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EP3995208A1 - Satz von kammern mit reagenzien - Google Patents

Satz von kammern mit reagenzien Download PDF

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Publication number
EP3995208A1
EP3995208A1 EP20206554.6A EP20206554A EP3995208A1 EP 3995208 A1 EP3995208 A1 EP 3995208A1 EP 20206554 A EP20206554 A EP 20206554A EP 3995208 A1 EP3995208 A1 EP 3995208A1
Authority
EP
European Patent Office
Prior art keywords
container
chamber
lysis
fluid
test
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
EP20206554.6A
Other languages
English (en)
French (fr)
Inventor
Markus Riester
Michael Diebold
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.)
Midge Medical GmbH
Original Assignee
Midge Medical GmbH
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 Midge Medical GmbH filed Critical Midge Medical GmbH
Priority to EP20206554.6A priority Critical patent/EP3995208A1/de
Priority to PCT/EP2021/059106 priority patent/WO2021204901A1/en
Priority to US17/995,735 priority patent/US20230158492A1/en
Priority to EP21715936.7A priority patent/EP4132702A1/de
Publication of EP3995208A1 publication Critical patent/EP3995208A1/de
Pending legal-status Critical Current

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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
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • 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
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0672—Integrated piercing tool
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • 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
    • B01L2400/0605—Valves, specific forms thereof check valves
    • B01L2400/0611—Valves, specific forms thereof check valves duck bill valves
    • 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
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0644—Valves, specific forms thereof with moving parts rotary valves
    • 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
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5029—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures using swabs

Definitions

  • the invention relates to a set of chambers containing reagents to be used in a system and a device for detecting a target analyte, in particular a target nucleic acid, for instance DNA or RNA, by way of isothermal nucleic acid amplification and fluorescence.
  • a target analyte in particular a target nucleic acid, for instance DNA or RNA
  • Nucleic acid amplification technologies are used to amplify the amount of a target nucleic acid in a sample in order detect such target nucleic acid in the sample.
  • a known nucleic acid amplification technology is Polymerase Chain Reaction (PCR). Isothermal nucleic acid amplification technologies offer advantages over polymerase chain reaction (PCR) in that they do not require thermal cycling or sophisticated laboratory equipment.
  • RPA Recombinase Polymerase Amplification
  • SIBA Strand Invasion Based Amplification
  • Recombinase polymerase amplification is a method to amplify the amount of a target analyte, in particular a nucleic acid such as DNA or RNA in a sample.
  • a target analyte in particular a nucleic acid such as DNA or RNA in a sample.
  • three core enzymes are used: a recombinase, a single-stranded DNA-binding protein (SSB) and a strand-displacing polymerase.
  • SSB single-stranded DNA-binding protein
  • Recombinases can pair oligonucleotide primers with homologous sequences in duplex DNA.
  • SSB binds to displaced strands of DNA and prevents the primers from being displaced.
  • the strand-displacing polymerase begins DNA synthesis at sites where the primer has bound to the target DNA.
  • an exponential DNA amplification reaction can be achieved to amplify a small amount of a target nucleic acid to detectable levels within minutes at temperatures between 37°C and 42°C.
  • the three core RPA enzymes can be supplemented by further enzymes to provide extra functionality. Addition of exonuclease III allows the use of an exo probe for real-time, fluorescence detection. If a reverse transcriptase that works at 37 to 42 °C is added then RNA can be reverse transcribed and the cDNA produced amplified all in one step.
  • fluorescence detection technique For detecting the presence of a targeted nucleic acid in a sample, fluorescence detection technique can be used. After the light source at specific wavelength illuminates on the targeted nucleic acids, the DNA-binding dyes or fluorescein- binding probes of the nucleic acids will react and enable fluorescent signals to be emitted. The fluorescent signal is an indication of the existence of the targeted nucleic acids.
  • a set of containers comprises a first container, in particular a lysis container that encloses at least a first chamber and a second container, in particular a test container that encloses at least a second chamber.
  • the lysis container may contain a liquid lysing fluid that causes lysing of the cells in a sample to thus release the nucleic acids (DNA or RNA).
  • the lysing fluid may comprise an acid, e.g. HCI or a weak alkali, and a surface active agent.
  • the test container contains a mixture of chemicals that can cause an amplification of nucleic acid in a sample.
  • the mixture comprises a recombinase, a single-stranded DNA-binding protein (SSB) and strand-displacing polymerase that causes a recombinase polymerase amplification (RPA).
  • the test container further preferably contains exonuclease III allows the use of an exo probe for real-time, fluorescence detection.
  • the mixture may be provided in form of a dry pellet.
  • the first container, the second container and the fluid transfer interface are configured to allow a limited amount of fluid being transferred from the first chamber into the second chamber.
  • the fluid transfer interface initially is closed so that the first container can be handled as a separate, closed unit.
  • a second aspect of the invention is a set of at least two distinct containers that can be combined to form a single, fluid tight assembly.
  • the first chamber that is enclosed by the first container comprises a first set of chemicals and/or agents.
  • the first chamber comprises a fluid for lysing a sample.
  • the first container preferably is a lysis container.
  • the first chamber is closed prior to use.
  • the second chamber that is enclosed by the second container comprises a second set of chemicals and/or agents that are at least in part distinct from the chemicals and/or agents of the first set of chemicals in the first chamber.
  • the second set of chemicals comprises chemicals required for testing for an analyte and in particular to amplify nucleic acids in a sample.
  • the second container preferably is a test container enclosing a test chamber.
  • the first container comprises an interface, in particular a lid, that can be opened when the first container and the second container are combined to form a single, fluid tight assembly, in order to allow contents of the first chamber to enter the second chamber.
  • the test container may comprise more than one, e.g, two, three or four separate test chambers. In each test chamber a different mixture of chemicals can be contained thus allowing for testing for different target analytes simultaneously.
  • the second aspect of the invention can implemented in combination with the first aspect of the invention or independently from the first aspect of the invention.
  • each container is an integral unibody.
  • the assembly of the first container and the second container is an integral unibody.
  • the containers can be connected by means of a fluid tight snap fit connection to thus form a single, fluid tight assembly.
  • a fluid tight snap fit connection a screw lock connection similar to a Luer-lock can be provided for tightly connecting the containers.
  • a press fit connection between the containers is another alternative.
  • the advantage of a fluid tight assembly of at least two containers is that the assembly can be disposed easily without the risk of contamination because the contents of the assembly is tightly secured within the assembly.
  • the second container has transparent walls that allow excitation and detection of luminescence and in particular fluorescence.
  • An assembly comprising two initially separate containers and a fluorescence detection device with a receptacle that can receive the assembly for luminescence detection makes it possible to perform a testing method that comprises two consecutive chemical or biochemical method steps - for instance lysis and amplification - and a luminescence testing step in a simple, clean and safe manner that minimizes the risk of contamination and infection while providing easy handling.
  • the fluorescence detection device can be re-used because in use it is not contacted by the sample or any agents or chemicals since these are tightly enclosed in the assembly of containers.
  • the assembly of containers and its contents can be safely disposed after use because the contents is reliably kept within the interior of the assembly.
  • the system also comprises a piston for transferring fluid from the first chamber to the second chamber.
  • the piston is configured to fit into the first chamber.
  • the travel of the piston is limited and corresponds to the amount of fluid to be transferred into the second chamber.
  • the piston can comprise a lid for closing the lysis container and the test container.
  • the combination of the lysis container and piston is arranged such that in the event of the piston moving into the lysis container pressure release is possible through venting.
  • the venting means are configured to prevent content of either the lysis container or the test container or both from escaping out of the respective chamber or chambers.
  • the first container's lid that allows fluid transfer from the first chamber to the second chamber, when the first container and the second container are connected, can be configured to be opened by connecting the first container and the second container.
  • a set of containers comprising at least one test container and a sample container that is configured to for collecting a fluid sample.
  • the test container is configured for collecting a sample by way of gargling or mouth washing.
  • sampling by means of a swab is replaced by a test using mouthwash or gargling.
  • This embodiment follows the basic concept as disclosed herein before featuring modified parts so that a simple testing can be achieved by mouthwashing and/or gargling. The reliability of the samples and subsequent test process is improved and the inconveniences of sample taking with a swab are avoided.
  • the set of containers preferably comprises a sample container, a lysis container and a test container.
  • the set of containers comprises a sample container that comprises a sample chamber and a compartment for a lysing fluid, said compartment initially being separated from the sample chamber.
  • no separate lysis container is needed.
  • the sample chamber of the sample container can comprise a liquid that can be used for gargling and that can lyse a sample thus acquired.
  • the set of container is part of a system that further comprises a fluorescence detection device.
  • the system is configured to implement an isothermal amplification method such as RPA and SIBA and other methods, preferably isothermal methods.
  • the amplification method is configured to be carried out in a temperature range between 25°C and 47°C.
  • initial heating may be applied.
  • Other embodiments implement continuous heating. There are also embodiments without any external heating in one or more of the method steps.
  • the fluorescence detection device comprises
  • the controller can be a microcontroller and/or a state machine.
  • the fluorescence detection device may further comprise heating means that allow heating of a test container that is inserted in the fluorescence detection device.
  • the system can either be a point of care (POC) system wherein the fluorescence detection device is arranged at a point of care, for instance in a medical doctor's office.
  • POC point of care
  • the system may be a personal system wherein the fluorescence detection device is self-contained and mobile, in particular pocketable.
  • the system 10 for detecting a target analyte comprises a fluorescence detection device 16 and a set of two containers 12 and 14.
  • a first container 12 is a lysis container that encloses a first chamber comprising a fluid and/or an agent for lysing a sample.
  • the second container 14 is a test container 14 that encloses a second chamber comprising reagents, for instance enzymes for amplifying nucleic acids in a sample that was lysed in the lysis container 12; cf. figure 1 .
  • the set of two containers 12 and 14 further comprises means that allow a limited transfer of fluid from the first chamber into the second chamber.
  • the means for limited transfer of fluid from the first container 12 to the second container 14 comprise a piston 18.
  • the lysis container 12 contains a lysing fluid that causes lysing of cells or viruses in a sample to be tested.
  • a lysing fluid that causes lysing of cells or viruses in a sample to be tested.
  • nucleic acids such as DNA or RNA are released by way of breaking down the cells or viruses in the sample to be tested. Lysing can be achieved by a lysing fluid that comprises an acid such as hydrochloric acid or a weak alkali.
  • the lysis container 12 has a lid 20 so lysis container 12 can be opened and a sample to be tested can be entered in the lysis container 12; cf. figure 2 .
  • the contents of the lysis container 12 is about 100 ⁇ l.
  • Lid of the lysis container 12 preferably is a membrane 20 that can be pierced by a cotton swab with a sample.
  • the membrane 20 can be a composite film, for instance made from plastic sheeted aluminum.
  • the membrane 20 can be an integral part of the lysis container, in particular a thin septum formed from the material of the lysis container walls.
  • the test container 14 encloses the second chamber comprising a mixture of enzymes that are needed for a recombinase polymerase amplification (RPA).
  • the mixture is provided in the form of a dry pellet 21 that is contained in the second chamber.
  • the test container 14 preferably is a cuvette that can be inserted in a receptacle 22 of the fluorescence detection device 16.
  • the receptacle 22 is part of a detection chamber 42 of the fluorescence detection device 16.
  • the test container 14 is dimensioned to allow inserting the lysis container 12 into the test container 14 (or vice versa) in a tight and defined manner.
  • An abutment 24 limits the depth of insertion.
  • the test container 14 may also be closed by a thin pierceable lid 28 or 28'.
  • the pierceable lid 28 maybe arranged at the otherwise open end of a guiding sleeve 37 of test chamber 37 or close to level of the abutment 24 (lid 28').
  • the thin lids 26 and 28 can be a composite film, for instance made from plastic sheeted aluminum.
  • the thin lid 26 can be an integral part of the lysis container 12, in particular a thin septum formed from the material of the lysis container's 12 walls.
  • Further preferred materials for the thin lids 26 and 28 are silicone or a thermoplastic elastomer (TPE).
  • a piercing fluid transfer interface member 27 is provided; see figure 3 .
  • the piercing fluid transfer interface member 27 comprises a fluid passageway 29 formed in tube-shaped protrusions 31 and 33 that extend centrally from a support disc 35 in opposite directions.
  • Each tube-shaped protrusion 31 and 33 has a pointed tip that can pierce lid 26 and 28, respectively.
  • the tube-shaped protrusions 31 and 33 maybe formed from a metal tube that extends through the support disc 35.
  • tube-shaped protrusions 31 and 33 maybe integrally formed with the support disc 35 from a plastic material.
  • Lysis container 12, test container 14 and piercing fluid transfer interface member 27 are held and guided in the guiding sleeve 37.
  • the fluid passageway 29 extends centrally along a common longitudinal axis of the lysis container 12, the test container 14 and the guiding sleeve 37.
  • Piercing fluid transfer interface member 27 could be fixed to guiding sleeve 37 or even an integral part of guiding sleeve 35 so that lysis chamber 12 and test chamber 14 could be inserted into guiding sleeve 35 until respective lid 26 or 28 is pierced. However, it is preferred if piercing fluid transfer interface member 27 can slide within guiding sleeve 37 because this would provide that both lids 26 and 28 are pierced simultaneously.
  • Test container 14 and guiding sleeve 37 could form an integral unibody similar to what is shown in figure 2 . If the test container 14 and the guiding sleeve 37 are firmly connected so as to form an integral part, it is mandatory that the fluid transfer interface member 27 is slidingly arranged within guiding sleeve 37.
  • Figure 3B shows an enlarged detail from figure 3B in semi-perspective view.
  • the lysis container 12, the test container 14 and the piston 18 are configured to engage in a fluid-tight manner when fully inserted. Such fluid tight engagement can be achieved by means of a snap fit connection wherein an annular protrusion 30 of one of the lysis container 12 and the test container 14 engages in an annular groove of the respective other container. Likewise, an annular protrusion 32 of one of the piston 18 and the lysis container 12 engages in an annular groove of the respective other part. Annular protrusions 30 and 32 act as sealings and may be integrally formed with the rest of the respective container or piston.
  • a screw lock connection similar to a Luer-lock can be provided for tightly connecting the lysis container 12 and the test container 14.
  • venting means (not shown) are provided.
  • test container 14 Once fully engaged, the test container 14, the lysis container 12 and the piston 18 form a tight assembly 34 that can be handled as a single, fluid tight unit.
  • Walls 36 of the test container 14 are transparent so as to allow light to enter the test container 14 and to exit the test container 14.
  • the transparent walls 36 of the test container 14 make it possible to expose the content of test container 14 to exiting light that can cause a luminescence.
  • the content of the test container 14 is luminescent luminescence of the sample in the test container 14 can be detected through the transparent walls 36 of the test container 14.
  • the pellet 21 that contains the mixture of enzymes for recombinase polymerase amplification preferably comprises a recombinase, a single-stranded DNA-binding protein (SSB) and a strand-displacing polymerase, exonuclease III and in case RNA is to be detected, a reverse transcriptase.
  • SSB single-stranded DNA-binding protein
  • a sample to be tested first is filled into lysis container 12. After lysing the cells in the sample to be tested, the entire content of lysis container 12 is transferred into the test container 14 by means of the piston 18 so that a recombinase polymerase amplification can occur in the test container 14.
  • test container 14 typically between 10 to 15 minutes after filling in the content of the lysis container 12 into the second chamber that is enclosed by the test container 14 - the test container 14 or alternatively only its content can be entered into the fluorescence detection device 18.
  • the entire assembly 34 is inserted in a receptacle 22 of the fluorescence detection device 16; cf. figure 4 .
  • a grip 38 is provided at a proximal end of the piston 18.
  • a collar 40 is provided that forms a lid for the receptacle 22.
  • the fluorescence detection device 16 comprises a detection chamber 42 that is configured to receive the test container 14 or the contents of the test container 14.
  • the receptacle 22 is part of the detection chamber 42.
  • a light source 44 and an optical sensor 46 are arranged within the detection chamber 42 or adjacent to the detection chamber 42.
  • the light source 44 is configured to illuminate the contents of the detection chamber 42 with a light that can cause luminescence in a sample to be tested during and after the sample has undergone recombinase polymerase amplification.
  • the optical sensor 46 is arranged and configured to detect luminescence in the detection chamber 42 in case luminescence occurs.
  • the detection chamber 42 is arranged in a detection chamber housing 70 that has outer dimension smaller than 10 cm by 10 cm by 4 cm.
  • the volume of the entire fluorescence detection device 16 is smaller than 200 cm 2 , and even more preferred smaller than 100 cm 2 .
  • the longest outer dimension is a least twice as long as the shortest outer dimension.
  • the fluorescence detection device 16' may provide a second receptacle wherein the lysis container 12 can be placed prior to the connection with the test container 14.
  • the second receptacle can also host the test container 14 and the lysis container 12 prior to use.
  • the lysis container 12 and the test container 14 it is an object to only transfer a limited amount of fluid from the lysis container 12 to the test container 14.
  • the amount to be transferred from the lysis container 12 into the test container 14 is reproducible within a range of tolerance of ⁇ 20% of the transferred volume. For instance, it is an object to transfer about 50 ⁇ l from the lysis container 12 into test container 14, while the total amount of liquid in lysis container 12 is larger, for instance more than 100 ⁇ l.
  • a level 80 of fluid is shown.
  • Piston 18 is configured to only displace about 50 ⁇ l of the fluid in lysis container 12. This is achieved by a piston 18 that is shorter than the length of the first chamber that is enclosed by the lysis container 12 so that bottom 82 of piston 18 will not reach the bottom 84 of the first chamber even if the piston 18 is fully introduced into the lysis container 12.
  • the transferred share of fluid may for example correspond to 50 ⁇ l of fluid.
  • Test container 14' can be connected to lysis container 12' by a snap fit connection.
  • the cylindrical side wall of the lysis container 12 extends beyond a bottom 84' and thus forms an extension 88.
  • Test container 14' has an annular flange 90 that allows for a snap fit connection with the lysis container 12' when the flange 90 engages with the extension 88; see figure 5B .
  • Test container 14' is closed by a lid 28' that is sealingly connected to the annular flange 90 of test container 14.
  • Lid 28' preferably is made from an annular composite film.
  • the thin lid 28' can be an integral part of the test container 14, in particular a thin septum formed from the material of the test container's 14 walls.
  • a pointed central tip 92 is arranged in the center of bottom 84' of lysis container 12' and a valve 94 extends through the central pointed tip 92.
  • the central pointed tip 92 maybe made from metal or from plastic material.
  • a piston 18' with limited travel is integrated in a screw-on cap 96.
  • Screw-on cap 96 that can be screwed on lysis container 12'. Accordingly, a swab with a sample can be inserted into the first chamber that is enclosed by a lysis container 12' and thereafter, lysis container 12' can be closed by screwing on the screw-on cap 96.
  • lysis container 12' can be connected to test container 14'.
  • test container 14' snaps into a lysis container 12', the pointed tip 92 at the center of bottom 88' of lysis container 12' pierces into lid 28'. Then, piston 18' can be pushed to thus press a limit amount of fluid from the first chamber enclosed by the lysis container 12' into the second chamber that is enclosed by the test container 14'.
  • lysis container 12" having a bottom 88" with a pointed central tip 92 and a valve 94 arranged therein can be inserted into a housing 98.
  • Lysis chamber 12" as an outer diameter that fits into a lysis container receptacle 100 that is formed by a test container extension 102.
  • Test container extension 102 is provided with a threating 104 on the outside of the test container extension 102.
  • the housing 98 is provided with an inner threating 106 that fits to the outer threating 104 of the test container 14".
  • housing 98 can be screwed on the test container 14" to thus press the lysis container 12" into the lysis container receptacle 100 of the test container 14".
  • the pointed central tip 92 at the bottom 88' of lysis container 12" pierces the lid 28' that initially closed the second chamber in the test container 14
  • fluid can be transferred from the lysis container 12" into the test container 14" by further compressing the lysis container 12".
  • Further rotating of housing 98 causes further compression of the lysis container 12" until an annular opening of the lysis container 14" overcomes an annular protrusion 114 on a central extension 116 of housing 98 extending into the lysis container 12". Compression of the lysis container 12" is thus limited by the force needed for the annular opening of the lysis container 14" to overcome the annular protrusion 114.
  • a swab with a sample Prior to piercing lid 28", a swab with a sample can be inserted into lysis container 12" to have the sample lysed by the lysing fluid in the lysis container 12".
  • a central opening 108 in the central extension 116 of the housing 98 is provided that allows insertion of a swab into the first chamber that is enclosed by the lysis container 12".
  • the central opening 108 can be closed by a push-on cap 110.
  • a helical spring 112 can be provided, that pushes the lysis container 12" away from the test container 14". The spring force of spring 112 is overcome by turning housing 98 and thus screwing housing 98 further onto the test container 14".
  • a central pointed tip could be arranged at the top of the test container instead of lid 28".
  • a pierceable lid would be arranged at the bottom of the lysis container.
  • the assembly 34'" also comprises a lysis container 12"' and a test container 14"'. At the bottom 84'" of lysis container 12'" an elastic valve 86 is arranged that opens, when the test container 14'" is inserted into an extension 88'" of lysis container 12"'.
  • test container 14"' is closed by a lid 28'" that is made from an aluminum composite film.
  • the chamber enclosed by test container is evacuated so that a vacuum exists within the test container 14'".
  • the lid 28'" of test container 14'" is sealingly connected to an annular flange 90'" of test container 14"'.
  • FIG 8 a fluid transfer interface of yet another embodiment of an assembly comprising a lysis container 12"" and a test container 14"" is illustrated.
  • Portioner 130 comprises a base member 132 having an annular groove 134 facing towards the first chamber that is enclosed by the lysis container 12"".
  • the annular groove 134 extends about 340° to 350°.
  • a through-hole 136 is provided that can be brought in alignment with an opening 138 being an fluid communication with the second chamber that is enclosed by the test container 14"".
  • a slide 140 is provided that can rotate with respect to the base member 132 to thus displace fluid in the annular groove 134.
  • FIGs 8A to 8C illustrate the operation of the portioner 130.
  • an annular segment shaped opening 142 in the bottom 84"" of the lysis container 12"" is in fluid communication to the annular groove 134 so that fluid from the first chamber that is enclosed by the lysis container 12"" can flow into the annular groove 134.
  • Rotating the lysis container 12"" with respect to the portioner 130 closes the fluid passage between the first chamber and the annular groove 134; see figure 8B .
  • the annular segment shaped opening 142 has moved due to rotation so that the annular groove 134 in the portioner 130 is closed.
  • a radial extension 146 of the test container 14"" can engage with a groove in the receptacle 22 of the detection chamber 42 of the fluorescence detection device 16.
  • the radial extension 146 prevents the test container 14"" from rotating.
  • the lysis container 12'"" may comprise the first chamber 150 and a third chamber 152 and a movable separation member 154.
  • the movable separation member 154 is configured to be moved between a first state and a second state. In the first state, the movable separation member 154 allows fluid to pass from the first chamber 150 to the third chamber 152. In the second state, movable separation member 154 blocks fluid from passing from the first chamber 150 to the third chamber 152.
  • the movable separation member 154 preferably is an integral wall part of lysis container 12'"" that is connected to a wall of lysis container 12'"" by a breaking score line 156.
  • Breaking of the score line 156 occurs, when the lysis container 12'"" is connected with the test container 14""' and causes the movable separation member 154 from moving from the first state to the second state.
  • the third chamber 154 that is enclosed by the lysis container 12'"" encloses a volume that corresponds to the volume of liquid that is to be transferred from the first chamber in the lysis container 12'"" to the second chamber in the test container 14""'.
  • lysis container 12"" encloses a first chamber 150"" and a third chamber 152""".
  • the third chamber 152"" is defined by a cylindrical side wall 160 and by the bottom 84""" of the lysis container 12""".
  • the end of the third chamber 151""” that faces away from the bottom 84'" is open so that the first chamber 150"" and the third chamber 152""" are not separated.
  • the inner diameter of the third chamber 152""" fits to an outer diameter of a piston 18""” that thus can be inserted into the third chamber 152""”.
  • test container 14"” In order to transfer fluid from the lysis container 12""" to the test container 14""", test container 14""” can be attached to the bottom 84""" of the lysis container 12""” and will be held by an extension 88""" of the lysis container 12""". Once attached, a pointed central tip 92""” pierces into a lid 28""" of the test container 14""". Further, a venting tip 162 pierces into the bottom 84""" of the lysis chamber 12""" outside of the third chamber 152""”. This is shown in figure 12B .
  • guiding ribs 164 are provided, that extend in the longitudinal direction of the lysis container 12'""
  • Lysis container 12""” may provide a guiding extension 166 for guiding the piston 18""".
  • a hole 168 in the extension 166 allows inserting a tip of a swab 170.
  • a cross slide for cutting the swap may be provided, the cross slide would have a cutting edge and would be arranged to move in a direction that is perpendicular to the longitudinal direction of the lysis container.
  • Cross slide guiding elements may be provided on the lysis container for guiding the cross slide.
  • the cross slide is arranged close to an end of the lysis container that faces away from the test container.
  • the lysis container is one part but consists of a lower hollow and an upper plain cylinder.
  • the test container plugs into the hollow part of the lysis container from the bottom.
  • the lysis container covers the test container on the edges.
  • the hollow cylinder is filled and the plain cylinder is filled with 50 ⁇ l to 70 ⁇ l.
  • the surface where the two containers meet needs to be opened and pushed to the edges, covering the liquids in the hollow cylinder but allowing the amount of 50 ⁇ l to 70 ⁇ l in the plain cylinder to mix with the pellets.
  • the surface of the inner circle and the outer ring (of the hollow cylinder) must be equivalent
  • the required amount (50 ⁇ l to 70 ⁇ l) is roughly the volume of a water-droplet.
  • the lysis container is connected to the test container with an M-shaped tube.
  • the "M” gets filled and when you turn it back around, liquid remains in the middle curvage. That amount can be calculated and used for further steps.
  • a third container 170 is provided that serves for collecting a liquid sample instead of a sample collected by means of a swab.
  • the third container can be a separate sample container 170 that is used for taking a sample for instance by way of gargling or mouthwash.
  • the sample container can be connected to a lysis container 12 vii and a test container 14 vii .
  • the lysis container 12 vll and the test container 14 vii can be configured as disclosed herein above.
  • a combination of a lysis container and a test container is called reaction containers hereinafter.
  • the reaction containers, i.e. the test container 14 vii and the lysis container 12 vii can form a single unitary unit while the sample container can be a separate component that can be attached to the reaction containers.
  • the sample container 170 comprises a sample chamber 172 that can be closed by a sample container lid 174.
  • the sample chamber can be initially empty or it may contain a liquid such as pure water, a solution containing H 2 O 2 or the like that can be used for gargling or mouth washing.
  • the sample container 170 is used for sampling while lysing and the test reaction, for instance the amplification, is performed in the reaction containers, i.e. the lysis container 12 vii and the test container 14 vii , respectively.
  • the correct dosing of the sample liquid is done through and during the connection of the two separate parts.
  • the containers can be connected, for example, by plugging them together or by a rotary movement, e.g. screwing, or a combination of both, for instance by way of a bayonet connection.
  • the containers are designed so that the movement for connecting the containers (plugging, screwing etc.) trigger a transfer of a defined amount of sample liquid to the reaction containers, thus triggering the detection reaction.
  • sample liquid is transferred from the sample container 170 into the lysis chamber in the lysis container 14 vii .
  • liquid is further transferred to the test chamber of test container 14 vii .
  • the amount of liquid transferred into the test chamber preferably is less than 100 ⁇ l, more preferred less than 50 ⁇ l. The amount depends and is adapted to the respective test.
  • the sample container contains the liquid for sampling.
  • a test person can take the liquid up for rinsing the mouth. Thereafter, the liquid comprising the sample is put back into the sample container. Then, the sample container is closed and can be connected with the reaction containers 12 vii and 14 vii .
  • the sample liquid initially contained in the sample chamber is such that it can be spat into the mouth of test persons without danger and that it can collect the sample obtained by mouthwash.
  • the sample liquid contained in the sample container can be a liquid that can lyse the viruses or bacteria so that a separate lysis step is no longer necessary.
  • This could typically be realized by an oxidation reaction, e.g. by a 1-3% H 2 O 2 solution. In such embodiment, no separate lysing chamber is needed.
  • no liquid is kept in the sample container for sampling, the test person rinses his mouth with cold tap water and spits this rinsing liquid into the sample container.
  • the sample container also contains another liquid for the lysis of the sample. The two liquids are only brought together after the sampling has taken place, i.e. the test person has spit the rinsing liquid into the sample container.
  • separate compartments are provided in the sample container to separate the lysing liquid from the sample liquid before mixing. By means of a mechanical, thermal or chemical process the two liquids can be treated in such a way that the liquids mix homogeneously after collecting the sample has occurred.
  • the sample container and the reaction containers are connected to each other by plugging or twisting, e.g. by a bayonet fastener 176 as shown in figure 15a ).
  • the arrangement of the lysis chamber and the sample container can be designed such that the sample container and lysis chamber are arranged on top of each other, as shown in figure 14 .
  • the containers are designed to be arranged side by side.
  • already lysed sample can be added to the sample container, thus avoiding a separated lysing step.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
EP20206554.6A 2020-04-07 2020-11-09 Satz von kammern mit reagenzien Pending EP3995208A1 (de)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP20206554.6A EP3995208A1 (de) 2020-11-09 2020-11-09 Satz von kammern mit reagenzien
PCT/EP2021/059106 WO2021204901A1 (en) 2020-04-07 2021-04-07 Set of chambers containing reagents
US17/995,735 US20230158492A1 (en) 2020-04-07 2021-04-07 Set of chambers containing reagents
EP21715936.7A EP4132702A1 (de) 2020-04-07 2021-04-07 Satz von kammern mit reagenzien

Applications Claiming Priority (1)

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EP20206554.6A EP3995208A1 (de) 2020-11-09 2020-11-09 Satz von kammern mit reagenzien

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000065022A1 (fr) * 1999-04-22 2000-11-02 Kikkoman Corporation Instrument pour tester un echantillon et instrument pour epreuve de contamination par frottis
WO2014072170A1 (de) * 2012-11-06 2014-05-15 Gerhard Bonecker Testset für eine photometrische messeinrichtung und photometrisches messverfahren für eine probenflüssigkeit
WO2019060950A1 (en) * 2017-09-27 2019-04-04 Axxin Pty Ltd SYSTEM AND METHOD FOR DIAGNOSTIC TESTING

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000065022A1 (fr) * 1999-04-22 2000-11-02 Kikkoman Corporation Instrument pour tester un echantillon et instrument pour epreuve de contamination par frottis
WO2014072170A1 (de) * 2012-11-06 2014-05-15 Gerhard Bonecker Testset für eine photometrische messeinrichtung und photometrisches messverfahren für eine probenflüssigkeit
WO2019060950A1 (en) * 2017-09-27 2019-04-04 Axxin Pty Ltd SYSTEM AND METHOD FOR DIAGNOSTIC TESTING

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