Automated clinical analysis

The method and system optimize sample preparation and analysis by grouping samples by assay type, addressing inefficiencies in clinical laboratories, enabling efficient and economical analysis of small batches with reduced turnaround time and calibration frequency.

GB2700748APending Publication Date: 2026-03-11MICROMASS UK LTD
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Patent Information

Authority / Receiving Office
GB · GB
Patent Type
Applications
Current Assignee / Owner
Filing Date
2025-06-06
Publication Date
2026-03-11

AI Technical Summary

Technical Problem

Clinical laboratories face inefficiencies in analyzing small numbers of patient samples due to varying sample preparation steps and the need for frequent reconfiguration of LC-MS systems, leading to increased turnaround times and calibration burdens.

Method used

A method and system for grouping samples by assay type, allowing simultaneous or successive sample preparation and analysis in batches, using magnetic beads and automated machinery to optimize sample processing and minimize system reconfiguration.

Benefits of technology

Enables efficient and economical analysis of small sample batches with reduced turnaround time and calibration frequency, improving laboratory efficiency and result turnaround.

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Abstract

A method of analysing samples using liquid chromatography mass spectrometry, comprises receiving samples to be analysed by liquid chromatography mass spectrometry, determining the type of assay that e
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Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority from and the benefit of United Kingdom patent application No. 2408176.2 filed on 7 June 2024. The entire contents of this application are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates to clinical analysis systems, such as clinical mass spectrometry systems, and in particular to grouping samples for analysis by such systems. BACKGROUND Mass spectrometry (MS), and in particular liquid chromatography-mass spectrometry (LC-MS), is often used within a clinical laboratory setting to perform analytical tests on patient samples. For example, a concentration of an analyte of interest in a sample may be determined. SUMMARY From a first aspect the present invention provides a method of analysing samples using liquid chromatography mass spectrometry, comprising: receiving samples to be analysed by liquid chromatography mass spectrometry; determining the type of assay that each of the samples is required to be analysed by; and grouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps. The present invention provide a liquid chromatography mass spectrometry (LC-MS) technique that allows multiple different assays to be performed on the same batch of samples. This allows the relatively frequent analysis of small numbers of samples of a given assay type in a convenient and economical manner. The different assay types may be used to determine whether or not different respective analytes of interest are present in the samples. Each assay type may also determine the concentration or quantity of the analyte of interest in any given sample. The samples in each batch include samples that are required to be analysed by at least two assay types. However, it is contemplated that the samples in each batch include samples that are required to be analysed by at least three, at least four or even more different assay types. The samples in the batch that undergo the same sample preparation steps undergo the same type of processing, e.g. using the same processing machinery and same process techniques, but the same or different reagents or particles may be used for the different samples in the batch. The batch of samples may be arranged on a sample plate having a fixed number of wells therein. The method may comprise performing said same sample preparation steps on at least some of the samples in the batch of samples e.g. simultaneously or successively. After the sample preparation steps have been performed on the samples in the batch of samples, the method may comprise performing liquid chromatography mass spectrometry on the samples in said batch. The samples in the batch may be analysed consecutively or in parallel by the liquid chromatography mass spectrometry. The method may comprise receiving the samples at an automated clinical analyser that comprises a liquid chromatography mass spectrometer for performing said liquid chromatography mass spectrometry; wherein said automated clinical analyser performs the step of determining the type of assay that each of the samples is required to be analysed by, by reading an identifier on each of the samples that it receives. For example, the clinical analyser may have a barcode reader that reads barcodes on the samples (i.e. on the vials that they are in) that are indicative of the types of assay that the samples are required to be analysed by. Alternatively, the samples may have identifiers other than barcodes, such as an RF ID tag, and the clinical analyser may have a corresponding reader device for reading the identifier to determine the types of assay that the samples are required to be analysed by. The automated clinical analyser may be configured to automatically perform said grouping of the received samples based on the identifiers that it reads on the samples. Multiple samples in each batch may be simultaneously subjected to said same sample preparation steps. Samples in each batch that are to undergo different assay types may be simultaneously subjected to said same sample preparation steps. The sample preparation steps may include: adding magnetic beads to the samples so as to bind an analyte of interest in each sample to the magnetic beads; and using a magnet to separate the magnetic beads and the analytes of interest that are bound to them from the samples. The magnetic beads may have functionalised surfaces for binding the analytes of interest. Magnetic beads having different functionalised surfaces may be provided in samples that are required to be analysed by different respective assay types. Alternatively, e.g. if the analytes of interest are similar for the different assay types, magnetic beads having the same functionalised surface may be provided in samples that are required to be analysed by different respective assay types. The step of using the magnet to separate the magnetic beads and their bound analyte of interest from each sample may comprises inserting the magnet into the sample containing the magnetic beads so as to attract the magnetic beads to it, and then removing the magnet from the sample. A non-magnetic (e.g. plastic) sheath may be arranged around the magnet in a manner such that it is able to be decoupled from the magnet. As such, the magnet may be arranged in the sheath to attract the beads onto the outside of the sheath, and when it is desired for the beads to no longer be attracted to the magnet the magnet may simply be removed from the sheath. The sheath also may be replaced when the magnet is used to prepare a new sample, preventing contamination between the samples. The method may comprise inserting the magnet having the magnetic beads, and bound analyte of interest, attracted thereto into a first reagent and causing the magnetic beads to no longer be attracted to the magnet. The method may then cause the magnet to attract the magnetic beads to it again, and may then move the magnet and the attracted magnetic beads having the analyte of interest bound thereto into a second reagent and causing the magnetic beads to no longer be attracted to the magnet. For example, in the embodiments having the sheath around the magnet, the magnetic beads may be caused not to be attracted to the magnet by withdrawing the magnet from the sheath. However, less preferable techniques are contemplated such as using electromagnets that may be switched on and off. The first reagent may be a washing agent for performing a washing step and / or the second reagent may be an elution agent configured to cause the analyte of interest not to be bound to the magnetic particles. Where the second reagent is an elution reagent, the magnetic bead may be removed from the elution reagent by reintroducing the magnet into the elution reagent and then removing the magnet from it. It is contemplated that the magnetic beads and their bound analytes of interest may be placed in additional reagents between being placed in the first and second reagents, e.g. to perform additional washing steps. Different reagents may be used for each of the first and / or second reagent for different respective assay types within each batch. Alternatively, the same reagent may be used for each of the first and / or second reagent for different respective assay types within each batch. Although sample preparation steps have been described that use magnetic beads and washing and elution reagents etc., it is contemplated that different or additional sample preparation steps may be performed. Accordingly, the sample preparation steps may include performing protein precipitation by adding a precipitating agent to each sample, and then subjecting the sample to centrifuging or filtration to remove the supernatant containing proteins. The remaining sample may then be reconstituted in a solvent, e.g. that is compatible with the LC-MS. The same or different precipitating agents may be used for the samples that are to undergo the different assays. Preferably, all samples in each batch are centrifuged, e.g. simultaneously or successively, or all samples in each batch are filtered, e.g. simultaneously or successively. Said grouping of the received samples into batches of samples may be performed such that it is only permitted to add samples to the batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of assay types. Said pre-selected group of assay types may include different assay types during different time periods. For example, the pre-selected group of assay types may include a first set of assay times during a first time period (e.g. on a first day), and may include a second, different set of assay times during a second time period (e.g. on a second day). This minimises the amount of reconfiguration of the system that is required to perform all of the different assay types. The pre-selected group of assay types may only include assay types that are able to be performed or optimised using the same LC column type and / or the same mobile phases for the LC column. This eradicates any need for manually exchanging the mobile phases or LC column when performing the assays. Alternatively, the pre-selected group of assay types may only include assay types that are able to be performed or optimised using only two different LC columns. The method may comprise providing automated machinery that automatically controls a valve system, based on the assay type that is required to be performed on any given sample, to select which of the LC columns is used to separate that sample and supply it to the mass spectrometer. The mass spectrometry may be performed on a mass spectrometer that is programmed to operate in different mass analysis modes and / or with different configurations for the different respective assay types that are to be performed on each batch of samples; and the method may be conducted on a clinical analyser that automatically controls the mass spectrometer to operate in one or the analysis modes and / or with one of the configurations, based on the assay that is required to be performed on the sample being mass analysed. The method may comprise not adding calibrators to at least some of the batches of samples. The method may comprise determining, for each of the assay types to be performed on the batch of samples, a calibration relationship that relates an ion signal determined for an analyte of interest for that assay type to the concentration or quantity of that analyte of interest in the sample being analysed; wherein the calibration relationship has been determined before the batch of samples has been mass analysed and / or wherein the determined calibration relationship us used when analysing multiple batches of the samples. Alternatively, a calibration relationship may be determined for each analyte of interest in each batch of samples being analysed by adding calibrators to one or more of the samples in the batch that contain the analyte of interest. A sample plate may be used to prepare each batch of samples for analysis. The sample plate may be is pre-prepared with sample preparation materials, such as reagents and magnetic beads etc. in order to perform the multiple assays. The samples to be analysed may then be added to these plates. Alternatively, the method may comprise receiving the samples at an automated clinical analyser that: performs the step of determining the type of assay that each of the samples is required to be analysed by, by reading an identifier on each of the samples that is received; automatically performs said grouping of the received samples based on the identifiers that it reads on the samples; and automatically adds sample preparation materials to the batch of samples that are required for preparing the samples for the assays, based on information read from the identifiers on the samples. For example, the sample preparation materials may be reagents and / or magnetic beads etc. These may be added directly into the samples or onto a sample plate. Embodiments are contemplated in which each batch of samples need not only include samples that are required to be analysed by assay types that have the same sample preparation steps. The received samples may be grouped into batches of samples such that it is only permitted to add samples to the batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types. Accordingly, from a second aspect the present invention provides a method of analysing samples using liquid chromatography mass spectrometry, comprising: receiving samples to be analysed by liquid chromatography mass spectrometry; determining the type of assay that each of the samples is required to be analysed by; and grouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types; wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types. This method may have any of the features described above in relation to the first aspect of the invention, except that each batch of samples need not only include samples that are required to be analysed by assay types that have the same sample preparation steps. For example, said pre-selected group of assay types may include different assay types during different time periods. For example, the pre-selected group of assay types may include a first set of assay times during a first time period (e.g. on a first day), and may include a second, different set of assay times during a second time period (e.g. on a second day). This minimises the amount of reconfiguration of the system that is required to perform all of the different assay types. The pre-selected group of assay types may only include assay types that are able to be performed or optimised using the same LC column type and / or the same mobile phases for the LC column. This eradicates any need for manually exchanging the mobile phases or LC column when performing the assays. Alternatively, the pre-selected group of assay types may only include assay types that are able to be performed or optimised using only two different LC columns. The method may comprise providing automated machinery that automatically controls a valve system, based on the assay type that is required to be performed on any given sample, to select which of the LC columns is used to separate that sample and supply it to the mass spectrometer. The mass spectrometry may be performed on a mass spectrometer that is programmed to operate in different mass analysis modes and / or with different configurations for the different respective assay types that are to be performed on each batch of samples; and wherein the method is conducted on a clinical analyser that automatically controls the mass spectrometer to operate in one or the analysis modes and / or with one of the configurations, based on the assay that is required to be performed on the sample being mass analysed. The present invention also provides a clinical mass spectrometry system configured to perform any of the methods described herein. Accordingly, the first aspect of the present invention provides a clinical mass spectrometry system comprising: a sample reader for reading identifiers on samples received at the system; a sample batching mechanism; and control circuitry configured to control the system to: automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; and automatically control the sample batching mechanism to group the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps. The system may include a computer storage memory that provides a link between the different sample identifiers and the different assay types, so that the system is able to determine the type of assay that each of the samples is required to be analysed by from the identifier. The computer storage memory may also provide a link between the assay types and the sample preparation steps that are required for each of them, so that the system is able to batch the samples so that each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps. The clinical mass spectrometry system may comprise one or more a liquid chromatography device for separating the samples and a mass spectrometer for mass analysing the separated samples. The clinical mass spectrometry system may be configured to perform any of the methods described in relation to the first aspect of the invention. For example, the system may have a sample preparation module for performing said same sample preparation steps on at least some of the samples in the batch of samples, e.g. simultaneously or successively. The second aspect of the present invention provides a clinical mass spectrometry system comprising: a sample reader for reading identifiers on samples received at the system; a sample batching mechanism; and control circuitry configured to control the system to: automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; and automatically control the sample batching mechanism to group the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types. The system may include a computer storage memory that provides a link between the different sample identifiers and the different assay types, so that the system is able to determine the type of assay that each of the samples is required to be analysed by from the identifier. The clinical mass spectrometry system may comprise one or more a liquid chromatography device for separating the samples and a mass spectrometer for mass analysing the separated samples. The clinical mass spectrometry system may be configured to perform any of the methods described in relation to the second aspect of the invention. Although embodiments have been described in which the samples are subjected to LC-MS, it is contemplated that the samples may be analysed using other techniques. For example, the samples may not be subjected to liquid chromatography, and / or may be subjected to a different sample separation step prior to mass analysis. Alternatively, or additionally, the samples may be subjected to an analysis technique other than mass spectrometry. Accordingly, from a third aspect the present invention provides a method of analysing samples, comprising: receiving samples to be analysed; determining the type of assay that each of the samples is required to be analysed by; and grouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types; and wherein either (i) each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps; and / or (ii) wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types. Said analysing may comprise, for example, ion mobility analysing. In such ion mobility analysing each sample is ionised and the resulting ions, or ions derived therefrom, are separated according to their ion mobility. The separated ions are then detected at an ion detector such that ions having different ion mobilities generate ion signals at different times. Alternatively, the samples may be analysed by techniques other than ion mobility analysis, such as optical analysis (e.g. spectroscopy). The third aspect of the present invention also provides a clinical mass spectrometry system comprising: a sample reader for reading identifiers on samples received at the system; a sample batching mechanism; and control circuitry configured to control the system to: automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; and automatically control the sample batching mechanism to group the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types; and wherein either: (i) each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps; and / or (ii) wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types. BRIEF DESCRIPTION OF THE DRAWINGS Various embodiments of the present invention will now be described by way of example only and with reference to the accompanying drawings, in which: Fig. 1 shows an automated clinical mass spectrometry system according to an embodiment of the present invention; Figs. 2A and 2B show embodiments of sample batching apparatus; Fig. 3 shows a representation of a sample plate used in a conventional technique for performing a single type of assay; Fig. 4 shows a sample plate according to an embodiment of the present invention, for use in the sample preparation of samples that are to undergo three different assay types; Fig. 5 shows an example of an embodiment in which two pumps supply mobiles phases to different LC columns; and Fig. 6 is an illustration comparing how samples are tested according to a conventional approach and according to an embodiment of the present invention, for the situation where each of the samples is required to be subjected to one of three different assays. DETAILED DESCRIPTION Liquid chromatography-mass spectrometry (LC-MS) is often used within a clinical laboratory setting to determine concentrations or quantities of various clinically relevant molecules in a biological patient sample, such as blood, blood plasma, blood serum, urine, stool, saliva, or cerebrospinal fluid. LC-MS is often referred to as the ‘gold standard’ and has become the accepted reference method for a variety of analytes due to its high sensitivity and specificity, and wide dynamic range. Examples of typical analytes that can be detected or quantified by LC-MS systems include steroid hormones, vitamins, ‘drugs of abuse’ (for example opiates), and therapeutic drugs such as immunosuppressants. There is also growing interest in peptide and protein analyses, particularly in the fields of oncology and neurology, as potential indicators of disease or disorder. Clinical laboratories that perform LC-MS analysis on patient samples typically receive a modest number of samples each week, which may be required to be subjected to different types of assays. As such, a relatively low number of samples are received each day that are required to be subjected to any given assay, e.g. the number of such samples received per day may be around ten or less. When so few samples are received each day, it is impractical and uneconomic to frequently analyse a batch of samples for any given assay. There are multiple reasons for this. For example, the sample preparation steps required in LC-MS techniques can vary significantly for different assays, from the most basic sample preparation such as a simple dilution of the sample, to more complex steps such as protein precipitation (with filtration or centrifugation), or solid phase extraction using positive or negative pressure manifolds. Sample preparation systems must be reset from one setup to another. Time is also lost in exchanging the reagents and internal standards etc. between performing the different assays, meaning that it is inefficient to swap sample preparation techniques on a frequent basis. Also, each LC-MS assay is typically optimised independently, meaning that many mobile phases and types of chromatography columns are required to cover a wide range of assays. It can be time consuming and inefficient to frequently exchange mobile phases and / or replace the chromatography column, particularly if the LC system requires flushing with a mobile phase between assays. Furthermore, the majority of tests today are laboratory developed tests. The calibration of such tests is determined by the test developer and they predominantly follow CLSI guidance (C62-A “Liquid Chromatography-Mass Spectrometry Methods; Approved Guideline”) which states “In the absence of good data demonstrating noninferiority of the new calibration scheme, the standard of practise is to calibrate with every batch of clinical samples...”. However, it is costly and risky for laboratories to attempt to demonstrate that an alternate calibration approach or calibration frequency is acceptable, especially given the fact that less frequent calibration, for example, may not be suitable given the interventions that may be made to the system to run an alternate assay (such as the abovementioned mobile phase or column exchanges) or between analysing two batches of samples. Therefore, running a relatively large number of sample batches, that each has a relatively small number of samples in it, leads to a greater calibration burden than running the same number of samples but in fewer batches. To mitigate the issues described above, it is common practise for clinical laboratories to wait for several days in order to accumulate a sufficient number of samples that are required to undergo a given assay before analysing a batch of those samples. This increases the overall inefficiency and complexity of the laboratory operations and, more important, negatively impacts the turnaround time in returning test results back to patients and physicians. Embodiments of the present invention provide a LC-MS clinical analyser that comprises a sample preparation means that allows multiple different assays to be performed on the same batch of samples, such that these samples are prepared concurrently and subsequently submitted and analysed by LC-MS as a single batch. This allows the relatively frequent analysis of small numbers of samples of a given assay in a convenient and economical manner. Fig. 1 shows schematically an automated clinical liquid chromatographymass spectrometry (LC-MS) system 1 according to an embodiment of the present invention. The system is operable to automatically perform different analytical tests (i.e. assays) on different samples, e.g. that may be selected from a predefined menu of assays. Fig. 1 shows the main elements of the system that are relevant to the operation of the present embodiment. As will be appreciated by those skilled in the art, there may be other elements of the system that are not illustrated in Fig. 1. The system includes a number of processing stages which operate automatically under the control of controller 2 to perform respective processing steps for samples 3 being analysed. The processing modules may be arranged to form a pipeline, with an output of one processing module being an input to the next processing module, and with samples being passed between processing modules by appropriate interfaces, e.g. automatically under the control of controller 2. Each processing module may be configured by the controller to perform appropriate processing steps on a sample for an assay (i.e. analytical test) that the sample is undergoing. As shown in Fig. 1, the system includes a sample batcher module 4 that may be interfaced to sample preparation module 5 by interface 6. Sample batcher module 4 receives samples 3, either individually or in groups. The sample batcher module temporarily buffers the received samples and outputs batches of samples that each contain only samples that are to be processed in a same or similar manner by a subsequent processing module of the system, such as the sample preparation module 5 and / or an LC module 7 and / or mass spectrometer module 8. The sample batcher module may thus output samples in a different order to the order in which samples were received. The sample preparation module 5 receives the batch of samples from the sample batcher module 4, e.g. via interface 6, and prepares the samples for LC-MS analysis. The sample preparation module may prepare different samples sequentially at different times and / or in parallel at the same time. The sample preparation steps used may include any one, or any combination of any number of the following steps:- sample pipetting, aliquoting, addition of solvent, addition of one or more reagents, addition of one or more internal standards, addition of one or more quality controls, addition of one or more calibrators, addition of magnetic beads (with or without a functionalised coating for binding an analyte of interest), magnetic bead processing, sample reacting / incubating, solid phase extraction, protein precipitation, enzymatic digestion, filtration, centrifugation, shaking / mixing, heating, etc. LC module 7 separates each of the samples supplied to it according to chromatographic retention in an LC separation column. The LC module may separate different samples sequentially, e.g. using the same column, and / or in parallel, e.g. using different columns. The LC module may comprise one or more sample injection systems, one or more pumping systems, one or more separation columns, one or more mobile phases, etc. The LC module may also be capable of flow injection. The LC module may have multiple different separation configurations available, e.g. such that it can use different column types, different mobile phase types, etc., and an appropriate configuration for a given sample may be selected by controller 2 based on the assay that is being performed. The MS module 8 mass analyses a given sample, after it has been prepared in sample preparation module 5 and separated in LC module 7, in order to detect and optionally quantify one or more analyte of interest in the sample. The MS module outputs analysis data 9, e.g. to a laboratory information management system. The MS module may analyse different samples sequentially and / or in parallel. The output data 9 may comprise analysis results, raw data, processed data, calibrated data, uncalibrated data, etc., and may be indicative of whether one or more analytes of interest have been detected in a given sample and optionally the quantity or concentration of such analytes of interest. For example, it may be indicated whether the quantity or concentration of an analytes of interest is above or below a defined threshold, for example. The MS module has one or more ionisation source for ionising the eluant from the LC module and one or more mass spectrometers for mass analysing the ions produced therefrom. The MS module may have multiple different analysis configurations and / or may be able to perform multiple different mass analysis modes, and the controller 2 may automatically select one of these configurations and / or modes for any given sample being analysed in the MS module based on the assay that is required to be performed. By way of example, the mass spectrometer may be a tandem (MS / MS) mass spectrometer that monitors certain multiple reaction monitoring (MRM) transitions and produces an ion chromatogram for each of these, i.e. records the detected ion signal as a function of time. For each of the analytical samples the mass spectrometer may monitor an MRM transition for the analyte of interest required by the assay that it is undergoing. As one skilled in the art will appreciate, in order to monitor any given MRM transition the mass spectrometer controls a first mass filter to have a mass transmission window such that it is only capable of transmitting precursor ions having a specific mass to charge ratio. The precursor ions that are transmitted by the first mass filter are guided into a fragmentation or reaction device, in which the precursor ions are fragmented or reacted so as to form fragment or product ion species. The fragment or product ions are then transmitted to a second mass filter, which is operated so as to have a mass transmission window such that it is only capable of transmitting ions having a specific mass to charge ratio to an ion detector. The mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that if ions are detected by the ion detector then it is determined that ions of interest are present in the sample being analysed. The ion signal may also be used to determine the quantity of ions in the sample. For the MRM transition for the analyte of interest, the mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that only ions having a mass to charge ratio corresponding to a specific fragment ion species of the analyte of interest are able to be detected by the ion detector. The ion signal for these ions may therefore be used to determine the presence, and optionally quantity or concentration, of the analyte of interest in the sample. A different MRM transition for the analyte of interest may also be monitored, wherein the mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that only ions having a mass to charge ratio corresponding to a different fragment ion species of the analyte of interest are able to be detected by the ion detector. The mass spectrometer may monitor this MRM transition so that if ions are detected for this MRM transition then it is confirmed that it is actually the analyte of interest that is being detected, since it is highly unlikely that a precursor ion other than the analyte of interest would give rise to ion signals for both MRM transitions. Interfaces 6, 10 and 11 may be provided between adjacent modules in order to transfer the samples between them. The interfaces may comprise one or more of an electro-mechanical assembly, track system, robotic system, fluidic connection, etc. Each interface may be controlled to transfer the samples automatically, or one or more of the interfaces may be performed manually by an operator. Fig. 2A schematically illustrates the sample batcher 4 in more detail. The sample batcher is operable to batch samples together and output batches of samples, where each batch contains samples that are to undergo multiple assays, i.e. multiple analytical tests. In the illustrated embodiment the sample batcher receives the samples via an input track 20, and sends batches of samples to a downstream processing module of the system by an output track 21, which corresponds to interface 6 in Fig. 1. However, other forms of interface are possible. The sample batcher includes a local controller 22 that may be in communication with system controller 2. The sample batcher further includes a sample receipt module 23 that receives samples 3 via the input track 20. When the sample receipt module receives a sample, it automatically identifies the assay that is to be performed on that sample, e.g. by reading a barcode provided on the sample container or some other identifier on the container (e.g. an RF ID tag). Sample transfer module 24 then transfers the identified sample to sample storage 25 which temporarily stores the sample, e.g. without performing any processing operations on the sample that may alter the sample. A sample may be transferred in its original container, or e.g. aspirated via pipette from its original container within the receipt area 23 to a secondary container with the storage area 25. As illustrated in Fig. 2A, the sample storage 25 may include a set of different storage regions that can each store a respective plurality of samples together so as to form a batch of samples. For each sample received by sample receipt module, controller 23 selects a storage region of the set of storage regions to transfer the respective sample to based on the assay that is to be performed on the respective sample, and the sample transfer module transfers the respective sample to the selected storage region. In this way, the sample batcher module can construct batches of samples within sample storage 25, where each batch contains samples that are to undergo different analytical tests. Each storage region of sample storage 25 may have a maximum storage capacity of a predetermined number of samples. For example, each batch may have a maximum size of 2, 4, 8, 16, 32, 64, or 96 samples, or another number of samples. However, it is preferred that the maximum number of samples in a batch is relatively small, such that the samples can be analysed with a short turnaround time, as will be described further below. Different storage regions may have the same or different maximum storage capacities, and thus may form batches of the same or different sizes. When a storage region becomes full, i.e. is storing the maximum number of samples, the batch transfer module 27 transfers the completed batch of samples from sample storage 25 to sample output module 26. The sample output module loads the batch of samples 28 onto output track 21, and the batch of samples is thus output. As described above, samples that are to undergo different assays, but which are to undergo the same or similar sample preparation steps, are grouped together in a batch and sent for analysis. As such, there is less delay in analysing the samples then there would be if waiting to fill a batch with samples that are to undergo the same assay. It will be appreciated that samples that are to undergo different assays can be output together as a batch, even where those samples were not received together (e.g. successively). The batcher module may only output full batches of samples, i.e. batches that include the maximum number of samples. However, the controller 22 may keep track of the length of time that each sample in sample storage 25 has been buffered for, and when a sample has been buffered for longer than a predetermined threshold period of time, batch transfer module 27 may transfer the corresponding incomplete batch of one or more samples from sample storage 25 to sample output module 26. The sample output module loads the incomplete batch of one or more samples onto output track 21, and the incomplete batch is thus output and analysed. The predetermined threshold period of time may be based on a desired turnaround time for the assay that is required to be performed on that sample. The predetermined threshold period of time may be the same for all assays or different for different assays. The sample batcher is able to recognise when a STAT sample is received, e.g. via its barcode or other identifier, and prioritises the output of STAT samples. When a STAT sample is received and recognised by sample receipt module 23, the sample may bypass sample storage 25, and be output as soon as practicable, e.g. by itself and not as a batch. Alternatively, a STAT sample may be transferred to an appropriate storage region of sample storage 25, and output as soon as practicable as a batch that includes one or more other stored samples that are to undergo the same assay as the STAT sample. As described above, the sample batcher outputs samples as a batch of samples that are to be prepared for analysis in the same or similar manner by sample preparation module 5. This allows samples that are to undergo different assays, but which are to undergo substantially the same sample preparation steps, to be output together as a batch and subsequently prepared together by the sample preparation module. This avoids having to wait to fill a batch with samples that are to undergo the same single assay. Although in the above embodiments, the sample batcher module is a dedicated module, other arrangements are possible. For example, Fig. 2B schematically illustrates an embodiment in which the sample batcher 4 and sample preparation module 5 are integrated in a single module 29. In this embodiment batches of samples 3 are formed in sample storage 25, e.g. as described above, and then transferred to sample preparation region 30. The samples in each batch 28 of samples are then prepared for analysis in sample preparation region 30, e.g. by adding reagents etc. as described elsewhere herein. The batches of prepared samples are then output from the module 29. In order to illustrate advantages of embodiments of the present invention, a known technique will be described in relation to Fig. 3. Fig. 3 is a representation of a 96 well sample plate used for preparing 16 different samples for analysis in parallel, e.g. for extracting DNA / RNA for PCR analysis. This plate is typically pre-prepared with magnetic beads and associated reagents and then the samples are subsequently added to wells on the plate. More specifically, each of the wells in the first column of wells contains magnetic beads. The 8 sample wells in the second column are filled with 8 respective samples to be prepared for analysis. Each of the wells in the third column of wells contains a first wash reagent. Each of the wells in the fourth column of wells contains a second wash reagent. Each of the wells in the fifth column of wells contains an elution reagent. The sixth column of wells is deliberately left empty, i.e. not used. The seventh to twelfth columns of wells are duplicates of the first to sixth columns of wells, respectively, so that a further eight samples that are provided in the sample wells of the eighth column may be prepared for analysis in the same way as the eight samples that are provided in the sample wells of the second column. The sample preparation steps will now be described in relation to the first row of wells, although corresponding sample preparation steps are simultaneously conducted on the other rows of wells. The magnetic beads from the first well in the first row are added to the analytical sample in the second well in the row. The beads are chosen such that they selectively bind to the molecules of the analyte of interest in the sample. A magnetic rod that is sheathed with a disposable plastic cover is then inserted into the sample and used to attract the beads onto the outer surface of the sheath. The magnetic rod and surrounding sheath are then transferred to the third well in the row so as to transfer the analyte of interest to that well. The magnetic rod is then withdrawn from both the sheath and the well, so as to allow the beads to mix into the first wash reagent. The magnetic rod is then reinserted into the sheath that is in the well so as to attract the beads onto the outer surface of the sheath, and the magnetic rod and surrounding sheath are then transferred to the fourth well in the row so as to transfer the washed analyte of interest to that well. The magnetic rod is then withdrawn from both the sheath and well, so as to allow the beads to mix into the second wash reagent. The magnetic rod is then reinserted into the sheath so as to attract the beads onto the outer surface of the sheath, and the magnetic rod and sheath are then transferred to the fifth well in the row so as to transfer the washed analyte of interest to that well. The magnetic rod is then withdrawn from both the sheath and the well, so as to allow the beads to be mixed into the elution reagent. The molecules of the analyte of interest are caused to be released from the magnetic beads by the elution reagent. The magnetic rod is then reinserted into both the sheath and well and then retracted out of it, so as to remove the magnetic beads from the well, leaving the analyte of interest suspended in the elution reagent. The sample is then ready to be analysed. A procedure corresponding to that described above is conducted for the seventh to eleventh wells in the first row. As described above, a problem with the approach used in Fig. 3 is that it is required to wait for sixteen samples that are to be subjected to the same assay before the batch of samples is complete are ready to undergo the sample preparation steps. This may incur a relatively large turnaround time, particularly for assays that are required relatively infrequently. Embodiments of the present invention provide a sample plate that for provides for multiple different assays. Fig. 4 shows a sample plate according to an embodiment of the present invention, for use in the sample preparation of samples that are to undergo three different assays. The eight samples that are labelled as “A” are to undergo a first assay, the four samples labelled as “B” are to undergo a second different assay, and the four samples labelled as “C” are to undergo a third different assay. The left half of the sample plate is the same as the left half of the sample plate shown in Fig. 3, and the eight samples labelled as “A” in the second column are processed in a corresponding manner to that described above. The samples labelled as “B” and “C” in the eighth column are also processed in a corresponding manner to that described above, except that after the sample preparation steps they are to undergo different assays to the samples labelled as “A”. Accordingly, the magnetic beads used in the sample preparation steps for samples “B” may have a different functionalised surface to those used for samples “A” and / or samples “C” since the magnetic beads may need to bond with different analytes of interest. Additionally, or alternatively, the wash reagents and elution reagent in the sample preparation steps for samples “B” may be different to those used for samples “A” and / or samples “C”. For example, the assays required to be performed on samples “A” and samples “B” may seek to detect analytes of interest having similar physicochemical properties and that bind to the same functionalised surface on a magnetic bead, and which can be prepared using the same wash reagents and elution reagent. In contrast, the assay required to be performed on samples “C” may seek to detect an analyte of interest having a different physicochemical property such that it requires a different functionalised surface on the magnetic bead in order to bind to it, and it may require different wash reagents and a different elution reagent. A magnetic rod may be provided for each row of wells in the sample plate, so that samples in all of the rows can undergo the sample preparation steps in overlapping time periods, e.g. simultaneously. After the magnetic rods have been used to perform the sample preparation steps on samples “A”, these rods may then be used to perform the sample preparation steps on samples “B” and samples “C”, although using new sheaths for the different samples. Alternatively, two magnetic rods may be provided for each row of wells in the sample plate, so that the two samples in each row can undergo the sample preparation steps in overlapping time periods, e.g. simultaneously. For example, a magnetic rod may be used to perform the sample preparation steps on sample “A” in the first row, whilst a second magnetic rod is used to perform the sample preparation steps on sample “B” in the first row. Similarly, a magnetic rod may be used to perform the sample preparation steps on sample “A” in the fifth row, whilst a different magnetic rod is used to perform the sample preparation steps on sample “C” in the fifth row. The magnetic beads may be functionalised with one or more of the following: reverse phase (C18), hydrophilic-lipophilic balance (HLB), mixed mode cationic exchange (MCX), mixed mode anion exchange(MAX), weak cation exchange(WCX), and weak anion exchange (WAX). Although the sample preparation process in the embodiments has been described as having two washing steps, it is contemplated that it may instead only have one washing step, or more than two washing steps. Although the samples on the sample plate have been described as being prepared for three different tests (assays), it is contemplated that the samples on the sample plate may only be prepared for two different assays, or for more than three assays. Accordingly, the number of samples that are prepared for each assay is merely illustrative and the invention contemplates preparing fewer or more samples for each of the assays than have been illustrated. Indeed, the sample plate may comprise fewer or more wells than are illustrated, so that fewer or more samples are prepared for testing. An example assay menu that the clinical analyser is able to perform is shown below in Table 1. Each row in the table indicates a different type of assay that may be required for a sample that is received at the clinical analyser. The final column in the table indicates which assays may be performed on a single batch of samples, e.g. based on the samples requiring the same sample preparation apparatus or steps, and / or based on the samples requiring the same analytical conditions such as the same LC column type and mobile phases. Assay types that may be performed in the same batch are indicated by having the same number in the final column of the table. Assay # Assay Description Assay Group # 1 Vitamin D 1 2 Fat Soluble Vitamins 1 3 Water Soluble Vitamins 2 4 TDM- Panel 1 (ADD) 3 5 TDM- Panel 2 (ADD) 3 6 TDM- Panel 3 (ADD) 3 7 TDM- Panel 4 (AED) 3 8 TDM- Panel 5 (APD) 3 9 TDM- Panel 6 (ADD) 3 10 TDM- Panel 7 (ADD) 3 11 TDM- Panel 8 (AAD) 3 12 Plama Cats &Mets 4 13 Urine Cats &Mets 4 14 Steroid Hormones - Panel 1 4 15 Steroid Hormones - Panel 2 4 16 Aldosterone 4 Table 1 Although sample preparation steps have been described that use magnetic beads and washing and elution reagents etc., it is contemplated that different sample preparation steps may be performed instead. For example, each sample may be caused to undergo protein precipitation. Protein precipitation involves adding a precipitating agent such as methanol or acetonitrile to each sample. After mixing the sample with the precipitating agent a centrifuge or filtration is used to separate the protein precipitate. The supernatant containing proteins can then be discarded and the remaining sample reconstituted in an LC-compatible solvent. Different samples in each batch of samples are prepared for different respective assays using the above described steps. The same or different precipitating agents may be used for the samples that are to undergo the different assays. Conventional LC-MS assays are typically independently optimised, leading to the requirement of a wide range of mobile phases and chromatography columns in order to optimise all of the different types of assays. In the embodiments of the current invention, all of the assays that are supported to run on the automated clinical analyser are developed and selected so that relatively few mobile phases and types of LC column (e.g. column chemistry and / or column length) are required. Accordingly, the clinical analyser may comprise an assay menu that is configured to allow a user to select assays that are to be performed on the samples, where the number of different assays in the menu are restricted to achieve the above. For example, the number of different assay types in the menu may be restricted so that all of the assays in the menu are able to be performed using a single LC column type and a single pair of mobile phases for that column type. This eradicates any need for manually exchanging the mobile phases or LC column when performing the assays. Alternatively, the number of different assays in the menu may be restricted so that all of the assay types in the menu are able to be performed using only two LC column types and a pair of mobile phases for each of the column types. The clinical analyser may comprise automated machinery, e.g. as shown in Fig. 5, that is configured to swap between the pairs of mobile phases using a valve arrangement prior to the input to the LC pump. Similarly, valves ahead of and subsequent to the two LC columns could be used to switch the LC column that the sample is sent to (and which subsequently supplies the sample to the mass spectrometer). Fig. 5 shows an example of an embodiment in which a first pump 50 supplies mobiles phases 51 to a first LC column 52 and a second pump 53 supplies mobiles phases to a second, different LC column 54. As is known to the skilled person, a pair of mobile phases is used to run a separation gradient on each LC column. For example, for a first assay, the first pump 50 may pump an aqueous mobile phase A1 and a solvent mobile phase B1 to the first column 52, with a sample therein, in order to separate the components of the sample in the column such that the components elute from the column over different time periods. The percentage of each mobile phase A1,B1 supplied by the first pump is varied during the separation time. During a second assay, the first pump may supply a different aqueous mobile phase A2 and a different solvent mobile phase B2 to the first column, with a sample therein, in order to separate the components of the sample in the column such that the components elute from the column over different time periods. The percentage of each mobile phase A2,B2 supplied by the first pump is varied during the separation time. Similarly, for a third assay, the second pump 53 may pump the aqueous mobile phase A1 and the solvent mobile phase B1 to the second column 54, with a sample therein, in order to separate the components of the sample in the column such that the components elute from the column over different time periods. The percentage of each mobile phase A1,B1 supplied by the second pump is varied during the separation time. During a fourth assay, the second pump may supply the aqueous mobile phase A2 and the solvent mobile phase B2 to the second column, with a sample therein, in order to separate the components of the sample in the column such that the components elute from the column over different time periods. The percentage of each mobile phase A2,B2 supplied by the second pump is varied during the separation time. The clinical analyser may be configured to automatically control a valve system, based on the assay that is required to be performed on any given sample, to select the column that is used to separate the sample and supply it to the mass spectrometer 55, and hence also to select the pump (and hence mobile phases) that are supplied to that column. The valve system is also controlled such that eluent from LC column that is not supplying the mass spectrometer is sent to a waste pipe. The mass spectrometer 55 may be programmed to operate in different mass analysis modes and / or with different configurations for the different respective assay types that are to be performed on each batch of samples. The clinical analyser may be configured to automatically control the mass spectrometer to operate in one or the analysis modes and / or with one of the configurations, based on the assay that is required to be performed on the sample being mass analysed (e.g. based on the barcode or other identifier that was detected for that sample). For a more extensive menu of assays, there may be more configurations than is practical to support simultaneously on a single system. In this case, the system could be configured with multiple different menus of assays, where the different menus are only available at a different time periods, such as on alternate days, so that the assays therein may only be performed on those alternate days. This minimises the amount of reconfiguration of the system that is required. Alternatively, different systems may be provided that have the different menus of assays. As has been described above, by having only a predefined menu of assays that the clinical analyser is able to perform it is possible to limit the number of sample preparation steps and / or methods of analysing the samples that are required, enabling a generic sample preparation workflow and limiting the physical complexity of the system. The clinical analyser may be a “closed” system, where only a proprietary assay menu is suitable for use on the analyser. Assay applications for such closed systems are optimised for them and verified by the manufacturer. Alternatively, the clinical analyser may be an “open” system, where customers or third parties can develop one or more assay to either supplement or replace the proprietary assay menu. In either case, according to the embodiments of the present invention, samples requiring different assays are assigned to a single batch. As mentioned above, the majority of tests today are laboratory developed tests, the calibration of which is determined by the test developer and they predominantly follow guidance which requires that each batch is calibrated unless there is good data demonstrating noninferiority of a new calibration scheme. As such, alternate calibration approaches are avoided due to the cost and risk of attempting to demonstrate that they are acceptable. However, as the embodiments of the present invention have a limited assay menu and / or a relatively small set of defined standard analytical methods which each assay is assigned to, it is possible to limit the sources that drive calibration to drift. This limits the verification and testing burden necessary to demonstrate that a single calibration relationship can be determined and used for multiple assays and for analysing multiple batches of samples, despite the appropriate column flushing or other interventions that are necessary between the assays and batches. For example, as mentioned above, a limited assay menu could be supported on a single pair of mobile phases and a single column type. In this situation most of the sources for the calibration to change in between assays and batches are completely eradicated and it becomes a simple exercise to demonstrate that a stored calibration relationship is acceptable over a defined time period. As such, the batches of samples need not include a set of calibrator samples for use in determining a calibration relationship, which would take up valuable space in the batch. Alternatively, a calibration relationship may be determined for each analyte of interest in each batch of samples being analysed. However, rather than providing a separate set of calibrator samples for determining each calibration relationship, calibrators may be added to one or more of the samples in the batch that contain the analyte of interest. Such calibrators have chemical properties that are similar to the analyte of interest, but each calibrator can be uniquely identified by the mass spectrometer in order to obtain the calibration signal. The ideal calibrators are stable isotope labelled versions of the analyte of interest, i.e. each calibrator corresponds to the analyte of interest except that one or more of its atoms has been replaced by a different stable isotope of that atom. Each sample plate that is used to prepare the batch of samples for analysis may be a sample plate that is pre-prepared with sample preparation materials, such as reagents and magnetic beads etc. in order to perform the multiple assays. The samples to be analysed are then added to these plates. Alternatively, the clinical analyser may automatically determine the assays that are required to be performed on samples as it receives them, e.g. by reading a barcode or other identifier on each sample, and to automatically add the samples to batches of samples. The clinical analyser may then automatically add the sample preparation materials, such as reagents and magnetic bead etc., to the batch of samples that are required for performing the assays that have been identified as being required to be performed on these samples (e.g. by adding them to a sample plate in which the batch of samples is located). Fig. 6 is an illustration comparing how samples are tested according to the conventional approach and according to an embodiment of the present invention, for the situation where each of the samples is required to be subjected to one of three different assays. The example shows samples arriving at the clinical analyser at different times during five consecutive days. More specifically, in this hypothetical example, on each of Days 1 to 5, three samples to be subjected to assay 1 are received, followed by two samples to be subjected to assay 2, followed by one sample to be subjected to assay 3. According to the conventional approach, the clinical analyser waits for a full batch of five samples for each assay before proceeding to perform that assay. Accordingly, there is a relatively long delay before analysing some of the samples. For example, no samples are subjected to assay 2 until half-way through Day 3 and no samples are subjected to assay 3 until the end of Day 5. In contrast, the embodiment of the present invention is able to perform the required sample preparation steps and analyses for all of assays 1, 2 and 3 on each batch of samples. As such, each batch may be filled with samples that are required to be subjected to any one of assays 1, 2 or 3, rather than having to wait and fill the batch with samples that are to be subjected to the same assay. As such, any given one of the samples is able to be analysed with a relatively small delay. For example, it can be seen that samples are subjected to assays 1 and 2 as early as Day 1, and a sample is subjected to assay 3 as early as Day 2. The sample preparation steps may be performed on all of the assays 1,2 and 3 simultaneously. However, in the case that there is not enough capacity to do this, the sample preparation steps may be performed on all of the assays 1, 2 and 3 successively. Although the present invention has been described with reference to various embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims. For example, although embodiments have been described in which a certain sized batch of samples is provided on a sample plate, it will be appreciated that fewer or more samples may be provided in each batch and / or that they need not be provided on a sample plate. Embodiments have been described in which the chromatographically separated samples are analysed by a tandem mass spectrometer, such as a triple quadrupole mass spectrometer, operating in an MRM mode. However, other mass analysis techniques and / or mass spectrometers may be used to obtain ion peaks for the analyte of interest. For example, a triple quadrupole mass spectrometer operating in a mode other than an MRM mode may be used. Alternatively, a single quadrupole mass spectrometer, time of flight mass spectrometer, Orbitrap mass spectrometer, FT-ICR mass spectrometer, or other mass spectrometer may be used. Although the samples have been described as being separated by liquid chromatography, the liquid samples need not be separated prior to analysis, or they may be separated by alternative techniques. For example, the samples may be subjected to capillary electrophoresis, infusion techniques or direct analysis prior to mass analysis. Although the samples have been described as being mass analysed, it is contemplated that the samples may additionally, or alternatively, be analysed using 5 ion mobility analysis. Alternatively, the samples may be analysed by other techniques, such as optical analysis (e.g. spectroscopy). Various sample types and analytes of interest have been described herein. However, the invention is not limited to these. For example, the analyte of interest may be a steroid hormone, a vitamin, a drug of abuse (for example an opiate), or a 10 therapeutic drug such as an immunosuppressant drug, an anti-epileptic drug, an anti-psychotic drug, an anti-infective drug, a steroid, or an anti-fungal drug etc. The analyte of interest may be an amino acid , a peptide or a proteins. 15

Claims

1. A method of analysing samples using liquid chromatography mass spectrometry, comprising:receiving samples to be analysed by liquid chromatography mass spectrometry;determining the type of assay that each of the samples is required to be analysed by; andgrouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps.

2. The method of claim 1, comprising subsequently performing said same sample preparation steps on at least some of the samples in the batch of samples.

3. The method of claim 2, wherein after the sample preparation steps have been performed on the samples in the batch of samples, the method comprises performing liquid chromatography mass spectrometry on the samples in said batch.

4. The method of claim 1, 2 or 3, comprising receiving the samples at an automated clinical analyser that comprises a liquid chromatography mass spectrometer for performing said liquid chromatography mass spectrometry; wherein said automated clinical analyser performs the step of determining the type of assay that each of the samples is required to be analysed by, by reading an identifier on each of the samples that it receives.

5. The method of claim 4, wherein the automated clinical analyser is configured to automatically perform said grouping of the received samples based on the identifiers that it reads on the samples.

6. The method of any preceding claim, wherein multiple samples in each batch are simultaneously subjected to said same sample preparation steps.

7. The method of claim 6, wherein samples in each batch that are to undergodifferent assay types are simultaneously subjected to said same sample preparation steps.

8. The method of any preceding claim, wherein the sample preparation steps include: adding magnetic beads to the samples so as to bind an analyte of interest in each sample to the magnetic beads; and using a magnet to separate the magnetic beads and the analytes of interest that are bound to them from the samples.

9. The method of claim 8, wherein the step of using the magnet to separate the magnetic beads and their bound analyte of interest from each sample comprises inserting the magnet into the sample containing the magnetic beads so as to attract the magnetic beads to it, and then removing the magnet from the sample.

10. The method of claim 9, comprising subsequently inserting the magnet having the magnetic beads, and bound analyte of interest, attracted thereto into a first reagent and causing the magnetic beads to no longer be attracted to the magnet; andoptionally, then causing the magnet to attract the magnetic beads to it again, and then moving the magnet and the attracted magnetic beads having the analyte of interest bound thereto into a second reagent and causing the magnetic beads to no longer be attracted to the magnet.

11. The method of claim 10, wherein the first reagent is a washing agent for performing a washing step and / or the second reagent is an elution agent configured to cause the analyte of interest not to be bound to the magnetic particles.

12. The method of any preceding claim, wherein the sample preparation steps include performing protein precipitation by adding a precipitating agent to each sample, and then subjecting the sample to centrifuging or filtration to remove the supernatant containing proteins.

13. The method of any preceding claim, wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to the batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of assay types.

14. The method of claim 13, wherein said pre-selected group of assay types includes different assay types during different time periods.

15. The method of claim 13 or 14, wherein the pre-selected group of assay types only includes assay types that are able to be performed or optimised using the same LC column type and / or the same mobile phases for the LC column.

16. The method of claim 13 or 14, wherein the pre-selected group of assay types only includes assay types that are able to be performed or optimised using only two different LC columns.

17. The method of claim 16, comprising providing automated machinery that automatically controls a valve system, based on the assay type that is required to be performed on any given sample, to select which of the LC columns is used to separate that sample and supply it to the mass spectrometer.

18. The method of any preceding claim, wherein the mass spectrometry is performed on a mass spectrometer that is programmed to operate in different mass analysis modes and / or with different configurations for the different respective assay types that are to be performed on each batch of samples; and wherein the method is conducted on a clinical analyser that automatically controls the mass spectrometer to operate in one or the analysis modes and / or with one of the configurations, based on the assay that is required to be performed on the sample being mass analysed.

19. The method of any preceding claim, comprising not adding calibrators to at least some of the batches of samples.

20. The method of any preceding claim, comprising determining, for each of the assay types to be performed on the batch of samples, a calibration relationship that relates an ion signal determined for an analyte of interest for that assay type to the concentration or quantity of that analyte of interest in the sample being analysed; wherein the calibration relationship has been determined before the batch of samples has been mass analysed and / or wherein the determined calibration relationship us used when analysing multiple batches of the samples.

21. The method of any preceding claim, comprising receiving the samples at an automated clinical analyser that:performs the step of determining the type of assay that each of the samples is required to be analysed by, by reading an identifier on each of the samples that is received;automatically performs said grouping of the received samples based on the identifiers that it reads on the samples; andautomatically adds sample preparation materials to the batch of samples that are required for preparing the samples for the assays, based on information read from the identifiers on the samples.

22. A method of analysing samples using liquid chromatography mass spectrometry, comprising:receiving samples to be analysed by liquid chromatography mass spectrometry;determining the type of assay that each of the samples is required to be analysed by; andgrouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types;wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a preselected group of multiple assay types.

23. A clinical mass spectrometry system configured to perform the method of any preceding claim.

24. A clinical mass spectrometry system comprising:a sample reader for reading identifiers on samples received at the system;a sample batching mechanism;andcontrol circuitry configured to control the system to:automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; andautomatically control the sample batching mechanism to group the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps.

25. A clinical mass spectrometry system comprising:a sample reader for reading identifiers on samples received at the system;a sample batching mechanism;andcontrol circuitry configured to control the system to:automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; andautomatically control the sample batching mechanism to group the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required to be analysed by different respective assay types, and wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been determined as being required to be analysed by an assay type that is within a pre-selected group of multiple assay types.

26. A method of analysing samples, comprising:receiving samples to be analysed;determining the type of assay that each of the samples is required to beanalysed by; andgrouping the received samples into batches of samples, wherein each batch of samples includes different samples that have been determined as being required5 to be analysed by different respective assay types; and wherein either(i) each batch of samples only includes samples that are required to be analysed by assay types that have the same sample preparation steps; and / or(ii) wherein said grouping of the received samples into batches of samples is performed such that it is only permitted to add samples to a batch if they have been10 determined as being required to be analysed by an assay type that is within a preselected group of multiple assay types.

Citation Information

Patent Citations

  • Method for processing chemistry and coagulation test samples in a laboratory workcell

    US20070020764A1

  • Method for Nucleic Acid Testing

    US20130157273A1

  • External files for distribution of molecular diagnostic tests and determination of compatibility between tests

    US20210147923A1