POINT-OF-CARE BIOMARKER ASSAY APPARATUS ARRANGED FOR MEASURING A PRESENCE OR CONCENTRATION OF A BIOMARKER IN A SAMPLE

Abstract

Point-of-care biomarker assay apparatus arranged for measuring a presence or concentration of a biomarker in a sample, said biomarker assay apparatus comprising cartridge receiving means arranged for receiving at least one cartridge having multiple chambers designed for receiving a plurality of liquid media comprising said sample, labelled binding reagent, magnetic beads reagent and wash buffer, a sample distribution unit arranged for processing pipetting steps with said chambers, thereby providing a liquid reactant mixture in one or more of said chambers, a magnetic coil assembly arranged for applying a magnetic field to said liquid reactant mixture for separating biomarkers bound to said magnetic beads and said labelled binding reagent, from said reactant mixture, a photo detector or assembly arranged for measuring said presence or concentration of said labelled binding reagent, a control unit arranged for controlling said processing pipetting steps with said chambers, and for controlling said sample distribution unit along said chambers according to a test protocol, wherein said test protocol comprises an order of subsequent processing steps performed in said plurality of chambers to be processed by said sample distribution unit, said processing steps comprising one or more processing pipetting steps by the sample distribution unit and one or more processing incubation steps of the reaction mixture within any of the chambers wherein the control unit being programmed for performing multiple, distinct test protocols.

Claims

1-14. (canceled)

15. A point-of-care biomarker assay apparatus arranged for measuring a presence or concentration of a biomarker in a sample, comprising: cartridge receiving means arranged for receiving at least one cartridge having chambers for receiving a plurality of liquid media comprising: (i) the sample comprising the biomarker; (ii) a labelled binding reagent capable of binding to the biomarker or capable of competing with the biomarker; (iii) a magnetic beads reagent capable of binding to the biomarker and/or capable of binding a competing binding reagent; (iv) a wash buffer; and (v) at least one substrate capable of initiating a light emission from the labelled binding reagent; a sample distribution unit arranged for processing pipetting steps with the chambers, thereby providing a liquid reactant mixture in one or more of the chambers, wherein the biomarker is allowed to bind to the labelled binding reagent and the magnetic beads reagent in a processing incubation step or to compete with the labelled binding reagent and bind the magnetic bead reagent in a processing incubation step; wherein the sample distribution unit further comprises at least one precision pipet for performing the pipetting steps, each of the at least one precision pipet comprising: (i) a hollow elongated tube arranged to detachably couple to a pipet tip provided at the at least one cartridge; and (ii) an adjustable volume container, coupled to the hollow elongated tube, wherein the sample distribution unit is arranged to set a volume of the adjustable volume container for pipetting a set volume of liquid media from the chambers; wherein the sample distribution unit is arranged to dispose the pipet tip at the at least one cartridge after the pipetting steps have been performed; a magnetic coil assembly arranged for applying a magnetic field to the liquid reactant mixture for separating biomarkers bound to the magnetic beads reagent and/or the labelled binding reagent, from the reactant mixture; a photo multiplier tube assembly arranged for measuring the presence or concentration of the labelled binding reagent bound to the biomarker, or bound to the magnetic beads in case of a competitive assay format; a control unit arranged for controlling the processing pipetting steps with the chambers, and for controlling the sample distribution unit along the chambers according to a test protocol, wherein the test protocol comprises an order of subsequent processing steps performed in the plurality of chambers to be processed by the sample distribution unit, the processing steps comprising one or more processing pipetting steps by the sample distribution unit and one or more processing incubation steps of the reaction mixture within any of the chambers; wherein the control unit is programmed for performing multiple, distinct test protocols; and heating means arranged for heating each of the chambers of the at least one cartridge, simultaneously and uniformly, when placed in the apparatus, to a predetermined temperature.

16. The point-of-care biomarker assay apparatus according to claim 15, wherein the heating means comprises a plurality of metal heating elements arranged to be in contact with the at least one cartridge, when received in the cartridge receiving means, wherein the heating means are arranged to heat a received cartridge to the predetermined temperature by heating the metal heating elements.

17. The point-of-care biomarker assay apparatus according to claim 15, wherein the predetermined temperature is between 28 and 40 degrees Celsius.

18. The point-of-care biomarker assay apparatus according to claim 15, wherein the predetermined temperature is between 34 and 38 degrees Celsius.

19. The point-of-care biomarker assay apparatus according to claim 15, wherein the predetermined temperature is between 30 and 95 degrees Celsius.

20. The point-of-care biomarker assay apparatus according to claim 15, wherein the predetermined temperature is between 45 and 65 degrees Celsius.

21. The point-of-care biomarker assay apparatus according to claim 15, wherein the adjustable volume container comprises an adjustable volume between 5 μl and 1000 μl.

22. The point-of-care biomarker assay apparatus according to claim 15, wherein the sample distribution unit is arranged to set a volume of the adjustable volume container, for each pipetting step separately, for pipetting a set volume of liquid media from the chambers.

23. The point-of-care biomarker assay apparatus according to claim 15, wherein the assay apparatus comprises the at least one cartridge, and wherein the pipet tips provided at the at least one cartridge are arranged to provide level detection for detecting an amount of liquid media in the chambers and to provide clot detection for detecting clots in the liquid media.

24. The point-of-care biomarker assay apparatus according to claim 23, wherein the assay apparatus is arranged to provide an alert signal when a detected amount of liquid media in any of the chambers is below a predetermined threshold.

25. The point-of-care biomarker assay apparatus according to claim 23, wherein the assay apparatus is arranged to provide a clot alert signal when detected clots in the liquid media in any of the chambers are above a predetermined threshold.

26. The point-of-care biomarker assay apparatus according to claim 15, wherein the control unit is programmed to set a duration of the at least one washing step.

27. The point-of-care biomarker assay apparatus according to claim 15, further comprising a wireless sensor for wirelessly reading a tag provided on the at least one cartridge.

28. The point-of-care biomarker assay apparatus according to claim 27, wherein the control unit is programmed to set a specific test protocol based on the read tag.

29. The point-of-care biomarker assay apparatus according to claim 27, wherein the wireless sensor is adapted to read an RFID tag on the at least one cartridge.

30. A method for measuring a presence or concentration of a biomarker in a sample using a point-of-care biomarker assay apparatus, the method comprising the steps of: receiving, with a cartridge receiving means, at least one cartridge having chambers for receiving a plurality of liquid media comprising: (i) the sample comprising the biomarker; (ii) a labelled binding reagent capable of binding to the biomarker; (iii) a magnetic beads reagent capable of binding to the biomarker; (iv) a wash buffer; and (v) at least one substrate capable of initiating a light emission from the labelled binding reagent; processing, with a sample distribution unit, pipetting steps with the chambers, thereby providing a liquid reactant mixture in one or more of the chambers, wherein the biomarker is allowed to bind to the labelled binding reagent and the magnetic beads reagent in a processing incubation step; applying, with a magnetic coil assembly, a magnetic field to the liquid reactant mixture for separating biomarkers bound to magnetic beads and the labelled binding reagent, from the reactant mixture; measuring, with a multiplier tube assembly, the presence or concentration of the labelled binding reagent bound to the biomarker; controlling, with a control unit, the processing pipetting steps with the chambers, and for controlling the sample distribution unit along the chambers according to a test protocol comprising an order of subsequent processing steps performed in the chambers to be processed by the sample distribution unit, the processing steps comprising one or more processing pipetting steps by the sample distribution unit and one or more processing incubation steps of the reaction mixture within any of the chambers; and heating the received at least one cartridge to a predetermined temperature; wherein the control unit is programmed to perform multiple, distinct test protocols.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0121] FIG. 1 is a block diagram illustrating an embodiment of a point-of-care biomarker assay apparatus according to the present invention.

[0122] FIG. 2 is a flowchart illustrating an embodiment of the method steps according to the present invention.

[0123] FIG. 3 is an example of a cartridge to be used with the point-of-care biomarker assay apparatus according to the present invention.

DETAILED DESCRIPTION

[0124] FIG. 1 is a block diagram illustrating an embodiment of a point-of-case biomarker assay apparatus 1 according to the present invention.

[0125] The point-of-care biomarker assay apparatus is arranged, or designed, for measuring a presence or concentration of a biomarker in a sample. According to the present invention, different types of biomarkers may be detected like Ribonucleic acid (RNA), Micro Ribonucleic acid (Mirco-RNA), Deoxyribonucleic acid (DNA), metabolites, peptides, proteins, etc.

[0126] The point-of-care biomarker assay apparatus comprises cartridge receiving means 22 arranged for receiving at least one cartridge 2 having multiple chambers 14-21 designed for receiving a plurality of liquid media.

[0127] The first chamber 14 may, for example contain the sample comprising the biomarker, the second chamber 15 may, for example, contain the labelled binding reagent, capable of binding to the biomarker, or capable of competing with the biomarker, the third chamber 16 may, for example, contain magnetic beads reagent, capable of binding to the biomarker and/or capable of binding competing binding reagent, the fourth chamber 17 may, for example, contain a wash buffer for washing any substance, a fifth chamber 18 may, for example, contain at least one substrate capable of initiating a light emission from the labelled binding reagent. The remaining chambers 19-21 may, for example, not be used, or may contain other reagents to be used during an immunoassay test protocol.

[0128] In accordance with the present invention, the at least one cartridge 2 may comprise a pipet tip (see FIG. 3) which is to be coupled to the sample distribution unit 12. After the test protocol is completed, the pipet tip may be returned in the at least one cartridge 2, and the at least one cartridge 2 including the pipet tip may be disposed of.

[0129] The point-of-care biomarker assay apparatus 1 further comprises the sample distribution unit 12 which is arranged for processing pipetting steps with the chambers 14-21, thereby providing a liquid reactant mixture in one or more of the chambers 14-21 wherein the biomarker is allowed to bind to the labelled binding reagent and the magnetic beads reagent in a processing incubation step or to compete with the labelled binding reagent and bind the magnetic bead reagent in a processing incubation step.

[0130] The sample distribution unit 12 may be directly, mechanically, coupled, or via electronic means, 13 such that the sample distribution unit 12 is able to directly control the cartridge receiving means 22.

[0131] A magnetic coil assembly 3 is further present in the point-of-care biomarker assay apparatus, which coil assembly 3 is arranged for applying a magnetic field to the liquid reactant mixture for separating biomarkers bound to the magnetic beads reagent and/or the labelled binding reagent, from the reactant mixture. This process may, preferably, take place in the pipet tips comprised on each of the chambers 14-21. Alternatively, this process may take place in each of the chambers 14-21 or each of the hollow elongated tubes present on the sample distribution unit 12.

[0132] Finally, a photo detector assembly 11 is comprised in the point-of-care biomarker assay apparatus, which photo detector assembly 11 is arranged for measuring the presence or concentration of labelled binding reagent bound to the biomarker, or bound to the magnetic beads in case of a competitive assay format.

[0133] All the above mentioned components of the point-of-care biomarker assay apparatus are under control of a control unit 4, coupled to a memory 5, which control unit 4 is arranged for controlling processing pipetting steps with the chambers 14-21, and for controlling the sample distribution unit 12 along the chambers 14-21 according to one of a multitude of test protocols 8-11 comprised in the test protocol setting block 6. The present figure only displays as an example four test protocols. In practice many more different test protocols may be available to be used with the point-of-care biomarker assay apparatus.

[0134] A test protocol 8-11 comprises an order of subsequent processing steps to be performed in the plurality of chambers to be processed by the sample distribution unit, wherein the processing steps comprising one or more processing pipetting steps by the sample distribution unit and one or more processing incubation steps of the reaction mixture within any of the chambers.

[0135] In accordance with the present invention, the control unit 4 is programmed for performing multiple, distinct test protocols. As such, the control unit may alter, amend, select and/or determine a test protocol 8-11 to be used for a particular immunoassay process.

[0136] In an example, the point-of-care biomarker assay apparatus comprises wireless sensor means in the form of Radio Frequency Identification means, which are arranged for wirelessly reading out a tag provided on the at least one cartridge 2. Based on the tag read out, the control unit may automatically select, amend, or create a specific test protocol 8-11 to be used during the immunoassay procedure.

[0137] One of the advantages of the present invention is that the point-of-care biomarker assay apparatus is suitable to be used for several, distinct and different types of assay procedures, which require different test protocols.

[0138] FIG. 2 is a flowchart illustrating an embodiment of the method steps 101 according to the present invention.

[0139] The method 101 is utilized for measuring a presence or concentration of a biomarker in a sample using a point-of-care biomarker assay apparatus according to any of the embodiments described above.

[0140] The method comprises several distinct method steps, such as receiving 102, by the cartridge receiving means 22, at least one cartridge 2 having multiple chambers 14-21 designed for receiving a plurality of liquid media.

[0141] Different types of liquid media may be contained in the chambers, such as, but not limited to, the sample comprising the biomarker, labelled binding reagent, capable of binding to the biomarker, magnetic beads reagent, capable of binding to the biomarker and, optionally wash buffer.

[0142] A further method step comprises processing 103, by the sample distribution unit 12, pipetting steps with the chambers 14-21, thereby providing a liquid reactant mixture in one or more of the chambers 14-21 wherein the biomarker is allowed to bind to the labelled binding reagent and the magnetic beads reagent in a processing incubation step.

[0143] Next, a magnetic field is applied 104, by the magnetic coil assembly 3, to the liquid reactant mixture for separating biomarkers bound to magnetic beads and the labelled binding reagent, from the reactant mixture.

[0144] Finally, the presence or concentration of the labelled binding reagent bound to the biomarker is measured 105, by the photo detector assembly 11.

[0145] According to the present invention, an inventive merit is obtained by the step of controlling 106, by the control unit 4, the processing pipetting steps with the chambers 14-21, and by the step of controlling the sample distribution unit along the chambers 14-21 according to a test protocol 8-11.

[0146] The test protocol 8-11 is tuned to a specific assay process, such that a test protocol 8-11 comprises an order of subsequent processing steps to be performed in the plurality of chambers 14-21 to be processed by the sample distribution unit 12, the processing steps comprising one or more processing pipetting steps by the sample distribution unit 12 and one or more processing incubation steps of the reaction mixture within any of the chambers 14-21.

[0147] The method is based on the inventive concept that the step of controlling 106 comprises setting or programming one of multiple, distinct test protocols 8-11. As such, the control unit 4 may select a test protocol 8-11 based on the specific assay process to be used.

[0148] FIG. 3 is an example of a cartridge 201 to be used with the point-of-care biomarker assay apparatus 1 according to the present invention.

[0149] The cartridge 201 comprises multiple chambers 203, 204, 205, 206, 208 (not all chambers have a reference sign) designed for receiving a plurality of liquid media. For example, the first chamber 203 is arranged for receiving the sample containing the biomarker. The second chamber 204 may be arranged for receiving the labelled binding reagent which is capable of binding to the biomarker. The third chamber 205 may contain magnetic beads reagent capable of binding to the biomarker and/or capable of binding competing binding reagent. The fourth chamber 206 may contain a wash buffer. A photo detector assembly may be arranged for measuring the presence or concentration of labelled binding reagent bound to the biomarker in the last chamber 208 of the cartridge 201.

[0150] The cartridge may further comprise a tag 207 in the form of a barcode or the like, which tag 207 may be read out by wireless sensor means comprised in the point-of-care biomarker assay apparatus. Based on the read out tag 207, the control unit may automatically set a specific test protocol. As such, the tag 207 may comprise information concerning what test protocol to be performed for the sample contained in the cartridge 201.

[0151] A pipet tip 202 is provided in the cartridge 201, which pipet tip 202 is arranged to be coupled to an hollow elongated tube present on the sample distribution unit. The sample distribution unit may autonomously and automatically couple the hollow elongated tube to the pipet tip 202 before the test protocol is initiated. After completion of the test protocol, the pipet tip 202 may be replaced, i.e. disposed, in the cartridge 201. The complete cartridge 201, including the pipet tip 202, may then be disposed of. The advantage hereof is that the point-of-care biomarker apparatus does not need to be equipped with pipet tips, as these pipet tips are readily available in the cartridge 201.

[0152] In the context of the present invention, a module, device, equipment, or the like may also be implemented as a computer program running on the processor.

[0153] The present invention is not limited to the embodiments as disclosed above, and can be modified and enhanced by those skilled in the art beyond the scope of the present invention as disclosed in the appended claims without having to apply inventive skills.