Automated clinical analysis

Abstract

A clinical liquid chromatography mass spectrometry system 100 that is operable to perform analytical tests on samples 410; the system comprising: a series of sample processing stages including a sampl

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority from and the benefit of United Kingdom patent application No. 2408104.4 filed on 7 June 2024, United Kingdom patent application No. 2408122.6 filed on 7 June 2024 and United Kingdom patent application No. 2505089.9 filed on 4 April 2025, the entire contents of which 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. LC-MS systems may typically be operated by highly trained staff in a labour-intensive manner, which can lead to slow turnaround times and high costs per test. There is therefore a desire to provide automated clinical LC-MS systems, particularly in order to reduce analytical test turnaround times and reduce costs per test. SUMMARY According to an aspect, there is provided a clinical liquid chromatography mass spectrometry system that is operable to (automatically) perform analytical tests on samples; the system comprising: a series of sample processing stages including a sample grouping stage followed by at least one subsequent sample processing stage; wherein the sample grouping stage comprises: a sample receiving unit configured to receive samples that may be subjected to different sample processing steps by the at least one subsequent sample processing stage; sample storage configured to temporarily store samples received by the sample receiving unit; a sample outputting unit configured to output samples stored in the sample storage to the at least one subsequent sample processing stage; and a controller configured to cause the sample outputting unit to output together, to the at least one subsequent sample processing stage, samples stored in the sample storage that are to be subjected to one or more same processing steps by the at least one subsequent sample processing stage. According to another aspect, there is provided a method of operating a clinical liquid chromatography mass spectrometry system that is operable to (automatically) perform analytical tests on samples, wherein the system comprises a series of sample processing stages; the method comprising: receiving samples that may be subjected to different sample processing steps by at least one subsequent sample processing stage; temporarily storing received samples in sample storage; and (automatically) outputting together, to the at least one subsequent sample processing stage, samples stored in the sample storage that are to be subjected to (a series of) one or more same processing steps by the at least one subsequent sample processing stage. In embodiments, the clinical mass spectrometry system can be configured to perform (automatically) a number of (e.g. a predefined set of) different analytical tests, e.g. to detect a plurality of different analytes of interest in a plurality of different types of patient sample. Each such analytical test may involve performing a predefined series of sample processing steps on a sample, such as one or more sample preparation steps, one or more sample separation steps, one or more sample analysis steps, etc.. In embodiments, the sample grouping stage (apparatus) may be able to receive samples in any order that are to undergo different sample processing steps / analytical tests, but output samples that are to undergo the same (e.g. series of) processing steps / analytical test together, e.g. successively or in a batch. In embodiments, to facilitate this, the sample grouping stage (apparatus) may include sample storage that can temporarily store (buffer) plural received samples. Samples buffered in the sample storage that are to undergo at least some of the same (e.g. series of) processing steps (e.g. the same analytical test) may be output from the storage together, e.g. successively or in a batch. Thus, in embodiments, the sample grouping stage (apparatus) can operate as a “re-ordering buffer” that temporarily buffers at least some input samples so as to allow “on-the-fly” re-ordering of samples that will be subject to one or more same subsequent processing steps, e.g. the same analytical test. As will be discussed below, this can reduce the frequency with which downstream processing steps / stages of the system may need to be reconfigured or recalibrated, in a straightforward manner. This can improve efficiency and sample throughput of the overall system, and thus facilitate shorter turnaround times and lower costs per test. A (each) sample may be a biological sample, such as from a patient. For example, a sample may be, or comprise, blood, blood plasma, blood serum, urine, stool, saliva or cerebrospinal fluid. A (each) sample may comprise one or more analytes of interest. An analyte of interest may be a steroid hormone, a vitamin, a drug of abuse (e.g. an opiate), a therapeutic drug such as an immunosuppressant, an anti-epileptic drug, an anti-infective drug, a steroid, an anti-fungal drug, an amino acid, a peptide, or a protein, a metabolite, etc.. An (each) analytical test on a sample may determine the presence of, quantity of, concentration of, etc., one or more analytes of interest in the sample. To do this, an analytical test may comprise performing a predefined series of sample processing steps on the sample. Different analytical tests may relate to different samples and / or different analytes of interest. Different analytical tests may comprise different sample processing steps, or at least some of the same sample processing steps. Samples may be received (by the sample receiving unit) in any order. Samples may be received as individual samples or as groups of samples, e.g. in individual containers or in one or more common containers. Samples may be received from an upstream (e.g. automated) processing stage of the system, or from a user input of samples, e.g. via an automated or manual interface. The sample storage temporarily stores (i.e. buffers) plural samples. Samples may be transferred from the sample receiving unit to the sample storage by a sample transfer unit, which may comprise a robotic arm or other automated mechanism. The sample storage may store a sample without performing any sample processing steps on the sample and / or without substantially altering properties of the sample. The sample storage may have an overall maximum storage capacity, such as <32, <64, <96, <192, <384, <1536 samples, or more than 1536 samples. The sample storage may store a sample in a same or different container to a container in which the sample was received (by the sample receiving unit). Samples are output from the sample storage by the sample outputting unit, which may comprise a robotic arm or other automated mechanism. Samples may be transferred to and from the sample storage by a same or different sample transfer unit, e.g. robotic arm or other automated mechanism. A sample may be output in a same or different container to a container in which the sample was stored in the sample storage. Samples may be output (by the sample outputting unit) to a downstream processing stage of the system, e.g. via an interface. The controller causes samples stored in the sample storage that are to undergo the same analytical test or one or more same sample processing steps (e.g. by a downstream processing stage of the system) to be output together (by the sample outputting unit). Samples that are to undergo all of the same processing steps, i.e. the same analytical test, may be output together. Additionally or alternatively, samples that are to undergo only some of the same processing steps may be output together. For example, samples that are undergoing different analytical tests that involve at least some of the same processing steps may be output together. The controller may maintain, or have access to, information indicating which processing step(s) / analytical test are to be performed on a (each) sample, and the controller may use the information to cause samples that are to undergo the same analytical test or one or more same sample processing steps to be output together. The information may be obtained in any suitable manner. The sample grouping stage (apparatus) may comprise a sample identifying unit that is configured to determine, for a (each) sample received by the sample receiving unit, information indicating an analytical test or (e.g. a series of) one or more sample processing steps that the sample is to undergo. The sample identifying unit may form part of the sample receiving unit, or may be a separate unit. The sample identifying unit may identify a received sample, e.g. from an identifier associated with the sample, such as a barcode or other identifier on a sample container. The identifier may directly indicate one or more sample processing steps or an analytical test that the sample is to undergo, or the identity of a sample may be used to determine one or more sample processing steps or an analytical test that the sample is to undergo from further information that indicates which processing steps / analytical tests are being performed on which samples. The (further) information may be maintained locally (e.g. by the controller) and / or externally (e.g. by a system controller or laboratory information management system (LIMS)), and may comprise a database, look-up table or other data structure. The sampling grouping stage (apparatus) may comprise a user interface that is configured to receive one or more user inputs. The information may be included in the one or more user inputs. Samples that are to undergo the same analytical test or one or more same sample processing steps may be caused to be output together in any suitable manner. The controller may cause the sample outputting unit to select and output samples together. In embodiments, the controller causes samples that are to be output together to be stored together in the sample storage, and the outputting unit outputs samples that are stored together in the sample storage. The sample storage may comprise a set of plural different storage regions where samples can be stored together. The sample storage may, for example, have <4, <8, <16, <32 different storage regions, or more than 32 different storage regions. A (each) storage region may have a maximum storage capacity, such as <4, <8, <16 samples, or more than 16 samples. Different storage regions may have the same or different maximum storage capacities. Samples that are to undergo one or more same sample processing steps, e.g. the same analytical test, may be stored in the same storage region. The information (e.g. determined by the sample identifying unit) may be used (e.g. by the controller) to select which sample storage region to store a (each) sample in, and the sample may be stored in the selected storage region. In this way, batches of samples that are to undergo one or more same processing steps, e.g. the same analytical test, may be formed in the sample storage. The sample storage may, for example, comprise a respective storage region for each analytical test that the system can perform, and a (each) received sample may be stored in the storage region corresponding to the analytical test that the sample is to undergo. Samples may be output together (by the sample outputting unit) successively / sequentially, one after the other, e.g. as a sequence of individual samples. Alternatively, samples may be output together (by the sample outputting unit), at the same time, e.g. as a batch of samples. For example, a batch of samples formed in a sample storage region of the sample storage may be output. A (each) batch may have a predetermined maximum size (which may correspond to a corresponding storage region maximum storage capacity), such as <4, <8, <16, <32, <64, <96 samples, or more than 96 samples. There may be different or the same batch sizes, e.g. for different analytical tests. Thus, another aspect provides a sample batching apparatus for use in a clinical mass spectrometry system that is operable to (automatically) perform analytical tests on samples; the apparatus comprising: a sample receiving unit configured to receive samples that are to undergo (a series of) one or more sample processing steps of an analytical test; sample storage configured to temporarily store samples received by the sample receiving unit; a batch outputting unit configured to output batches of samples; and a controller configured to cause the batch outputting unit to output a batch of samples stored in the sample storage that are to undergo the same analytical test or (series of) one or more same sample processing steps. Another aspect provides a method of operating a clinical mass spectrometry system that is operable to (automatically) perform analytical tests on samples; the method comprising: receiving samples that are to undergo (a series of) one or more sample processing steps of an analytical test; temporarily storing received samples in sample storage; and (automatically) outputting a batch of samples stored in the sample storage that are to undergo the same analytical test or (series of) one or more same sample processing steps. These aspects and embodiments can, and in embodiments do, comprise one or more, e.g. all, optional features of other aspects and embodiments described herein, as appropriate. For example, the batches of samples may be formed in the sample storage by storing a (each) received sample in a sample storage region that is selected according to the analytical test or (series of) one or more sample processing steps that (the information indicates) the sample is to undergo. Samples may be output together in response to a number of the samples stored in the sample storage reaching a predetermined maximum number of samples. For example, a batch of samples may be output in response to a number of samples of the batch reaching the predetermined maximum batch size. For example, the samples stored in a sample storage region may be output together (e.g. as a batch) in response to a number of the samples stored in the sample storage region reaching the maximum storage capacity of the sample storage region. Additionally or alternatively, in response to a number of the samples stored in the sample storage reaching the overall maximum storage capacity of the sample storage, a sample stored in the sample storage may be output together with one or more of any other samples stored in the sample storage that (the information indicates) are to undergo the same analytical test or (e.g. series of) one or more same sample processing steps. For example, a sample that has been buffered for a longest period of time may be output, or samples may be output together that comprise a largest number of samples stored in the sample storage that are to undergo the same analytical test or (e.g. series of) one or more same sample processing steps. Additionally or alternatively, a sample may be output in response to the sample having been stored for a predetermined maximum period of time. In this case, the sample may be output by itself, or together with one or more (e.g. all) other samples that are to undergo the same analytical test or (e.g. series of) one or more same sample processing steps. The predetermined maximum period of time may be based on a desired maximum turnaround around for an analytical test. The predetermined maximum period of time may be the same or different for different analytical tests. The predetermined maximum period of time may be <240 minutes, such as <120 minutes, such as <90 minutes, such as <60 minutes, such as <30 minutes, or another period of time. Additionally or alternatively, a sample may be output in response to the sample being identified (e.g. by the sample identifying unit) as a STAT sample, i.e. a sample that should be analysed without delay. In this case, output of a STAT sample may be prioritised, e.g. performed without delay and / or before any other sample that could potentially be output. In this case, the STAT sample may be output by itself (and not in a batch), or together with one or more (e.g. all) other samples that are to undergo the same analytical test or (e.g. series of) one or more same sample processing steps. Additionally or alternatively, a sample may be output in response to the sample being identified (e.g. by the sample identifying unit) as a low volume sample, i.e. a sample that arrives infrequently. In this case, the low volume sample may be output by itself, or together with one or more (e.g. all) other samples that are to undergo the same analytical test or (e.g. series of) one or more same sample processing steps. A (each) sample output from a sample processing stage in the series of sample processing stages may be input to a following sample processing stage in the series of sample processing stages, with a (each) sample processing stage in the series of sample processing stages performing some of a predefined series of sample processing steps of an analytical test. Samples that are to be subjected to (e.g. a series of) one or more same processing steps by the at least one subsequent sample processing stage may be output together (by the sample outputting unit) to the at least one subsequent sample processing stage, and the at least one subsequent sample processing stage may subject the output samples to the (e.g. series of) one or more same processing steps. Samples output together may be subjected by the at least one subsequent sample processing stage to (the) (e.g. series of) one or more same processing steps, e.g. successively / sequentially, one sample after the other, e.g. as a sequence of individual samples, or at the same time (in parallel), e.g. as a batch of samples. The system may be able to perform a predefined set of different analytical tests. Correspondingly, a (each) sample processing stage may be able to perform, for an (each) analytical test of the set of different analytical tests, (a series of) one or more corresponding sample processing steps. The system may be configurable to perform a selected analytical test of the set of different analytical tests on a sample. Correspondingly, a (each) sample processing stage may be configurable to perform (a series of) one or more sample processing steps corresponding to a selected analytical test. The system may comprise a system controller configured to configure a (each) sample processing stage to perform (a series of) one or more sample processing steps corresponding to a selected analytical test for a sample. The system may comprise a sample interface between an (each) adjacent pair of sample processing stages that passes sample between the processing stages. The system may comprise a sample preparation stage that performs (a series of) one or more sample preparation steps on a sample to prepare the sample for subsequent processing. The sample preparation stage may be configurable (by the system controller) to perform (a series of) one or more sample preparation steps corresponding to a selected analytical test. The sample grouping stage may be provided (e.g. immediately) prior to the sample preparation stage, and samples that are to be subjected to (e.g. a series of) one or more same sample preparation steps by the sample preparation stage may be output together (by the sample outputting unit), e.g. to the sample preparation stage. The system may comprise a sample separation stage that performs (a series of) one or more sample separation steps on a sample to separate the sample according to a physico-chemical property. The sample separation stage may comprise one or more liquid chromatography (LC) separation columns, and the physico-chemical property may correspond to chromatographic retention time. The sample separation stage may be configurable (by the system controller) to perform (a series of) one or more sample separation steps corresponding to a selected analytical test. The sample grouping stage may be provided (e.g. immediately) prior to the sample separation stage, and samples that are to be subjected to (e.g. a series of) one or more same sample separation steps by the sample separation stage may be output together (by the sample outputting unit), e.g. to the sample separation stage. For example, samples that are to be separated using a same LC separation column and / or same mobile phase may be output together. The system may comprise a sample analysis stage that performs (a series of) one or more sample analysis steps on a sample to analyse the sample. The sample analysis stage may comprise a mass spectrometer, and the sample analysis may be mass analysis. The sample analysis stage may be configurable (by the system controller) to perform (a series of) one or more sample analysis steps corresponding to a selected analytical test. The sample grouping stage may be provided (e.g. immediately) prior to the sample analysis stage, and samples that are to be subjected to (e.g. a series of) one or more same sample analysis steps by the sample analysis stage may be output together (by the sample outputting unit), e.g. to the sample analysis stage. The system may comprise a (the) sample preparation stage followed by a (the) sample separation stage followed by a (the) sample analysis stage. Correspondingly, a (each) analytical test that the system can perform may comprise one or more sample preparation steps performed by the sample preparation stage, followed by one or more sample separation steps performed by the sample separation stage, followed by one or more sample analysis steps performed by the sample analysis stage. The system may be a liquid chromatography-mass spectrometry system. The system may comprise only one sample grouping stage, or plural sample grouping stages, e.g. provided prior to different sample processing stages. For example, a first sample grouping stage (apparatus) may be provided (e.g. immediately) prior to the sample preparation stage and a second grouping stage (apparatus) may be provided (e.g. immediately) prior to the sample separation stage. Sample grouping and one or more other sample processing stages may be integrated into a single stage. For example, a combined sample grouping and sample preparation stage (apparatus) may be provided. The system may further comprise a manual sample input interface to a sample processing stage that bypasses at least one earlier sample processing stage in the series of sample processing stages. The manual sample input interface may bypass the sample grouping stage and / or the sample preparation stage. The manual sample input interface may be an input to the sample separation stage and / or the sample analysis stage. The system may not be limited to a clinical mass spectrometry system. That is, the system may comprise a clinical analysis system. All of the processing steps / stages may be automated, i.e. the system may comprise an automated system. Alternatively, one or more of the processing steps / stages may be automated, i.e. the system may comprise a semi-automated system. In this case, the system may require manual transfer of samples between the processing steps / stages, e.g. between the sample grouping stage, sample preparation stage, sample separation stage, or sample analysis stage. Another aspect provides a sample grouping apparatus for use in an automated clinical analysis system that is operable to (automatically) perform analytical tests on samples, the apparatus comprising: a sample receiving unit configured to receive samples that are to undergo one or more sample processing steps of an analytical test; sample storage configured to temporarily store samples received by the sample receiving unit; a sample outputting unit configured to output samples stored in the sample storage; and a controller configured to cause the sample outputting unit to output together samples stored in the sample storage that are to undergo the same analytical test or one or more same sample processing steps. A further aspect provides an automated clinical analysis system that is operable to (automatically) perform analytical tests on samples; the system comprising: a series of sample processing stages including a sample grouping stage followed by at least one subsequent sample processing stage; wherein the sample grouping stage comprises: a sample receiving unit configured to receive samples that may be subjected to different sample processing steps by the at least one subsequent sample processing stage; sample storage configured to temporarily store samples received by the sample receiving unit; a sample outputting unit configured to output samples stored in the sample storage to the at least one subsequent sample processing stage; and a controller configured to cause the sample outputting unit to output together, to the at least one subsequent sample processing stage, samples stored in the sample storage that are to be subjected to one or more same processing steps by the at least one subsequent sample processing stage. In these embodiments, the sample grouping apparatus may operate as a standalone apparatus in conjunction with an automated clinical analysis system, such as a clinical mass spectrometry system, or may form an integrated part (stage) of an automated clinical analysis system, e.g. clinical mass spectrometry system. Another aspect provides a clinical mass spectrometry system that is operable to (automatically) perform analytical tests on samples, the system comprising: a series of sample processing stages including a sample grouping apparatus, followed by at least one subsequent sample processing stage; wherein the sample grouping apparatus comprises: a sample receiving unit configured to receive samples that are to undergo one or more sample processing steps of an analytical test; sample storage configured to temporarily store samples received by the sample receiving unit; a sample outputting unit configured to output samples stored in the sample storage; and a controller configured to cause the sample outputting unit to output together samples stored in the sample storage that are to undergo the same analytical test or one or more same sample processing steps. Another aspect provides a method of operating a clinical mass spectrometry system that is operable to (automatically) perform analytical tests on samples; the method comprising: receiving samples that are to undergo one or more sample processing steps of an analytical test; temporarily storing received samples in sample storage; and (automatically) outputting together samples stored in the sample storage that are to undergo the same analytical test or one or more same sample processing steps. These aspects and embodiments can, and in embodiments do, comprise one or more, e.g. all, optional features of other aspects and embodiments described herein, as appropriate. 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: Figure 1A and Figure 1B show an automated clinical mass spectrometry system; Figure 2 shows an automated clinical mass spectrometry system according to an embodiment; Figure 3 shows an automated sample re-sequencing stage of an automated clinical mass spectrometry system according to an embodiment; Figure 4 shows an automated sample batching stage of an automated clinical mass spectrometry system according to an embodiment; Figure 5 shows an automated sample batching stage of an automated clinical mass spectrometry system according to an embodiment; Figure 6 shows simulation results demonstrating the operation of an automated sample batching stage according to an embodiment; Figure 7 shows an automated clinical mass spectrometry system according to an embodiment; Figure 8 shows an automated clinical mass spectrometry system according to an embodiment; Figure 9 shows an automated sample batching and sample preparation stage of an automated clinical mass spectrometry system according to an embodiment; and Figure 10 shows an automated clinical mass spectrometry system according to an embodiment. DETAILED DESCRIPTION Liquid chromatography-mass spectrometry (LC-MS) is often used within a clinical laboratory setting to determine concentrations of various clinically relevant molecules in a biological patient sample, such as blood, blood plasma, blood serum, urine, stool, saliva, or cerebrospinal fluid (CSF). 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 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. LC-MS systems are typically operated with highly trained staff which, combined with the manual nature of operation, can lead to high costs per test. There is therefore a desire to provide automated LC-MS systems suitable for deployment within a core laboratory and capable of being operated by lower skilled staff. Figure 1A shows schematically an automated clinical liquid chromatography-mass spectrometry (LC-MS) system 100. The system 100 includes a number of processing stages which operate automatically under the control of controller 101 to perform respective processing steps for samples 110 being analysed, including sample preparation module 140, liquid chromatography (LC) module 160, and mass spectrometry (MS) module 180. As illustrated in Figure 1, these different 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 sample being passed between adjacent processing modules by an appropriate interface 150, 170, automatically under the control of controller 101. As illustrated in Figure 1A, sample preparation module 140 receives an input sample 110 and prepares the sample for LC-MS analysis. Interface 150 passes a sample prepared by sample preparation module 140 on to LC module 160. LC module 160 separates a sample it has received from interface 150 according to chromatographic retention time. Interface 170 passes a sample separated by LC module 160 on to MS module 180. MS module 180 mass analyses a sample it has received from interface 170 and may output an analysis result 190, e.g. to a laboratory information management system (LIMS). The system 100 may be designed around the concept of “single piece flow”, whereby samples move from one step in the process to the next one at a time, but with some workflow steps potentially overlapping (performed at the same time) for different samples. To facilitate synchronisation and scheduling, all of the processing modules are synchronised to a common clock, with each processing module being able to begin processing a maximum of one sample per clock period, and to complete the processing of a maximum of one sample per clock period. This is illustrated by Figure 1B. As shown in Figure 1B, controller 101 includes a common clock 102 that is used to synchronise the operation of sample preparation module 140, interface 150, LC module 160, interface 170 and MS module 180. Samples may move between stages at a maximum rate of one sample per clock period. The inventors have recognised that in order to be able to separate and detect a broad range of clinically relevant analytes, a wide range of different sample preparation processes and instrument configurations may be required. This means that reconfiguration of one or more of the processing modules may be required, which reconfiguration operation may prevent sample processing and reduce sample processing throughput. For example, when changing from one LC separation type to another, it may be necessary to purge the mobile phases from a prior analysis and flush the system through with alternative mobile phases appropriate to the upcoming analysis. It may also be necessary to perform a recalibration operation. Such reconfiguration and recalibration can be time consuming, e.g. requiring multiple clock periods to complete. This can decrease efficiency and sample throughput of the system, and thus increase turnaround times and costs per test. Figure 2 shows schematically an automated clinical liquid chromatographymass spectrometry (LC-MS) system 200 according to an embodiment. The system 200 of Figure 2 is operable to automatically perform different analytical tests on different samples, e.g. from a predefined “menu” of analytical tests. Figure 2 shows the main elements of the system 200 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 200 that are not illustrated in Figure 2. As with the arrangement of Figure 1, the system 200 of Figure 2 includes a number of processing stages which operate automatically under the control of controller 201 to perform respective processing steps for samples 210 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 201. Each processing module may be configured by the controller 201 to perform appropriate processing steps on a sample for an analytical test that the sample is undergoing. Sample preparation module 240 receives samples 210 and prepares the samples for LC-MS analysis. Sample preparation module 240 may prepare different samples sequentially (at different times) and / or in parallel (at the same time). Sample preparation steps may include sample pipetting, aliquoting, addition of solvent, addition of reagents, addition of internal standards, QCs or calibrators, addition of magnetic beads (with or without a functionalized coating), magnetic bead processing, sample reacting / incubating, solid phase extraction (SPE), protein precipitation, enzymatic digestion, filtration, centrifugation, shaking / mixing, heating, etc.. Sample preparation module 240 may have multiple different sample preparation workflows available, and an appropriate workflow for a sample may be selected (by controller 201) based on the analytical test that is being performed. LC module 260 separates a sample according to chromatographic retention in an LC separation column. LC module 260 may separate different samples sequentially (e.g. using the same column) and / or in parallel (e.g. using different columns). LC module 260 may comprise one or more sample injection systems, one or more pumping systems, one or more separation columns, one or more mobile phases, etc.. LC module 260 may also be capable of flow injection. LC module 260 may have multiple different separation configurations available (e.g. column type, mobile phase type, etc.), and an appropriate configuration for a sample may be selected (by controller 201) based on the analytical test that is being performed. MS module 280 mass analyses prepared and separated samples to detect analytes of interest, and outputs analysis data 290, e.g. to a laboratory information management system (LIMS). MS module 280 may analyse different samples sequentially and / or in parallel. The output data 290 may comprise analysis results, raw data, processed data, calibrated data, uncalibrated data, etc., and may be indicative of a quantity or concentration of a particular molecule or molecules within a sample, or may indicate whether the quantity / concentration is above / below a defined threshold, for example. MS module 280 may have one or more ionisation source types (e.g. ESI, APCI, etc.), one or more mass spectrometry geometries (e.g. comprising quadrupole, ToF, ion trap, ion mobility, etc), one or more data analysis workflows, etc.. MS module 280 may have multiple different analysis configurations available, and an appropriate configuration for a sample may be selected (by controller 201) based on the analytical test that is being performed. An interface 230, 250, 270 between modules may comprise an electromechanical assembly, track system, robotic system, fluidic connection, etc.. A (each) interface 230, 250, 270 may be configured for a sample appropriately (by controller 201) based on the analytical test that is being performed, or may be operated manually. As shown in Figure 2, the system 200 further includes a batcher / re-sequencing (grouping) module 220 that may be interfaced to sample preparation module 240 by interface 230. Batcher / re-sequencing module 220 can receive input samples 210 in any order, and may receive input samples 210 individually or in groups. Batcher / re-sequencing module 220 temporarily buffers received samples, and attempts to output together buffered samples that are to be processed in a same or similar manner by a subsequent processing module of the system 200. Batcher / re-sequencing module 220 may thus output samples in a different order to the order in which samples were received. Figure 3 schematically illustrates batcher / re-sequencing (grouping) module 220 in more detail according to an embodiment. Figure 3 illustrates re-sequencing module 220, 300 interfaced to an upstream processing module of the system 200 by an input track 320, and to a downstream processing module of the system 200 by an output track 380 (e.g. corresponding to interface 230). Other forms of interface are possible. As shown in Figure 3, re-sequencing module 300 includes a local controller 301 that may be in communication with system controller 201. Re-sequencing module 300 further includes a sample receipt module 330 that receives samples 310 via input track 320. When sample receipt module 330 receives a sample, it identifies the sample, e.g. based on a barcode provided on the sample container, and this may be used by local controller 301, e.g. in conjunction with system controller 201 and / or a remote (e.g. LIMS) system, to determine what analytical test is to be performed on the sample. Other identifiers are possible. Sample transfer module 340 transfers the identified sample to sample storage 350 which temporarily stores the sample, e.g. without performing any processing steps 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 330 to a secondary container with the storage area 350. In the present embodiment, sample storage 350 has a maximum storage capacity of 384 samples. Other maximum numbers of samples are possible. Controller 301 keeps track of the analytical test that is to be performed on each sample buffered in the sample storage 350. When sample storage 350 becomes full (i.e. is storing the maximum numbers of samples), sample transfer module 340 transfers the sample that has been buffered for the longest period of time, and any other buffered samples that are to undergo the same analytical test, from sample storage 350 to sample output module 370. Again, a sample may be transferred in its container, or e.g. aspirated via pipette to another container. Sample output module 370 loads the samples onto output track 380, and the samples that are to undergo the same analytical test 390 are thus output together, e.g. successively. In this way, samples that are to undergo the same analytical test can be output together (e.g. successively), even where those samples were not received together (e.g. successively). Moreover, buffering samples allows this resequencing operation to be performed “on-the-fly”, e.g. without prior knowledge of the order / type of input samples, and without the need for complex sequencing algorithms. This can increase the frequency with which processing modules downstream of the re-sequencing module 300 receive successive samples that are to be processed in the same or similar way. This can accordingly reduce the frequency with which the downstream processing modules (e.g. sample preparation module 240, LC module 260 and MS module 280) need to be reconfigured / recalibrated to perform different processing / analysis. This can improve efficiency and sample throughput of the overall system 200. Re-sequencing module 300 could process all samples in substantially the same manner, however, in the present embodiment re-sequencing module 300 is able to recognise when a STAT sample is received (i.e. a sample that should be analysed without delay), and prioritises the output of STAT samples. When a STAT sample is received and recognised by sample receipt module 330, the sample bypasses sample storage 350, and is output as soon as practicable, e.g. with or without any other stored samples that are to undergo the same analytical test. For example, a STAT sample may be output by itself and not as part of a batch. In the present embodiment, re-sequencing module 300 is also able to recognise when a low volume sample is received (i.e. a sample that arrives infrequently). When a low volume sample is received and recognised by sample receipt module 330, the sample bypasses sample storage 350, and is output, e.g. with or without any other stored samples that are to undergo the same analytical test. Figure 4 schematically illustrates batcher / re-sequencing (grouping) module 220 in more detail according to another embodiment. In this embodiment, batcher module 220, 400 is operable to batch and output a batch of samples that are to undergo the same analytical test. Figure 4 illustrates batcher module 400 interfaced to an upstream processing module of the system 200 by an input track 420, and to a downstream processing module of the system 200 by an output track 480 (e.g. corresponding to interface 230). Other forms of interface are possible. As shown in Figure 4, batcher module 400 includes a local controller 401 that may be in communication with system controller 201. Batcher module 400 further includes a sample receipt module 430 that receives samples 410 via input track 420. When sample receipt module 430 receives a sample, it identifies the analytical test that is to be performed on the sample, e.g. as described above. Sample transfer module 440 then transfers the identified sample to sample storage 450 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 transferred to another container, e.g. as described above. As illustrated in Figure 4, in the present embodiment, sample storage 450 includes 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 430, controller 401 selects a storage region of the set of storage regions to transfer the respective sample to based on the analytical test that is to be performed on the respective sample, and sample transfer module 440 transfers the respective sample to the selected storage region. In this way, batcher module 400 can construct batches of samples that are to undergo the same analytical test within sample storage 450. In the present embodiment, each storage region of sample storage 450 has a maximum storage capacity of 8 samples, and can thus form a batch of 8 samples. Other maximum numbers of samples / batch sizes are possible, such as 2, 4, 16, 32, 64, 96, or another number. Different storage regions may have the same or different maximum storage capacities, and thus may form batches of the same or different sizes. Furthermore, batch size may be determined dynamically, e.g. based on a signal from an upstream or downstream processing module of the system 200. When a storage region becomes full (i.e. is storing the maximum numbers of samples), batch transfer module 460 transfers the completed batch of samples from sample storage 450 to sample output module 470. Samples of a batch may be transferred in or to individual containers, or in or to the same container. Sample output module 470 loads the batch of samples onto output track 480, and the batch of samples that are to undergo the same analytical test 490 is thus output. In this way, samples that are to undergo the same analytical test can be output together as a batch, even where those samples were not received together (e.g. successively). Moreover, buffering samples allows this batching operation to be performed “on-the-fly”, e.g. without prior knowledge of the order / type of input samples, and without the need for complex sequencing algorithms. This allows processing modules downstream of the batcher module 400 (e.g. sample preparation module 240, LC module 260 and MS module 280) to receive batches of samples that are to be processed in the same or similar manner, and to conveniently process the samples of a batch in parallel (at the same time). This can reduce reconfiguration / recalibration frequency, and improve efficiency and sample throughput of the overall system 200. Batcher module 400 may only output complete batches of samples (i.e. batches that include the maximum number of (e.g. 8) samples). However, the inventors have recognised that this can increase turnaround times for some types of tests, e.g. relatively rare analytical tests where it may be expected to take a relatively long period of time to receive a full batch of (e.g. 8) samples of that type. To account for this, in the present embodiment, controller 401 keeps track of the length of time that each sample in sample storage 450 has been buffered for, and when a sample has been buffered for longer than a predetermined threshold period of time, batch transfer module 460 transfers the corresponding “incomplete batch” of one or more samples from sample storage 450 to sample output module 470. Sample output module 470 loads the “incomplete batch” of one or more samples onto output track 480, and the “incomplete batch” of one or more samples is thus output. The predetermined threshold period of time may be based on a desired turnaround time for an analytical test, such as 90 minutes, or another period of time. The predetermined threshold period of time may be the same for all analytical tests or different for different analytical tests. Output of an “incomplete batch” of one or more samples may also be triggered by all of the sample storage regions in sample storage 450 being in use, and / or by a signal from an upstream or downstream processing module of the system 200. Batcher module 400 could process all samples in substantially the same manner, however, in the present embodiment batcher module 400 is able to recognise when a STAT sample is received, and prioritises the output of STAT samples, e.g. as described above. When a STAT sample is received and recognised by sample receipt module 430, the sample may bypass sample storage 450, and be output as soon as practicable, i.e. by itself and not as a batch. Alternatively, a STAT sample may be transferred to an appropriate storage region of sample storage 450, and output as soon as practicable as a batch together with any other stored samples that are to undergo the same analytical test. In the present embodiment, batcher module 400 is also able to recognise when a low volume sample is received. When a low volume sample is received and recognised by sample receipt module 430, the sample may bypass sample storage 450, and be output. Alternatively, a low volume sample may be transferred to an appropriate storage region of sample storage 450, and output as a batch together with any other stored samples that are to undergo the same analytical test. Figure 5 illustrates batcher module 400 in more detail according to an embodiment. In this embodiment, robotic arm 510 functions as both sample transfer module 440 and batch transfer module 460. However, separate mechanisms could be provided. Figure 6 illustrates simulation results that demonstrate the operation of batcher module 400. Table 1 shows a “menu” of 11 different analytical tests that system 200 may be configured to perform, together with a representative frequency at which each test is expected to be performed. The relative frequencies in Table 1 were used to synthesize a representative sequence of 240 samples arriving at batcher 400 to be batched as described above. Assay # Assay Description Relative Frequency 1 Endocrine Steroids Panel 1 16 2 Endocrine Steroids Panel 2 4 3 Endocrine Steroids (Thyroid) 1 4 Vitamin D 24 5 Immunosupressants panel 4 6 Drugs of abuse panel 1 - Opioids 4 7 Drugs of abuse panel 2 - Benzos 2 8 Drugs of abuse panel 3 - Amphetamines 2 9 Drugs of abuse panel 4 - Canabinoids 1 10 Drugs of abuse panel 5 - Other 1 11 Anti-infective drugs 1 TOTAL 60 Table 1: representative frequencies of different analytical tests to be performed by an automated LC-MS system Figure 6 plots the cumulative number of samples output from the batcher 400 as a function of the number of samples received by the batcher 400 for three different sets of operating conditions: (i) a maximum batch size of 8 samples, and a maximum buffer time of 90 minutes; (ii) a maximum batch size of 16 samples, and a maximum buffer time of 90 minutes; and (iii) a maximum batch size of 8 samples, and a maximum buffer time of 240 minutes. As can be seen in Figure 6, all three datasets show a small buffering delay between the input of the first sample and the first batch of samples being ready for output, but thereafter the output rate broadly keeps pace with that of the input rate. Although in the above embodiment, batcher / re-sequencing module 220, 300, 400 attempts to output together samples that are to undergo the same analytical test, other arrangements are possible. For example, batcher / re-sequencing module 220, 300, 400 may attempt to output together samples that are to be prepared in the same or similar manner by sample preparation module 240. This may allow samples with common sample preparation workflows to be prepared together, e.g. sequentially or in parallel. In this case, samples that are to undergo different analytical tests, but which are to undergo the same sample preparation steps, may be output together and subsequently prepared together by sample preparation module 240 (sequentially or in a batch). Figure 7 shows schematically an automated clinical liquid chromatographymass spectrometry (LC-MS) system 700 according to another embodiment. The system may operate substantially as described above, but with batcher or resequencing module 720 being provided between sample preparation module 740 and LC module 760. In this embodiment, batcher / re-sequencing module 720 attempts to output together samples that are to be separated in a same or similar manner by LC module 760. Samples may thus be batched / re-sequenced based upon the LC-MS method. This can allow samples separated with common columns and / or mobile phases to be analysed together (sequentially and / or in parallel), thus minimising the number of times that the operating method / conditions for the LC-MS may need to be altered, hence minimising time spent re-setting the system for analysis. This may also reduce the frequency of recalibration that may be necessary when changing LC-MS method. In this case, samples that are undergoing different analytical tests, but which are to undergo the same LC separation, may be output together and subsequently separated together by LC module 760 (sequentially or in a batch). Figure 8 shows schematically an automated clinical liquid chromatographymass spectrometry (LC-MS) system 800 according to another embodiment. The system may operate substantially as described above, but with a first batcher or resequencing module 820A being provided before sample preparation module 840, and a second batcher or re-sequencing module 820B being provided between sample preparation module 840 and LC module 860. In this embodiment, first batcher / re-sequencing module 820A attempts to output together samples that are to be prepared in a same or similar manner by sample preparation module 840, and second batcher / re-sequencing module 820B attempts to output together samples that are to be separated in a same or similar manner by LC module 860, e.g. as described above. In this embodiment, samples 810 may be received in a first order, prepared by sample preparation module 840 in a second order, and separated by LC module 860 in a third order. Although in the above embodiments, batcher / re-sequencing module 220, 300, 400 is a dedicated module, other arrangements are possible. For example, Figure 9 schematically illustrates an embodiment in which batching / re-sequencing and sample preparation are integrated in a single module 900. As illustrated in Figure 9, in this embodiment batches of input samples 910 are formed in sample storage 950, e.g. as described above, transferred to sample preparation region 960, and then prepared batches of samples 990 are output. Figure 10 shows schematically an automated clinical liquid chromatographymass spectrometry (LC-MS) system 200 according to a further embodiment. The system may operate substantially as described above with reference to Figure 2. As shown in Figure 10, the system 200 further includes a manual input interface 261 to the LC module 260 which allows batches of samples to be input directly to the LC module 260 for LC-MS analysis, bypassing the batcher module 220 and the sample preparation module 240. This can allow batches of samples to be manually prepared and input to the system for analysis. Although the above embodiments have been described with reference to a batcher / re-sequencing module 220, 300, 400 being used in an automated LC-MS system, other embodiments are possible. For example, batcher / re-sequencing module 220, 300, 400 may be used in an automated immunoassay or PCR system. In other embodiments, it is not necessary that the automated system comprises an MS module 280. For example, the automated system may comprise an LC module 260, and the MS module 280 may be replaced by an optical detector. Alternatively, the automated system may comprise an MS module 280, but not an LC module 260. The foregoing detailed description has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the technology to the precise form disclosed. Many modifications and variations are possible in the light of the above teaching. The described embodiments were 5 chosen in order to best explain the principles of the technology and its practical application, to thereby enable others skilled in the art to best utilise the technology in various embodiments and with various modifications as are suited to the particular use contemplated. It is intended that the scope be defined by the claims appended hereto. 10

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