Automated clinical analysis

Abstract

A clinical mass spectrometry system comprising: a series of sample processing stages including one or more sample preparation stages 240, followed by one or more sample separation and / or analysis stag

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 automated clinical analysis systems, such as clinical mass spectrometry systems, and in particular to buffering samples for automated 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 patent 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 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 one or more sample preparation stages, followed by one or more sample separation and / or analysis stages; one or more sample interfaces configured to automatically provide samples prepared by the one or more sample preparation stages to the one or more sample separation and / or analysis stages for separation and / or analysis; and one or more bypass interfaces for: (i) outputting samples prepared by the one or more sample preparation stages from the system, bypassing the one or more sample separation and / or analysis stages, and / or (ii) inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages, bypassing the one or more sample preparation stages. According to another aspect, there is provided a method of operating 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 one or more sample preparation stages, followed by one or more sample separation and / or analysis stages; one or more sample interfaces configured to (automatically) provide samples prepared by the one or more sample preparation stages to the one or more sample separation and / or analysis stages for separation and / or analysis; and one or more bypass interfaces for: (i) outputting samples prepared by the one or more sample preparation stages from the system, bypassing the one or more sample separation and / or analysis stages, and / or (ii) inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages, bypassing the one or more sample preparation stages; the method comprising: outputting samples prepared by the one or more sample preparation stages from the system using one or more of the one or more bypass interfaces; and / or inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages using one or more of the one or more bypass interfaces. The system may be a clinical mass spectrometry system. According to an aspect, there is provided a clinical mass spectrometry system comprising: a series of sample processing stages including one or more sample preparation stages, followed by one or more sample separation and / or analysis stages; one or more sample interfaces configured to (automatically) provide samples prepared by the one or more sample preparation stages to the one or more sample separation and / or analysis stages for separation and / or analysis; and one or more bypass interfaces for: (i) outputting samples prepared by the one or more sample preparation stages from the system, bypassing the one or more sample separation and / or analysis stages, and / or (ii) inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages, bypassing the one or more sample preparation stages. According to another aspect, there is provided a method of operating a clinical mass spectrometry system that comprises: a series of sample processing stages including one or more sample preparation stages, followed by one or more sample separation and / or analysis stages; one or more sample interfaces configured to (automatically) provide samples prepared by the one or more sample preparation stages to the one or more sample separation and / or analysis stages for separation and / or analysis; and one or more bypass interfaces for: (i) outputting samples prepared by the one or more sample preparation stages from the system, bypassing the one or more sample separation and / or analysis stages, and / or (ii) inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages, bypassing the one or more sample preparation stages; the method comprising: outputting samples prepared by the one or more sample preparation stages from the system using one or more of the one or more bypass interfaces; and / or inputting samples to the system for separation and / or analysis by the one or more sample separation and / or analysis stages using one or more of the one or more bypass interfaces. The system may be a clinical liquid chromatography-mass spectrometry (LC-MS) system. Embodiments relate to an automated clinical analysis system, such as a clinical mass spectrometry system. In embodiments, the automated clinical analysis system (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 system comprises a series of sample processing stages and one or more sample interfaces, whereby a (each) sample that has been processed by a sample processing stage in the series of sample processing stages may be provided (automatically) by a sample interface to a following sample processing stage in the series of sample processing stages for processing by that sample processing stage, with a (each) sample processing stage in the series of sample processing stages (automatically) performing some of a predefined series of sample processing steps of an analytical test. For example, the series of sample processing stages may comprise a sample preparation stage that performs one or more sample preparation steps on a sample (e.g. forming batches of samples and / or one or more biochemical processes), followed by a sample separation stage that performs one or more sample separation steps on the sample (e.g. liquid chromatography separation), followed by a sample analysis stage that performs one or more sample analysis steps on the sample (e.g. mass analysis). In embodiments, as well as being able to be passed automatically between all of the sample processing stages of the series of sample processing stages by the one or more sample interfaces, the system comprises one or more bypass interfaces via which a sample can, and in embodiments does, bypass one or more of the sample processing stages of the series of sample processing stages. In particular, in embodiments, the system comprises one or more output (bypass) interfaces via which samples that have been prepared by one or more sample preparation stages of the series of sample processing stages can be output from the system, bypassing one or more subsequent sample separation and / or analysis stages. In embodiments, the system comprises one or more input (bypass) interfaces via which samples can be input to the system for separation and / or analysis by one or more sample separation and / or analysis stages of the series of sample processing stages, bypassing one or more earlier sample preparation stages. In embodiments, an output (bypass) interface and an input (bypass) interface may be a combined output / input (bypass) interface via which samples can be output from and / or input to the system. The provision of one or more such bypass interfaces can allow the system to be operated in a particularly flexible manner. For example, some samples may automatically pass though (and be processed by) all of the sample processing stages of the series of sample processing stages of the system, whereas other samples may pass through (and be processed by) only some of the sample processing stages of the series of sample processing stages of the system. For example, some samples may be input to the one or more sample preparation stages and automatically prepared for separation and / or analysis by the one or more sample preparation stages, and then automatically provided by the one or more sample interfaces to the one or more sample separation and / or analysis stages and subjected to sample separation and / or analysis by the one or more sample separation and / or analysis stages. Other samples may be input to the one or more sample preparation stages and automatically prepared for separation and / or analysis by the one or more sample preparation stages, but then output from the system using the one or more bypass interfaces without being subjected to sample separation and / or analysis by the one or more sample separation and / or analysis stages of the system. The output samples may, for example, be separated and / or analysed by another system (e.g. at the same time as (in parallel with) other samples that have been prepared by the one or more sample preparation stages are separated and / or analysed by the one or more sample separation and / or analysis stages of the system). Other samples may be input to the system using the one or more bypass interfaces and subjected to separation and / or analysis by the one or more sample separation and / or analysis stages without having been subjected to sample preparation by the one or more sample preparation stages of the system. The input samples may, for example, be prepared for separation and / or analysis by another system or manually. Furthermore, samples may be input to the one or more sample preparation stages and automatically prepared for separation and / or analysis by the one or more sample preparation stages, then output from the system using the one or more bypass interfaces, then optionally subjected to one or more further processing steps e.g. manually or by another system, then re-input to the system using the one or more bypass interfaces, and subjected to separation and / or analysis by the one or more sample separation and / or analysis stages of the system. As well as flexibility, embodiments can facilitate efficient operation where different sample processing stages of the system can operate asynchronously, e.g. with different sample throughputs. For example, where the one or more sample preparation stages have a higher maximum sample throughput than the one or more sample separation and / or analysis stages, additional throughput capacity of the one or more sample preparation stages may be utilised by outputting a portion of samples prepared by the one or more sample preparation stages from the system using the one or more bypass interfaces for separation and / or analysis by another system (and automatically providing a portion of samples prepared by the one or more sample preparation stages to the one or more sample separation and / or analysis stages of the system). Similarly, where the one or more sample preparation stages have a lower maximum sample throughput than the one or more sample separation and / or analysis stages, additional throughput capacity of the one or more sample separation and / or analysis stages may be utilised by inputting samples to the system using the one or more bypass interfaces for separation and / or analysis by the one or more separation and / or analysis stages of the system. This can improve efficiency and sample throughput of the overall system, and thus facilitate shorter turnaround times and lower costs per test. The one or more sample preparation stages may have a different (higher or lower) maximum sample throughput to the one or more sample separation and / or analysis stages. That is, the maximum number of samples that the one or more sample preparation stages can prepare in a given amount of time may be different to, i.e. higher than or lower than, the maximum number of samples that the one or more sample separation and / or analysis stages can separate and / or analyse in the given amount of time. The one or more sample preparation stages may thus be a first set of one or more sample processing stages that operate according to a first timing regime, and the one or more sample separation and / or analysis stages may be a second set of one or more sample processing stages that operate according to a second, different timing regime. Thus, in embodiments, the system includes sample processing stages that operate according to different timing regimes. To allow for this, in embodiments, a sample interface at the interface between sample processing stages that are operating according to different timing regimes can operate as a buffer that receives samples output according to a first timing regime, and outputs samples according to a second, different timing regime. Thus, according to another aspect, there is provided 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 first set of one or more sample processing stages operating according to a first timing regime, followed by a second set of one or more sample processing stages operating according to a second, different timing regime; and a sample buffer between the first set of one or more sample processing stages and the second set of one or more sample processing stages; wherein the sample buffer is configured to: receive samples output by the first set of one or more sample processing stages according to the first timing regime, and output samples to the second set of one or more sample processing stages according to the second timing regime. According to another aspect, there is provided a method of operating an automated clinical analysis system that is operable to (automatically) perform analytical tests on samples; wherein the system comprises a series of sample processing stages including a first set of one or more sample processing stages operating according to a first timing regime, followed by a second set of one or more sample processing stages operating according to a second, different timing regime; the method comprising: providing a sample buffer between the first set of one or more sample processing stages and the second set of one or more sample processing stages; and the sample buffer: receiving samples output by the first set of one or more sample processing stages according to the first timing regime, and outputting samples to the second set of one or more sample processing stages according to the second timing regime. According to another aspect, there is provided a clinical mass spectrometry system comprising: a series of sample processing stages including a first set of one or more sample processing stages operating according to a first timing regime, followed by a second set of one or more sample processing stages operating according to a second, different timing regime; and a sample buffer between the first set of one or more sample processing stages and the second set of one or more sample processing stages; wherein the sample buffer is configured to: receive samples output by the first set of one or more sample processing stages according to the first timing regime, and output samples to the second set of one or more sample processing stages according to the second timing regime. According to another aspect, there is provided a method of operating a clinical mass spectrometry system; wherein the system comprises a series of sample processing stages including a first set of one or more sample processing stages operating according to a first timing regime, followed by a second set of one or more sample processing stages operating according to a second, different timing regime; the method comprising: providing a sample buffer between the first set of one or more sample processing stages and the second set of one or more sample processing stages; and the sample buffer: receiving samples output by the first set of one or more sample processing stages according to the first timing regime, and outputting samples to the second set of one or more sample processing stages according to the second timing regime. 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 system may include one or more bypass interfaces. Embodiments relate to an automated clinical analysis system, such as a clinical mass spectrometry system. In embodiments, the automated clinical analysis system (e.g. 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 system comprises a series of sample processing stages, whereby 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. For example, the series of sample processing stages may comprise a sample preparation stage that performs one or more sample preparation steps on a sample, followed by a sample separation stage that performs one or more sample separation steps on the sample, followed by a sample analysis stage that performs one or more sample analysis steps on the sample. In embodiments, to facilitate synchronisation and scheduling, a (each) sample processing stage operates according to a particular timing regime. For example, the processing steps that a sample processing stage performs may be synchronised to a clock, e.g. such that each processing step takes (exactly) one or more clock periods to be performed, and / or such that processing of up to one or more samples can begin or complete per clock period. In embodiments, the system includes sample processing stages that are operating according to different timing regimes. Thus, different sample processing stages may be synchronised based on different clock periods and / or phases. To allow for this, in embodiments, a sample buffer is provided at the interface between sample processing stages that are operating according to different timing regimes. The sample buffer receives samples output according to a first timing regime, and outputs samples according to a second, different timing regime. This can allow different processing stages to be optimised according to different timing regimes, with the sample buffer providing a seamless interface between the different timing regimes. 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 me 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, or an amino acids, 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. The system may be able to perform a predefined set of different analytical tests / modes of operation. 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 / mode of operation for a sample. Where a sample bypasses one or more sample processing stages, the system controller may configure a (each) bypassed sample processing stage to omit performing sample processing steps for the sample. The (one or more sample interfaces of the) system may comprise a (respective) sample interface between an (each) adjacent pair of sample processing stages that can (automatically) pass samples between the processing stages. A (the) system controller may configure a (each) sample interface to pass samples between processing stages in accordance with a (the) selected analytical test / mode of operation. 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 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 be a liquid chromatography stage. 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 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 be a mass spectrometry stage. 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 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 clinical mass spectrometry system, such as a liquid chromatography-mass spectrometry system. The first set of one or more processing stages may comprise the sample preparation stage which may operate according to the first timing regime. The second set of one or more processing stages may comprise the sample separation stage and the sample analysis stage (e.g. liquid chromatography stage and mass spectrometry stage), which may operate according to the second, different timing regime. Thus, the first set of one or more sample processing stages may comprise (i) a sample preparation stage; and the second set of one or more sample processing stages comprises one or more of: (ii) a sample separation stage; and (iii) a sample analysis stage. The sample buffer may thus be provided after the sample preparation stage and before the sample separation stage and sample analysis stage (e.g. liquid chromatography stage and mass spectrometry stage). The system may have only two different timing regimes, or more than two different timing regimes. Correspondingly, the system may have only one sample buffer at the interface between only two different timing regimes, or there may be more than one sample buffer, e.g. a sample buffer at each interface between different timing regimes. A (each) timing regime may be defined by a (respective) clock period and / or phase. Different timing regimes may thus differ in a clock period and / or phase. That is, different timing regimes may have a different clock period and / or a different clock phase. A (each) timing regime may be defined by a (respective) clock that may be maintained by the system controller. Thus, the system controller may comprise two or more clocks that define different timing regimes. A (each) sample processing stage may be constrained to perform a (each) processing step during (exactly) one or more clock periods. A (each) sample processing stage may be constrained to begin and / or complete the processing of one or more samples during (exactly) one or more clock periods. The system may be configured such that each of the one or more sample processing stages in the first set is governed by a first clock having a first clock period so that these one or more sample processing stages process samples on a timescale that corresponds to an integer number of the first clock period, and each of the one or more sample processing stages in the second set is governed by a second clock having a second clock period so that these one or more sample processing stages process samples on a timescale that corresponds to an integer number of the second clock period. The first clock period may have a different duration to the second clock period. The first and second clock periods may have the same duration but occur out of phase with each other. By providing first and second clock periods that have different durations, the first and second sets of sample processing stages are not restricted to performing processing steps based on the same clock rate. This provides the system with greater flexibility and may enable a higher efficiency of sample processing. Similarly, providing the first and second clock periods out of phase from each other also enables more flexibility in the timescales over which the samples are processed by the first and second sets of sample processing stages. The sample buffer acts to interface that the sample processing performed by the first and second sets of sample processing stages. A (the) sample buffer (interface) receives samples output by a first set of one or more sample processing stages according to a first timing regime, and outputs samples to a second set of one or more sample processing stages according to a second, different timing regime. The sample buffer may comprise a sample receiving unit configured to receive samples according to the first timing regime. Samples may be received (by the sample receiving unit) in any order. The sample buffer may comprise sample storage configured to temporarily store samples (received by the sample receiving unit). 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 samples, or more than 192 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). The sample buffer may comprise a sample outputting unit configured to output samples (stored in the sample storage) according to a second, different timing regime. A sample may be output in a same or different container to a container in which the sample was stored in the sample storage. The first set of one or more sample processing stages (e.g. sample preparation stage) may process and output samples to the sample buffer according to the first timing regime, and (the sample receiving unit of) the sample buffer receives samples from the first set of one or more sample processing stages according to the first timing regime. The first set of one or more sample processing stages may process and output samples, and the sample buffer may receive samples, in a serial manner, e.g. successively / sequentially, one after the other, or in parallel (at the same time), e.g. as a batch of samples. The (sample outputting unit of the) sample buffer outputs samples according to the second timing regime, and the second set of one or more sample processing stages (e.g. sample separation stage and sample analysis stage) may receive and process samples according to the second timing regime. The sample buffer may output samples, and the second set of one or more sample processing stages may receive and process samples, in a serial manner, e.g. successively / sequentially, one after the other, or in parallel (at the same time), e.g. as a batch of samples. A (each) batch of samples may have a predetermined size, / V, such as 2, 4, 8, 16 samples, or another number. There may be different or the same batch sizes, e.g. for different analytical tests. The (sample outputting unit of the) sample buffer may output samples / batches in a same order to an order in which the samples / batches were received (by the sample receiving unit). For example, the sample buffer may operate as a FIFO (first-in-first-out) buffer. Alternatively, the (sample outputting unit of the) sample buffer may output samples / batches in a different order to an order in which the samples / batches were received (by the sample receiving unit). For example, output of a STAT sample (i.e. a sample that should be analysed without delay) may be prioritised, e.g. performed without delay and / or before any other sample that could potentially be output. Additionally or alternatively, the sample buffer may be able to receive samples in any order that are to undergo different sample processing steps / analytical tests, but may output samples that are to undergo the same (e.g. series of) processing steps / analytical test together, e.g. successively. This can reduce the frequency with which downstream processing steps / stages of the system may need to be reconfigured or recalibrated, and thus improve efficiency and sample throughput. The first timing regime may correspond to a rate of up to one sample per clock period or up to one batch of samples per clock period. The second timing regime may correspond to a rate of up to one sample per clock period or up to one batch of samples per clock period. The first timing regime may correspond to a first maximum sample throughput, and the second timing regime may correspond to a second, different maximum sample throughput. The sample buffer may be able to receive up to one sample per clock period of the first timing regime from the first set of one or more sample processing stages, form batches of / V samples, and output up to one batch of / V samples per clock period of the second timing regime to the second set of one or more sample processing stages. Alternatively, the sample buffer may be able to receive up to one batch of / V samples per clock period of the first timing regime from the first set of one or more sample processing stages, and output up to one sample per clock period of the second timing regime to the second set of one or more sample processing stages. The clock period of the first timing regime, T^, and the clock period of the second timing regime, T2, may have a common factor. For example, = nT2 or T2 = nTt, where n is a positive integer. For example, = NT2 or T2 = NT^, where N is batch size. Alternatively, dividing the clock periods may result in a non-integer value. The (one or more bypass interfaces of the) system may 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 be an input to a sample processing stage of the second set of one or more sample processing stages, and may bypass the first set of one or more sample processing stages. The (manual) sample input interface may be an input to the sample separation stage and / or the sample analysis stage. The (manual) sample input interface may bypass the sample preparation stage. The sample input (bypass) interface may be configured to receive input samples (from a user), and (automatically) provide the samples to the one or more sample separation and / or analysis stages for separation and / or analysis. The sample input interface may comprise an input port for receiving input samples (from a user). The sample input interface may comprise a unit configured to (automatically) provide samples from the input port to the one or more sample separation and / or analysis stages. The (one or more bypass interfaces of the) system may comprise a (manual) sample output interface from a sample processing stage that bypasses at least one later sample processing stage in the series of sample processing stages. The (manual) sample output interface may be an output from a sample processing stage of the first set of one or more sample processing stages, and may bypass the second set of one or more sample processing stages. The (manual) sample output interface may be an output from the sample preparation stage. The (manual) sample output interface may bypass the sample separation stage and / or the sample analysis stage. The sample output (bypass) interface may be configured to receive samples prepared by the one or more sample preparation stages, and (automatically) provide the samples for output (to a user). The sample output interface may comprise an output port for outputting samples (to a user). The sample output interface may comprise a unit configured to (automatically) provide samples from the one or more sample preparation stages to the output port. The (one or more bypass interfaces of the) system may comprise a combined (manual) sample input and output interface that combines the functions of a (manual) sample input interface and a (manual) sample output interface. The combined sample input and output (bypass) interface may comprise a combined input and output port for receiving input samples (from a user) and outputting samples (to a user). The combined sample input and output interface may comprise a unit configured to (automatically) provide samples from the combined input and output port to the one or more sample separation and / or analysis stages for separation and / or analysis, and / or (automatically) provide samples from the one or more sample preparation stages to the combined input and output port for output. In embodiments, a (each) bypass interface is configurable by a (the) system controller to handle samples in accordance with a selected mode of operation. For example, the system may be configured (by the system controller) to process a sample (or batch of samples) in a “sample preparation-only” mode of operation, comprising the sample (or batch of samples) being prepared by the one or more sample preparation stages, and then being provided for output using the one or more bypass interfaces. The system may be configured (by the system controller) to process a sample (or batch of samples) in a “sample separation and / or analysis-only” mode of operation, comprising the sample (or batch of samples) being input using the one or more bypass interfaces and provided to the one or more sample separation and / or analysis stages for separation and / or analysis. Other modes of operation are possible. Each aspect can, and in embodiments does, comprise one or more, e.g. all, optional features of other aspects 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 2A and Figure 2B show an automated clinical mass spectrometry system according to embodiments; Figure 3 shows a sample buffer stage of an automated clinical mass spectrometry system according to an embodiment; Figure 4 shows a sample buffer stage of an automated clinical mass spectrometry system according to an embodiment; Figure 5 shows an automated clinical mass spectrometry system according to an embodiment; Figure 6 shows an automated clinical mass spectrometry system according to an embodiment; Figure 7 shows an automated clinical mass spectrometry system according to an embodiment; and Figure 8 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 term "clock" should be interpreted broadly as a reference to timing mechanisms or timescales that define or regulate temporal behaviour, and which may be defined or measured through a variety of methods. For example, the term “clock” may encompass a time period, a time span, a duration, an interval, a frequency, a rate, a cadence, a periodicity, a cycle time, a sampling rate, etc.. The inventors have recognised that imposing a single timing regime of a common clock over the entire system may not be optimal in all situations. For example, it can be difficult to select a single clock period that is ideally suited for all of the steps associated with sample preparation, liquid chromatography and mass spectrometry. Thus, typically, a compromise common timing regime may be selected, which may be optimal or close to optimal for one element of the system but sub-optimal for others. This can decrease efficiency and sample throughput of the system, and thus increase turnaround times and costs per test. Figure 2A shows schematically an automated clinical liquid chromatography-mass spectrometry (LC-MS) system 200 according to an embodiment. The system 200 of Figure 2A is operable to automatically perform different analytical tests on different samples, e.g. from a predefined “menu” of analytical tests. Figure 2A 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 2A. As with the arrangement of Figure 1, the system 200 of Figure 2A 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 270 between modules may comprise an electro-mechanical assembly, track system, robotic system, fluidic connection, etc.. An interface 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. In the present embodiment, the controller 201 maintains two different timing regimes, corresponding to a first clock 202 that is used to synchronise the operation of sample preparation module 240, and a second clock 203 that is used to synchronise the operation of LC module 260, interface 270 and MS module 280. Each clock may be matched, optimised or otherwise determined based upon the specific needs and demands of the workflow within the particular sub-system that the clock governs, without regard to any other sub-system. As shown in Figure 2A, to successfully mate sub-systems together and avoid timing conflicts, the system 200 further includes a buffer module 250 that is provided in between modules operating in the two different timing regimes. Buffer module 250 receives sample from an upstream module (sample preparation module 240) operating in a first timing regime, and outputs samples to a downstream module (LC module 260) operating in a second, different timing regime. For example, Figure 2B shows schematically an embodiment in which sample preparation module 240 operates asynchronously with LC module 260 and MS module 280. In this embodiment, sample preparation module 240, LC module 260 and MS module 280 can each begin and complete processing of (up to) one sample per clock period, but the clock governing sample preparation module 240 is out of phase with the clock governing LC module 260 and MS module 280. Figure 3 schematically illustrates buffer module 250 in more detail according to an embodiment. Figure 3 illustrates buffer module 250, 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. Other forms of interface are possible. As shown in Figure 3, buffer module 300 includes a local controller 301 that may be in communication with system controller 201. Buffer 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 from upstream processing module, sample transfer module 340 transfers the 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. When the downstream processing module is ready to receive a next sample, sample transfer module 340 transfers the sample that has been buffered for the longest period of time from sample storage 350 to sample output module 370. Sample output module 370 loads the sample onto output track 380, and the sample 390 is thus output. In this way, samples may be buffered in a FIFO (first-in-first-out) arrangement. Other buffering arrangements, such as LIFO (last-in-first-out) or prioritised are possible. This can allow upstream (e.g. sample preparation module 240) and downstream processing modules (e.g. LC module 260 and MS module 280) to be seamlessly operated in different timing regimes, which can facilitate improved robustness, reliability efficiency, and sample throughput of the overall system 200. To avoid buffer overflow, system controller 201 may temporarily pause an upstream process, such as acceptance of new samples into the system 200. This may be triggered by system controller 201 using knowledge of the entire workflow, or by local controller 301 determining that sample storage 350 is full. Buffer module 300 could process all samples in substantially the same manner, however, in the present embodiment buffer 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 by sample receipt module 330, the sample bypasses sample storage 350, and is output as soon as practicable. In another embodiment, buffer module 300 attempts to output together (e.g. sequentially) buffered samples that are to be processed in a same or similar manner by a subsequent processing module of the system 200. Buffer module 300 may thus output samples in a different order to the order in which samples were received. In this embodiment, 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. Controller 301 keeps track of the analytical test that is to be performed on each sample buffered in the sample storage 350. When the downstream processing module is ready to receive a next sample, any buffered sample that is to undergo the same analytical test as a previously output sample is preferentially output. 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). This can increase the frequency with which processing modules downstream of the buffer module 300 (e.g. LC module 260 and MS module 280) 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 need to be reconfigured / recalibrated to perform different processing / analysis. As well as, or instead of, operating with different clock phases, sample preparation module 240 may operate with a different clock period to LC module 260 and MS module 280. For example, Figure 4 schematically illustrates buffer module 250 in more detail according to another embodiment. In this embodiment, buffer module 250, 400 is operable to receive individual samples according to a first clock period of first clock 202, form batches of samples, and output batches of samples according to a second clock period of second clock 203. Correspondingly, sample preparation module 240 may be able to begin and complete processing of (up to) one sample per first clock period of first clock 202, and LC module 260 and MS module 280 may be able to begin and complete processing of (up to) one batch per second clock period of second clock 203. As illustrated in Figure 4, in this 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, e.g. based on the analytical test that is to be performed on the respective sample. Sample transfer module 440 transfers the respective sample to the selected storage region. In this way, buffer module 400 can construct batches of samples within sample storage 450, e.g. that are to undergo the same analytical test. 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. When the downstream processing module is ready to receive a next batch of samples, batch transfer module 460 transfers a batch of samples from sample storage 450 to sample output module 470. Sample output module 470 loads the batch of samples onto output track 480, and the batch of samples 490 is thus output. Figure 5 shows schematically another embodiment in which sample preparation module 240 may be able to begin and complete processing of (up to) one batch of samples per first clock period of first clock 202, and LC module 260 and MS module 280 may be able to begin and complete processing of (up to) one sample per second clock period of second clock 203. As shown in Figure 5, in this embodiment, a batcher module 220 is provided before the sample preparation module 240. The batcher module 220 may operate substantially as described above with respect to Figure 4 to output batches of samples that may be processed in parallel by the sample preparation module 240. In this embodiment, the buffer module 250 is operable to receive batches of samples from sample preparation module 240 according to first clock period of first clock 202, and output individual samples to LC module 260 according to second clock period of second clock 203. Figure 6 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 5. As shown in Figure 6, the system 200 further includes a manual input interface 261 to the LC module 260 which allows 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. Input interface 261 may comprise an input port for receiving (e.g. a batch of) samples input by a user, and a system (e.g. electromechanical assembly, track system, robotic system, fluidic connection, etc.) for providing (e.g. a batch of) samples received at the input port to LC module 260 (e.g. under the control of controller 201). This can allow samples to be manually prepared, or prepared by another system, and input to the system for analysis. Where the timing regimes are such that sample preparation module 240 has a lower sample throughput than LC module 260 and / or MS module 280, this can allow efficient utilisation of the additional throughput capacity of the LC module 260 and / or MS module 280. For example, a batch of samples that has been prepared separately may be input to the system 200 via input interface 261 and subjected to LC-MS analysis by LC module 260 and MS module 280 while waiting for sample preparation module 240 to complete the preparation of another batch of samples. Figure 7 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 6, and includes a manual input interface 261 to the LC module 260 which allows samples to be input directly to the LC module 260 for LC-MS analysis, e.g. without having been prepared for analysis by the sample preparation module 240. In this embodiment, the controller 201 maintains three different timing regimes, corresponding to a first clock 202 that is used to synchronise the operation of batcher module 220 and buffer interface 230, a second clock 203 that is used to synchronise the operation of sample preparation module 240 and buffer interface 250, and a third clock 204 that is used to synchronise the operation of LC module 260, interface 270 and MS module 280. Each clock may be matched, optimised or otherwise determined based upon the specific needs and demands of the workflow within the particular sub-system that the clock governs, without regard to any other sub-system. As shown in Figure 7, the system 200 further includes a manual output interface 262 from the sample preparation module 240 which allows samples that have been prepared for analysis by the sample preparation module 240 to be output without being separated or analysed by the LC module 260 or MS module 280. Output interface 262 may comprise an output port for outputting (e.g. a batch of) samples to a user, and a system (e.g. electro-mechanical assembly, track system, robotic system, fluidic connection, etc.) for providing (e.g. a batch of) samples from sample preparation module 240 to the output port (e.g. under the control of controller 201). Samples output via the manual output interface 262 may be analysed by a different e.g. LC-MS analyser. Where the timing regimes are such that sample preparation module 240 has a higher sample throughput than LC module 260 and / or MS module 280, this can allow efficient utilisation of the additional throughput capacity of the sample preparation module 240. For example, a first batch of samples prepared by sample preparation module 240 may be automatically provided by interface 250 to LC module 260 and MS module 280 for LC-MS analysis, and a second batch of samples prepared by sample preparation module 240 may be output via output interface 262 and analysed separately while waiting for the LC-MS analysis of the first batch of samples to complete. Figure 8 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 7. As shown in Figure 7, the system 200 includes a combined manual input and output interface 263 via which samples can be input directly to the LC module 260 for LC-MS analysis and / or output after having been prepared for analysis by the sample preparation module 240. Combined interface 264 may comprise a combined input / output port for receiving (e.g. a batch of) samples input by a user and outputting (e.g. a batch of) samples to a user, and a system (e.g. electromechanical assembly, track system, robotic system, fluidic connection, etc.) for providing (e.g. a batch of) samples received at the input / output port to LC module 260 or providing (e.g. a batch of) samples from sample preparation module 240 to the input / output port (e.g. under the control of controller 201). Although in the above embodiments, buffer module 250 is a dedicated module, other arrangements are possible. For example, an LC injection loop, an autosampler, or a sample organiser may act as the buffer. Although the above embodiments have two or three timing regimes and one or two buffers, more than three timing regimes and more than two buffers may be used. 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 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.

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