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WO2025003087A1 - Appareil de mesure d'une quantité d'analyte dans un échantillon biologique - Google Patents

Appareil de mesure d'une quantité d'analyte dans un échantillon biologique Download PDF

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Publication number
WO2025003087A1
WO2025003087A1 PCT/EP2024/067713 EP2024067713W WO2025003087A1 WO 2025003087 A1 WO2025003087 A1 WO 2025003087A1 EP 2024067713 W EP2024067713 W EP 2024067713W WO 2025003087 A1 WO2025003087 A1 WO 2025003087A1
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WO
WIPO (PCT)
Prior art keywords
sample cup
wash
sample
conduit
dispensing
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
PCT/EP2024/067713
Other languages
English (en)
Inventor
Birgitte Høiriis KAAE
Jonas ROHDE
Carl Peder Troldborg
Ole Kudsk HANSEN
Steffen Michael COLDING-JØRGENSEN
Allan Milton Byrnard
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.)
Radiometer Medical ApS
Original Assignee
Radiometer Medical ApS
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 Radiometer Medical ApS filed Critical Radiometer Medical ApS
Publication of WO2025003087A1 publication Critical patent/WO2025003087A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/34—Purifying; Cleaning
    • 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
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B01L3/527—Containers specially adapted for storing or dispensing a reagent for a plurality of reagents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • 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
    • B01L2200/0689—Sealing
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/10—Means to control humidity and/or other gases
    • B01L2300/105—Means to control humidity and/or other gases using desiccants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0437—Cleaning cuvettes or reaction vessels

Definitions

  • the present invention relates to various aspects of an apparatus for measuring an amount of analyte in a biological sample.
  • various aspects disclosed herein relate to such an apparatus, to a wash unit for such an apparatus and to a method for washing a sample cup of such an apparatus.
  • Apparatus for measuring amounts of analytes in biological samples, in particular in blood samples, by means of respective detectors or sensors are widely used in the medical and clinical field.
  • Such apparatus are often simply referred to as analyzer units or simply analyzers.
  • constraints include a need for low operating costs, low down times, ease of use, efficiency of use, in particular reduced need for sample preparation, etc.
  • a blood sample to be analyzed is dispensed in a sample cup that includes one or more binding partners of the analyte which is desired to be detected, so that the analytes present in the blood sample are allowed to interact with the binding partners included in the cup.
  • Some analyzer units may be operable to analyze blood samples for a variety of analytes. To this end, the analyzer unit may perform a variety of assays targeted at respective analytes. The different assays may thus involve different binding partners.
  • US 10,132,800 discloses a method for measuring an analyte amount in a whole-blood sample. This prior art method includes pouring a blood sample into a well.
  • the surface of the well is coated with a layer of a first binding partner of the analyte which is desired to be detected, so that the analytes present in the blood sample conjugate with the first binding partners fixed to the well wall.
  • the process further comprises a washing of the well to remove the elements of no interest for the ongoing analysis, for example, antibodies and antigens which are not searched for.
  • elements of no interest are generally material that has not interacted with, and is not bound to, the first binding partner.
  • blood samples may include blood clots and it is desirable to provide a washing process and a washing device that allows such blood clots to be reliably and efficiently removed from the sample cup.
  • an apparatus for measuring an amount of analyte in a biological sample when the biological sample is present inside an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to interact with, in particular bind to, the one or more binding partners.
  • the apparatus comprises a wash unit for washing the sample cup, in particular to remove elements of no interest for the ongoing analysis from the sample cup.
  • the wash unit comprises: a wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup to an operational position of the dispensing conduit for dispensing a wash buffer into the sample cup, a suction conduit having a distal open inlet end configured to be lowered into the sample cup to an operational position of the suction conduit for sucking material from at least a bottom portion of the sample cup out of the sample cup.
  • the wash buffer dispensing conduit is separate from the conduit through which waste material is sucked out of the sample cup, thereby reducing the risk of contamination between samples.
  • the provision of separate dispensing and suction conduits also facilitates suction and dispensing to be performed concurrently. Dispensing wash buffer into the sample cup and sucking material from at least a bottom portion of the sample cup out of the sample cup effectively removes the part of the biological sample that has not interacted with the one or more binding partners and, in particular, is not bound to the one or more binding partners as a result of said interaction. Removal of this part of the biological sample is desired as the unbound part of the biological sample is of no interest for the analysis.
  • the apparatus comprises a drive unit and is configured to control the drive unit to selectively lower the dispensing conduit and the suction conduit into the sample cup, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, in particular from a periphery of the bottom.
  • the apparatus is configured to control the drive unit, at least during a part of a wash operation, to cause a reciprocating movement of the suction conduit between at least a lower operational position and an elevated operational position of said suction conduit.
  • the reciprocating movement includes a downward movement towards the lower operational position and an upward movement towards the elevated operational position.
  • the upward movement may be followed by the downward movement or vice versa.
  • the apparatus may apply suction to the suction conduit during at least a part of said reciprocating movement.
  • the apparatus may further be configured to control the drive unit, at least during a part of a wash operation, to cause a reciprocating movement of the dispensing conduit between at least a lower operational position and an elevated operational position of said dispensing conduit.
  • the difference in elevation between the lower and elevated operational positions of the wash buffer dispensing conduit may be the same as, or different from, the corresponding difference in elevation between the lower and elevated operational positions of the suction conduit.
  • the apparatus may dispense wash buffer through the dispensing conduit during at least a part of said reciprocating movement of the suction conduit and/or of the wash buffer dispensing conduit.
  • the apparatus may be configured to dispense wash buffer before and/or during the reciprocating movement, in particular a sufficient amount of wash buffer to ensure that the distal open inlet end of the suction conduit is, at least at its lower operational position, immersed in the dispensed wash buffer present in the sample cup.
  • the inventors have realized that at least some forms of waste material, in particular blood clots, non-liquid waste material, or the like, can more efficiently be removed from the sample cup when the suction conduit and, optionally, the dispensing conduit repeatedly performs a reciprocating movement with the open inlet end of the suction conduit being immersed in the wash buffer during at least a part of the reciprocating movement.
  • the application of suction to the suction conduit during at least a portion of said reciprocating movement of the suction conduit has been found to be particularly effective.
  • the reciprocating movement is performed repeatedly, i.e. the reciprocating movement is repeated a number of times, such as 2, 3, 4, 5 or even more times.
  • the reciprocating movement refers to a relative movement of the respective conduits relative to the sample cup.
  • the drive unit may cause the reciprocating movement by actuating the respective conduits and/or by actuating the sample cup.
  • the apparatus is configured, at least during a part of the wash operation, to repeatedly perform a pulsed wash operation, the pulsed wash operation comprising: dispensing a predetermined amount of wash buffer into the sample cup at a predetermined dispense rate;
  • the apparatus is configured to intermittently or continuously apply suction during a part of or during the entire pulsed wash operation so as to to remove wash buffer from the sample cup at a predetermined removal rate, in particular at a removal rate no smaller than the dispense rate.
  • repeatedly performing the pulsed wash operation comprises performing the pulsed wash operation at least 5 times, such as at least 10 times, such as at least 15 times, such as between 5 times and 20 times.
  • the repetitions of the pusled wash operation may be separated by a suitable waiting time between consecutive bursts, e.g. waiting times between 50 ms and 500 ms, e.g. between 100 ms and 400 ms, or by another suitable waiting time.
  • the dispense rate is between 100 pL/s and 500 pL/s, such as between 200 pL/s and 400 pL/s, such as between 250 pL/s and 350 pL/s.
  • the removal rate may be between 100 pL/s and 500 pL/s, such as between 200 pL/s and 400 pL/s, such as between 250 pL/s and 350 pL/s.
  • the predetermined amount of wash buffer dispensed as part of the pulsed wash operation may be between 50 pL and 200 pL, such as between 75 pL and 150 pL.
  • the apparatus is configured, prior to initiating the repeated performance of the pulsed wash operation, to dispense a predetermined amount of wash buffer into the sample cup.
  • the apparatus is configured to select one of a plurality of wash programs in dependence of a type of assay being performed, in particular in dependence of the binding partner included in the sample cup to be washed and/or in dependence of a type of analyte to be detected in the biological sample, and to control operation of the wash unit based on the selected wash program. Accordingly, reliable washing results may be achieved for a variety of assay types while avoiding unnecessarily long washing cycles and/or excess use of wash buffer. For example, some test assays may require a longer wash process than others, a stronger flushing of the sample cup and/or require other assay-specific modifications of the wash process.
  • the plurality of wash programs may include a wash program that comprises a pulsed wash cycle comprising repeatedly performing a pulsed wash operation as disclosed herein.
  • the plurality of wash programs may include a wash program, in particular a blood clot removal program, that comprises repeatedly performing a reciprocating movement of the suction conduit as described herein.
  • the apparatus comprises a data storage device having stored thereon a plurality of predetermined wash programs, each associated with one or more identifiers indicative of respective types of binding partners and/or indicative of respective analytes. Accordingly, an efficient mechanism for selecting assay-specific, in particular analyte-specific and/or binding-partner-specific wash programs is provided.
  • the wash programs may be stored in a configuration file, as part of the apparatus firmware and/or in another suitable manner. Accordingly, wash programs may be changed and new wash programs, e.g. for new assay types, may conveniently be added, thereby allowing convenient configuration of the wash process.
  • the apparatus is configured to control the wash unit to perform one or more wash cycles, e.g. a sequence of two or more wash cycles.
  • Each wash cycle may comprise pumping a wash buffer into the sample cup, sucking material out of the sample cup.
  • the number of wash cycles to be performed and/or the process parameters of each wash cycle may be defined by the respective wash programs. Accordingly, different wash programs may differ from each other in the number of wash cycles to be performed, the order in which they are performed and/or the process parameters of the individual wash cycles.
  • the plurality of wash programs includes a first wash program and a second wash program, wherein the second wash program differs from the first wash program in at least one process parameter of at least one wash cycle, the at least one process parameter being selected from: a pump rate at which wash buffer is pumped into the sample cup during said wash cycle, an amount of wash buffer pumped into the sample cup during said wash cycle, a pump duration during which wash buffer is pumped into the sample cup during said wash cycle, an amount of waste material sucked out of the sample cup, a suction rate, a suction duration, and a number of repetitions of said wash cycle.
  • the suction conduit comprises a proximal portion and an inclined distal portion, the inclined distal portion being inclined relative to the proximal portion and comprising said distal open inlet end.
  • the proximal portion may be an upper portion and the inclined distal portion may be a lower portion of the suction conduit.
  • the inclined distal portion may extend downward and radially outward from a distal end of the proximal portion. Accordingly, the inclined distal portion with the distal open inlet end may be directed radially away from the downwardly oriented proximal portion and towards a periphery of the sample cup, thereby facilitating an efficient cleaning and a complete removal of unwanted material from the cup.
  • the inclined distal portion may define an angle of inclination relative to the proximal portion between 40° and 50°.
  • the inclined portion may comprise a curved portion, e.g. defining a bend radius of between 3 mm and 4 mm.
  • the inclined portion may have a downward extent, defined along a longitudinal direction of the proximal portion, of between 2 mm and 3 mm.
  • the apparatus is configured to control the drive unit to selectively lower the dispensing conduit into the sample cup to an operational position, in particular to the lower operational position, of the dispensing conduit with the outlet end positioned at a dispensing height above the bottom of the sample cup, and to selectively lower the suction conduit into the sample cup to an operational position, in particular to the lower operational position, of the suction conduit, at the bottom of the sample cup or at a suction height above the bottom.
  • the drive unit may be configured to lower the suction conduit and the dispensing conduit individually, e.g. one after the other or partly or completely concurrently.
  • the suction conduit and the dispensing conduit may be mounted to respective movable wash heads, and the drive unit may be configured to selectively lower one or both of the wash heads with the suction and dispensing conduits mounted thereto, respectively.
  • the wash heads may be arranged adjacent to each other so as to allow them to be individually moved upwards and downward, or otherwise.
  • the drive unit may be configured to lower the suction conduit and the dispensing conduit together.
  • the suction conduit and the dispensing conduit may both be mounted to a single movable wash head or to separate wash heads, and the drive unit may be configured to selectively lower the wash head(s) with the suction and dispensing conduits mounted thereto.
  • the lowering of the dispensing conduit and/or the suction conduit refers to a relative movement of the respective conduits relative to the sample cup.
  • the drive unit may cause the lowering by actuating the respective conduits or by actuating the sample cup.
  • the open inlet end of the suction conduit may, when the suction conduit is at its elevated operational position of the reciprocating movement, also be immersed into the dispensed wash buffer present in the sample cup, i.e. the open inlet end may be immersed in the dispensed wash buffer during the entire reciprocating movement, e.g. during all repeated reciprocating movements.
  • the open inlet end of the suction conduit may, when the suction conduit is at its elevated operation position of the reciprocating movement, be located above an upper surface of the dispensed wash buffer present in the sample cup, i.e. the open inlet end may dip into the wash buffer during the downward movement of the reciprocating movement and/or be moved out of the wash buffer during the upward movement of the reciprocating movement.
  • the open inlet end may be immersed in the dispensed wash buffer during some repetitions of the reciprocating movement, and dipped into and/or withdrawn from the wash buffer during other repetitions of the reciprocating movement.
  • the lower and/or elevated operational positions may be the same for all repetitions of the reciprocating movement. In some embodiments, the lower and/or elevated operational positions may be different for some or all repetitions of the reciprocating movement.
  • the proximal portion of the suction conduit when the dispensing conduit and the suction conduit are in their respective operational positions, the proximal portion of the suction conduit extends downwardly into the sample cup, adjacent to the dispensing conduit, the inclined distal portion extends radially outward from the proximal portion and away from the outlet end of the dispensing conduit, in particular such that the open inlet end is positioned at or above a peripheral portion of the bottom of the sample cup. Accordingly, the suction conduit may efficiently withdraw unwanted material from the periphery of the sample cup.
  • the apparatus may be configured to cause relative rotation of the sample cup relative to the wash unit or otherwise cause the open inlet end to be directed towards different parts of the periphery of the bottom of the sample cup.
  • the apparatus may cause the bottom of the sample cup to be downwards inclined towards the radial direction along which the inclined portion of the suction conduit projects towards the periphery of the sample cup, thereby causing remaining unwanted material to accumulate at the periphery of the sample cup close to the open inlet end of the suction conduit.
  • the apparatus is configured to bring the suction conduit and the sample cup into a tilted orientation relative to each other, when the distal open inlet end of the suction conduit has been lowered into the sample cup, such that a radial distance between the distal open end and a periphery of a bottom of the sample cup is reduced.
  • the distal open inlet end of the suction conduit is positioned closer to the bottom of the sample cup than the distal open outlet end of the dispensing conduit, i.e. such that the dispensing height is larger than the suction height, thereby facilitating an efficient rinsing and removal of undesired waste material.
  • the dispensing conduit and the suction conduit each have multiple respective operational positions, e.g. including respective lower and upper operational positions, at which they dispense wash buffer and withdraw material, respectively.
  • the distal open inlet end of the suction conduit may be positioned closer to the bottom of the sample cup than the distal open outlet end of the dispensing conduit in some or even all of said operational positions, in particular when both conduits are in their respective upper operational positions and/or when both conduits are in their respective lower operational positions.
  • the suction height i.e. the distance between the distal open inlet end and the bottom of the sample cup, is between 0 mm and 1 mm. Accordingly, the distal open inlet end may touch or be positioned immediately above the bottom of the sample cup, in some embodiments without touching the bottom of the sample cup.
  • the suction height may be defined by a vertical distance between the bottom of the sample cup and a bottommost point of an edge of the distal open inlet end.
  • the suction height when the suction conduit is at its upper operational position, the suction height is between 3 mm and 5 mm.
  • the dispensing height i.e. a distance between the distal open outlet end and the bottom of the sample cup may between 1 mm and 9 mm, such as between 1.5 and 8.5 mm. Accordingly, an efficient rinsing of the sample cup may be achieved.
  • the dispensing height may be defined by a vertical distance between the bottom of the sample cup and a bottommost point of an edge of the distal open inlet end.
  • the suction may be applied to the suction conduit in a number of ways.
  • the wash unit comprises a pump unit configured to selectively apply suction to the suction conduit to remove material from the sample cup and configured to selectively pump wash buffer through the dispending conduit into the sample cup.
  • the apparatus may be connectable to an external pump or other source of vacuum/suction.
  • the apparatus is configured to apply suction to the suction conduit during at least a part of a downward movement of the suction conduit into the sample cup to the operational position of the suction conduit, thereby providing a particularly efficient removal of undesired waste material.
  • the wash buffer dispensing conduit defines an elongated channel having an inside diameter between 0.1 mm and 1 mm.
  • the suction conduit defines an elongated channel having an inside diameter between 0.9 mm and 1.5 mm.
  • the dispensing conduit defines an elongated channel having a inside diameter and wherein the distal outlet end has an outlet opening having an outlet diameter smaller than the inside diameter.
  • Embodiments of the apparatus with the above geometry of the dispensing and/or suction conduits have been found to provide particularly efficient removal of waste material.
  • the apparatus may include a pump unit configured to pump wash buffer through the dispensing conduit so as to dispense wash buffer, in particular to dispense wash buffer at a predetermined dispensing rate.
  • the wash unit comprises a wash head movably arranged relative to the sample cup, wherein the dispensing conduit and the suction conduit are mounted to the wash head and extend downward from the wash head, thereby facilitating coordinated movement of the conduits.
  • the dispensing conduit and the suction conduit may be formed as respective tubes made from a suitable material, such as metal, in particular stainless steel.
  • the apparatus is configured to perform a wash operation of the sample cup after the biological sample has been added to the sample cup and before a measurement of an amount of analyte that has interacted with, in particular been bound to, the one or more binding partners.
  • the biological sample may be a blood sample, in particular a whole-blood sample.
  • the analyte is an antigen.
  • the one or more binding partners may include an immobilized binding partner, which is immobilized in the sample cup such that it is not removed from the sample cup during the wash process.
  • the immobilized binding partner may be immobilized in a variety of ways, e.g. as described below in the context of capture antibodies.
  • the one or more binding partners may further include one or more additional binding partners, e.g. a tracer binding partner that is capable of interacting with the analyte.
  • the analyte and, optionally, the one or more additional binding partners may be captured by the immobilized binding partner, such that the captured analyte, and optionally the captured tracer binding partner, remain in the sample cup after the wash process and can subsequently be detected.
  • the one or more binding partners may be selected from antibodies, e.g. a set of one or more capture antibodies capable of interacting with the analyte and one or more tracer antibodies for interacting with the analyte.
  • the term “capture antibody” means an antibody that is immobilized, e.g. on the inner surface of the sample cup, and that “captures” an analyte that is thereby also immobilized/bound in the sample cup, e.g. to the inner surface of the sample cup.
  • the capture antibody is immobilized to a solid surface of, e.g., water insoluble particles (like polymer beads), glass beads, gold particles, and magnetic particles (e.g. polymer beads having a magnetic core or having magnetic particles dispersed therein), i.e. a solid phase that will not be removed from the cup upon washing.
  • the capture antibody is directed against the analyte of interest as the antigen.
  • the capture antibody may be immobilized to the surface of the measuring cell covalently or non-covalently.
  • the immobilization relies on the interaction between biotin and streptavidin.
  • the capture antibody may be biotinylated and the inner surface of the measuring cell may be coated with covalently bound streptavidin.
  • the capture antibody is then immobilized on the inner surface of the sample cup through the interaction between biotin and streptavidin.
  • the interaction between biotin and streptavidin is so strong that it is essentially irreversible.
  • other immobilization methods are equally suitable to immobilize the capture antibody.
  • the capture antibody is however not removed or substantially removed from the inner surface of the sample cup during the washing, incubation and drying steps of an immunoassay.
  • the term “tracer antibody” refers to an antibody that is labelled with a detection label.
  • the tracer antibody is directed against the analyte or complex of analyte and capture antibody.
  • the label may then subsequently e.g. provide a detectable signal using an appropriate sensor, e.g. a colorimetric signal or a fluorescence signal.
  • the label may be attached covalently or non-covalently to the tracer antibody.
  • labels attached to the antibody include, but are not limited to, fluorescent tags such as green fluorescent protein or variants thereof, enzymatic tags such as galactosidase that catalyses a colorimetric reaction, radioactive isotopes, small molecule fluorescent or phosphorescent dyes, other small moleculecolored dyes, nanoparticles and the like.
  • labels in particular include, but are not limited to, lanthanide chelate labels e.g. as described in in EP 0 892 927 B1 or US 9,944,657.
  • the tracer antibody binds to the analyte forming a ternary complex between the analyte, tracer antibody and capture antibody (see Figure 1).
  • antibody when used herein in the context of the terms “capture antibody” and “tracer antibody” is used in the conventional sense within the field of immunoassays, i.e. , for example to encompass monoclonal antibodies, polyclonal antibodies as well those fragments of antibodies that binds to a relevant epitope of the analyte (e.g. antigen), etc. Further, antibodies (or fragments thereof) may be produced in e.g. animals or in cell lines, including utilizing recombinant techniques and synthetic or semi-synthetic methodologies.
  • one, two or several or all binding partners are aptamers, like capture “capture aptamer(s)” and/or “tracer aptamer(s)”, respectively.
  • Aptamers are single stranded DNA or RNA, or synthetic version hereof (XNA, like e.g. LNA) or hybrids thereof, e.g. selected from large random sequence pools.
  • XNA synthetic version hereof
  • antibodies as well as aptamers can be chosen such as to be able to bind to a specific analyte (target molecule).
  • the present disclosure relates to different aspects including the apparatus described above and in the following, corresponding systems, methods, apparatus, and/or products, each yielding one or more of the benefits and advantages described in connection with one or more of the other aspects, and each having one or more embodiments corresponding to the embodiments described in connection with one or more of the other aspects and/or disclosed in the appended claims.
  • a wash unit for an apparatus for measuring an amount of analyte in a biological sample, when the the biological sample is present inside an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to bind to the one or more binding partners, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, wherein the wash unit comprises: a wash head, a wash buffer dispensing conduit extending from the wash head, the wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup for dispensing a wash buffer into the sample cup; and a suction conduit extending from the wash head and having a having a distal open inlet end configured to be lowered into the sample cup for sucking material from at least a bottom portion of the sample cup out of the sample cup; wherein the suction conduit comprises a proximal portion, proxi
  • the dispensing conduit extends from the wash head parallel to the proximal portion of the suction conduit.
  • the dispensing conduit has a length between the wash head and the distal open outlet end equal to or larger than a length of the proximal portion between the wash head and the distal end of the proximal portion.
  • the wash end may define a height reference from which the respective lengths are defined.
  • the height reference may be defined by the point at which the suction conduit projects out of the wash head.
  • the antibody sandwich complex is sensitive to temperature during the washing step when washing excess tracer antibodies away from the cup. In these cases, depending on the temperature, the antibodies may dissociate and result in the antibody being washed away. This effect of temperature dependency can be removed or sufficiently removed for the application of the assay.
  • control of various embodiments of the apparatus disclosed herein and, in particular, of the wash unit and/or of the drive unit, and/or of a pump or other mechanism for dispensing wash buffer and/or for applying suction may be performed by a suitable control circuit.
  • the apparatus may include a control circuit configured to control various operations of the apparatus and, in particular, operation of the wash unit and/or of the drive unit and/or of a pump or other mechanism for dispensing wash buffer and/or for applying suction may be performed by a suitable control circuit.
  • the control circuit may be implemented as a suitably programmed CPU, microprocessor and/or the like, and/or as an ASIC or other suitable processing circuitry, or as a combination thereof.
  • the control circuit may be implemented as a single control unit or as multiple control units, e.g. nultiple programmed processors.
  • the apparatus may further include, or be operationally connectable to, one or more pumps and/or other device(s) for applying suction and/or for dispensing wash buffer.
  • the apparatus disclosed herein is operable to measure an amount of analyte in a biological sample that is present inside an upwardly open sample cup.
  • the biological sample may be provided inside the sample cup in any suitable manner, e.g. by pouring, pumping, or otherwise dispensing the biological sample into the sample cup.
  • the apparatus may comprise a sample handling system for dispensing the biological sample into the sample cup.
  • the sample handling system may receive a biological sample to be analysed and to dispense the received biological sample into the sample cup.
  • Suitable sample handling systems for biological samples, in particular for blood samples are well known as such in the art of analyzer units and will not be described in detail herein.
  • Another aspect disclosed herein relates to a method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, wherein the method comprises: dispensing the biological sample into the sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the blood sample is allowed to bind to the one or more binding partners, selecting one of a plurality of wash programs in dependence of a type of binding partner included in the sample cup to be washed and/or in dependence of a type of analyte to be detected in the biological sample, performing one or more washing cycles according to the selected wash program.
  • Yet another aspect disclosed herein relates to a method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, wherein the method comprises:
  • a suction conduit into the sample cup, the suction conduit having a distal open inlet end for sucking material from at least a bottom portion of the sample cup out of the sample cup;
  • FIG. 1 schematically illustrates an example of an analyzer unit.
  • FIG. 2A schematically illustrates an exploded view of an example of an assay cartridge for use with an embodiment of an analyser unit.
  • FIG. 2B schematically illustrates an example of a sample cup.
  • FIG. 3 shows a schematic block diagram of a portion of an embodiment of an analyser unit.
  • FIG. 4 shows a schematic sectional view of an embodiment of a wash unit of an analyser unit.
  • FIG. 5 shows an enlarged sectional view of an example of a wash head with a dispensing conduit and a suction conduit.
  • FIGs. 6A-C schematically illustrate different operational positions of the wash unit described in connection with FIGs. 4 and 5.
  • FIG. 7 shows a flow diagram of an example of a measurement process performed by an embodiment of an analyser unit.
  • FIG. 8 shows a flow diagram of an example of a wash process performed by an embodiment of an analyser unit.
  • FIG. 9 shows a flow diagram of an example of an assay-specific wash process performed by an embodiment of an analyser unit.
  • FIG. 1 schematically illustrates an example of an analyzer unit, generally designated 100.
  • the analyzer unit 100 comprises a control unit 110, an analyte sensor 130, a wash unit 120, an assay cartridge 140, a cup holder 180, a fluid handling system, a drive unit 160 and a waste collection container 173.
  • the analyzer unit may include one or more additional components which are not explicitly shown in FIG. 1 and which are known per se in the art of analyzer units.
  • additional components include a sample inlet for receiving a blood sample, a sample handling system for dispensing the received blood sample into a sample cup for presenting the received blood sample to the analyte sensor, further components for transporting one or more buffer solutions and/or for transporting and storing waste material, etc.
  • the analyzer unit may further comprise a suitable user interface allowing a user to interact with the analyzer unit.
  • the user interface may include a display for displaying measurement results.
  • the analyte sensor 130 may employ a suitable measurement methodology for measuring the concentration of one or more analytes in a whole-blood sample.
  • the analyte sensor may be configured to measure concentration of an analyte by use of an immunoassay as is known as such in the art.
  • the analyte sensor may be a cartridge-based sensor and the analyzer may be configured to receive an assay cartridge 140.
  • the cartridge may comprise a plurality of sample cups 141.
  • the apparatus may remove a sample cup 141 from the cartridge and place it in a cup holder 180.
  • the analyte sensor 130 may perform the desired analysis and the used sample cup may be deposited in a waste collection container 173.
  • the assays are based on a drychemistry concept and on a suitable detection method, e.g. based on non-enhanced time-resolved fluorescence (TRF) technology.
  • TRF time-resolved fluorescence
  • dry-chemistry means that the required assay-specific reagents, e.g. including tracer antibody, capture antibody and stabilizing reagents, are dry-coated into one or more assay-specific sample cups 141 of the assay cartridge 140.
  • the sample cups 141 may be prepacked into sealed cartridges 140, each cartridge containing a plurality of sample cups, e.g. 16 sample cups or another suitable number of sample cups.
  • the cartridge may further include a desiccant in a pouch to control humidity.
  • Each sample cup may be individually sealed in a separate chamber to improve shelf life.
  • the cartridge may thus be a replaceable consumable of the analyzer unit.
  • An example of an assay cartridge is shown in FIG. 2A.
  • a reagent buffer in particular a liquid reagent buffer, is used to carry out an analysis, in particular a liquid reagent buffer, which may be the same for all tests/assays.
  • a wash buffer in particular a liquid wash buffer, for washing the sample cup during the analysis process may be needed.
  • the analyzer unit may include an onboard solution pack, which may be a closed system containing one or more buffer solutions in a bag and which also has receptacles for waste collection, both waste sample cups and liquid waste. This means a user does not need to come into direct contact with the sample or any used reagents.
  • the analyte sensor 100 may be configured to analyze a blood sample.
  • the blood sample can be either whole blood or plasma.
  • the analyzer unit During normal use of the analyzer unit, e.g. during clinical use, it is often preferred to perform the measurements directly on whole-blood samples so as to reduce the time and effort needed for sample preparation prior to the measurement.
  • the sample may be received by the analyzer unit in a sample tube, in particular a closed sample tube.
  • the analyzer unit 100 may perform aspiration from the closed sample tube automatically.
  • the analyzer unit may obtain a small amount of sample and add the obtained sample to the sample cup 141 for analysis.
  • the analyzer unit may initially remove a sample cup from the cartridge 140 and position it into a suitable cup holder 180.
  • the analyzer unit may otherwise bring a fresh sample cup into an operational position relative to the analyte sensor 130.
  • An example of the measurement process will be described with reference to FIG. 7 below.
  • the wash unit 120 may be configured to dispense wash buffer into the sample cup and to suck waste material out of the sample cup. Embodiments of the wash unit 120 will be described in greater detail below.
  • the apparatus further comprises a fluid handling system 150, which may comprise one or more pumps for supplying wash buffer to the wash unit 120 and for withdrawing waste material from the sample cup 141 by means of the wash unit 120.
  • the apparatus further comprises a drive unit 160, e.g. a motor, such as a servo motor, or another suitable actuator for causing movement of the wash unit so as to bring the wash unit into an operational position relative a sample cup.
  • the control unit 110 may include a suitable programmed CPU 111 and a data storage device 112.
  • the control unit 110 is configured for executing program code 113 to control operation of the analyzer unit.
  • the data storage device 112 may be a hard drive, an EEPROM, a solid-state drive, or another suitable data storage device.
  • the data storage device may have stored thereon the program code 113.
  • the control unit 110 may thus load the program code 113 from the data storage device 112 into the CPU 111 which may execute the loaded program code.
  • the program code 113 is configured to cause the control unit 110, responsive to the obtained measurement values from the analyte sensor, to process the measurement values and present the processed measurement results to the user, e.g. via a suitable display or in another form, and/or to communicate the processed measurement results to a remote data processing system.
  • the processing of the measurement values comprises the computation of an analyte concentration based on a measurement performed on a whole-blood sample.
  • FIG. 2B schematically illustrates an example of a sample cup 141.
  • the sample cup 141 is an upwardly open vessel shaped and sized to accommodate a sample, in particular a blood sample.
  • the sample cup has a bottom 1411 and a circumferential side wall 1412 upwardly extending from a periphery of the bottom.
  • the bottom and/or sidewall such as a lower portion of the sidewall, may be coated, such as dry-coated, or otherwise prepared with one or more binding partners configured to react with one or more analytes present in a sample to be analyzed, when the sample is added to the sample cup.
  • the material resulting from the reaction may be immobilized at the bottom and/or sidewall of the sample cup, where they may be detected by a suitable detection technique, such as based on electrical, optical or other suitable measurement technique.
  • a suitable detection technique such as based on electrical, optical or other suitable measurement technique.
  • any unbound material and/or other waste material that might otherwise interfere with the measurement process may need to be removed.
  • the sample cup may be washed after the sample has been allowed to react with the binding partners in the sample cup.
  • the analysis is based on immunoassays.
  • the immunoassays may be based on a dry-chemistry concept and a detection method based on nonenhanced time-resolved fluorescence (TRF) technology.
  • TRF time-resolved fluorescence
  • dry-chemistry means that the required assay-specific reagents, e.g. including tracer antibody, capture antibody and stabilizing reagents, are dry-coated into one or more assay-specific sample cups 141.
  • each sample cup is coated with streptavidin 1413.
  • Biotinylated capture antibodies 1414 may be immobilized at the cup surface through the binding between streptavidin and biotin.
  • FIG. 3 shows a schematic block diagram of a portion of an embodiment of an analyser unit, e.g. of the analyser unit shown in FIG. 1 .
  • the apparatus comprises a wash unit 120, a fluid handling system 150 and a drive unit 160, e.g. as described in connection with FIG. 1.
  • the drive unit 160 may be configured to cause a linear movement of the wash unit 120 relative to the sample cup 141 to be washed, selectively towards and away from a sample cup 141 , in particular a downward and upward movement. It will be appreciated that the drive unit may cause the movement of the wash unit by moving the wash unit and/or by moving the cup holder and/or by otherwise causing a relative movement between the wash unit and the sample cup.
  • the fluid handling system 150 is fluidly connected via suitable fluid supply lines to a wash buffer supply container 171 and to the wash unit 120, and the fluid handling system 150 comprises a supply pump 151 for pumping wash buffer from the wash buffer supply container 171 to the wash unit 120. Similarly, the fluid handling system 150 is fluidly connected via suitable waste fluid lines to a waste collection container 172 and to the wash unit 120.
  • the fluid handling system 150 comprises a waste pump 152 for applying suction to the wash unit 120 for withdrawing waste material from the sample cup 141 , and for pumping the withdrawn waste material into the waste collection container 172.
  • the wash buffer supply container 171 and the waste collection container 172 may be provided as replaceable components of the analyser unit, either as separate replaceable components or, as illustrated in FIG. 3, as a single replaceable solution pack 170. It will be appreciated that various embodiments of the fluid handling system may include additional or alternative components, e.g. fewer or more pumps, one or more valves, one or more sensors and/or other components.
  • FIG. 4 shows a schematic sectional view of an embodiment of a wash unit 120 of an analyser unit, e.g. of the analyser unit shown in FIG. 1.
  • the wash unit 120 is shown in an operational position relative to a sample cup 141 , which is placed in a cup holder 180.
  • the sample cup 141 has a bottom 1411 and a circumferential side wall 1412 upwardly extending from a periphery of the bottom 1411, thus defining an upwardly open well.
  • the wash unit 120 comprises a housing 122 and a wash head 121 mounted in the housing 122.
  • the wash head 121 may be mounted movably inside the housing 122, in particular spring-loaded by spring 123 against a lower seat portion 1221 of the housing 122.
  • the wash head 121 may comprise a temperature sensor 126 configured to measure the wash buffer temperature.
  • the wash unit 120 further comprises a wash buffer dispensing conduit 124 and a suction conduit 125, which may both be mounted, e.g. rigidly mounted, to the wash head 121.
  • the dispensing conduit 124 and the suction conduit 125 may each extend downward through the wash head 121 and project downward out of the wash head 121 such that they can extend into the sample cup 141 when the wash unit is lowered into its operational position above the sample cup.
  • the upper ends of the dis- pensing conduit 124 and the suction conduit 125 respectively, may be fluidly connected to a fluid handling system, e.g. as described in connection with FIG. 3.
  • a fluid handling system e.g. as described in connection with FIG. 3.
  • FIG. 5 shows an enlarged sectional view of an example of a wash head 121 with a dispensing conduit 124 and a suction conduit 125.
  • the wash head 121 may have a generally cylindrical shape that can be accommodated inside an opening of the housing of a wash unit, e.g. as described in connection with FIG. 4 above.
  • the wash head includes a bulged portion 1213 which bulges radially outward and allows the wash head to be spring-loaded against a lower seat portion at the opening of the wash unit housing.
  • the outer surface of the bulged portion 1213 may have a toroidal shape so as to allow the wash unit to tilt when seated with its bulged portion in the seat portion of the wash unit housing.
  • the wash head 121 comprises a downward protrusion 1212 at its lower end.
  • the downward protrusion is positioned at the periphery of the wash head at one side of the lower end of the wash head.
  • the downward protrusion is configured to abut with the cup holder so as to define a stop of the downward movement of the wash head towards the cup holder.
  • the dispensing conduit 124 is a downwardly extending tube made from a suitable material, such as metal, e.g. stainless steel.
  • the dispensing conduit 124 may be a straight tube.
  • the dispensing conduit 124 projects downward from the wash head 121 and has a distal open outlet end 1243. When the wash head 121 is brought in its operational position above a sample cup to be washed, the dispensing conduit 124 extends into the sample cup with the distal open outlet end 1243 positioned at a certain dispensing height above the bottom of the sample cup.
  • the wash head 121 may have more than one operational positions relative to the sample cup, in particular such that the dispensing and suction conduits extend more or less into the sample cup at the respective operational positions, i.e. the dispensing height of the distal open outlet end above the bottom of the sample cup differs between different operational positions.
  • wash buffer is dispensed through the distal open outlet end 1243 of the dispensing conduit 124 into the sample cup.
  • the dispensing conduit 124 has a suitable length and diameter. For example, inside diameters of the dispensing conduit 124 of between 0.1 mm and 1 mm, may in some embodiments be suitable.
  • the suction conduit 125 is a downwardly extending tube made from a suitable material, such as metal, e.g. stainless steel.
  • the suction conduit 125 may have a straight proximal portion 1251 and an inclined distal portion 1252.
  • the suction conduit 125 projects downward from the wash head 121 and has a distal open inlet end 1253.
  • the inclined distal portion 1252 is directed downward and radially away from the proximal portion 1251 , in particular in a direction away from the dispensing conduit 124.
  • the suction conduit 125 extends into the sample cup with the distal open inlet end 1253 positioned at a certain suction height above the bottom of the sample cup, in some embodiments without touching the bottom, or, in other embodiments, even touching the bottom of the sample cup.
  • the inclined distal portion 1252 is directed downward and radially outward relative to the sample cup, i.e. from the proximal portion 1251 towards the periphery of the bottom of the sample cup.
  • the wash head 121 may have more than one operational positions, i.e. the height of the distal open inlet end above the bottom of the sample cup differ between different operational positions.
  • the suction conduit in the operational position of the wash head, such as in each operational position of the wash head, the suction conduit extends further into the sample cup than the dispensing conduit, i.e. such that the suction height of the distal open inlet end of the suction conduit above the bottom of the sample cup is smaller than the corresponding dispensing height of the distal open outlet end of the dis- pensing conduit.
  • the suction conduit may extend further into the sample cup than the dispensing conduit for several, such as all, the operational positions of the wash head.
  • the suction conduit 125 When lowered into the sample cup, suction is applied to the suction conduit 125 so as to withdraw waste material from the sample cup.
  • the suction conduit 125 has a suitable length and diameter. For example, inside diameters of the suction conduit 125 of between 0.9 mm and 1.5 mm.
  • the inclined distal portion 1252 may be or include a curved or bent portion.
  • the curved or bent portion may define a bend radius of between 3 mm and 4 mm.
  • the inclined portion defines an angle a of inclination relative to the proximal portion 1251 between 40° and 50°.
  • the inclined portion may include a bent portion and a distal straight portion.
  • the inclined distal portion 1252 has a downward extent L, defined along a longitudinal direction of the proximal portion 1251 , starting from a bottommost end of the straight proximal portion 1251.
  • the downward extent L of the inclined distal portion 1252 may be between 2 mm and 3 mm.
  • the dispensing conduit 124 and the proximal portion 1251 of the suction conduit 125 are parallel to each other. They are radially spaced apart from each other, e.g. at a distance of between 1 mm and 2 mm from each other.
  • each of the conduits may be positioned off-center relative to the sample cup. For example, they may be positioned along a diameter of the sample cup, on respective sides of the center of the sample cup.
  • the shortest radial distance between the dispensing conduit 124 and the side wall of the sample cup may be between 4 mm and 5 mm.
  • This periodical readout can be started when the cup wash processing is started.
  • Other ways of synchronizing the temperature readouts with the cup wash process can be done including reading the temperature before performing the cup wash procedure. Processing of the results can then be done and the relevant temperature sensor readouts can be selected. Then the temperature readout can be summarized, one preferred embodiment of this is to make an average of all temperature readings performed during the cup wash process. This summarized temperature will be referred to as T.
  • the temperature sensor 126 is preferably included in the wash unit 120, in particular the wash head 121 , or otherwise in close proximity to the wash unit 120, preferably such that sufficient thermal isolation is provided between the temperature sensor 126 and the from the housing 122 and/or other larger mass of the wash unit 120.
  • One suitable placement of the sensor is at a proximal portion of the suction conduit 125, e.g. as illustrated in FIG. 5.
  • the temperature sensor preferably has a low mass to allow for rapid adjustment to changing temperatures in the waste material withdrawn from the cup. This applies both to the sensor itself and the tube connector connecting the sensor and the suction tube 126 tube through which the waste material flows.
  • the measured temperature, T can be used as a predictor for the cup wash temperature dependency of the measurement.
  • the signal from the measurement of the cup can be modelled with the following formula
  • MS s_blank * f_blank(T) + s_specific * f(T,c)
  • MS is the measured signal from the cup.
  • s_blank is the signal from the cup coming from other sources than the assay sandwich complex; this is typically known from an adjustment process on the analyzer
  • f_blank(T) is a temperature-dependent factor on the blank signal
  • s_specific is the signal needed to calculate the concentration f(T,c) is a temperature- and concentration-dependent factor on the specific signal. This is a surface, e.g. a plane, in the temperature-concentration-factor space that describes how the factor depends on both temperature and concentration.
  • f_blank Since s_blank is known and f_blank(T) is known this addend can be removed. f(T,c) is depending on the concentration, which is not possible to use directly as the concentration is what needs to be calculated from the measurement. It is sufficient to use an approximation to the concentration.
  • a signal from a known medium-high signal (denoted: ks) can be used to normalize the signal when finding the value of f(T,c), which then becomes f(T,s/ks), where s is s_specific*f(T,c) f_blank(T) can be seen as a single slice of the surface in f(T,c) with known concentration.
  • One preferred embodiment is to use a bilinear approximation with a pivotal point in the middle of the temperature range.
  • Other embodiments are also used, such as polynomial or spline functions or other mathematical functions.
  • f(T,s/ks) is a surface, e.g. a plane, but can be described as a set of functions each for a given s/ks value. Each of those function can also be a bilinear function with a pivotal point in the middle of the temperature range.
  • Other embodiments are also used, such as polynomial or spline functions or other mathematical functions.
  • f(T,s/ks) can also be used; it may be preferred to limit the set of parameters for the individual functions for each s/ks value.
  • the parameters themselves can be modelled as a function over the range of s/ks.
  • FIGs. 6A-C schematically illustrate different operational positions of the wash unit 120 described in connection with FIGs. 4 and 5, where the dispensing conduit 124 and the suction conduit 125 extend more or less into the sample cup 141.
  • FIG 6A illustrates the wash unit 120 in an upper operational position. In this position, the distal open inlet end 1253 of the suction conduit 125 is positioned between 3 mm and 5 mm above the bottom 1411 of the sample cup 141 .
  • the distal open outlet end 1243 of the dispensing conduit 124 is located at a dispensing height above the bottom 1411 of the sample cup 141 , which is higher than the location of the distal open inlet end 1253 of the suction conduit 125.
  • the distal open outlet end 1243 of the dispensing conduit 124 may be positioned between 4 mm and 14 mm above the bottom 1411 of the sample cup 141 .
  • the distal open outlet end 1243 of the dispensing conduit 124 is positioned at a height above the bottom 1411 of the sample cup 141 which is lower than the height of the sample cup.
  • FIGs. 6B and 6C illustrate how the wash unit may be lowered further so as to bring it into a lower operational position, which is illustrated in FIG. 6C.
  • the wash unit 120 may be lowered until the downward protrusion 1212 of the wash head 121 touches an upper surface of the cup holder 180. At this position, the distal open inlet end 1253 of the suction conduit 125 touches, or almost touches, the bottom 1411 of the sample cup 141 , as illustrated in FIG. 6B. In some embodiments, in the lowered position, the distal open inlet end 1253 of the suction conduit 125 does not touch the bottom 1411 of the sample cup 141. The housing 122 of the wash unit 120 may then be lowered further, causing the wash head 121 to be pushed upwards into the housing 122 against the force of the spring 123, because the downward protrusion abuts the cup holder.
  • the wash head 121 As the wash head 121 is pushed upwards at the protrusion 1212, which is located at the periphery of the wash head 121 , the wash head 121 is slightly tilted in its seat inside the housing, as illustrated in FIG. 6C. This, in turn, causes the distal open inlet end 1253 of the suction conduit 125 to be moved radially outward toward the periphery of the bottom of the sample cup, thereby facilitating a complete removal of any waste material from the periphery of the sample cup.
  • the distal open inlet end 1253 of the suction conduit 125 touches the bottom 1411 of the sample cup or is positioned immediately above the bottom, e.g. 1 mm or less above the bottom, while the distal open outlet end 1243 of the dispensing conduit is elevated above the bottom 1411 of the sample cup, e.g. at a height between 3 mm and 5 mm above the bottom 1411.
  • FIG. 7 shows a flow diagram of an example of a measurement process performed by an embodiment of an analyser unit, e.g. by the analyser unit of FIG. 1.
  • the analyser unit prepares the analyser unit for the measurement.
  • the analyser unit may place a new sample cup from a cartridge into a cup holder.
  • the analyser unit may further receive a blood sample to be analysed and, optionally, prepare the blood sample for the analysis, e.g. including aspiration of the sample.
  • the process adds a small amount of the blood sample to the sample cup.
  • the process further adds a reagent buffer to the sample cup to dilute the sample.
  • the sample cup When the sample and, optionally, reagent buffer is added, it will dissolve the insulating layer of the sample cup. This may occur over a relatively short period of time, such as in less than 15 seconds.
  • the sample cup is incubated at a suitable temperature, such as at 37 °C.
  • the analyte to be detected may interact with the corresponding binding partner of the sample cup.
  • an antibody-antigen-an- tibody "sandwich" complex may be formed, and the complex may remain immobilized at the bottom of the sample cup by the capture antibody.
  • the sample cup is washed to remove all unbound material. The washing step is followed by a drying step S5.
  • the analyte sensor detects the amount of bound analyte.
  • the analyte sensor may expose the sample cup to excitation light and measures a response to the excitation light.
  • the response may be expressed in counts per second or in another suitable manner.
  • the response may be in direct proportion to the emitted photons, which may be directly proportional to the amount of analyte present.
  • a concentration can be determined from the measurement, e.g. based on a lot-specific and/or instrument-specific calibration curve. Accordingly, the measured response may serve as a measurement value indicative of the concentration of the analyte in the sample.
  • the measured response may serve as a whole-blood measurement value indicative of the concentration of the analyte in the whole-blood sample.
  • the measured response may serve as a plasma measurement value indicative of the concentration of the analyte in the plasma sample, e.g. a plasma sample of, i.e. obtained from, a corresponding whole-blood sample.
  • an analyzer unit may include a different type of analyte sensor or be configured to perform the measurement of the analyte concentration in a different manner.
  • FIG. 8 shows a flow diagram of an example of a wash process performed by an embodiment of an analyser unit, e.g. by the analyser unit of FIG. 1.
  • the cup wash process generally serves to wash away excess sample prior to the measurement that follows after it.
  • the washing is performed by pumping a wash buffer, which may be the same as the reagent buffer, into the sample cup and, in this way, diluting the sample. Subsequently the sample cup is emptied by pumping away the diluted samples.
  • Some embodiments of the washing process comprises a number of repetitions of one or more wash cycles.
  • the wash process comprises dispensing a wash buffer into the sample cup and withdrawing all undesired waste material, in particular all unbound material, from the sample cup.
  • a thorough and consistent washing of the sample cup is important for obtaining an accurate and reproducible measurement during the subsequent measurement step. Nevertheless, it is also desirable to keep the time required for the washing step as short as possible and to use as small amounts of wash buffer as possible.
  • the process is preferably optimized so as to remove unreacted material efficiently and effectively.
  • Embodiments of the cup wash disclosed herein remove unbound material and reduces unspecific binding.
  • the cup wash is robust towards assay lot variations, variations within the analyzer, sample variations and reproducible to ensure performance.
  • analyser units are capable of performing different types of assays, in particular for detecting different types of analytes in blood samples.
  • the present inventors have realised that different types of assays, in particular using different binding partners included in a sample cup, for measuring different analytes benefit from different wash procedures.
  • the wash process receives an input indicative of the type of assay included in the current sample cup to be washed.
  • the analyser unit may receive the identity of the assay to be used via a suitable user command and/or read the information from a machine-readable tag on the assay cartridge.
  • the input may e.g. be indicative of an assay identifier or otherwise provide suitable information for selecting a wash procedure.
  • step S41 based on the received input, the process retrieves a suitable wash program, e.g. in the form of a wash script represented in a suitable script language and/or in the form of a set of configuration parameters, or otherwise.
  • the different wash programs may be stored in a memory or other data storage device of the analyser unit or they may be retrieved from an external database via a suitable communication link.
  • the wash programs may e.g. be stored in a local or remote lock-up table, which may be indexed by the assay identifier or otherwise.
  • step S42 the process brings the wash unit into an operational position relative to the sample cup, e.g. using a suitable drive unit or otherwise.
  • the process may move the suction and dispensing conduits above or slightly into the sample cup.
  • step S43 the process executes the retrieved wash program.
  • An example of an execution of an assay-specific wash program will be described below in connection with FIG. 9. It may be appreciated that, in some embodiments, multiple assays may share a common wash program, i.e. the assay-specific wash program of one assay does not necessarily have to differ from the wash programs for all other assays. However, at least one assay-specific wash program will typically differ from at least one other wash program for at least one other assay.
  • FIG. 9 shows a flow diagram of an example of an assay-specific wash process performed by an embodiment of an analyser unit, e.g. by the analyser unit of FIG. 1 .
  • the assay-specific wash process is controlled by an assay-specific wash script or other form of assay-specific wash program.
  • the assay-specific wash program may include a number of wash cycles, such as one, two, three or more wash cycles.
  • Each wash cycle may be defined by one or more operational parameters. Examples of operational parameters include: a pump rate at which wash buffer is pumped into the sample cup during the wash cycle, an amount of wash buffer pumped into the sample cup during said wash cycle, a pump duration during which wash buffer is pumped into the sample cup during said wash cycle, a suction rate and/or suction duration and/or suction volume, and a number of repetitions of said wash cycle.
  • the process may parse the wash script or other wash program and successively perform the individual wash cycles. Specifically, in step S431 the process initializes the next wash cycle and, in subsequent step S432, the process performs the wash cycle. If the wash script or program includes further wash cycles, the process returns to step S431 to initialize the next wash cycle; otherwise the process terminates.
  • one or more, such as each, of the wash programs may include a clot removal cycle configured to remove blood clots or similar clumps of nonliquid, such as gel-like or solid material, from the sample cup.
  • the clot removal cycle is performed as the initial wash cycle of a wash program.
  • the process may cause a reciprocating movement of the wash head between at least a lower operational position and an elevated operational position, thus causing a reciprocating vertical movement of the dispensing conduit and the suction conduit relative to the sample cup.
  • the process may dispense wash buffer and/or apply suction during the reciprocating movement of the wash head.
  • one or both of the suction and dispensing conduits may be individually movable, and one or both of the conduits may perform an individual reciprocating movement, separately from the other conduit.
  • the clot wash cycle initially includes an initial suction step, where suction is applied to the suction conduit, optionally while lowering the wash head into the sample cup, e.g. to the lower operational position. This step may be performed with or without concurrent dispensing of wash buffer. Optionally, this step is followed by a short pause.
  • the process may dispense a predetermined amount of wash buffer, e.g. while the wash head is stationary at its lower operational position.
  • this step is followed by a short pause.
  • suction is applied to the suction conduit while the wash head performs a reciprocating movement and, optionally, with or without concurrently dispensing further wash buffer.
  • the wash head may perform an upwards movement to lift the open inlet end of the suction conduit away from the bottom of the sample cup to an elevated position, and then a downward movement back towards the bottom of the sample cup.
  • the wash head may be kept stationary at the elevated position for a short period of time before proceeding with the downward movement.
  • the reciprocating movement may be repeated one or several times.
  • the process performs the following steps:
  • the wash program may include one or more wash cycles that each include a dispensing and a suction step, optionally separated by a pause to allow for soaking.
  • the number of such wash cycles included in a wash program may vary from wash program to wash program.
  • at least one, such as each, of the steps of a wash cycle may be configurable.
  • the dispensing step may have a configurable dispensing rate and/or a configurable amount of wash buffer (e.g. defined by the duration of the dispensing step and the dispensing rate).
  • the pause separating the dispensing and suction steps may have a configurable length, or the pause may be omitted.
  • the pause may even be configurable to have a negative duration, indicating that the suction step may start even before the dispensing step is completed, i.e. the dispensing and suction steps may be performed partly or completely concurrently.
  • the suction step may have a configurable suction rate and/or duration.
  • One example of a wash program may include the following wash cycles:
  • a predetermined number of repetitions, e.g. four repetitions, of a diffusion cycle for dissolving unspecific bound material using diffusion e.g. using a high wash buffer volume and long soak time.
  • each diffusion cycle may include the following steps: Dispense a predetermined amount, e.g. between 100 pL and 300 pL, of wash buffer into the cup at a predetermined rate, e.g. at between 50 pL/s and 300 pL/s
  • a predetermined soak time e.g. between 1 s and 10 s Apply sufficient suction to empty a predetermined amount, e.g. between 400 pL and 1500 pL from the sample cup at a predetermined rate e.g. between 50 pL/s and 400 pL/s
  • An example of the jet cycle may include the following steps:
  • Dispense a predetermined amount e.g. between 100 pL and 300 pL, wash buffer into the sample cup at predetermined rate, e.g. at between 100 pL/s and 400 pL/s
  • a predetermined soak time e.g. between 0.5 and 10 s
  • An example of the final wash step may include the following steps:
  • Dispense a predetermined amount e.g. between 100 pL and 300 pL, wash buffer into the cup at a predetermined rate, e.g. at between 100 pL/s and 400 pL/s
  • a predetermined soak time e.g. between 0.5 and 10 s
  • wash cycles may use other parameters.
  • the types and/or number of wash cycles performed and/or the configurable parameters of each wash cycle may be assay specific and vary from assay to assay.
  • wash program has been found suitable for a hsTnl assay, other wash programs may be more suitable for other types of assays.
  • a wash cycle is a pulsed wash cycle, which may comprise repeatedly performing a pulsed wash operation, the pulsed wash operation comprising: dispensing a predetermined amount of wash buffer into the sample cup at a predetermined dispense rate;
  • the apparatus may intermittently or continuously apply suction so as to to remove wash buffer from the sample cup at a predetermined removal rate, in particular at a removal rate no smaller than the dispense rate.
  • the pulsed wash cycle comprisies:
  • Analyzers are subjected to samples which vary with respect to matrices and quality to be measured at different assays. An efficient removal of unspecific binding as well as unreacted tracer antibodies has been found to improve the measurement result. In particular, it has been found that some assays are more sensitive than others and the variation in measurement result can, among other factors, be caused by variations in the cup wash efficiency.
  • a suitable assay-specific wash program for a particular assay may be configured based on measurement results from a pool of analyzers.
  • cup wash process may be optimized in multiple ways for the respective assays to ensure a reliable, reproducible and fast removal of unreacted material as well as unspecific binding leaving only the immuno sandwich complex to be measured and reported.
  • embodiments of the wash unit and the cup wash process have been configured so as to reduce contamination to the surrounding parts of the analyzer unit and to remove unwanted blood clots in the cup.
  • the combination of specific dimensions and arrangement of the suction and dispensing conduits disclosed herein provide a cup wash unit that is capable of ensuring liquid turbulence during dispensing, without the risk of being blocked by salt crystallization. Moreover, the wash unit is capable of emptying the cup to a degree where the cup is diluted to a point where there are nothing left in the cups together.
  • the wash buffer disclosed herein enhances the cup wash efficiency. Yet further the assay-specific cup wash scripts may be specifically optimized to the individual assays, thus ensuring optimal performance.
  • the wash buffer used during the cup wash may be the same liquid used as reagent buffer for diluting the sample prior to and/or during the incubation.
  • the same buffer is used for some or all of the following purposes:
  • wash buffer for washing one or more components of the analyzer system between sample measurements to ensure that there is no carry-over between the patient measurements.
  • the wash buffer and, in particular a combined buffer for use as a wash buffer and reagent buffer is stable at room temperature for an extended period of time, preferably for more than a year to allow easy storage for the user, is stable at elevated temperatures for a reasonable time, e.g. for more than a month to allow long onboard usage, shows commutability with patient samples, and is compatible with various, preferably all, assays used in combination with the analyser, i.e. is capable of dissolving the cup content and stabilize the formation of the antibody-antigen-antibody "sandwich" complex.
  • the wash buffer may be a buffered saline solution.
  • the buffer was a buffered saline solution (buffer) having pH 7.0-7.5.
  • the buffer comprised HEPES, or alternatively Imidazole and/or MOPS in order to provide a buffering capacity comparable to that of whole blood.
  • the surface tension of the buffer was lowered using detergents such as Tween 20, or alternatively Brij- 35 and/or Dynol 604 to facilitate the cup wash. (Other detergents - Pluronic F-127, Synperonic PE/P84, Kolliphor P188 were investigated but were found to cause interference with the immuno-assays).
  • the ionic strength of the buffer was set to 14.00 - 17.00 mS/cm 3 using a combination of sodium chloride, calcium chloride and Na2EDTA.
  • composition of the buffered saline solution is given in table 3.
  • Embodiments of the buffer disclosed herein provide Long stability both for storage and onboard Support for closed system where the user does not need to handle used cups, liquid.
  • Embodiment 1 An apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to interact with the one or more binding partners, wherein the apparatus comprises a wash unit for washing the sample cup, in particular to remove elements of no interest for the ongoing analysis from the sample cup, wherein the apparatus is configured to select one of a plurality of wash programs in dependence of a type of binding partner included in the sample cup to be washed and/or in dependence of a type of analyte to be detected in the biological sample, and to control operation of the wash unit based on the selected wash program.
  • Embodiment 2 The apparatus according to embodiment 1 , comprising a data storage device having stored thereon a plurality of predetermined wash programs, each associated with one or more identifiers indicative of respective types of binding partners and/or indicative of respective analytes.
  • Embodiment 3 The apparatus according to embodiment 1 or 2, wherein the apparatus is configured to control the wash unit to perform one or more wash cycles, each wash cycle comprising: pumping a wash buffer into the sample cup, sucking material out of the sample cup.
  • Embodiment 4 The apparatus according to embodiment 3, wherein the plurality of wash programs includes a first wash program and a second wash program, wherein the second wash program differs from the first wash program in at least one process parameter of at least one wash cycle, the at least one process parameter being selected from: a pump rate at which wash buffer is pumped into the sample cup during said wash cycle, an amount of wash buffer pumped into the sample cup during said wash cycle, a pump duration during which wash buffer is pumped into the sample cup during said wash cycle, an amount of waste material sucked out of the sample cup, a suction rate, a suction duration, and a number of repetitions of said wash cycle.
  • the at least one process parameter being selected from: a pump rate at which wash buffer is pumped into the sample cup during said wash cycle, an amount of wash buffer pumped into the sample cup during said wash cycle, a pump duration during which wash buffer is pumped into the sample cup during said wash cycle, an amount of waste material sucked out of the sample cup, a suction rate, a suction
  • Embodiment 5 The apparatus according to any one of embodiments 1 through 4, wherein the wash unit comprises: a wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup to an operational position of the dispensing conduit for dispensing a wash buffer into the sample cup, a suction conduit having a distal open inlet end configured to be lowered into the sample cup to an operational position of the suction conduit for sucking material from at least a bottom portion of the sample cup out of the sample cup.
  • Embodiment 6 The apparatus according to embodiment 5, wherein the suction conduit comprises a proximal portion and an inclined distal portion, the inclined distal portion being inclined relative to the proximal portion and comprising said distal open inlet end.
  • Embodiment 7 The apparatus according to any one of embodiments 5 through 6, comprising a drive unit and configured to control the drive unit to selectively lower the dispensing conduit and the suction conduit into the sample cup, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, wherein the apparatus is configured to control the drive unit to selectively lower the dispensing conduit into the sample cup to an operational position of the dispensing conduit with the outlet end positioned above the bottom of the sample cup, and to selectively lower the suction conduit into the sample cup to an operational position of the suction conduit.
  • Embodiment 8 The apparatus according to embodiment 7, configured to position the sample cup in an operational position of the sample cup with an inclined bottom so as to define a bottommost portion of a periphery of the bottom, and wherein, when the suction conduit is in its operational position, the inclined distal portion is directed radially towards the bottommost portion of the periphery.
  • Embodiment 9 The apparatus according to embodiment 7, when directly or indirectly dependent on embodiment 6, wherein, when the dispensing conduit and the suction conduit are in their respective operational positions, the proximal portion of the suction conduit extends downwardly into the sample cup, adjacent to the dispensing conduit, the inclined distal portion extends radially outward from the proximal portion and away from the outlet end of the dispensing conduit.
  • Embodiment 10 An apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to bind to the one or more binding partners, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, wherein the apparatus comprises a wash unit, the wash unit comprising: a wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup for dispensing a wash buffer into the sample cup, a suction conduit having a distal open inlet end configured to be lowered into the sample cup for sucking material from at least a bottom portion of the sample cup out of the sample cup; wherein the apparatus comprises a drive unit and is further configured to control the drive unit to selectively lower the dispensing conduit into the sample cup to an operational position of the dispensing conduit with the outlet end positioned above
  • Embodiment 11 The apparatus according to any one of embodiments 9 through 10, wherein the inclined portion extends downward and radially outward from a distal end of the proximal portion.
  • Embodiment 12 The apparatus according to any one of embodiments 9 through 11 , wherein the inclined portion defines an angle of inclination relative to the proximal portion between 40° and 50°.
  • Embodiment 13 The apparatus according to any one of embodiments 9 through 12, wherein the inclined portion comprises a curved portion, e.g. defining a bend radius of between 3 mm and 4 mm.
  • Embodiment 14 The apparatus according to any one of embodiments 9 through 13, wherein the inclined portion has a downward extent, defined along a longitudinal direction of the proximal portion, of between 2 mm and 3 mm.
  • Embodiment 15 The apparatus according to any one of embodiments 9 through 14, configured to bring the suction conduit and the sample cup into a tilted orientation relative to each other, when the distal open inlet end of the suction conduit has been lowered into the sample cup, such that a radial distance between the distal open end and a periphery of a bottom of the sample cup is reduced.
  • Embodiment 16 The apparatus according to any one of embodiments 8 through 15, configured to control the drive unit, at least during a part of a wash operation, to cause a reciprocating movement of at least one of the dispensing conduit and the suction conduit relative to the sample cup between at least a lower operational position and an elevated operational position of said at least one the of the dispensing conduit and the suction conduit.
  • Embodiment 17 An apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to bind to the one or more binding partners, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, wherein the wash unit comprises: a wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup for dispensing a wash buffer into the sample cup; and a suction conduit having a distal open inlet end configured to be lowered into the sample cup for sucking material from at least a bottom portion of the sample cup out of the sample cup, wherein the apparatus comprises a drive unit and is configured to control the drive unit to selectively lower the dispensing conduit into the sample cup to an operational position of the dispensing conduit with the outlet end positioned above the bottom of the sample cup, and to selective
  • Embodiment 18 The apparatus according to embodiment 16 or 17, configured to dispense wash buffer and/or to apply suction to the suction conduit during at least a portion of the reciprocating movement of the at least one of the dispensing conduit and the suction conduit.
  • Embodiment 19 The apparatus according to embodiment 18, configured to control the drive unit, at least during a part of the wash program, to cause a reciprocating movement of at least the suction conduit between at least a lower operational position and an elevated operational position of the suction conduit, and wherein the apparatus is configured to apply suction to the suction conduit during at least a portion of said reciprocating movement.
  • Embodiment 20 The apparatus according to any one of embodiments 16 through
  • Embodiment 21 The apparatus according to any one of embodiments 16 through
  • Embodiment 22 The apparatus according to any one of embodiments 16 through 20, wherein, when the wash buffer dispensing conduit is at its lower operational position, a distance between the distal open outlet end and the bottom of the sample cup is between 1 mm and 9 mm, such as between 1.5 and 8.5 mm.
  • Embodiment 23 The apparatus according to any one of embodiments 6 through 22, comprising at least one pump configured to selectively apply suction to the suction conduit to remove material from the sample cup and configured to selectively pump wash buffer through the dispending conduit into the sample cup.
  • Embodiment 24 The apparatus according to any one of embodiments 6 through 23, configured to apply suction to the suction conduit during at least a part of a downward movement of the suction conduit into the sample cup to the operational position of the suction conduit.
  • Embodiment 25 The apparatus according to any one of embodiments 6 through 24, wherein the wash buffer dispensing conduit defines an elongated channel having an inside diameter between 0.1 mm and 1 mm.
  • Embodiment 26 The apparatus according to any one of embodiments 6 through 25, wherein the suction conduit defines an elongated channel having an inside diameter between 0.9 mm and 1.5 mm.
  • Embodiment 27 The apparatus according to any one of embodiments 6 through 26, wherein the dispensing conduit defines an elongated channel having an inside diameter and wherein the distal outlet end has an outlet opening having an outlet diameter smaller than the inside diameter.
  • Embodiment 28 The apparatus according to any one of embodiments 6 through 27, wherein the wash unit comprising a wash head movably arranged relative to the sample cup, wherein the dispensing conduit and the suction conduit are mounted to the wash head and extend downward from the wash head.
  • Embodiment 29 The apparatus according to any one of embodiments 6 through 28, wherein the dispensing conduit and the suction conduit are formed as respective metal tubes, in particular stainless steel tubes.
  • Embodiment 30 The apparatus according to any one of the preceding embodiments, configured to perform a wash operation of the sample cup after the biological sample has been added to the sample cup and before a measurement of an amount of analyte that has been bound to the one or more binding partners.
  • Embodiment 31 The apparatus according to any one of the preceding embodiments, wherein the biological sample is a blood sample, in particular a whole-blood sample.
  • Embodiment 32 A wash unit for an apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into an upwardly open sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the biological sample is allowed to bind to the one or more binding partners, the sample cup having a bottom and a circumferential side wall upwardly extending from the bottom, wherein the wash unit comprises: a wash head, a wash buffer dispensing conduit extending from the wash head, the wash buffer dispensing conduit having a distal open outlet end configured to be lowered into the sample cup for dispensing a wash buffer into the sample cup; and a suction conduit extending from the wash head and having a having a distal open inlet end configured to be lowered into the sample cup for sucking material from at least a bottom portion of the sample cup out of the sample cup; wherein the suction conduit comprises a proximal portion and an inclined distal portion, inclined relative to
  • Embodiment 33 The wash unit according to embodiment 32, wherein the dispensing conduit extends from the wash head parallel to the proximal portion of the suction conduit.
  • Embodiment 34 The wash unit according to embodiment 32 or 33, wherein the dispensing conduit has a length between the wash head and the distal open outlet end equal to or larger than a length of the proximal portion between the wash head and the distal end of the proximal portion.
  • Embodiment 35 A method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into the sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the blood sample is allowed to bind to the one or more binding partners, wherein the method comprises: selecting one of a plurality of wash programs in dependence of a type of binding partner included in the sample cup to be washed and/or in dependence of a type of analyte to be detected in the biological sample, performing one or more washing cycles according to the selected wash program.
  • Embodiment 36 A method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, the apparatus being configured to dispense the biological sample into the sample cup, the sample cup including one or more binding partners of the analyte so that the analyte present in the blood sample is allowed to bind to the one or more binding partners, wherein the method comprises:
  • Embodiments of at least some steps of the method described herein may be computer-implemented or computer-controlled.
  • embodiments of at least some steps of the method may be implemented by means of hardware comprising several distinct elements, and/or at least in part by means of a suitably programmed microprocessor.
  • several of these means can be embodied by one and the same element, component or item of hardware. The mere fact that certain measures are recited in mutually different dependent claims or described in different embodiments does not indicate that a combination of these measures cannot be used to advantage.

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Abstract

L'invention concerne des modes de réalisation d'un appareil permettant de mesurer une quantité d'analyte dans un échantillon biologique, l'échantillon biologique étant présent à l'intérieur d'une coupelle pour échantillon ouverte vers le haut, la coupelle pour échantillon comprenant un ou plusieurs partenaires de liaison de l'analyte, de telle sorte que l'analyte présent dans l'échantillon biologique peut se lier au(x) partenaire(s) de liaison. L'appareil comprend une unité de lavage pour laver la coupelle pour échantillon, en particulier pour éliminer de la coupelle pour échantillon les éléments sans intérêt pour l'analyse en cours.
PCT/EP2024/067713 2023-06-26 2024-06-25 Appareil de mesure d'une quantité d'analyte dans un échantillon biologique Pending WO2025003087A1 (fr)

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Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4073620A (en) * 1977-01-03 1978-02-14 Gray And Stanton Binder-substrate analyzer
EP0235236B1 (fr) * 1985-09-16 1991-04-17 Flow Laboratories Limited Appareil de lavage a cavites multiples
WO1992005425A1 (fr) * 1990-09-20 1992-04-02 Biohit Oy Procede et moyen pour retirer un liquide d'une cuve
JP2001091423A (ja) * 1999-09-28 2001-04-06 Bekkuman Koorutaa Kk 自動標本作成装置
EP0892927B1 (fr) 1996-04-08 2004-05-19 Innotrac Diagnostics Oy Dosage immunologique a reactif sec, d'un seul tenant, mene en une seule etape
US9944657B2 (en) 2011-08-19 2018-04-17 Radiometer Turku Oy Luminescent lanthanide chelates having three chromophores an their use
US20180180607A1 (en) * 2016-12-28 2018-06-28 Sysmex Corporation Analysis method and analyzer
US10132800B2 (en) 2013-05-13 2018-11-20 Biomerieux Method for measuring the plasma concentration of an analyte directly on a whole blood sample
WO2020028406A1 (fr) * 2018-07-30 2020-02-06 Curiox Biosystems Pte Ltd. Procédés, dispositifs et appareil pour laver des échantillons contenant des cellules
US11344924B2 (en) * 2019-01-31 2022-05-31 Jvckenwood Corporation Washing apparatus and washing method
WO2022219543A1 (fr) * 2021-04-13 2022-10-20 Curiox Biosystems Co., Ltd. Procédés, dispositifs et appareils de lavage d'échantillons
US11549938B2 (en) * 2019-03-06 2023-01-10 Jvckenwood Corporation Analysis unit, washing device, and washing method

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4073620A (en) * 1977-01-03 1978-02-14 Gray And Stanton Binder-substrate analyzer
EP0235236B1 (fr) * 1985-09-16 1991-04-17 Flow Laboratories Limited Appareil de lavage a cavites multiples
WO1992005425A1 (fr) * 1990-09-20 1992-04-02 Biohit Oy Procede et moyen pour retirer un liquide d'une cuve
EP0892927B1 (fr) 1996-04-08 2004-05-19 Innotrac Diagnostics Oy Dosage immunologique a reactif sec, d'un seul tenant, mene en une seule etape
JP2001091423A (ja) * 1999-09-28 2001-04-06 Bekkuman Koorutaa Kk 自動標本作成装置
US9944657B2 (en) 2011-08-19 2018-04-17 Radiometer Turku Oy Luminescent lanthanide chelates having three chromophores an their use
US10132800B2 (en) 2013-05-13 2018-11-20 Biomerieux Method for measuring the plasma concentration of an analyte directly on a whole blood sample
US20180180607A1 (en) * 2016-12-28 2018-06-28 Sysmex Corporation Analysis method and analyzer
WO2020028406A1 (fr) * 2018-07-30 2020-02-06 Curiox Biosystems Pte Ltd. Procédés, dispositifs et appareil pour laver des échantillons contenant des cellules
US11344924B2 (en) * 2019-01-31 2022-05-31 Jvckenwood Corporation Washing apparatus and washing method
US11549938B2 (en) * 2019-03-06 2023-01-10 Jvckenwood Corporation Analysis unit, washing device, and washing method
WO2022219543A1 (fr) * 2021-04-13 2022-10-20 Curiox Biosystems Co., Ltd. Procédés, dispositifs et appareils de lavage d'échantillons

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