Improvements to processing of biological samples

Abstract

A method of decontaminating biological sample tubes comprises providing one or more biological sample tubes (403, fig 4b) in the apertures (402, fig 4b) of a rack (401, fig 4b). The rack is provided o

Description

FIELD OF INVENTION 5 The present invention relates to improvements to the processing of biological samples. BACKGROUND 10 Testing of patient conditions is typically carried out by collecting biological samples from patients and sending those samples for testing and analysis at a lab. In order to provide test results to patients, a record must be kept of which patient a biological sample is associated with. The results of the testing and analysis of that sample are then, likewise, associated with the correct patient who can be i U / 15 informed of the test result. CM 20 To this end, traditional systems associate biological samples with unique identifiers, for example in the form of a barcode. When the results of testing or analysis have been obtained, the unique identifiers are then used to provide those results to the correct patients. The unique identifiers also make it possible to identify whether a sample has been safely received at a laboratory for processing. However, although traditional systems are capable of identifying when a sample is safely received, they are limited in the degree to which they can monitor the 25 processing of biological samples and are therefore not suited to preventing biological samples from expiring prior to testing. This is problematic because biological samples are typically only stable for a short period of time after they have been collected, which is often just a few days. Furthermore, processing of the samples can affect their stability, which is especially disadvantageous when 30 repeat testing of samples is required. Since traditional systems do not monitor the stability of biological samples, the processing of those samples cannot be adequately controlled to ensure that samples do not expire. In order to reduce the rate of biological samples expiring during processing, what is needed are improvements to the processing of biological samples. SUMMARY 5 According to the invention, a method of decontaminating biological sample tubes is provided, as defined in claim 1. The method comprises: providing one or more biological sample tubes in a rack comprising a plurality of apertures for receiving biological sample tubes; providing said rack on a first frame, the first frame 10 comprising: support elements for supporting the rack from below; and legs for holding the support elements at a height such that when the apparatus is provided on a flat surface the biological sample tubes received by the rack are suspended above said flat surface, the legs being separated to provide a space so as to expose biological sample tubes received by the rack to a fluid directed at the i U / 15 apparatus; conveying the frame through a decontamination chamber while C\J directing a decontamination fluid at the biological sample tubes from two or more CO sides of the frame so as to expose substantially the whole surface of each biological sample tube to said decontamination fluid; removing the rack from the CM first frame; providing the rack on a second frame. 20 In this method, by exposing substantially the whole surface of each biological sample tube to a decontamination fluid, full decontamination of the biological sample tubes can be ensured. 25 BRIEF DESCRIPTION OF THE FIGURES The invention will now be described with reference to the figures, in which: Figure 1 shows a flowchart of the steps of an embodiment of a method of monitoring and controlling the processing of biological samples; 30 Figure 2 shows a flowchart illustrating the process of receiving a plurality of biological samples in more detail; Figure 3 shows a decontamination machine used in embodiments of the present invention; and Figures 4a, 4b, and 4c show an apparatus for use in decontaminating biological sample tubes according to an embodiment of the invention. DETAILED DESCRIPTION 5 The typical steps of a method of monitoring and controlling the processing of biological samples are shown in Figure 1. Some of these steps are optional and are not present in all embodiments of the invention. In the following description, the terms “user” and “patient” are interchangeable. 10 In a first step 101 a plurality of sample containers, each of which contains biological material provided by a patient, are received at a laboratory for processing. As will be described in more detail below with reference to Figure 2, step 101 may include a number of sub-steps. LO 15 After the plurality of sample containers have been received, a priority is assigned CO to each sample container in step 102. These priorities are typically used to indicate the stability of the biological material in each sample container, although CM they may also be based on other factors such as the urgency with which a test 20 result is required, and as such are preferably based at least in part on the age of the biological material in the sample container, which is to say how much time has expired since a patient provided the biological material. Therefore, in addition to indicating how close the biological material is to expiry, with a higher priority indicating that the biological material is closer to expiry, the priority can be based 25 on other factors. For example, as is discussed below, a sample container which is to be retested following an inconclusive result may be given a higher priority regardless of the stability of the biological material. After priorities have been assigned to the biological samples in step 102, the 30 assigned priorities are used in step 103 to queue the biological samples for analysis. The queueing of biological samples is based on the assigned priorities to ensure that higher priority samples are analysed before lower priority samples. As will be explained in more detail below, the queue samples include both samples which have not yet undergone analysis and samples for which further analysis is required. The samples requiring further analysis may have a higher priority, in which case these will be placed ahead of samples that have not yet undergone analysis. 5 As part of the queueing step 103, biological samples may be sorted into batches based on the priorities assigned to the biological samples. This typically involves grouping together biological samples which have been assigned similar priorities. For example, if each batch includes N samples then the N samples with the 10 highest priorities might be sorted into the first batch, the N samples with the next highest priorities might be sorted into the next batch, and so on. Sorting the samples into batches is particularly advantageous when analysis can be performed on multiple samples in parallel. For example, quantitative 15 polymerase chain reaction (qPCR) analysis machines often perform qPCR analysis on multiple biological samples in parallel, and the samples are therefore sorted into batches to maximise throughput during analysis. Another possibility is for the samples in a batch to be pooled into a single biological 20 sample for analysis. This is beneficial when testing for the presence or absence of a biological factor, such as a virus, in samples provided by patients. If said factor was not present in the pooled sample, then a negative result indicating the absence of that biological factor could be associated with all of the biological samples in the batch. In this example, individual testing of biological samples 25 would only be necessary in the event of a positive result indicating that the biological factor was present in one or more of the samples in the batch. After queueing, a biological sample is extracted 104 from the biological material in each sample container. The extraction of biological samples in step 104 will be 30 based on the form of the biological material and the sample containers. Often, liquid biological material is provided in biological sample tubes, such as test tubes, in which case the extraction of biological samples in step 104 comprises aspirating the biological material. The extraction of biological samples in step 104 occurs directly before analysis of the biological samples in step 105. After analysis in step 105, the results of the analysis are then provided in step 106 5 in the form of a valid result or an inconclusive result. The expression “valid result” refers to a distinct result which can be associated with a specific biological sample. For example, if the biological samples are tested individually for the presence or absence of a biological factor then a valid result would be a positive or negative result associated with a specific biological sample. In the case of pooled samples 10 in a batch, a valid result would be provided in cases where individual testing of the samples in the batch was not required. For example, if a negative result was provided for the pooled biological sample then this result could be associated with each of the biological samples in the batch. Conversely, a positive result may not indicate that the biological factor which has been tested for is present in all of the i U / 15 biological samples. In this case, it is not possible to associate the positive result C\J with each of the biological samples in the batch and an inconclusive result would CO be issued. In the case that the samples in a batch have been pooled, the inconclusive result may also include an indication that those samples are not to CM be pooled again. 20 If an inconclusive result has not been provided, then step 107 directs the process to step 108 in which the valid result is provided to the patient, either directly or via an intermediary. The latter is preferable, with the intermediary providing any analysis of the result which might be required. 25 However, if an inconclusive result is provided, which indicates that further analysis of the biological sample is required, then step 107 directs the process to step 109 in which a new priority may be assigned to the sample container. The assigning of a new priority reflects that biological material may degrade over time. As such, 30 the biological material in the sample container may be less stable after analysis of the extracted biological sample, in which case the priority of the sample container may need updating. After step 109, the sample container is retrieved in step 110 and the process returns to step 103 in which the retrieved sample is queued for analysis along with the other sample containers. If a new priority has been assigned then this will be used in step 103. In preferred embodiments, when a repeat analysis is required 5 the sample containers are given the highest priority and biological samples are extracted from the repeat sample containers before any of the newly received sample containers. Figure 1 illustrates an exemplary process in which sample containers are frozen 10 in step 111 after biological samples have been extracted in step 104, in which case step 110 includes thawing the sample container. In such embodiments, after a new biological sample has been extracted from the sample container in step 104, the sample container is frozen again in step 111. Freezing the sample containers improves the stability of the biological material and is therefore particularly 15 advantageous in use cases where the biological material in the sample containers is unstable or in processes in which repeat analysis is likely. Nevertheless, some embodiments do not include a step 111 of freezing the sample container, although it is usual in such cases to nevertheless keep the sample 20 containers chilled in cold storage. In some embodiments, a decision may be taken after an inconclusive result is provided on whether to carry out further analysis. For example, it may be decided that the biological material in a sample container is too degraded for further useful 25 analysis to be possible. In another example, if analysis of biological samples extracted from a sample container repeatedly gives an inconclusive result then this could indicate that useful analysis of the biological material in the sample container is not possible. As such, this decision could be based on the age of the biological material in the sample container, on the number of inconclusive results 30 provided after analysis of biological samples extracted from the sample container, or on any other indicators that useful analysis of the biological material in the sample container is not possible. Step 101 of receiving a plurality of sample containers will now be described in more detail with reference to Figure 2. The process of receiving a plurality of sample containers begins with users 5 providing biological material in step 201. In the following description of the process illustrated in Figure 2, the term “biological material” is used to refer to a sample provided by a user in a sample container. This is different from the biological samples referred to above in relation to Figure 1 which should be understood as a sample extracted from the biological material which has been 10 provided by a user in a sample container. The sample container may contain a reagent prior to the provision of biological material by a user in step 201. Returning to step 201, the biological material may be provided directly in a sample container or may be collected and then transferred to a sample container. For i U / 15 example, the biological material may be provided in the form of a nasal swap C\J which is then provided in a sample container, such as a biological sample tube. CO As noted above, the sample container may contain a reagent prior to the provision of the biological material by the user in step 201. CM 20 In some embodiments multiple users may each provide biological material in the same sample container. This approach may be preferable, for example, when testing a large population, in which case the members of individual households might provide samples in the same sample container. 25 After providing biological material, a user (or users) will register the sample container in which the biological material has been provided in step 202. This allows a result provided after subsequent analysis to be provided to the user, such as in step 108, either directly or, more preferably, via an intermediary. The sample container will typically have been provided along with a barcode or other unique 30 identifier which is registered by the user in step 202. After step 202, the sample containers are received at a laboratory facility for processing in step 203. Note that this step is distinct from step 101, which occurs subsequent to step 210. As a first step after receiving the sample containers in step 203, the sample containers undergo quality control in step 204. This step may include assessing whether any sample containers have leaked or become damaged during transit. The step may also (or instead) include assessing whether 5 the biological material in any of the sample containers has already degraded beyond the point where useful analysis is possible, typically by determining how much time has elapsed since the user registered the sample container in step 202. Sample containers which are considered low quality, which is to say sample 10 containers which are either damaged or which container biological material for which useful analysis is not considered possible, are discarded in step 206. This is typically also communicated to the user or users who provided the discarded samples. i U / 15 The remaining samples are then identified in step 207 in order to associate the C\J biological material in each sample container with the corresponding user. This CO step often involves scanning a barcode or other unique identifier provided on the sample container. CM 20 The remaining sample containers are then sorted onto racks in step 207 and decontaminated in step 208, as will be described in more detail below, after which the sample containers are identified in step 209 in order to associate the biological material in each sample container with the corresponding user or users. This step often involves scanning a barcode or other unique identifier provided on the 25 sample container. Finally, the sample containers are sent for processing in step 210. It should be noted that the sorting of sample containers onto racks in step 207 is distinct from the step of 30 Figure 3 shows a schematic diagram of a decontamination machine 300 as would be used in step 207 to decontaminate sample containers. The decontamination machine 300 includes a conveyor 301 which runs in uniform manner, that is to say it runs in one direction at a consistent speed, from an idle end 302 to a drive end 303. The belt 304 of the conveyor 301 includes perforations (not shown) to allow for a decontamination fluid to be provided from below, while 5 the upper 305 and side walls 306 of the machine 300 are impermeable to the decontamination fluid. The decontamination fluid is provided by misters 307 so as to create a mist within the decontamination machine 300. It will be convenient at this point to describe the apparatus used to convey sample 10 containers, typically in the form of biological sample tubes such as test tubes, through the machine. This apparatus 400 is shown in Figures 4a to 4c and includes a rack 401 comprising a plurality of apertures 402 for receiving biological sample tubes 403 i U / 15 and a frame 404 for supporting the rack 401. The rack 401 is removable and is C\J typically supported only from below, thereby allowing the rack 401 to be lifted off CO of the frame 404. CM The frame 404 itself includes support elements 405 for supporting the rack 401 20 from below, typically in the form of two or more lips 405 for supporting a corresponding two or more edges of the rack 401. The support elements 405 are connected to legs 406 which hold said support elements 405 sufficiently high above the surface of the conveyor belt 304 that biological sample tubes 403 provided in the rack 401 are suspended above the conveyor belt 304 surface, 25 which is to say that the lower ends of the biological sample tubes 403 do not contact the conveyor belt 304. The skilled person will understand that biological sample tubes come in standard sizes, typically from around 80 to 110 mm in height, and the biological sample tubes 403 are therefore preferably held at a height of at least 80 mm from the conveyor belt 304, more preferably at a height 30 of at least 100 mm from the conveyor belt 304, and still more preferably at a height of at least 120 mm from the conveyor belt 304. To this end, in a particularly preferable embodiment, the legs 406 are 121 mm in length. The legs 406 may be connected at their lower ends, as shown in Figures 4a and 4b, by cross-support members 407, but they are advantageously separated from each other in order provide a space so as to expose biological sample tubes 403 received by the rack 401 to a fluid directed at the apparatus 400 from the sides. 5 Likewise, a space is provided between any cross-support members 407 so as to expose biological sample tubes 403 received by the rack 401 to a fluid directed at the apparatus 400 from below. Returning to the decontamination machine shown in Figure 3, biological sample 10 tubes 403 are loaded into the rack 401, often while the rack 401 is supported by a different frame to that shown in Figures 4a and 4b. The rack 401 is then transferred to the frame 404 where it is supported by support elements 405, after which the apparatus 400 is conveyed through the decontamination machine 300. A mist may be provided prior to the apparatus 400 being conveyed, and in typical 15 embodiments the mist is also provided by the misters 307 as the apparatus 400 is being conveyed. The spaces between the legs 406 and cross-support members 407 of the frame 404 expose the biological sample tubes 403 to the mist, which decontaminates the surfaces of the biological sample tubes 403. 20 The rack 401 is then transferred to another frame for further processing of the biological sample tubes 403. 11

Claims

1. A method of decontaminating biological sample tubes, the method comprising:providing one or more biological sample tubes in a rack comprising a5 plurality of apertures for receiving biological sample tubes;providing said rack on a first frame, the first frame comprising: support elements for supporting the rack from below; and legs for holding the support elements at a height such that when the apparatus is provided on a flat surface the biological sample tubes received by the rack are suspended above said flat10 surface, the legs being separated to provide a space so as to expose biological sample tubes received by the rack to a fluid directed at the apparatus;conveying the frame through a decontamination chamber while directing a decontamination fluid at the biological sample tubes from two or more sides of the frame so as to expose substantially the whole surface of each biological15 sample tube to said decontamination fluid;removing the rack from the first frame;providing the rack on a second frame.

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