Apparatus for measuring an amount of analyte in a biological sample

Abstract

Disclosed herein are embodiments of an apparatus for measuring an amount of analyte in a biological sample, the biological sample being 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 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.

Description

[0001] Apparatus for measuring an amount of analyte in a biological sample

[0002] TECHNICAL FIELD

[0003] The present invention relates to various aspects of an apparatus for measuring an amount of analyte in a biological sample. In particular, 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.

[0004] BACKGROUND

[0005] 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.

[0006] In addition to general requirements in respect of accuracy, precision, and reliability, apparatus for clinical applications are often subject to further critical constraints. Such 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.

[0007] Many apparatus perform measurements on biological samples that comprise blood plasma or blood with all its components, in particular including the plasma as well as the red blood cells. The latter has the advantage that the need for pre-processing the blood sample prior to performing the desired measurements is kept to a minimum, if not eliminated altogether. Generally, a blood sample including both plasma and red blood cells is referred to as a “whole blood” sample.

[0008] In many apparatus, 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. For example, 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. Such elements of no interest are generally material that has not interacted with, and is not bound to, the first binding partner.

[0009] In this respect, it is desirable to provide a washing process and a washing device that reliably removes elements of no interest and, in particular, elements that might interfere with the subsequent analysis. The process should ensure that any unbound material is removed and unspecific binding reduced.

[0010] It is further generally desirable to provide a washing process and a washing device that uses only small amounts of consumables and / or results in only small amounts of waste that needs to be disposed of, thereby reducing the operational costs and increasing the efficiency of the apparatus, since the consumption of costly consumables may be kept small and since the time required for replacing containers with consumable and / or for removing waste collecting containers can be kept small.

[0011] It is further generally desirable to provide a washing process and a washing device that results in short process times and a high throughput.

[0012] It is further generally desirable to provide a washing process and a washing device that allows for a sample analysis which is robust against possible variations in the pre- analytical sample preparation.

[0013] Yet further, it is desirable to provide a washing process and a washing device that allows for the processing of whole-blood samples. In this respect, 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.

[0014] Accordingly, despite previous efforts it remains desirable to provide a washing process and / or a washing device that solve one or more of the above problems and / or that have other benefits, or that at least provide an alternative to existing solutions.

[0015] SUMMARY

[0016] On this background, according to various aspects, disclosed herein are embodiments of 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.

[0017] In various embodiments, 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.

[0018] Accordingly, 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.

[0019] In various embodiments, 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.

[0020] In various embodiments, 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.

[0021] In some embodiments, 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.

[0022] In some embodiments, 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.

[0023] At least when the suction conduit is at its lower operational position, the distal open inlet end of the suction conduit is immersed in the dispensed wash buffer present in the sample cup of the suction conduit, thereby efficiently removing material, such as blot clots, that are immersed in the wash buffer or are located at the bottom of the sample cup. To this end, 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.

[0024] 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. In particular, 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.

[0025] 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.

[0026] In various embodiments, 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;

[0027] - waiting for a predetermined period of time; wherein 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. By applying such bursts of wash buffer into the cup bottom and by removing the buffer from the bottom, preferably before the next pulse, turbulence is created and thereby facilitating removal of any unspecific binding that might be left.

[0028] In some embodiments, 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.

[0029] In some embodiments, 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.

[0030] In some embodiments, 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.

[0031] In various embodiments, 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. Other test assays may be less sensitive to the wash process or may otherwise not require a particularly extended or otherwise special wash pro- cess. Accordingly, the provision of different wash programs that are selectively chosen dependent on the binding partner and / or analyte, allows the apparatus to account for specific requirements of certain assays without having to spend unnecessary washing resources on assays where this is not needed. 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. Alternatively or additionally, 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.

[0032] In some embodiments, 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.

[0033] In some embodiments, 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.

[0034] 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.

[0035] In some embodiments, 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.

[0036] In some embodiments, 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. For example, the inclined distal portion may define an angle of inclination relative to the proximal portion between 40° and 50°. Alternatively or additionally, the inclined portion may comprise a curved portion, e.g. defining a bend radius of between 3 mm and 4 mm. Yet additionally or alternatively, 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 above embodiments, in particular embodiment having some or all of the above dimensions, have been found to result in a particularly efficient cleaning of the sample cup.

[0037] In some embodiments, during at least a part of the wash operation, 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. To this end, 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. Alternatively, the drive unit may be configured to lower the suction conduit and the dispensing conduit together. To this end, 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.

[0038] In some embodiments, 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. In other embodiments, 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. In some embodiments, the 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. In some embodiments, 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. In some embodiments, 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. Alternatively or additionally, 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. To this end, in some embodiments, 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.

[0039] In some embodiments, when the dispensing conduit and the suction conduit are in their respective operational positions, 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. In some embodiments, 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. In such embodiments, 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. In some embodiments, when the suction conduit is at its lower operational position, 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.

[0040] In some embodiments, when the suction conduit is at its upper operational position, the suction height is between 3 mm and 5 mm. When the wash buffer dispensing conduit is at its lower operational position, 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.

[0041] The suction may be applied to the suction conduit in a number of ways. In some embodiments 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. Alternatively, the apparatus may be connectable to an external pump or other source of vacuum / suction.

[0042] In some embodiments, 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.

[0043] In some embodiments 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. In some embodiments, 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.

[0044] In some embodiments, 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.

[0045] In some embodiments, 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. In some embodiments the analyte is an antigen.

[0046] Generally, 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. During the measurement, 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. In some embodiments, 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.

[0047] As used herein, 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. Alternatively, 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. Thus, 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. In one embodiment, the immobilization relies on the interaction between biotin and streptavidin. For example, 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. However, 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.

[0048] As used herein, 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. Examples for 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. Examples of the label 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).

[0049] It will be appreciated that the term “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.

[0050] Alternatively, 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. However, antibodies as well as aptamers can be chosen such as to be able to bind to a specific analyte (target molecule).

[0051] 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.

[0052] In particular, according to one aspect, disclosed herein are embodiments of 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, proximal to the wash head, and an inclined distal portion, inclined relative to the proximal portion, the inclined distal portion extending from a distal end of the proximal portion and comprising said distal open inlet end; and wherein, the proximal portion of the suction conduit extends from the wash head adjacent to the dispensing conduit along a longitudinal direction, the inclined distal portion extends radially outward relative to the longitudinal direction and away from the outlet end of the dispensing conduit.

[0053] In some embodiments, the dispensing conduit extends from the wash head parallel to the proximal portion of the suction conduit.

[0054] In some embodiments 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. To this end, the wash end may define a height reference from which the respective lengths are defined. For example, the height reference may be defined by the point at which the suction conduit projects out of the wash head.

[0055] In some embodiments, it may be desirable to measure the temperature of the wash buffer and use the measured temperature to provide an adjustment of the measured signal from the cup. In some embodiments of the assays used in the cups 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. Generally, 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. Accordingly, 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.

[0056] 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.

[0057] 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. To this end, 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. In particular, the apparatus may comprise a sample handling system for dispensing the biological sample into the sample cup. To this end, 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.

[0058] 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.

[0059] 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:

[0060] 1) 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,

[0061] 2) lowering a wash buffer dispensing conduit into the sample cup, the wash buffer dispensing conduit having a distal open outlet end for dispensing a wash buffer into the sample cup;

[0062] 3) lowering, e.g. separately or concurrently with the lowering of the dispensing conduit, 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;

[0063] 4) repeatedly performing, at least during a part of the wash operation, a reciprocating movement of at least the suction conduit relative to the sample cup between at least a lower operational position and an elevated operational position of said suction conduit, wherein the distal open inlet end of the suction conduit is, at least at the lower operational position, immersed in the dispensed wash buffer present in the sample cup.

[0064] BRIEF DESCRIPTION OF THE DRAWINGS

[0065] Preferred embodiments will be described in more detail in connection with the appended drawings, where:

[0066] FIG. 1 schematically illustrates an example of an analyzer unit.

[0067] FIG. 2A schematically illustrates an exploded view of an example of an assay cartridge for use with an embodiment of an analyser unit.

[0068] 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.

[0069] FIG. 4 shows a schematic sectional view of an embodiment of a wash unit of an analyser unit.

[0070] FIG. 5 shows an enlarged sectional view of an example of a wash head with a dispensing conduit and a suction conduit.

[0071] FIGs. 6A-C schematically illustrate different operational positions of the wash unit described in connection with FIGs. 4 and 5.

[0072] FIG. 7 shows a flow diagram of an example of a measurement process performed by an embodiment of an analyser unit.

[0073] FIG. 8 shows a flow diagram of an example of a wash process performed by an embodiment of an analyser unit.

[0074] FIG. 9 shows a flow diagram of an example of an assay-specific wash process performed by an embodiment of an analyser unit.

[0075] DETAILED DESCRIPTION

[0076] 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.

[0077] It will be appreciated that 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. Examples of such 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. To this end, the user interface may include a display for displaying measurement results.

[0078] The analyte sensor 130 may employ a suitable measurement methodology for measuring the concentration of one or more analytes in a whole-blood sample. In particular, 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. To this end, 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. For example, during operation, 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.

[0079] In some embodiments, the assays, in particular immunoassays, are based on a drychemistry concept and on a suitable detection method, e.g. based on non-enhanced time-resolved fluorescence (TRF) technology. In this respect, the term 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.

[0080] Generally, 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.

[0081] Still referring to FIG. 1 , in some embodiments, in addition to the sample itself, 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. Moreover, a wash buffer, in particular a liquid wash buffer, for washing the sample cup during the analysis process may be needed. To this end, 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. In some embodiments, the same buffer may be used both as reagent buffer and as wash buffer, thus simplifying the liquid handling system. The analyte sensor 100 may be configured to analyze a blood sample. The blood sample can be either whole blood or plasma. 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. To this end, the analyzer unit may initially remove a sample cup from the cartridge 140 and position it into a suitable cup holder 180. Alternatively, 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.

[0082] The measurement process comprises a washing step, following a step where the blood sample has been allowed to react with the binding partners in the sample cup 141. During the washing step, the reacted assay sample cup is washed thoroughly to remove any unbound material prior to performing a measurement step. The quality of the measurement result depends on an efficient and effective cup wash that ensures that unbound material is removed and unspecific binding is reduced. The cup wash should be robust towards assay lot variations, variations within the analyzer, sample variations and reproducible to ensure performance. Various embodiments of the wash unit and the process performed by the wash unit provide such an efficient, reliable and robust cup wash.

[0083] 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.

[0084] 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.

[0085] The analyte sensor 130, the wash unit 120, the fluid handling system 150 and the drive unit 160 are communicatively coupled to the control unit 110, which controls operation of the components of the analyzer unit. The analyte sensor 130 forwards its measurement results to the control unit 110 for further processing. It will be appreciated that the sensor may forward raw measurement signals or pre-processed measurement signals or data, such as A / D converted signals, filtered signals, amplified signals and / or otherwise preprocessed signals or data to the control unit 110. In will be appreciated that the control of the various components of the analyzer unit and the processing of the measurement results may be performed by a single processing unit or by separate processing units.

[0086] 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.

[0087] In particular, 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. In various embodiments of the analyzer unit, the processing of the measurement values comprises the computation of an analyte concentration based on a measurement performed on a whole-blood sample.

[0088] The control unit 110 may be configured to control the wash unit 120 to perform an assay-specific, in particular a binding-partner-specific and / or an analyte-specific, wash program. To this end, the data storage device 112 may have stored thereon a plurality of wash programs, each associated with a particular binding partner and / or a particular analyte, or with a group of binding-partners and / or a group of analytes. When the analyte unit is controlled to perform a particular analysis of a particular analyte and / or using a particular assay, the control unit 110 may be configured to retrieve the associated assay-specific wash program from the data storage device 112 and to control the wash unit 120 to perform the corresponding wash program. The stored wash programs may be indicative of one or more parameters of the respective wash programs, e.g. indicative of the number of wash cycles to be performed and configuration parameters of each wash cycle.

[0089] FIG. 2A schematically illustrates an exploded view of an example of an assay cartridge 140 for use with an embodiment of an analyser unit, e.g. the analyser unit of FIG. 1. The essay cartridge 140 comprises a plurality of individually sealable chambers 143, such that each chamber holds a sample cup 141. The cartridge may e.g. be sealed by an upper sealing foil 142 and a lower sealing foil 144. The cartridge may comprise a machine-readable tag 145, e.g. an RFID tag, a bar code or other form of machine-readable code. The tag may comprise one or more identifiers, e.g. a serial number, identifying the cartridge and / or being indicative of the type of binding partners included in the sample cups, i.e. the type of analyte the sample cups of the cartridge are configured to detect. The cartridge may further comprise a pouch 146 or other container accommodating a suitable desiccant.

[0090] 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.

[0091] Generally, 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. To this end, prior to the measurement, any unbound material and / or other waste material that might otherwise interfere with the measurement process, may need to be removed. To this end, the sample cup may be washed after the sample has been allowed to react with the binding partners in the sample cup.

[0092] In some embodiments, 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. In this respect, the term 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. In one example, as schematically illustrated in FIG. 2B, 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. Streptavidin and biotin form a strong non-covalent biological interaction. An insulation layer 1415 containing carbohydrates and all specific additives needed in the assay prevents any contact between capture and tracer antibodies. Europium-labeled tracer antibodies 1416 may be added on top of the insulating layer.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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. An example of a wash head 121 with a dispensing conduit 124 and a suction conduit 125 will now be described in more detail with reference to FIG. 5.

[0099] 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.

[0100] 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. At its lower end, 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.

[0101] 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.

[0102] As will be described in detail below, 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. When lowered into the sample cup, 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.

[0103] 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. When the wash head 121 is brought in its operational position above a sample cup to be washed, 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. When the wash head 121 is brought in its operational position above a sample cup to be washed, 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.

[0104] As mentioned above and as will be described in detail below, 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.

[0105] It is preferred that 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. When the wash head has multiple operational positions, 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.

[0106] 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.

[0107] 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°. In some embodiments the inclined portion may include a bent portion and a distal straight portion.

[0108] 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.

[0109] 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. When in their operational positions relative to the sample cup, 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. Similarly, the shortest radial distance between the proximal portion 1251 of the suction conduit 125 and the side wall of the sample cup may be between 4 mm and 5 mm. The shortest radial distance between the inclined distal portion 1252 of the suction conduit 125 and the side wall of the sample cup may be between 0.5 and 0.6 mm. The wash head 121 may comprise a temperature sensor 126 configured to measure the wash buffer temperature and of the waste material sucked out of the wash cup. Measuring the temperature of the wash buffer and waste material may done by measuring the temperature using the cup wash temperature sensor 126. Various embodiments of this procedure are used or can be used. For example, the cup wash temperature sensor can be read periodically, e.g. every second. 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.

[0110] 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.

[0111] 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

[0112] MS = s_blank * f_blank(T) + s_specific * f(T,c) where

[0113] 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.

[0114] 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.

[0115] Other embodiments for 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.

[0116] 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. In particular, 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. For example, 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 . In some embodiments, 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.

[0117] 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.

[0118] In particular, 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. 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.

[0119] Accordingly, in its lower operational position, as illustrated in FIG. 60, 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.

[0120] 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. In initial step S1, the analyser unit prepares the analyser unit for the measurement. In particular, 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. In step S2, the process adds a small amount of the blood sample to the sample cup. Optionally, the process further adds a reagent buffer to the sample cup to dilute the sample. 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. During the subsequent incubation step S3, the sample cup is incubated at a suitable temperature, such as at 37 °C. During this incubation time, the analyte to be detected may interact with the corresponding binding partner of the sample cup. In particular, 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. In subsequent step S4, the sample cup is washed to remove all unbound material. The washing step is followed by a drying step S5. After drying, during the subsequent measurement step S6, the analyte sensor detects the amount of bound analyte. For example, 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. In general, 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. In particular, when the sample is a whole-blood sample, the measured response may serve as a whole-blood measurement value indicative of the concentration of the analyte in the whole-blood sample. Similarly, when the sam- pie is a plasma 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.

[0121] It will be appreciated that other embodiments of 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.

[0122] 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.

[0123] 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.

[0124] Generally, 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.

[0125] Generally, 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.

[0126] Accordingly, various embodiments of the wash process involve assay-specific wash procedures. Accordingly, the wash process receives an input indicative of the type of assay included in the current sample cup to be washed. For example, 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.

[0127] In 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.

[0128] In 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. In particular, the process may move the suction and dispensing conduits above or slightly into the sample cup.

[0129] In 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.

[0130] 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.

[0131] In particular, 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.

[0132] Accordingly, 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.

[0133] In some embodiments, 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. In some embodiments, the clot removal cycle is performed as the initial wash cycle of a wash program.

[0134] During the clot removal cycle, 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. In some embodiments, the process may dispense wash buffer and / or apply suction during the reciprocating movement of the wash head. It will be appreciated that, in alternative embodiments, 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. In some embodiments, 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.

[0135] Subsequently, the process may dispense a predetermined amount of wash buffer, e.g. while the wash head is stationary at its lower operational position. Optionally, this step is followed by a short pause.

[0136] Subsequently, 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. In particular, 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. Optionally, the wash head may be kept stationary at the elevated position for a short period of time before proceeding with the downward movement. In some embodiments, the reciprocating movement may be repeated one or several times.

[0137] In one embodiment of the clot removal cycle, the process performs the following steps:

[0138] 1) Empty the sample cup, e.g. at a predetermined rate, e.g. between 50 pL / s and 500pL / s, while moving the wash unit to the bottom of the cup sample cup, and wait for a predetermined period, e.g. between 1 s and 10 s.

[0139] 2) Dispense a predetermined amount, e.g. between 100 pL and 400pL, of wash buffer into the sample cup, e.g. at a predetermined rate, such as a rate between 50 pL / s and 500pL / s

[0140] 3) Empty the sample cup, e.g. at a predetermined rate, e.g. between 50 pL / s and 500pL / s, while moving a predetermined distance at a predetermined speed away from the bottom of the sample cup, and wait for a predetermined period, e.g. between 0.5 s and 10 s. 4) Empty the sample cup, e.g. at a predetermined rate, e.g. between 100 pL / s and 500pL / s, while moving the wash head towards the bottom of the sample cup, and wait for e.g. between 1 s and 10 s.

[0141] Regardless of whether a wash program includes a clot removal cycle, 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. Alternatively or additionally, at least one, such as each, of the steps of a wash cycle may be configurable. For example, 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. In some embodiments, 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.

[0142] One example of a wash program may include the following wash cycles:

[0143] 1) A clot removal cycle

[0144] 2) 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.

[0145] 3) A predetermined number of repetitions, e.g. four repetitions, of a jet cycle using a higher dispensing rate.

[0146] 4) A final wash cycle for emptying the sample cup completely

[0147] For example, 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

[0148] Wait for 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

[0149] An example of the jet cycle may include the following steps:

[0150] 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

[0151] Wait for a predetermined soak time, e.g. between 0.5 and 10 s

[0152] - Apply sufficient suction to empty a predetermined amount, e.g. between 300 pL and 1500 pL from the sample cup at a predetermined rate, e.g. at between 50 pL / s and 400 pL / s.

[0153] An example of the final wash step may include the following steps:

[0154] 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

[0155] Wait for a predetermined soak time, e.g. between 0.5 and 10 s

[0156] - Apply sufficient suction to empty a predetermined amount, e.g. between 500 pL and 1500 pL from the sample cup at a predetermined rate, e.g. between 50 pL / s and 400 pL / s.

[0157] It will be appreciated that the above examples, including the numerical values of the various wash parameters, are merely intended to be illustrative. Other embodiments of wash cycles may use other parameters. Generally, 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. For example, while the above example of a wash program has been found suitable for a hsTnl assay, other wash programs may be more suitable for other types of assays.

[0158] Another example of 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;

[0159] - waiting for a predetermined period of time.

[0160] During a part of the pulsed wash operation, or during the entire pulsed wash operation, 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.

[0161] In one embodiment, the pulsed wash cycle comprisies:

[0162] 1. Dispense between 50 and 150 pL of wash buffer into the sample cup at a dispense rate between 200 pL / s and 300 pL / s

[0163] 2. Wait between 150 ms and 350 ms

[0164] 3. Repeat steps 1 and 2 between seven and thirteen times while continuously emptying the cup at a removal rate between 200 pL / s and 300 pL / s. The total volume of wash buffer used for this example of a pulsed wash cycle is between 350 pL and 1950 pL.

[0165] 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.

[0166] By using assay-specific cup wash programs, smaller variations between repeated measurements may be obtained independently of the type of assay. A robust and consistent cup wash increases the reliability and makes the analyzer unit less sensitive to sample variations. Embodiments of the cup wash process disclosed herein 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.

[0167] Furthermore, 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.

[0168] 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.

[0169] Generally, 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. In some embodiments, the same buffer is used for some or all of the following purposes:

[0170] - As a reagent buffer for pre-dilution of the sample to be analyzed and / or for incubation of the assay.

[0171] - As a wash buffer for washing the sample cup to remove all unbound material

[0172] - As a 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.

[0173] - As a calibration buffer, e.g. for calibration of an Het measurement cell

[0174] Generally it is desirable that 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.

[0175] Generally, the wash buffer may be a buffered saline solution.

[0176] Embodiments of a suitable buffer, suitable as both wash buffer and reagent buffer will now be described:

[0177] In one particular example, the buffer was a buffered saline solution (buffer) having pH 7.0-7.5.

[0178] 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 / cm3using a combination of sodium chloride, calcium chloride and Na2EDTA. Preservation of the buffer was ensured by using Propyl-p-hydroxybenzo- ate Sodium salt, Germal II, NeoIone 950 (ProClin950), or any combination thereof. Members of the classes of buffer components are listed in the table 1 and their chemical structure is given in table 2:

[0179] In one example the composition of the buffered saline solution is given in table 3.

[0180] 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.

[0181] - A reduced number of false negatives as a result of improved buffer capacity and stability

[0182] - A reduced number of false positives as a result of improved cleaning of the system and thereby reduced carry-over

[0183] Improved performance as measurement result variation is generally reduced.

[0184] At least some aspects disclosed herein may be summarized by the following embodiments:

[0185] 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.

[0186] 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.

[0187] 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.

[0188] 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.

[0189] 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.

[0190] 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.

[0191] 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.

[0192] 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 a central portion of 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; 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; and 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.

[0193] 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.

[0194] 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.

[0195] 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.

[0196] 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.

[0197] 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.

[0198] 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 selectively lower the suction conduit into the sample cup to an operational position of the suction conduit, wherein the apparatus is further configured to control the drive unit, at least during a part of the wash operation, to perform 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.

[0199] 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.

[0200] 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.

[0201] Embodiment 20: The apparatus according to any one of embodiments 16 through

[0202] 19, wherein, when the suction conduit is at its lower operational position, a distance between the distal open inlet end and the bottom of the sample cup is between 0 mm and 1 mm.

[0203] Embodiment 21 : The apparatus according to any one of embodiments 16 through

[0204] 20, wherein, when the suction conduit is at its upper operational position, a distance between the distal open inlet end and the bottom of the sample cup is between 3 mm and 5 mm. 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.

[0205] 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.

[0206] 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.

[0207] 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.

[0208] 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.

[0209] 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.

[0210] 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.

[0211] 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.

[0212] 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.

[0213] 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 the proximal portion, the inclined distal portion extending from a distal end of the proximal portion and comprising said distal open inlet end; and wherein, the proximal portion of the suction conduit extends adjacent to the dis- pensing conduit along a longitudinal direction, the inclined distal portion extends radially outward relative to the longitudinal direction and away from the outlet end of the dispensing conduit.

[0214] 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.

[0215] 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.

[0216] 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.

[0217] 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:

[0218] 1) lowering a wash buffer dispensing conduit into the sample cup, the wash buffer dispensing conduit having a distal open outlet end for dispensing a wash buffer into the sample cup; 2) lowering 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;

[0219] 3) performing, at least during a part of the wash operation, a reciprocating movement of at least one of the dispensing conduit and the suction conduit 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.

[0220] Embodiments of at least some steps of the method described herein may be computer-implemented or computer-controlled. In particular, 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. In the apparatus claims enumerating several means, 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.

[0221] It should be emphasized that the term "comprises / comprising" when used in this specification is taken to specify the presence of stated features, elements, steps or components but does not preclude the presence or addition of one or more other features, elements, steps, components or groups thereof.

Claims

CLAIMS1. An apparatus for measuring an amount of analyte in a biological sample, the biological sample being 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 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 selectively lower the suction conduit into the sample cup to an operational position of the suction conduit, wherein the apparatus is further configured to control the drive unit, at least during a part of the wash operation, to repeatedly perform a reciprocating movement of at least the suction conduit relative to the sample cup between at least a lower operational position and an elevated operational position of said suction conduit, wherein the distal open inlet end of the suction conduit is, at least at the lower operational position, immersed in the dispensed wash buffer present in the sample cup.

2. The apparatus according to claim 1, 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.

3. The apparatus according to claim 2, configured to apply suction to the suction conduit during at least a portion of said reciprocating movement, in particular during the entire reciprocating movement.

4. The apparatus according to claim 2 or 3, configured to dispense wash buffer before initiating the reciprocating movement and / or during at least a portion of the reciprocating movement of the at least one of the dispensing conduit and the suction conduit, in particular during the entire reciprocating movement.

5. The apparatus according to any one of the preceding claims, wherein, when the suction conduit is at its lower operational position, a distance between the distal open inlet end and the bottom of the sample cup is between 0 mm and 1 mm.

6. The apparatus according to any one of the preceding claims, wherein, when the suction conduit is at its upper operational position, a distance between the distal open inlet end and the bottom of the sample cup is between 3 mm and 5 mm.

7. The apparatus according to any one of the preceding claims, wherein the apparatus is further configured to control the drive unit, at least during a part of the wash operation, to repeatedly perform a reciprocating movement of the wash buffer dispensing conduit relative to the sample cup between at least a lower operational position and an elevated operational position of said wash buffer dispensing conduit.

8. The apparatus according to claim 7, 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.

9. The apparatus according to any one of the preceding claims, wherein the distal open inlet end of the suction conduit is, at the elevated operational position during the reciprocating movement, immersed in the dispensed wash buffer present in the sample cup.

10. The apparatus according to any one of the preceding claims, wherein the apparatus is further 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;- waiting for a predetermined period of time; wherein the apparatus is configured to continuously apply suction during the pulsed wash operation 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.11 . An apparatus for measuring an amount of analyte in a biological sample, the biological sample being 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 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 is further 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;- waiting for a predetermined period of time; wherein the apparatus is configured to apply suction during the pulsed wash operation 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.

12. The apparatus according to claim 10 or 11 , wherein repeatedly performing comprises performing the pulsed wash operation at least 8 times, such as at least 10 times, such as at least 15 times, such as between 10 times and 20 times.

13. The apparatus according to any one of claims 10 through 12, wherein 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.

14. The apparatus according to any one of claims 10 through 13, wherein the removal 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.

15. The apparatus according to any one of claims 10 through 14, wherein the predetermined amount of wash buffer is between 50 pL and 200 pL, such as between 75 pL and 150 pL.

16. The apparatus according to any one of claims 10 through 15, wherein the apparatus is configured, prior to initiating the pulsed wash operation, to dispense a predetermined amount of wash buffer into the sample cup.

17. The apparatus according to any one of claims 11 through 16, 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.

18. The apparatus according to any one of the preceding claims, 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.

19. The apparatus according to claim 18, comprising a data storage device having stored thereon a plurality of predetermined wash programs, each associated withone or more identifiers indicative of respective types of binding partners and / or indicative of respective analytes.

20. The apparatus according to any of of the preceding claims, 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.21 . The apparatus according to any one of the preceding claims, 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.

22. The apparatus according to claim 21 , 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.

23. The apparatus according to claim 22, 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.

24. The apparatus according to any one of the preceding claims, 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.

25. The apparatus according to any one of the preceding claims, 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.

26. The apparatus according to any one of the preceding claims, 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.

27. The apparatus according to any one of the preceding claims, 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.

28. The apparatus according to any one of the preceding claims, wherein the biological sample is a blood sample, in particular a whole-blood sample.

29. A method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, wherein the method comprises:1) 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,2) lowering a wash buffer dispensing conduit into the sample cup, the wash buffer dispensing conduit having a distal open outlet end for dispensing a wash buffer into the sample cup;3) lowering 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;4) repeatedly performing, at least during a part of the wash operation, a reciprocating movement of at least the suction conduit relative to the sample cup between at least a lower operational position and an elevated operational position of said suction conduit, wherein the distal open inlet end of the suction conduit is, at least at the lower operational position, immersed in the dispensed wash buffer present in the sample cup.

30. A method for washing a sample cup of an apparatus for measuring an amount of analyte in a biological sample, the method comprising:1) 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,2) lowering a wash buffer dispensing conduit into the sample cup, the wash buffer dispensing conduit having a distal open outlet end for dispensing a wash buffer into the sample cup;3) lowering 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; 4) 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;- waiting for a predetermined period of time; 5) applying suction during the pulsed wash operation 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.

Images