with lid 208 in a nearly fully closed, over-center position.
  • fourth interface link 274, third interface link 268, second fixed pivot 278, second floating pivot 276, and first floating pivot 264 are aligned in an “over-center” configuration along an imaginary axis labeled “B” in FIG. 12.
  • FIG. 13 is a partial side view of the cartridge interface linkage assembly 220, the cartridge interface block 222, reaction cartridge 10, and lid 208, with lid 208 in a fully closed position.
  • the linkage system is past the over-center position, and second floating pivot 276 is past the aligned position with respect to second fixed pivot 278 and first floating pivot 264.
  • Second interface link 260 is rotated to its full clockwise extent, thereby moving the first interface links 232 and cartridge interface block 222 to their full, positive Y-positions in full engagement with the reaction cartridge 10, thereby clamping the reaction cartridge 10 to the cartridge holder frame 210.
  • each of first interface links 232a, 232b includes a cartridge alignment ridge 242a (corresponding alignment ridge of first interface link 232b is not visible in FIG. 7) extending in the Y-direction on a side of the associated interface link 232a or 232b facing the cartridge interface block 222.
  • cartridge alignment ridges 242a, 242b engage upper notches 18 of the reaction cartridge 10 held in the cartridge holder frame 210 (not shown in FIG.
  • pressure tubes 224a-224c, and frangible seal pins 228a-228e are mounted within a block 222 secured between the first interface links 232a, 232b. As shown in FIG. 8, each pressure tube 224a-224c and each frangible seal pin 228a-228e is positioned within an associated through-bore formed through the block 222. Each pressure tube 224 is pre-loaded within its associated through-bore by an associated spring 226, and each frangible seal pin 228 is preloaded within its associated through-bore by a spring 230.
  • Each pressure tube 224a-224c may include a barded end - e.g. barbed end 225 of pressure tube 224b shown in FIG. 8 - on which a pneumatic tube (not shown) is attached for connecting the pressure tube to a pressure source, such as a pump (not shown)
  • FIG. 9 is a partial transverse cross-sectional view of the cartridge interface block 222 pressed against the reaction cartridge 10 held in the cartridge holder frame 210.
  • the cartridge interface linkage 220 moves the cartridge interface block 222 into contact, or engagement, with the reaction cartridge 10.
  • Pressure tubes 224a-224c press against the respective pressure ports 42, 44, 46.
  • FIG. 9 shows pressure tube 224b pressed against pressure port 44.
  • frangible seal pins 228a-228d press against the respective frangible seals 48, 52, 56, 60, 66 with sufficient force, and causing sufficient deflection of the respective seal, to open each of the seals to permit fluid flow therethrough.
  • FIG. 9 shows frangible seal pin 228b pressed against frangible seal 52.
  • a cartridge lid sealer mechanism includes a cartridge lid sealer gantry 370 attached at gantry pivots 374a, 374b to the cartridge holder frame 210.
  • Gantry 370 includes a cartridge lid sealer plug 376 disposed within a sealer plug housing 378.
  • Yokes 372a, 372b at the upper ends of the gantry 370 capture a rear gantry pin 236 extending from the first interface links 232 (right side gantry pin 236b is shown in FIG. 15) so that as the first interface links 232a, 232b are moved in the positive Y direction as the lid 208 is closed, gantry 370 pivots toward the reaction cartridge 10 so as to press the cartridge lid sealer plug 376 against the cap 20 of the reaction cartridge 10 - or, more specifically, against sealing membrane 21 of cap 20.
  • a spring 380 may be installed between the cartridge lid sealer plug 376 and the sealer plug housing 378 so that the plug 376 is compliant but also provides sufficient force against the cartridge cap 20.
  • a thermal/magnetic module 330 is shown in FIGS. 17, 18, 19.
  • the thermal/magnetic module 330 includes a thermal block 332 supported on a thermal block mounting bracket 338 that is slidably mounted within the housing 202 of the processing device 200.
  • Thermal block 332 includes a thermal interface recess 334 that receives the portion 92 of the reaction chamber of the reaction cartridge 10.
  • One or more magnets 336 may be mounted within the thermal interface recess 334, and thus thermal block 332 also functions as a magnet carrier.
  • Thermal block 332 may be heated to a temperature above ambient temperature by electrical resistive heating, and module 330 may include a thermistor in communication with embedded control elements to provide temperature control of the thermal block 332.
  • Thermal/magnetic module 330 is configured to move the thermal block 332 in the Y- direction from a first position, shown in FIG. 18, in which the thermal block 332 does not contact any portion of the reaction cartridge 10, to a second position, shown in FIG. 19, in which the thermal block 332 covers portion 92, and portion 92 of the reaction chamber of reaction cartridge 10 is received within the thermal interface recess 334 to apply a magnetic force and thermal energy to the contents of the reaction chamber.
  • Movement of the thermal block 332 is effected by a motor 340 that drives a jack screw thread 342 engaged with a jack screw thread housing 344 that is attached to the thermal block 332. Accordingly, movement of the jack screw thread 342 by the motor 340 in a first direction move the thermal block 332 from its first position (FIG. 18) to its second position (FIG. 19), and reverse motion of the jack screw thread 342 by the motor 340 moves the thermal block 332 from its second position to its first position.
  • Motor 340 may be controllably coupled to a switch, such as a switch operably coupled to lid 208, to activate the motor 340 to move the thermal block 332 from its first position (FIG. 18) to its second position (FIG. 19) when lid 208 is closed, and to activate the motor 340 to move the thermal block 332 from its second position (FIG. 19) to its first position (FIG. 18) when lid 208 is opened.
  • An exemplary motor that may be employed is a 6 volt gear motor with a 150: 1 gear reduction ratio available from Pololu (www.poloiu.com).
  • module 330 may be configured to apply only one of thermal energy and magnetic force to portion 92 of the reaction cartridge. If only thermal energy is required, thermal block 332 may be heated to a temperature above ambient temperature by electrical resistive heating and magnet(s) 336 may be omitted from the block 332. Alternatively, if only magnetic force is required, thermal block 332 may be heated to a temperature above ambient temperature by electrical resistive heating and magnet(s) 336 may be omitted from the block 332.
  • FIGS. 20 and 21 show a cartridge marking module 350.
  • reaction cartridge 10 may include a result marking area providing locations to be punched, or otherwise marked or altered, for indicating a test result, such as at location 36 to indicate a positive test result, at location 38 to indicate a negative test result, and at location 34 to indicate an invalid test (see FIG. 2).
  • the cartridge marking module 350 may include three cartridge marking mechanisms 352a, 352b, 352c positioned adjacent to the cartridge holder frame 210 and configured to be selectively advanced in the Y-direction to punch a hole in the label 26 of the reaction cartridge 10 at one of the locations 34, 36, 38.
  • Each cartridge marking mechanism is aligned and associated with one of the marking locations 34, 36, 38.
  • cartridge marking mechanisms 352a is aligned with marking location 34 for indicating an invalid result
  • cartridge marking mechanisms 352b is aligned with marking location 38 for indicating a negative result
  • cartridge marking mechanisms 352c is aligned with marking location 36 for indicating a positive result.
  • each cartridge marking mechanism 352a-352c includes a motor
  • FIG. 22 which shows a single cartridge marking mechanism 352
  • motor 354 drives a jack screw thread 358 engaged with a jack screw thread housing 360 having a marking pin 366 projecting therefrom.
  • An upper slide connector 362 and a lower slide connector 364 slidably supports the jack screw thread housing 360 within a supporting structure (not shown) above and below the jack screw thread housing 360. Accordingly, movement of the jack screw thread 358 by the motor 354 advances the jack screw thread housing 360 and marking pin 366 to punch a hole in, or effect another mark on, the label of the reaction cartridge 10.
  • An exemplary motor that may be employed is a 6 volt gear motor with a 150: 1 gear reduction ratio available from Pololu ( ww w .
  • An optics module 280 is shown in FIGS. 23 and 24. The function of the optics module 280 is to excite and measure an optical emission from the contents of portion 92 of the reaction chamber of the reaction cartridge 10.
  • Optics module includes a first excitation channel 282, a second excitation channel 300, and an emission channel 310.
  • First excitation channel 282 includes a first excitation source 284 (e.g., an LED) attached to a printed circuit board assembly (“PCBA”) 283.
  • First excitation channel 282 further includes one or more excitation optic elements defining a first excitation optic path, including a collimating lens 286 (e.g., ball lens), a spectral bandpass filter 288, and an illumination condenser 290.
  • An excitation signal generated by the source 284 passes through components 286, 288, and 290 and through the optical detection window 214 of the cartridge holder frame 210 and into portion 92 of the excitation chamber of the reaction cartridge 10.
  • the signal is conditioned by source 284 and filter 288 to be a first excitation wavelength.
  • light from the first excitation source 284 (LED) is collimated through the ball lens 286 and passes through optical bandpass filter 288 to remove low intensity tail of the LED's output spectrum, and then the light is focused onto a spot through the optical detection window 214 and within portion 92 using the double convex lens 290.
  • Exemplary specifications for first excitation channel 282 are as follows:
  • Fluorophore FAMTM (495 nm)
  • Second excitation channel 300 includes a second excitation source 302 (e.g., an LED) attached to a PCBA 301.
  • Second excitation channel 300 further includes one or more excitation optic elements defining a second excitation optic path, including a collimating lens 304 (e.g., ball lens), a spectral band pass filter 306, and an illumination condenser 308.
  • An excitation signal generated by the source 302 passes through components 304, 306, and 308 and through the optical detection window 214 of the cartridge holder frame 210 and into portion 92 of the excitation chamber of the reaction cartridge 10.
  • the signal is conditioned by source 302 and filter 306 to be a second excitation wavelength different from the first excitation wavelength.
  • light from the second excitation source 302 (LED) is collimated through the ball lens 304 and passes through optical bandpass filter 306 to remove low intensity tail of the LED's output spectrum, and then the light is focused onto a spot through the optical detection window 214 and within portion 92 using the double convex lens 308.
  • Exemplary specifications for second excitation channel 300 are as follows:
  • Emission channel 310 includes one or more emission optic elements defining an emission optic path, including an objective lens 312, a dual band pass filter 314, a detector focusing lens 316 (e.g., ball lens), and a photodetector 318, such as a photodiode, attached to aPCBA 311.
  • Emission channel 310 is configured to received optical emission from chamber portion 92 of reaction cartridge 10 through optical detection window 214 of the cartridge holder frame 210.
  • dual band pass filter 314 either of two different emission wavelengths can be detected by photodetector 318.
  • the light from the sample within portion 92 of cartridge 10 is collimated through the double convex lens 312 and passes through a dual-band emission filter 314 that transmits fluorescence from the fluorophores associated with each of the first and second excitation channels 282, 300 and highly attenuates the illumination LED spectra, after which ball lens 316 will focus the light onto photodetector 318.
  • Exemplary specifications for emission channel 310 are as follows:
  • first, and second excitation channels 282, 300 are oriented at an angle with respect to each other (e.g., 90 deg.) and the emission channel 310 bisects the angle between the excitation channels, and the first and second excitation channels 282, 300 and the emission channel 310 are disposed in a common plane, so that mirrors or beam splitters are not required to separate the first and second excitation signals from the first and second emission signals.
  • FIG. 25 is a block diagram that schematically illustrates a control architecture for the processing device 200.
  • An exemplary control architecture may include a controller 400, which monitors, communicates with, and controls aspects of processing device 200, including a lid switch 408, a barcode reader 406, pneumatics 410, optics module 280, cartridge marking module 350, thermal/magnetic module 330, and a power supply 404 that is controllable by the controller 400.
  • a controller 400 to be “connected” to another component means that signals, data, and/or power are transmitted between the controller 400 and the component to which it is connected, either directly or through, or via, one or more intermediate components or other controllers.
  • Controller 400 may comprise a computer system for executing software (which may include firmware) that effects operation, control, and monitoring of the processing device 200. Controller 400 may be implemented via one or more logic elements, e.g., a computer, embedded controller, programmable gate array, application specific integrated circuit, programmable logic device, etc., and may include or access data storage memory 402, which may include random access memory (RAM), read only memory (ROM), flash memory, and other types of memory now known or later developed. Controller 400 may also include additional memory, including, for example, a hard disk drive and/or a removable storage drive, representing a magnetic tape drive, an optical disk drive, USB slot, memory card interface, internet memory, cloud-based memory, or any storage medium or format now known or later developed.
  • software which may include firmware
  • Controller 400 may be implemented via one or more logic elements, e.g., a computer, embedded controller, programmable gate array, application specific integrated circuit, programmable logic device, etc., and may include or access data storage memory 402, which may include random access memory (RAM
  • Memory devices and storage units used herein may comprise any storage medium for persistent and/or volatile storage of electronic data now known or later developed.
  • data may be stored within the storage medium in a database, which may comprise any data structure and format now known or later developed, including, for example, a relational database, an object database, a flat file, list, and so on, or some combination thereof.
  • some or all of the memory may include other similar means for allowing computer programs or other instructions to be loaded into a computer system.
  • Such means can include, for example, a removable storage unit and an interface. Examples of such can include a memory stick and memory stick interface, a secure digital card and interface, and other portable media and interfaces which allow software and data to be transferred to controller 400.
  • Software/firmware comprises instructions stored on non-transitory computer- readable media which, when executed by the logic element(s) of the controller 400, cause the control and computing hardware to perform one or more automated or semi-automated processes.
  • the computer system of controller 400 may also include a communications interface, which allows information (e.g., power, control and feedback signals, software, data, etc.) to be transferred between controller 400 and external devices.
  • communications interfaces can include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, a USB-port, a Firewire port, Bluetooth, cloud-based, or any interface now known or later developed.
  • Information transferred via a communications interface is in the form of signals which can be electronic, electromagnetic, optical or other signals capable of being received by the communications interface.
  • the computer system of controller 400 can also include one or more input devices, such as a touch screen, stylus, keyboard, mouse or other pointing device, microphone, data scanners (e.g ., barcode, RFID, etc.), and so on.
  • One or more input devices may be incorporated into display panel 204.
  • Various output devices may also be included in the computer system, including indicator lights, a display, printer, tactile (e.g., vibratory) indicators, and audio speakers.
  • Software embodied in computer programs may be stored in one or more portions of the memory 402, including firmware, that is part of or accessed by controller 400. Computer programs can also be received via a communications interface. Such computer programs may include algorithms, such as the algorithm 150 illustrated in FIG. 27 and described below, that, when executed, enable the computer system of controller 400 to control the operation of the processing device 200 in accordance with aspects disclosed herein.
  • the software may be stored in a computer program product and loaded into the computer system of controller 400 using a removable storage drive, a hard drive, an interface, and/or a communications interface.
  • the control logic when executed by the processor of the controller 400, causes the processor to perform functional aspects of the subject matter as described herein via the systems, devices, apparatuses, sensors, switches, etc. described above.
  • An operating system may perform basic tasks such as recognizing input from an input device, sending output to an output device, managing data and system resources, signal processing, and managing the various processes embodying computer programs running on the computer system.
  • Controller 400 may comprise a stand-alone system dedicated to the processing device 200, or one or more components of controller 400 - e.g., processor, memory, interfaces, input/output devices, etc. - may be a shared part of a global controller that controls one or more components of an instrument or laboratory of which the processing device 200 is a component, in addition to the processing device 200.
  • components of controller 400 - e.g., processor, memory, interfaces, input/output devices, etc. - may be a shared part of a global controller that controls one or more components of an instrument or laboratory of which the processing device 200 is a component, in addition to the processing device 200.
  • controller 400 is connected to, and receives signals from, a lid switch 408 operatively coupled to the lid 208, wherein signals from the switch 408 indicate that the lid 208 is in an open and/or closed position.
  • controller 400 is connected to, and receives signals from, a barcode reader 406 disposed within the housing 202 and configure to read a barcode on the label 26 of the cartridge 10 placed in the cartridge holder frame 210.
  • the barcode has information relating to the cartridge 10, such as information about expiration, lot code, test type, and a unique cartridge identification number. This identification number is then used to report results.
  • a patient ID may be connected to the cartridge ID in a patient database.
  • Data/signals from the barcode reader 406 may be used by the controller 400 for a number of purposes, such as to confirm (1) the presence of a cartridge in the cartridge holder frame 210 and (2) that the cartridge within the cartridge holder frame 210 has not already been processed by the processing device 200 (i.e., to make sure a cartridge is not mistakenly placed in the device 200 a second time). If the barcode reader 406 fails to read a valid barcode, or if the barcode that it does read belongs to a cartridge that has previously been processed in the device 200, controller 400 may prevent further operation of the device 200 and generate an error signal that may be displayed on control/di splay panel 204.
  • controller 400 is connected to and controls various pneumatics components of the processing device 200, as represented by reference number 410, including the pressure tubes 224a, 224b, 224c and a pump 412 located within the housing 202.
  • controller 400 transmits signals that control valves operatively associated with each of the pressure tubes 224a, 224b, 224c to selectively (1) apply positive pressure from pump 412 to the associated pressure tube, (2) close the associated pressure tube, or (3) open and vent the associated pressure tube.
  • Controller 400 may transmit a signal to activate pump 412 upon receiving a signal from the lid switch 408 indicating that the lid 208 has been closed and receiving a valid barcode signal from the barcode reader 406.
  • Controller 400 may also transmit a signal to deactivate the pump 412 at the conclusion of the assay 150 and/or upon receiving a signal from the lid switch 408 indicating that the lid 208 has been opened.
  • controller 400 is connected to thermal/magnetic module 330. Controller 400 may be configured to transmit an activate signal to motor 340 of module 330 upon receiving a signal from the lid switch 408 indicating that lid 208 is closed and a signal from barcode reader 406 indicating that a proper cartridge is in the device 200 to move the thermal block 332 into interfacing engagement with the portion 92 of the sample reaction chamber of the cartridge.
  • Controller 400 may be further configured to cause power to be transmitted to the thermal block 332 to heat the thermal block, and controller 400 may be configured to receive signals from the thermistor 414 and to control the temperature of the thermal block 332 by controlling the amount of power transmitted to the thermal block based on the signals from the thermistor 414.
  • Controller 400 maybe further configured to terminate power to the thermal block 332 at the conclusion of an assay and may likewise be configured to activate the motor 340 to retract the thermal block 332 from interfacing engagement with the cartridge 10 at the conclusion of the assay.
  • controller 400 is connected to optics module 280 and is configured to selectively activate the first excitation source 284 of the first excitation channel 282 and the second excitation source 302 of the second excitation channel 300. Controller 400 also receives and processes signals from the photodetector 318 and compares the received signals to stored thresholds for identifying positive and negative reaction outcomes. In an embodiment, controller 400 may be configured to sequentially activate first excitation source 284, then measure a resulting emission with photodetector 318, then activate second excitation source 302, and then measure the resulting emission from photodetector 318.
  • One of the excitation channels 282, 300 may be configured to excite and the emission channel is configure to detect a signal having a wavelength (or other detectable property) associated with the control, and the other excitation channel may be configured to excite and the emission channel is configured to detect an emission signal having a wavelength (or other detectable property) associated with the sample.
  • controller 400 is connected to cartridge marking module 350 to control operation of the cartridge marking mechanisms 352a, 352b, 352c. Controller 400 transmits activation signals to selectively activate motor 354a, motor 354b, or motor 354c. For example, controller 400 may transmit a signal to activate motor 354a to punch or otherwise mark location 34 on cartridge label 26, indicating an invalid test result, if, for example, controller 400 does not receive a positive control result from the optics module 280 or if controller 400 does not receive a valid temperature indication signal from the thermal/magnetic module 330 (e.g., temperature is above or below a desired set point).
  • controller 400 may transmit a signal to activate motor 354a to punch or otherwise mark location 34 on cartridge label 26, indicating an invalid test result, if, for example, controller 400 does not receive a positive control result from the optics module 280 or if controller 400 does not receive a valid temperature indication signal from the thermal/magnetic module 330 (e.g., temperature is above or below a desired set point).
  • Controller 400 may transmit a signal to activate motor 354b to punch or otherwise mark location 38 on cartridge label 26, indicating a negative test result, if the controller 400 receives a signal from the optics module 280 indicating a positive control result but does not receive a signal from the optics module 280 indicating a positive test result. Controller 400 may transmit a signal to activate motor 354c to punch or otherwise mark location 36 on cartridge label 26, indicating a positive test result, if the controller 400 receives a signal from the optics module 280 indicating a positive control result and receives a signal from the optics module 280 indicating a positive test result.
  • Controller 400 may also be in communication with display panel 204 and/or audio device 440 housed in processing device 200 for providing visual or audio notification of device status, test results, etc.
  • Controller 400 may be in communication with a transmitter 420 configured to communicate with a remote device/system 430 to provide notifications and/or data records to the remote device/system 430.
  • Remote device/system 430 may be a portable, wireless device, such as a smart phone or tablet computer with which transmitter 420 communicates wirelessly, e.g., by Bluetooth. Communication with a portable device may be text message, csv, or an application residing on the portable device.
  • remote device/system 430 may comprise a hospital and/or laboratory information system or other data collection environment in which electronic health records (EHR) are stored and with which controller 400 and transmitter 420 communicates by any appropriate wired or wireless communication interface. Information may be communicated by text, csv, or by proprietary format file to the remote system (e.g., Epic).
  • EHR electronic health records
  • FIG. 27 is a flowchart showing a process 150 for performing an assay on the cartridge 10 with the processing device 200.
  • a sample solution is introduced into the sample reaction chamber 88 through the sample inlet port 86.
  • cartridge 10 is “pre-loaded” with a rehydration buffer in rehydration buffer storage reservoir 70 and dehydrated reagent pellets 78, 80 in reagent chamber 76.
  • the sample solution may include a sample material combined with a target capture reagent incorporating magnetic beads (e.g., nucleic acid binding bead).
  • the bead may be coated or otherwise treated so as to have an affinity for a particular material (e.g., a target sequence) so that it can be used to capture, concentrate or otherwise enrich the particular material.
  • the sample material may include a biological sample containing whole cells and/or live cells and/or cell debris.
  • the biological sample may contain (or be derived from) a “bodily fluid.”
  • Exemplary bodily fluids from which a biological sample may be obtained may include amniotic fluid, aqueous humour, vitreous humour, bile, blood serum, breast milk, cerebrospinal fluid, cerumen (earwax), chyle, chyme, endolymph, perilymph, exudates, feces, female ejaculate, gastric acid, gastric juice, lymph, mucus (including nasal drainage and phlegm), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum (skin oil), semen, sputum, synovial fluid, sweat, tears, urine, vaginal secretion, vomit and mixtures of one or more thereof.
  • Biological samples include cell cultures, bodily fluids, cell cultures from bodily fluids. Bodily fluids may be obtained from a mammal organism, for example by puncture, or other collecting or sampling procedures. Sample materials may also include non-biological samples, such as chemical samples collected from industrial or municipal processing facilities.
  • the hinged cap 20 is then closed, and, at step S154, the cartridge 10 is then inserted into a processing device 200 in a vertical orientation as shown in FIG. 2 so that the sample solution collects in the lower portion 92 of the sample reaction chamber 88. While sample is being added to cartridge 10, and before the cartridge is placed in a processing device 200, all of the flow control elements 48, 52, 56, 60, and 66 are closed so as to prevent fluid (air or liquid) flow therethrough.
  • flow control elements 48, 56, 66 prevent sample solution from escaping the sample reaction chamber 88, and flow control elements 52, 60 prevent rehydration buffer from escaping rehydration buffer storage reservoir 70.
  • step SI 54 After cartridge 10 is placed in a processing device, lid 208 is closed in step SI 54, and each of the flow control elements 48, 52, 56, 60, and 66 is opened by frangible seal pins 228a, 228b, 228c, 228d, 228e, respectively, within device 200.
  • step SI 56 the barcode 40 is read by a barcode reader 406 within the processing device 200 to confirm (1) the presence of a cartridge in the processing device 200 and (2) that the cartridge within the processing device 200 has not already been processed.
  • step S158 magnet/heat module 330 is activated by controller 400 - e.g., in response to a signal from lid switch 408 actuated when lid 208 is closed - and thermal block 332 is advanced by motor 340 to cause thermal interface recess 334 to interface with portion 92 of sample reaction vessel 88.
  • a magnetic field is applied to the sample solution within the lower portion 92 of the sample reaction chamber 88 by magnets 336 to isolate and immobilize magnetic target capture beads contained within the sample solution.
  • controller 400 activates pneumatics 410 to transfer supernatant, e.g., lysis buffer, from the sample reaction chamber 88 to the waste chamber 84 via first conduit 50, and waste chamber 84 is vented via fifth conduit 65, by applying positive pressure at third pneumatic port 46 by pressure tube 224c, which pressure is communicated with sample reaction chamber 88 by third conduit 58, closing second pneumatic port 44 via pressure tube 224b, and venting first pneumatic port 42 by pressure tube 224a.
  • supernatant e.g., lysis buffer
  • step SI 62 after the supernatant is moved from the sample chamber 88 to the waste chamber 84, controller 400 activates pneumatics 410 to rehydrate the dried or lyophilized reagents within the reagent chamber 76 by moving rehydration buffer from the rehydration buffer storage reservoir 70 to the reagent chamber 76 via first serpentine conduit 62.
  • the rehydration buffer may be moved back-and-forth through the reagent chamber 76, for which purpose the serpentine arrangement of the first serpentine conduit 62 and the second serpentine conduit 68 provide sufficient volumetric capacity.
  • third pneumatic port 46 is closed by pressure tube 224c, positive pressure is applied at second pneumatic port 44 by pressure tube 224b, which pressure is communicated with reservoir 70 by second conduit 54, and first pneumatic port 42 is closed by pressure tube 224a.
  • third and first pneumatic ports 46 and 42 remain closed and pressure applied at second pneumatic port 44 by pressure tube 224b is alternately increased and decreased as controlled by controller 400.
  • controller 400 activates pneumatics 410 to move the reconstituted reagent solution from the reagent chamber 76 to the sample reaction chamber 88 via the second serpentine conduit 68 and the fourth conduit 64.
  • third pneumatic port 46 is vented by pressure tube 224c, positive pressure is applied to second pneumatic port 44 by pressure tube 224b, which pressure is communicated through reservoir 70 and reagent chamber 76 and to sample reaction chamber 88 by second conduit 54, first serpentine conduit 62, second serpentine conduit 68, and fourth conduit 64, and first pneumatic port 42 is closed by pressure tube 224a.
  • controller 400 activates the thermal/magnetic module 330 to expose the contents of the reaction chamber to reaction conditions, such as elevated temperature, which may be isothermal or thermocyclic, to incubate the contents of lower portion 92 of sample reaction chamber 88, and a reaction takes place in the lower portion 92 of sample reaction chamber 88 (e.g. a nucleic acid amplification).
  • reaction conditions such as elevated temperature, which may be isothermal or thermocyclic
  • controller 400 controls the thermal block 332 of the thermal/magnetic module 330 to heat the reaction mixture isothermally to 60 deg. C.
  • control can be a known nucleic acid sequence that is unrelated to the sequence(s) of interest.
  • a probe i.e., a control probe
  • having specificity for the control sequence and having a unique fluorescent dye i.e., the control dye
  • the control dye is added to the sample, along with one or more amplification reagents needed to amplify the control sequence, as well as the target sequence(s).
  • the sample After exposing the sample to appropriate amplification conditions, the sample is alternately exposed to light energy at different excitation wavelengths (including the excitation wavelength for the control dye) and emission light is detected. Detection of emission light of a wavelength corresponding to the control dye confirms that the amplification was successful (i.e., the control sequence was indeed amplified), and thus, any failure to detect emission light corresponding to the probe(s) of the target sequence(s) is not likely due to a failed amplification. Conversely, failure to detect emission light from the control dye may be indicative of a failed amplification, thus calling into question the results from that assay.
  • controller 400 activates optics module 280 to take measurements of optical emissions from the reaction mixture within the lower portion 92 of the sample reaction chamber 88, for which purpose, at least a portion of lower portion 92 is optically transparent or translucent.
  • Obtaining measurements of optical emissions from the contents of the lower portion 92 may include exposing the contents to an optical excitation signal of a prescribed optical wavelength through optical detection window 214 formed in cartridge holder frame 210 and measuring the magnitude or other measurable attribute of a resulting optical emission signal (e.g., a fluorescent emission) having a prescribed optical wavelength.
  • the sample material is combined with a control material having a known response to the applied reaction conditions to ensure completion of the reaction.
  • a detection probe reagent associated with the sample will be configured, or formulated, to emit an optical signal at a first optical wavelength and a detection probe reagent associated with the control material will be configured, or formulated, to emit an optical signal at a second optical wavelength different from the first optical wavelength.
  • step SI 68 may comprise alternately transmitting with first excitation source 284 a first excitation signal at a first optical excitation wavelength associated with the sample and measuring with photodetector 318 the amount of fluorescence at a first optical emission wavelength associated with the sample and then transmitting with second excitation source 302 a second excitation signal at a second optical excitation wavelength associated with the control and measuring with photodetector 318 the amount of fluorescence at a second optical emission wavelength associated with the control.
  • step SI 70 controller 400 monitors the amount of fluorescence at the second optical emission wavelength associated with the control that is measured with the photodetector 318 to determine if the received signal is indicative of a valid test. Should an expected response (e.g., measured optical emission of the second optical wavelength measured by photodetector 318 at step S168) not be obtained from the control material, an invalid test is indicated, and, in step SI 72, controller 400 will activate cartridge motor 354a of cartridge marking mechanism 352a of marking module 350 to mark location 34 on label 26 (e.g., punch a hole with marking pin 366a) thereby indicating an invalid test.
  • a visible notification of an invalid test may also be provided on display panel 204, and an audible notification may be provided as well.
  • step SI 70 If it is determined at step SI 70 that the test is valid, controller 400 proceeds to step SI 74 and monitors the sample signal (e.g., the amount of fluorescence at the first optical emission wavelength associated with the sample that is measured with the photodetector 318) to determine if the sample signal indicates a positive or negative test result. Should the sample signal indicate a positive test result, in step SI 76, controller 400 will activate cartridge motor 354c of cartridge marking mechanism 352c of marking module 350 to mark location 38 on label 26 (e.g., punch a hole with marking pin 366c) thereby indicating a positive test result.
  • the sample signal e.g., the amount of fluorescence at the first optical emission wavelength associated with the sample that is measured with the photodetector 3128
  • controller 400 will activate cartridge motor 354b of cartridge marking mechanism 352b of marking module 350 to mark location 36 on label 26 (e.g., punch a hole with marking pin 366b thereby indicating a negative result.
  • controller 400 After marking a positive test result in step SI 76 or a negative test result in step SI 78, controller 400 terminates the assay.
  • controller 400 instructs optics module 280 to cease making optical measurements, terminates power transmitted to thermal block 332, and deactivates pump 412.
  • Controller 400 will also activate motor 340 of thermal magnetic module 330 to retract thermal block 332 from the reaction chamber of the cartridge 10 either at the conclusion of the assay, i.e., as part of step S176 or step S178 or upon receiving a signal from lid switch 408 indicating that lid 208 has been opened.
  • Lid 208 is then opened, and cartridge interface linkage assembly 220 retracts cartridge interface block 222 out of engagement with the cartridge 10, so that cartridge 10 may be removed from the processing device 200.
  • controller 400 monitors the amount of fluorescence at the second optical emission wavelength associated with the control that is measured with the photodetector 318 (the control signal) to determine if the control signal is indicative of a valid test
  • controller 400 monitors the amount of fluorescence at the first optical emission wavelength associated with the sample that is measured with the photodetector 318 (the sample signal) to determine if the sample signal indicates a positive or negative test result.
  • controller 400 determines if the control signal indicates a valid test or if the sample signal indicates a positive or negative test result by detecting that the control signal or sample signal, as applicable, exceeds a predefined threshold.
  • a first signal e.g., fluorescent control signal F
  • control signal (Fc) will be monitored for a first period of time - e.g., 30 minutes - and if the control signal ratio Fcn/Fco does not meet the control signal’s ratiometric threshold within that first period of time, an invalid test is indicated, and processing of the cartridge terminates. If the control signal ratio Fcn/Fco does reach the control signal’s ratiometric threshold within the first period of time, the sample signal (Fs) may be monitored for a second period of time - e.g., the first period of time plus 10 minutes.
  • optics module 280 may be controlled by controller 400 to thereafter monitor only the sample signal until a positive sample result is indicated or the second period of time expires.
  • controller 400 compares instantaneous gradients of the control signal and sample signal (signal strength vs time curve) to corresponding gradient thresholds. For each signal, controller 400 computes a gradient as the difference between the current fluorescent measurement and the previous fluorescent measurement divided by the time increment (e.g., 60 seconds) between the two measurements, i.e., (F n+i - F n ) / D ⁇ , and compares the gradient to a corresponding gradient threshold. If the gradient meets or exceeds the corresponding gradient threshold, a positive result is indicated, and if the gradient fails to reach the corresponding gradient threshold after a predefined period of time, a negative result is indicated.
  • the time increment e.g. 60 seconds
  • control signal (Fc) will be monitored for a first period of time - e.g., 30 minutes - and if the control signal gradient (Fcn+i - Fen) / D ⁇ does not meet the control signal’s gradient threshold within that first period of time, an invalid test is indicated, and processing of the cartridge terminates. If the control signal gradient (Fcn+i - Fen) / D ⁇ does reach the control signal’s gradient threshold within the first period of time, the sample signal (Fs) may be monitored for a second period of time - e.g., the first period of time plus 10 minutes.
  • optics module 280 may be controlled by controller 400 to thereafter monitor only the sample signal until a positive sample result is indicated or the second period of time expires.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un dispositif de traitement d'une cartouche de réaction fluidique, comprenant une ou plusieurs chambres de fluide, un ou plusieurs orifices de mise sous pression et une pluralité de canaux d'écoulement de fluide, qui comprend un boîtier présentant une ouverture pour recevoir une cartouche de réaction fluidique, un couvercle pour fermer l'ouverture, une interface de cartouche et une liaison d'interface de cartouche. L'interface de cartouche comprend un ou plusieurs tubes de mise sous pression et est mobile entre une première position dans laquelle les tubes de mise sous pression ne sont pas fonctionnellement en prise avec les orifices de mise sous pression d'une cartouche disposée à l'intérieur du boîtier et une seconde position dans laquelle les tubes de mise sous pression sont fonctionnellement en prise avec les orifices de mise sous pression de la cartouche disposée à l'intérieur du boîtier. L'ensemble de liaison d'interface de cartouche accouple le couvercle à l'interface de cartouche de sorte que l'interface de cartouche se trouve dans sa première position lorsque le couvercle se trouve dans une position ouverte et l'interface de cartouche se déplace de sa première position à sa seconde position lorsque le couvercle est déplacé de la position ouverte à une position fermée.
PCT/US2022/031156 2021-05-28 2022-05-26 Dispositif de traitement de cartouche de réaction WO2022251515A2 (fr)

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US202163194659P 2021-05-28 2021-05-28
US63/194,659 2021-05-28

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Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6818185B1 (en) * 1999-05-28 2004-11-16 Cepheid Cartridge for conducting a chemical reaction
US6495104B1 (en) * 1999-08-19 2002-12-17 Caliper Technologies Corp. Indicator components for microfluidic systems
US6677151B2 (en) * 2002-01-30 2004-01-13 Applera Corporation Device and method for thermal cycling
US8506908B2 (en) * 2007-03-09 2013-08-13 Vantix Holdings Limited Electrochemical detection system
GB2472454B (en) * 2009-08-08 2014-10-22 Bibby Scient Ltd An apparaus for treating a test sample
EP2301666B1 (fr) * 2009-09-09 2021-06-30 Cole-Parmer Ltd. Système optique pour réactions multiples
JP7466515B2 (ja) * 2018-07-10 2024-04-12 ナノサイトミクス，エルエルシー 自動化試料堆積および染色システムならびに関連方法

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WO2022251515A3 (fr) 2023-01-12

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