GB2616869A - Sample processing line - Google Patents

Sample processing line Download PDF

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Publication number
GB2616869A
GB2616869A GB2204030.7A GB202204030A GB2616869A GB 2616869 A GB2616869 A GB 2616869A GB 202204030 A GB202204030 A GB 202204030A GB 2616869 A GB2616869 A GB 2616869A
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United Kingdom
Prior art keywords
sample
sample processing
stage
receptacle
processing stage
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GB2204030.7A
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GB202204030D0 (en
Inventor
Haffenden Ross
Soar Tom
Newman-Smith Jon
Johnson Chris
Flores Carlos
Crook Malcolm
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UK Secretary of State for Health and Social Care
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UK Secretary of State for Health and Social Care
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Priority to GB2204030.7A priority Critical patent/GB2616869A/en
Publication of GB202204030D0 publication Critical patent/GB202204030D0/en
Publication of GB2616869A publication Critical patent/GB2616869A/en
Pending legal-status Critical Current

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • G01N35/0092Scheduling
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00326Analysers with modular structure
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584Control arrangements for automatic analysers
    • G01N35/0092Scheduling
    • G01N2035/0094Scheduling optimisation; experiment design
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0401Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418Plate elements with several rows of samples

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  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Robotics (AREA)
  • Engineering & Computer Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

A sample processing line 100 comprises: a receiving stage OP10 configured for receiving a sample in a first receptacle (302, fig 3); a first transfer means configured for transferring the sample from the receiving stage to a first sample processing stage OP20, wherein the first sample processing stage is configured for transferring a portion of the sample from the first receptacle to a second receptacle; a second sample processing stage OP30 configured for receiving the sample in the second receptacle from the first sample processing stage; dispensing a reagent into a third receptacle (402, fig 4); dispensing at least a portion of the sample from the second receptacle into the third receptacle; a testing stage OP40 configured for receiving the sample in the third receptacle from the second sample processing stage, and performing a test on the sample. Preferably, the first receptacles are returned to the receiving stage. A returned sample that tests negative may be transferred to a waste portion (704, fig 7) by a sorting apparatus (505, fig 7) at the receiving stage. Alternatively, the sorting apparatus may be configured for sorting a returned sample that tests positive for re-testing.

Description

SAMPLE PROCESSING LINE
The present invention relates to a sample processing line. In particular the invention relates to, but is not limited to, a sample processing line for processing samples for a loop-mediated isothermal amplification (LAMP) test. The test may be, for example, part of a testing programme, e.g. for determining the current or past presence of the SARS-CoV-2 virus, or other such pathogens, among members of the general population.
Background
Testing laboratories are used to process and test samples for the presence of a pathogen, such as the SARS-CoV-2 virus. Such laboratories typically receive large numbers of samples (e.g. samples of saliva provided in a receptacle such as a tube or vial) that are then processed at the laboratory to generate corresponding test results. The laboratory may be required to process many thousands, tens of thousands, or hundreds of thousands of samples per day, in order to analyse the samples as quickly as possible and to promptly provide test results to the respective test subjects (i.e. the people from whom the fluid samples were taken). Samples are typically received at the laboratory by post or courier, in a sealed vial or tube. The samples are then subjected to one or more preparatory steps, such as opening the sample tube and combining the sample with a reagent, before performing a diagnostic test. It is important that a test subject that is infected with a virus is notified as soon as possible of a corresponding positive test result, for example so that the test subject can begin a period of self-isolation to prevent further infections, and therefore there is a need for the processing of the samples at the laboratory to be performed efficiently and reliably.
VVhen a testing laboratory is required to receive and process very large numbers of samples (which may happen, for example, during an outbreak of a new and highly contagious virus), even marginal improvements in efficiency are of importance for increasing the testing capacity. However, increasing the rate of sample processing whilst also maintaining reliable tracking and processing of the large number of samples to generate accurate test results is a significant operational challenge.
Moreover, when the samples are received directly from test subjects from the general population via post, a significant number of the received samples are likely to have defects such as an insufficient amount of sample material, a deficiency in the way in which the sample has been packaged, or damage to the sample container sustained during transit to the laboratory. It is desirable that sample testing laboratories are able to reliably handle such defects, whilst minimising any reductions in the overall testing capacity.
Summary
The present invention seeks to provide apparatus and methods for addressing or at least partially ameliorating one or more of the above issues.
In a first aspect the invention provides a sample processing line comprising: a receiving stage configured to receive a sample in a first receptacle; a first transfer means configured to transfer the sample from the receiving stage to a first sample processing stage, wherein the first sample processing stage is configured for transferring a portion of the sample from the first receptacle to a second receptacle; a second sample processing stage configured to: receive the sample in the second receptacle from the first sample processing stage; dispense a reagent into a third receptacle; and dispense at least a portion of the sample from the second receptacle into the third receptacle; and a testing stage configured to: receive the sample in the third receptacle from the second sample processing stage, and perform a test on the sample.
By virtue of the configuration of the sample processing line, samples can be processed efficiently and reliably to generate accurate test results. The provision of the first sample processing stage and the second sample processing stage enable the samples to be automatically prepared for testing, reducing the amount of manual input needed from a user.
Some or all of the above stages may be integrated with one another and physically connected in series. For example, the receiving stage, the first sample processing stage and the second sample processing stage may be physically connected. The receiving stage may be physically connected to the second sample processing stage via the first sample processing stage. Advantageously, the sample processing line may be fully or partially automated.
The sample processing line may further comprise a second transfer means configured for returning the sample in the first receptacle from the first sample processing stage to the receiving stage, after the portion of the sample has been transferred to the second receptacle.
By virtue of the second transfer means, samples can advantageously be returned to the receiving stage for subsequent processing and/or re-testing of the samples.
One or both of the first transfer means and the second transfer means may comprise a conveyor (e.g. a conveyor belt).
The receiving stage may comprise sorting apparatus configured for sorting the samples that are returned to the receiving stage.
The sorting apparatus may comprise a robotic arm.
The sorting apparatus may be configured for sorting a sample that is returned to the receiving stage based on a corresponding test result from the testing stage.
By virtue of the configuration of the sorting apparatus, the samples can therefore be sorted for re-testing or discarding, based on a corresponding test result from the testing stage. This enables samples for which a negative test result has been generated to be efficiently discarded, and enables the samples for which a positive test result has been generated to be efficiently separated for subsequent processing at the receiving stage.
The sorting apparatus may be configured for sorting a sample that is returned to the receiving stage based on at least one of an indication output from the first sample processing stage or an indication output from the second sample processing stage.
The sorting apparatus may be configured for transferring a sample that is returned to the receiving stage to a waste output, based on a corresponding negative test result output from the testing stage for the sample. Advantageously, therefore, samples for which a corresponding negative test result has been generated can be efficiently discarded.
The sorting apparatus may be configured for sorting a sample that is returned to the receiving stage for subsequent re-testing of the sample, based on a corresponding first positive test result output from the testing stage for the sample. The sorting apparatus may be configured for sorting a sample that is returned to the receiving stage for subsequent re-testing, based on a corresponding positive test result, until three positive test results have been generated for the sample at the testing stage.
Advantageously, by virtue of the configuration of the sorting apparatus, the sample processing line is able to automatically sort the sample for re-testing until a predetermined number of positive test results have been generated for the sample, thereby increasing the confidence level in the positive test result.
The sorting apparatus may be configured for sorting a sample that is returned to the receiving stage based on an indication output from the first sample processing stage or based on an indication output from the second sample processing stage; and the sorting apparatus may be configured to output an indication to a user of a processing step to be performed at the receiving stage based on the indication output from the first sample processing stage or the indication output from the second sample processing stage.
By virtue of the configuration of the sorting apparatus, samples (or first receptacles) that have defects, or for which there has been a failure in processing, can be efficiently sorted for manual inspection at the receiving stage, thereby reducing disruption to overall testing process, and increasing the throughput of the sample processing line.
The indication to the user may comprise at least one of: an indication that a user should manually remove a lid from the first receptacle that contains the sample, based on an indication from the first sample processing stage of a failure to remove the lid from the first receptacle; or an indication that a user should manually check the amount of the sample in the first receptacle, based on an indication from the first sample processing stage of a failure in an extraction the sample from the first receptacle; or an indication that a user should manually check an identifying mark or number provided on the first receptacle, based on an indication from the first sample processing stage of a failure to identify the sample.
The sample may be a sample of saliva.
The test may be a loop-mediated isothermal amplification, LAMP, test, although the present disclosure is not limited to such a test, and alternative tests may be performed instead, or additionally, in the testing stage.
The first sample processing stage may be configured for: removing a lid from the first receptacle; extracting a portion the sample from the first receptacle; and transferring the extracted portion of the sample to the second receptacle.
The first sample processing stage may be configured for extracting the portion of the sample from the first receptacle by aspiration.
The first sample processing stage may comprise a vision system configured for verifying that the portion the sample has been extracted from the first receptacle.
By virtue of the provision of the vision system, the successful extraction of the sample from the first receptacle can be verified, thereby preventing samples for which there has been a failure in extraction from proceeding to the subsequent stages of the sample processing line, reducing disruption to the overall testing process.
The first sample processing stage may be configured for attaching a lid to the first receptacle after the portion of the sample has been extracted from the first receptacle.
The first sample processing stage may be configured for sealing the second receptacle before transfer of the second receptacle to the second sample processing 15 stage.
The first sample processing stage may be configured for dispensing a buffer solution into the second receptacle. The buffer solution may be a lysis buffer solution.
The first sample processing stage may be configured for storing the buffer solution at a temperature of 4 °C before it is dispensed into the second receptacle.
The first sample processing stage may be configured for heating the sample in the second receptacle. The first sample processing stage may be configured for heating the sample in the second receptacle to a predetermined sterilisation temperature to deactivate a virus in the sample. The first sample processing stage may be configured for heating the sample in the second receptacle to a temperature of approximately 80 °C.
By virtue of the heating of the sample at the first processing stage, a virus in the sample can be deactivated. Therefore, the safety of operators at the subsequent processing stages is improved. Moreover, the protection and precautions for containment of the sample at the subsequent processing stages can be safely reduced, enabling the size, complexity and cost of the second sample processing stage and the testing stage to be reduced.
The second sample processing stage may be configured for cooling the sample in the third receptacle. The second sample processing stage may be configured for cooling the sample to be within a temperature range of 1 °C to 6 °C, for example around 4 °C.
The second sample processing stage may be configured for cooling the sample to be within a threshold range of a first predetermined temperature. The second sample processing stage may be configured for maintaining the cooled sample within the threshold range of the first predetermined temperature until the sample is output to the testing stage. The first predetermined temperature may be around 4 °C.
The second sample processing stage may be configured for maintaining the temperature of the reagent to be within a range of 1 °C to 6 °C, for example around 4 °C.
The second sample processing stage may be configured for maintaining the temperature of the reagent in the second sample processing stage to be within a threshold range of a second predetermined temperature. The second predetermined temperature may be around 4 °C.
By virtue of the cooling of the reagent and/or sample to a predetermined temperature, the accuracy of the test result generated at the testing stage is improved.
The first receptacle may be a tube or vial. The second receptacle may be a well of a well plate. The third receptacle may be a test tube, or a tube of a test tube strip.
The third receptacle may be for insertion into a testing machine to perform the test on the sample.
In a second aspect the invention provides a method for processing a sample using a sample processing line according to the first aspect, the method comprising: receiving, at the receiving stage, a sample in the first receptacle; transferring the sample from the receiving stage to the first sample processing stage, and transferring a portion of the sample from the first receptacle to the second receptacle at the first sample processing stage; receiving, at the second sample processing stage, the sample in the second receptacle from the first sample processing stage; dispensing, at the second sample processing stage, a reagent into the third receptacle; and dispensing, at the second sample processing stage, at least a portion of the sample from the second receptacle into the third receptacle; receiving, at the testing stage, the sample in the third receptacle from the second sample processing stage, and performing, at the testing stage, a test on the sample.
Aspects of the invention extend to computer program products such as computer readable storage media having instructions stored thereon which are operable to program a programmable processor to carry out a method as described in the aspects and possibilities set out above or recited in the claims and/or to program a suitably adapted computer to provide the functionality of the apparatus recited in any of the claims.
Each feature disclosed in this specification (which term includes the claims) and/or shown in the drawings may be incorporated in the invention independently (or in combination with) any other disclosed and/or illustrated features. In particular but without limitation the features of any of the claims dependent from a particular independent claim may be introduced into that independent claim in any combination or individually.
Brief description of the drawings
Embodiments of the invention will now be described by way of example only with reference to the attached figures in which: Figure 1 shows an overview of a sample processing line; Figure 2 shows a further view of the sample processing line; Figure 3 shows a rack of sample receptacles; Figure 4 shows a block of receptacles for a testing machine; Figure 5 shows a simplified block diagram of a receiving stage; Figure 6 shows a view of the receiving stage; Figure 7 shows a plan view of the receiving stage; Figure 8 shows a further view of the receiving stage; Figure 9 shows a robotic arm; Figure 10 shows a simplified block diagram of a first sample processing stage; Figure 11 shows a view of the receiving stage and the first sample processing stage; Figure 12 shows a plan view of the first sample processing stage; Figure 13 shows a further plan view of the first sample processing stage; Figure 14 shows a further view of the first sample processing stage; Figure 15 shows a part of a de-capping station; Figure 16 shows a user interface of a vision system for verifying an amount of extracted liquid; Figure 17 shows a liquid handling gripper; Figure 18 shows a further robotic arm; Figure 19 shows a tube-handling gripper assembly for a robotic arm; Figure 20 shows side grip fingers of a robotic arm; Figure 21 shows a simplified block diagram of a second sample processing stage; Figure 22 shows an overview of the second sample processing stage; Figure 23 shows a further view of the second sample processing stage; Figure 24 shows a view of a liquid handling platform and robotic arm in the second sample processing stage; Figure 25 shows a view of the second sample processing stage; Figure 26 shows a plan view of the liquid handling platform in the second sample processing stage; Figure 27 shows a user access point of the second sample processing stage; Figure 28 shows a simplified diagram of the second sample processing stage, illustrating the location of a user access point; Figure 29 shows a simplified block diagram of a testing stage Figure 30 shows an overview of the testing stage; Figure 31 shows a user interface of the testing stage; Figure 32 shows a method for the receiving stage; Figure 33 shows a method for the first sample processing stage; Figure 34 shows step 3324 of the method illustrated in Figure 32; Figure 35 shows a method for the second sample processing stage; Figure 36 shows step 3350 of the method illustrated in Figure 34; Figure 37 shows a method for the testing stage; Figure 38 shows method steps for the receiving stage and the first sample processing stage; Figure 39 shows method steps for the first sample processing stage; Figure 40 shows further method steps for the first sample processing stage; Figure 41 shows method steps for the first sample processing stage and the second sample processing stage Figure 42 shows method steps for the second sample processing stage; Figure 43 shows method steps for the second sample processing stage and the testing stage; Figure 44 shows method steps for the testing stage; Figure 45 shows a flow diagram illustrating a method for the receiving stage and the first sample processing stage; and Figure 46 shows a flow diagram illustrating a method for the second sample processing stage and the testing stage.
Detailed description
The present embodiments represent the best ways known to the Applicant of putting the invention into practice. However, they are not the only ways in which this can be 25 achieved.
Overview Figure 1 shows, for illustrative purposes, an overview of a sample processing line 100. The sample processing line comprises a receiving stage OP10, a first sample processing stage 0P20, a second sample processing stage 0P30, and a testing stage 0P40. The receiving stage OP10, first sample processing stage 0P20 and second sample processing stage 0P30 are physically connected in series. The testing stage 0P40 may or may not be physically connected to the second sample processing stage 0P30. When a loop-mediated isothermal amplification (LAMP) test is performed at the testing stage 0P40, the sample processing line 100 may also be referred to an automated LAMP preparation system.
As described below, the receiving stage OP10 is configured for receiving a sample in a first receptacle. The sample processing line 100 comprises a first transfer means configured for transferring the sample from the receiving stage OP10 to the first sample processing stage 0P20. The first sample processing stage 0P20 is configured for transferring a portion of the sample from the first receptacle 302 to a second receptacle. The second sample processing stage 0P30 is configured for receiving the sample in the second receptacle from the first sample processing stage 0P20, dispensing a reagent into a third receptacle 402, and dispensing at least a portion of the sample from the second receptacle into the third receptacle 402. The testing stage 0P40 is configured for receiving the sample in the third receptacle 402 from the second sample processing stage, and performing a test on the sample.
Figure 2 shows an alternative view of the sample processing line 100 shown in Figure 1, in which operator stations 201a, 201b can also be seen. As described in detail later, users at the operator stations 201a, 201b process samples from the boxes 101 of samples, and load the samples into sample racks for subsequent transfer from the receiving stage OP10 to the first sample processing stage 0P20. The users at the operator stations 201a, 201b are also referred to as 'operators' in the present disclosure.
Boxes of samples 101 of received at the receiving stage. Figure 3 shows a sample rack 301 that is filled with samples by a user at the receiving stage 10. As described in detail below, the user opens sample bags from the box of received samples 101, and places test tubes containing the samples into the sample rack 301. Twenty four sample tubes 302 are inserted into corresponding holes in a base portion of the sample rack 301, each sample tube 302 containing a single sample. Each of the sample tubes 302 is provided with a lid 304. The lid 304 of a sample tube 302 may also be referred to as a 'cap' (and the processes of removing a cap 304 from a sample tube 302 may be referred to as 'de-capping). The sample tubes 302 are also referred to as 'first receptacles' in the present disclosure.
The samples are transferred to the testing stage 0P40 for testing, via the first sample processing stage 0P20 and the second sample processing stage 0P30.
Each of the receiving stage OP10, first sample processing stage 0P20, second sample processing stage 0P30, and testing stage 0P40 are provided with a computer for controlling the equipment and instruments provided in the corresponding stage. The computers may communicate using a private local network, but may also be connected to an external network (e.g. the internet). The external network may be used, for example, to access external databases, or may be used for remote control of the apparatus of the sample processing line 100.
Receiving stage (0P10) The receiving stage OP10 will now be described in more detail, with reference to Figures 5 to 9.
Figure 5 shows a simplified block diagram of the receiving stage OP10. The receiving stage OP10 comprises a system PC 501, a barcode reader 502, an ethernet switch 503, other system PCs 504, and a robotic arm 505. The system PC 501 is connected to the other system PCs 504 via the ethernet switch 503. The other system PCs 504 need not necessarily be provided.
As shown in Figure 2, the receiving stage OP10 is also provided with an extraction hood unit 202 (for example, a comprising a class 1 extraction hood). The extraction hood 202 may comprise an inlet grille with disposable pre-filters. A perforated equalization grid may be used to 'even out' the air as it enters the HEPA filters. A diagnostic airflow display may be provided. A remote control panel may be provided, containing equipment and/or user interface elements for operating the extraction hood, including a power on indication, a fan run indication, an airflow fail indication, an on/off button, an alarm mute, and a filter pressure drop indication gauge.
The barcode scanner (or 'barcode reader') 502 may be, for example, a Cognex Dataman 70. The robotic arm 505 may be any suitable robotic arm for moving sample tubes 302 in the receiving stage OP10.
As shown in Figure 6, the receiving stage OP10 comprises two operator stations 201a, 201b. In this example the samples received in the boxes 101 contain bagged saliva sample kits for testing. A sample kit comprises an outer sealed plastic bag (with barcode), a secondary sealable bag, a sample tube/vial (with barcode) and an absorbent pad.
In operation, the operator at the first operator station 201a picks a sample bag from the box 101 of samples. The operator visually inspects for signs of leaks inside the bag. The operator then scans the barcode on the bag using the barcode scanner 502. A display of the system PC 501 outputs an indication based on the reading from the barcode scanner 502. The indication may indicate that the sample can be processed through the receiving stage OP10 normally, or may indicate that there is a problem with the sample (e.g. the barcode is invalid), in which case the operator may place the sample in a separate box for separate offline processing.
The operator at the second operator station 201b picks a sample bag that has been processed by the operator at the first operator station 201a. The operator then opens the sample bag, e.g. using a safety knife mounted to the worktop of the receiving stage OP10. The operator then extracts the sample tube 302 from the bag, and places the sample tube 302 in a sample tube rack 301. The operator disposes of the sample bag and the absorbent pad. The operator adds one negative control sample to each rack 301 (no sample control -nuclease free water). Once a sample rack 301 is full, the rack is transferred to the first sample processing stage OP20 by the conveyor 701a, and the operator starts to process sample tubes into a new sample rack 301.
As shown in Figure 7, the receiving stage OP10 is provided with a conveyor 701a for transferring sample racks 301 to the first sample processing stage 0P20. As described in detail below, a return conveyor 701b returns samples from the first sample processing stage OP20 to the receiving stage OP10, where the samples are then sorted by the robotic arm 505. The robotic arm 505 sorts the samples and transfers each sample to either a waste position 704 (also referred to as a 'waste outlet') for subsequent disposal of the sample, or a sample return position 706. As shown in Figure 8, a raised platform is located at the end of the conveyor 701b and contains a container 709 (e.g. a 60 L container) for bleach or a similar cleaning solution. The platform has a powder coated chute to allow the empty sample racks 301 to slide into the liquid. A splash guard is provided to minimise spills. A manually adjustable bar 710 is positioned horizontally across the conveyor at a height suitable for preventing any sample blocks 303 which contain sample tubes 302 from entering the decontamination bath.
In other words, the sample processing line 100 comprises a second transfer means 701b configured for returning the sample in the first receptacle from the first sample processing stage 0P20 to the receiving stage OP10, after the portion of the sample has been transferred to the second receptacle. The receiving stage OP10 comprises sorting apparatus 505 configured for sorting the samples that are returned to the receiving stage OP10. The sorting apparatus 505 comprises a robotic arm 505.
Samples transferred to the sample return position 706 are subsequently transferred back to the first sample processing stage 0P20 via the conveyor 701a (e.g. by an operator manually processing the samples from the sample return position 706). Samples for which a corresponding first positive test result has been output by the testing stage 0P40 are transferred (sorted) by the robotic arm 505 to the sample return position 706. Samples for which a corresponding error or indication has been generated in the first sample processing stage 0P20 or in the second sample processing stage 0P30 are also transferred (sorted) to the sample return position 706. Samples for which a corresponding negative test result has been output by the testing stage 0P40 are transferred (sorted) by the robotic arm 505 to the waste position 704. The receiving stage OP10 may also comprise a sequencing storage rack for storing samples that should be sequenced (genetic sequencing), and the robotic arm 505 may be configured to transfer (sort) samples, for which multiple (e.g. two, or three) corresponding positive test results have been output from the testing stage 0P40, to the sequencing storage rack.
Table 1 below shows results output from the testing stage, indications output from the first sample processing stage 0P20, and corresponding steps and actions to be performed.
Result Step Action Negative Sample should be Move to waste position 704 disposed of Positive (1st test) Sample should be Move to sample return position 706 to return to the first sample processing stage 0P20.
retested Positive (Retest) Sample should be Move to sequencing storage rack segregated for sequencing Void (< 24 hours old) Sample should be Move to sample return position 706 to return to the first sample processing stage 0P20.
retested Decap failure' indicated by the first sample processing stage OP20 Operator crack off cap Move to sample return position 706 to return to the first sample processing stage 0P20.
and retest Aspirate failure' indicated by the first sample processing stage OP20 Operator check liquid and Move to sample return position 706 to return to the first sample processing stage OP20.
retest Barcode scan failure' indicated by the first sample processing stage OP20 Operator check barcode Move to sample return position 706 to return to the first sample processing stage OP20.
and retest
Table 1
As shown in the table, when the testing stage 0P40 outputs a negative test result for a sample, the sample should be disposed of, and is therefore moved to the waste position 704 by the robotic arm 505. In other words, the sorting apparatus 505 is configured for transferring a sample that is returned to the receiving stage OP10 to a waste output 704, based on a corresponding negative test result output from the testing stage 0P40 for the sample.
VVhen the testing stage 0P40 has output multiple (e.g. two, or three) corresponding positive test results for a sample, the robotic arm 505 transfers the sample to the sequencing storage rack.
In other words, the sorting apparatus 505 is configured for sorting a sample that is returned to the receiving stage OP10 based on a corresponding test result from the testing stage. The sorting apparatus is configured for sorting a sample that is returned to the receiving stage OP10 for subsequent re-testing of the sample, based on a corresponding first positive test output from the testing stage 0P40 for the sample.
A 'void' indication may be generated at any one of the receiving stage OP10, the first sample processing stage 0P20, the second sample processing stage 0P30, or the testing stage 0P40. For example, the barcode reader 502 at the receiving stage OP10 could be used to identify a sample by reading a corresponding barcode on the sample tube 302. In response to the indication, if the 'void' indication was generated within the last 24 hours the robotic arm 505 transfers the sample to the sample return position 706 for subsequent transfer to the first sample processing stage 0P20 and subsequent retesting. Periods other than 24 hours could be used to determine whether to retest the sample, depending on the nature of the samples and the type of test performed at the testing stage 0P40.
A Decap failure' indication may be output from the first sample processing stage 0P20 when a failure to remove a lid from a sample tube 302 has occurred. This may occur, for example, when the test subject has screwed the lid excessively tightly onto the sample tube 302. In response to the indication, the robotic arm 505 transfers the sample to sample return position 706, for subsequent processing by a user. The user manually removes the cap from the sample tube 302, and processes the sample at the receiving stage OP10 for subsequent transfer by the conveyor 701a back to the first sample processing stage 0P20.
In other words, an indication that a user should manually remove a lid from the first receptacle that contains the sample, based on an indication from the first sample processing stage 0P20 of a failure to remove the lid from the first receptacle, is output at the receiving stage OP10.
An 'Aspirate failure' may be output from the first sample processing stage 0P20 when a failure to extract (aspirate) a sufficient quantity of the sample from the sample tube 302 has occurred. This may occur, for example, when an insufficient amount of sample is present in the sample tube 302. In response to the indication, the robotic arm 505 transfers the sample to sample return position 706, for subsequent processing by a user. The user manually inspects the amount of sample in the sample tube 302 In other words, an indication that a user should manually check the amount of the sample in the first receptacle, based on an indication from the first sample processing stage 0P20 of a failure in an extraction the sample from the first receptacle, is output at the receiving stage OP10.
A Barcode scan failure may be output from the first sample processing stage 0P20 when a failure to read (scan) a barcode on the sample tube 302 has occurred. This may occur, for example, when the barcode is provided as a sticker on the sample tube 302, but the sticker has peeled off. In response to the indication, the robotic arm 505 transfers the sample to sample return position 706, for subsequent processing by a user. The user inspects the sample tube 302 to verify that the sample tube 302 has a readable bar code (e.g. using a barcode scanner).
In other words, an indication that a user should manually check an identifying mark or number provided on the first receptacle, based on an indication from the first sample processing stage 0P20 of a failure to identify the sample, is output at the receiving stage OP10.
The sample return position 706 contains a plurality of collection bins (in Figure 7, six collection bins are shown) where the robotic arm 505 can deposit sample tubes 302, dependant on the required action. These bins are located between the two operator positions 201a, 201b to balance the tasking between the two operators. Each location will be identified with the action required by the operator.
In other words, the sorting apparatus 505 is configured for sorting a sample that is returned to the receiving stage OP10 based on at least one of an indication output from the first sample processing stage 0P20 or an indication output from the second sample processing stage 0P30. The sorting apparatus 505 is configured to output an indication to a user of a processing step to be performed at the receiving stage OP10 based on the indication output from the first sample processing stage 0P20 or the indication output from the second sample processing stage 0P30.
Figure 9 shows the robotic arm 505 in more detail. The robotic arm 505 comprises a stand 904, one or more articulated joints 903 and an end effector 902 for moving the sample tubes 302. The robotic arm 505 may also be referred to as a 'sorting apparatus' or a 'robot'. The robotic arm 505 may be configured to stop safely on human contact. The robotic arm 505 may be a so-called "fully collaborative" robot (referring, for example, to ISO/TS 15066) For example, the robotic arm 505 may be configured to be compliant with safety standard ISO 10218 1:2011. Advantageously, this reduces the need for guarding or other additional safety measures around the location of the robotic arm 505. The robotic arm 505 may be linked to a safety system so that power is cut to all drives in the event of an emergency stop button being pressed.
The robotic arm 505 may be provided with shoulder and wrist axes having 360° continuous rotation. The robotic arm 505 may be provided with "drag-to-teach" technology.
In this example, the end effector 902 is a "Tube" electric gripper for handling the capped sample tubes 302. The gripper 902 uses force feedback to verify a successful gripping operation. The gripper jaws can be moved by hand when the motor is disabled. The robotic arm 505 is also provided with an optical sensor for detecting the presence of an item being held.
As shown in Figure 6, in this example the receiving stage OP10 is provided with one or more waste bins 601. The waste bins may be provided with ultrasonic sensors mounted above, to monitor waste levels and alert the user if the waste bin 601 becomes too full.
First sample processing stage (0P20) The first sample processing stage 0P20 will now be described in more detail, with reference to Figures 10 to 20. The first sample processing stage 0P20 is arranged for transferring a portion of the sample in the sample tube 302 (first receptacle) to a well (second receptacle) of a well plate, and for adding a lysis buffer to the well plate.
The sealed well plate is then heated to deactivate any virus (or other pathogen) present in the sample, before the well plate is output to the second sample processing stage 0P30.
Figure 10 shows a simplified block diagram of the first sample processing stage 0P20. As shown in the figure, a system PC 1001 is connected to two 6-position carousels 1003, 1004 and liquid dispensers/extractors 1005 via a serial hub 1002. The system PC is connected to a decapper/recapper 1007 via an ethernet switch 1006, and is connected to robotic arms 1009 via robot controller(s) 1008 and the ethernet switch 1006. The system PC is also connected to a barcode scanner 1015 and a sealer via a USB hub 1012, and is connected to heating/cooling apparatus 1017 and a shaker 1018 via a corresponding controller 1016 and the USB hub 1012. The system PC 1001 is connected to a vision system 1021. In this example, the system PC 1001 is also connected to other system PCs 1011 via an ethernet switch 1010.
The liquid dispenser 1005 may be, for example, a Multidrop Combi reagent dispenser for dispensing a reagent On this example, a lysis buffer solution) into a well plate. The liquid extractor is configured for extracting a portion of a sample from a sample tube 302, for example via aspiration, for subsequent transfer to a well of a well plate (e.g. a 96 well plate). The sealer 1014 may be an automatic roll heat sealer for sealing well plates (for example, a Brooks A4S automatic roll heat sealer). The heating/cooling apparatus 1017 comprises a cooled position (tooled nest' position) for cooling the lysis buffer solution. The heating/cooling apparatus 1017 also includes a heated position (cheated nest' position) for heating the sealed well plates, to deactivate a virus in the samples. In this example, the heated position is configured to heat the samples in the well plate to a temperature of 80 °C, for a period of 30 seconds. In other words, the first sample processing stage 0P20 is configured for heating the sample in the second receptacle to a predetermined sterilisation temperature to deactivate a virus (or other pathogen) in the sample.
Thus, the first sample processing stage 0P20 is configured for sealing the second receptacle before transfer of the second receptacle to the second sample processing stage 0P30. The first sample processing stage 0P20 is configured for dispensing a lysis buffer solution into the second receptacle. The first sample processing stage 0P20 is configured for storing the buffer solution at a temperature of 4 °C before it is dispensed into the second receptacle.
The barcode scanner 1015 may be, for example, a Cognex Dataman 70. The decapper 1007 is configured for removing the caps 304 from the sample tubes 302, and for reattaching caps 304 to the sample tubes 302 after a portion of the example has been extracted from the sample tube 302.
The system PC 1001 may be connected to a touchscreen monitor, mouse and keyboard, to provide a user interface for the first sample processing stage 0P20. RGB illuminated clear acrylic panels may be provided so that users can easily see the status of the first sample processing stage 0P20.
As illustrated in Figure 11, the apparatus of the first sample processing stage 0P20 is arranged inside an enclosure 104. The enclosure 104 may be, for example, a BioMAT Robotic Class II Recirculation Microbiological Enclosure. The enclosure is provided with two filter sets. A downflow filter is positioned at the top of the work area, supplied with air from above, and is mounted in a negative pressure zone to form a total laminar downflow. An exhaust filter is positioned at high level on a discharge from an exhaust fan housing.
In this example, the robotic arms include a first type of robotic arm 1013 and a second type of robotic arm 1009, although conceivably a single type of robotic arm could instead be used. One of the robotic arms is configured to pick up sample tubes 302 received from the receiving stage OP10 via the conveyor 701a, and transfer the sample tubes 302 to a liquid handling platform. The robotic arms are also configured for dispensing a portion of the sample from the sample tube 302 to a well of a well plate, dispensing the lysis buffer into the well, and moving the well plate between different positions in the first sample processing stage OP20, using appropriate end effectors to perform each of these tasks.
As shown in Figures 12 to 14, the first sample processing stage 0P20 includes a liquid handling platform 1201. In this example, a robotic arm of the second type 1009 is arranged for transferring sample tubes 302 received via the conveyor 701a to the liquid handling platform 1201, for subsequent processing of the sample tubes 302. The robotic arm of the second type 1009 is also configured for return sample tubes 302 to a sample rack 301 on the conveyor, so that the sample tubes 302 can be returned back to the receiving stage OP10 via the return conveyor 701b, to be sorted by the robotic arm 505 of the receiving stage OP10.
The robotic arm of the first type 1013 is mounted generally centrally inside the first sample processing stage 0P20, adjacent to the liquid handling platform 1201. The robotic arm of the first type 1013 is configured for transferring labware to and from the liquid handing platform, for moving well plates to the sealer 1014, and for moving well plates for output to the second sample processing stage OP30. In this example, the robotic arm of the first type 1013 stops safely on human contact and is compliant with safety standard ISO 10218 1:2011. The robotic arm of the first type 1013 is configured for 360° continuous rotation of shoulder and wrist axes, and is provided with "drag-to-teach" technology. The robotic arm of the first type 1013 is fully collaborative, so no guarding is required. Nevertheless, the robot 1013 can be linked into a safety system so that, for example, power is cut to all drives in the event of an emergency stop button being pressed. An example of an end effector of the robotic arm of the first type 1013 is illustrated in Figure 20. The end effector shown in Figure is a "side-grip" electric gripper 2000 for handing labware in a portrait profile. The gripper 2000 comprises a pair of jaws 2001a, 2001b. The gripper 2000 uses force feedback to verify a successful gripping operation. The gripper jaws 2001a, 2001b can be moved by hand by a user when the motor is disabled. The gripper 2000 is also provided with an optical sensor for detecting the presence of an item being held.
The robotic arms of the second type 1009 are configured for moving sample tubes around the first sample processing stage 0P20. The robotics arms 1009 are programmable to move at variable speeds and with different acceleration profiles. This enables the robot movements to be optimised for a specific task. An example of the robotic arm is shown in Figure 18. As shown in the figure, the robotic arm comprises a base portion 1801, one or more moveable members 1802, and attachment point 1803 for an end effector, for example the liquid dispenser/extractor 1005 illustrated in Figure 17. The robotic arm 1009 is provided with collision detection and collision avoidance, where appropriate. The collision detection acts as a protection mechanism for the robot 1009 and its end effector. Even if the collision detection does not prevent a collision, it may nevertheless reduce the forces involved in the collision. A further example of an end effector for the robotic arms of the second type 1009 is shown in Figure 19, which shows a gripper assembly 1900 (a so-called 'robotic hand'). The gripper comprises four 3-point grippers, similar to those provided for the decapper/recapper 1007. Each gripper assembly is located on a floating bearing, allowing each head to lift individually. The tool contains part present sensors and a torque lock off mechanism. This can be used to ensure that all four tubes are correctly located into the de-capping station and mechanically locates the tool to prevent torque transmission into the robot arm. Once in position, de-capping can commence by rotating the sample tubes 302 relative to the sample caps 304.
The individual workstations/devices of the first sample processing stage 0P20 are positioned so that the corresponding robotic arm(s) can access them. Advantageously, the layout of the apparatus in the first sample processing stage 0P20 provides a particularly beneficial balance of user access and machine throughput.
The first sample processing stage 0P20 may be provided with a user interface for use by a user to 'teach' the robotic arms 1009, 1013 positions within the first sample processing stage 0P20. In other words, the user interface can be used by the user when the system is a manual (leach') mode to "jog" the robot and teach positions. In operation, the robotics arms 1009, 1013 operate in an automatic mode to move between the taught positions, to perform the processing of the samples in the first sample processing stage 0P20. In the automatic mode, the robotic arms 1009 are operated according to programs stored at the robot controller 1009. In this example, the robots 1009 will only move in automatic mode when all doors/guarding are in a closed/safe position, so that it is impossible for a user of the system to enter the working envelope of the robots 1009 while the robots 1009 are operating in the automatic mode. These safety mechanisms may be overridden when the robots 1009 are being taught positions in the manual mode, so that the user can interact directly with the robotic arms 1009, but the maximum permissible speed of the robot arms 1009 may be reduced to ensure safety of the user.
The apparatus of the first sample processing stage 0P20 are positively located using locator feet, or physically mounted to the worksurface to aid positional repeatability, and to allow instruments to be removed and replaced for servicing requirements without the need for reteaching of the robots.
The two 6-position carousels 1003, 1004 are arranged next to corresponding access windows provided in the enclosure 104. This enables access to the carousels 1003, 1004 by a user for inserting and removing labware stacks. Twelve SS45-SPC portrait stacks are used to store labware for the automation. The capacity of the stacks is equivalent to 45 96-well plates, or 10 Tip Boxes (for aspiration of samples from the sample tubes 302), providing a total capacity of 270 96-well plates and 60 Tip Boxes. A user is able to manually rotate each carousel by use of a two-handed button press, for ease of loading and unloading of the labware.
In this example, the sealer 1014 and cooling apparatus 1017 are arranged on a raised platform, adjacent to the robot of the second type 1013. The heated position (heated nest) is advantageously positioned under the raised platform, to prevent cooling by a downflow hood of the first sample processing stage 0P20.
As shown in Figure 12, the conveyor has a 'horseshoe' shape for transferring sample racks 301 into the first sample processing stage 0P20, and for returning the sample racks 301 back to the receiving stage OP10 via the return conveyor 701b, out of the same side of the first sample processing stage 0P20.
Splash guards may be provided to ensure that there is no possibility for liquids to come into contact with any electrical equipment.
The barcode scanner 1015 scans a barcode provided on the sample rack 301 to obtain the identify of the sample rack 301. After the sample rack 301 has entered the enclosure 301 on the conveyor 701, a series of pneumatic clamping and positioning actuators locate the sample rack 301 ready for robot picking. Once the entire sample rack has been processed, the pneumatic actuator releases a single rack 301 which will run along the conveyor 701b and depart the first sample processing stage OP20 on the same face. The sample rack 301 may reach an end stop where it may wait for the operator to unload at the outfeed of the first sample processing stage 0P20. The conveyor may be continuously running during operation of the sample processing line 100, except for in the event of a system error, or in the event that an emergency stop button is pressed.
In this example, the conveyor 701a, 701b is a side-flexing modular chain variant, which is easily wiped down. The tail end of the conveyor 701b is provided with undriven rollers to allow sample racks 301 to accumulate. The belt material may be formed of, for example, blue acetal, which is resistant to chemicals. The conveyor may be provided with side-guards to ensure that sample racks 301 do not fall from the conveyor. The speed of the conveyor may be, for example, between 0.3 m/s and 0.7 m/s (e.g. 0.45 m/s).
In this example, the liquid dispenser 1005 is configured for dispensing 50 pL of a lysis buffer into the wells of a 96-well well plate, before the well plates are transferred to the liquid handling platform 1201. Sample from sample tube 302 is then transferred into one of the wells of the well plate. In this example, the liquid dispenser 1005 comprises a peristaltic pumping system which uses disposable pump cassettes. The fluid lines are connected to a cooled position 1017 (temperature controlled) to maintain the temperature of the reagent container. The lysis buffer is maintained at a temperature of approximately 4 °C.
The shaker 1018 is configured to shake the well plate after the lysis buffer and samples have been added to a well, to mix the lysis buffer with the sample. The shaker 1018 may be configured to shake the well plate when the well plate is in the heated position. The heating position of the heating/cooling apparatus 1017 and the functions of the shaker 1018 may be provided by a single apparatus, for example an I nheco Teleshake 95.
The decapper/recapper 1007 comprises four de-capping positions. A view of a de-capping station 1007 is shown in Figure 15. Four sample tubes can be loaded at the de-capping station 1007. The station may contain individual tube barcode readers to decrease cycle time and improve reliability. De-capping of the sample tubes 302 is achieved using four pneumatic three-point grippers attached to individual high torque DC motors. The tubes are clamped and de-capped before being transferred to the liquid handling platform 1201. After the tubes have been de-capped, the robotic arm 1009c moves clear of the open tubes in the bunded area. Any drips from the caps are contained within this area.
A liquid extractor of the liquid dispensers / extractors 1005 is configured for extracting a portion of a sample from a sample tube 302. The vision system 1021 is configured to verify that the portion of the sample has been correctly extracted from the sample tube 302. The vision system 1021 may comprise a camera and a computer program for analysing images obtained by the camera. The vision system 1021 may also comprise one or more light sources for illuminating the extracted sample as an image of the sample is obtained by the camera. The computer program may comprise, for example, a suitable trained algorithm (e.g. neural network) for determining whether the sample has been correctly extracted (e.g. a sufficient amount of fluid has bene extracted) based on a corresponding image obtained by the camera. In other words, the first sample processing stage 0P20 comprises a vision system configured for verifying that the portion the sample has been extracted from the first receptacle 302.
Four de-capped sample tubes 302 are loaded into the liquid handling platform 1201, along with one 96-well plate and one tip box. 50pL of sample is aspirated from each of the sample tubes 302. The vision system 1021 is used to verify that a fresh tip has been picked, and that the sample has been correctly aspirated. The vision system 1021 is configured with a threshold boundary to ensure enough sample material has been aspirated. The system is designed to over aspirate, to ensure there will be sufficient material to dispense 50pL of the sample into a well of the well plate. An example of a volume check window 1600 of the vision system 1021 is shown in Figure 16. The meniscus of the liquid inside the tip is identified within the bounding box 1601 and used to verify that amount of liquid that has been aspirated. In this example, volume check window 1600 comprises two visual indications 1602, 1603 that indicate to a user that a sufficient quantity of sample has been aspirated. The vision system 1021 outputs and logs a pass/fail for sample volume. The vision system 1021 is also configured to confirm the presence of tips on the dispense head.
After the sample has been aspirated from the sample tube 302, the sample is then dispensed into a well the 96-well plate (the well may also be referred to as a 'second receptacle'). Once the 96-well plate is full of samples, it exits the liquid handling platform 1201, and the tipbox is disposed of and replaced.
A pneumatically actuated drip tray protects the 96-well plate, to ensure that there are no drips into the working mechanisms. When the sample tubes 302 have been processed, they are be recapped by the decapper/recapper 1007 and placed back into the sample rack 301 on the conveyor.
Each liquid handling robot is equipped with a dual dispense head 171. A view of a liquid handling gripper showing the dual dispense head 171 is shown in Figure 17.
Each head 171 is mounted on a pneumatic floating bearing to ensure that each head 171 applies the same amount of force for picking up tips. The is able to vary the pitch between the heads, to allow the span to be increased when aspirating, and to allow the span to be decreased during the dispensing.
The dispense heads use air displacement dispensing technology to aspirate and dispense the samples. Advantageously, this technology enables an aliquoting and dispensing tolerance for a saliva sample of ±10% to be achieved.
The first sample processing stage may be provided one or more waste bins (waste receptacles). The waste bins may receive, for example, liquid waste from the liquid dispensers/extractors 1005, or used tip boxes from the liquid handling platform 1201.
Separate waste bins may be provided for biological waste and non-biological waste. Each of the waste bins may be provided with one or more ultrasonic sensors, mounted to monitor waste levels in the bin, and alert a user if the bin becomes overly full and should be emptied.
In other words, the first sample processing stage 0P20 is configured for: removing a lid 304 from the first receptacle 302; extracting a portion the sample from the first receptacle 302; and transferring the extracted portion of the sample to the second receptacle. The first sample processing stage 0P20 is configured for extracting the portion of the sample from the first receptacle 302 by aspiration.
The first sample processing stage is configured for attaching a lid to the first receptacle after the portion of the sample has been extracted from the first receptacle. The lid 304 is reattached to the first receptacle 302 using the decapper/recapper 1007, before the first receptacle 302 is output for transfer back to the receiving stage OP10 Second sample processing stage (0P30) The second sample processing stage 0P30 will now be described in more detail, with reference to Figures 21 to 28.
Figure 21 shows a simplified schematic block diagram of the second sample processing stage 0P30. The second sample processing stage 0P30 comprises a system PC 2201 that is connected to two 6-position carousels 2205, 2206 via a serial hub 2204. The system PC 2201 is connected to a liquid handler 2208 via an ethernet switch 2207. The system PC 2201 is connected to a robotic arm 2210, a barcode scanner 2211 and a cooler controller 2212 via a USB hub 2209. The cooler controller 2212 controls two coolers 2213, 2214. In this example, the system PC 2201 is also connected to other system PCs 2203 via an ethernet switch 2202. As illustrated in Figures 22 and 23, apparatus of the second sample process stage 0P30 is arranged inside a corresponding enclosure 105.
The 6-position carousels 2205, 2206 may be, for example, Peak Robotics 6 Position Microplate Storage Carousels. The barcode scanner 2211 may be, for example, the Cognex Dataman 70. The coolers 2213, 2214 may be, for example, Inheco CPAC.
In operation, the sealed 96-well plates are received from the first sample processing stage 0P20. In this example, the sealed well plates may be transferred to the second sample processing stage 0P30 manually by a user. Alternatively, the well plates could be transferred from the first sample processing stage 0P20 to the second sample processing stage 0P30 using a conveyor or robotic arm. The enclosure 105 is provided with access windows 2302 to allow a user to insert labware into (or remove labware from) the enclosure. The user adds three sealed plates onto respective positions of the liquid handler 2208. The three sealed plates include a Mastermix plate, a positive control plate, and a negative control plate.
Figure 4 shows a test tube block 401 for use at the liquid handler 2208, and for subsequent use in a testing machine of the testing stage 0P40. Strips of test tubes 402 are held in a base portion 403 of the test tube block 401. The test tube block 401 may be a 'Genie Block'. Each block 401 is provided with a barcode for identifying the block 401. Each of the test tube strips 402 is also provided with a barcode for identifying each test tube strip 402.
As shown in Figure 26, the liquid handler 2208 is configured with three linear axis for feeding consumables into the working envelope of the unit. One linear actuator is for loading two different types of tip boxes. The other two linear axis are fitted with cooled test tube block 401 loading positions, and are both connected to an external chilling unit. The deck is fitted with four cooled positions (for a Mastermix plate, negative and positive control plates, and sample plate) that are connected to an external chilling unit mounted to the side of the liquid handler 2208. In this example, the binding reagents used in the assay are temperature sensitive, cold start, and a chain reaction. Advantageously, the chilling of all reagent positions to 4 °C ensures that the reaction will not start prematurely. In other words, the second sample processing stage 0P30 is advantageously configured to cool and maintain the temperature of the sample and reagents at a temperature of 4 °C, so that the reaction does not being prematurely.
Thus, the second sample processing stage 0P30 is configured for cooling the sample in the third receptacle 402. The second sample processing stage 0P30 is configured for cooling the sample received from the first sample processing stage 0P20 to be within a threshold range of a first predetermined temperature On this example, the first predetermined temperature is 4 °C). The second sample processing stage 0P30 is configured for maintaining the cooled sample within the threshold range of the first predetermined temperature until the sample is output to the testing stage OP40. The second sample processing stage 0P30 is configured for maintaining the temperature of the reagent in the second sample processing stage 0P30 to be within a threshold range of a second predetermined temperature On this example, the second predetermined temperature is 4 °C).
The 96 well sample plate, tipbox and test tube block 401 are presented to the liquid handler 2208 automatically. 5 pL of sample is aspirated from the 96 well plate into the test tubes 402 of the test tube block 401. The robotic arm 2210 maintains the supply of labware and transfers the processed test tube blocks 401 to cooled positions, cooled by the coolers 2213, 2214.
The liquid handler 2208 is provided with three dispense heads 2604 (for example, a dispense head of the type illustrated in Figure 17). In this example, the dispense heads achieve an aliquoting and dispensing tolerance for Newtonian liquids of ±10%.
As shown in Figure 26, the dispense heads 2604 are moveably mounted to two longitudinal rails 2602a, 2602b and one transverse rail 2603 for movement around the liquid handler 2208.
Two tipboxes (one for transfer of 200pL of sample mix from the well plate, and one for transfer of 50pL for the control) are transferred by the robotic arm 2210 from a carousel 2205, 2206 to the liquid handler 2208. Before the well plate is collected, a first test tube block 401 is loaded onto a first linear track 2601. The linear track 2601 is shown in Figure 26, which shows a plan view of the liquid handler 2208. Once the well plate (also referred to as a 'microplate'), tips and test tube block 401 have been loaded, the liquid handler 2208 transfers Mastermix solution (or another suitable reagent), then sample and controls (at predefined intervals) from the well plates into a test tube 402 of the test tube block 401. The Liquid handler is configured to aspirate 160 pL of Mastermix from the sealed plate, and then dispenses 20pL of Mastermix into each tube 402 of the test tube block 401. While this transfer is taking place, the robotic arm 2210 loads a second test tube block 401 onto the second linear track 2609.
Once the first test tube block 401 has been filled, it is collected from the liquid handler by the robotic arm 2210 and placed on a cooled position (tooled nest position') of a cooler 2213, 2214, while the second test tube block 401 is moved into the system, repeating the process described above. Once both test tube blocks 401 have been filled with the samples, they are stored on the cooled positions of the coolers 2213, 2214, until a user presses two buttons to eject a transfer station and collect the plates.
This process is then repeated, transferring the second half of the contents in the microplate to two further test tube blocks 401. Once the third and fourth test tube blocks 401 are on the transfer station, the robotic arm 2210 unloads the empty tipbox and microplate, discarding both into separate bins for disposal/recycling.
As shown in Figure 24, the robotic arm 2210 is mounted generally centrally inside the enclosure 105, and the individual workstations/apparatus are be positioned for access by the robotic arm 2210. As shown in Figure 25, the overall layout of the second sample processing stage 0P30 has been designed to provide a balance of user access and machine throughput.
Apparatus in the second sample processing stage 0P30 is positively located using locator feet or physically mounted to the worksurface to aid positional repeatability, and to allow instruments to be removed and replaced for servicing requirements without the need for reteaching of the robotic arm 2210.
The two 6-position carousels 2205, 2206 are positioned adjacent to corresponding access windows 2302 in the enclosure 105, such that a user can access the carousels to insert and remove labware stacks. As shown in Figure 25, the positions of the carousels enable a good automation flow, but also to provide good user access for loading and unloading the stacks. A user can manually rotate each carousel by use of a two-handed button press, for ease of loading and unloading.
In this example, process controls are used during normal operation of the system to provide validation and feedback of correct operation of the apparatus, and to detect contamination inside the system. In this example, the following controls are used: o No Sample Control (NSC): 50p1 Water to 50p1 RapiLyse (E2E control) o Positive Control (PC): 5plOptiGene Control to 20p1 Mastermix o No Template Control (NTC): 5p1 Water to 20p1 Mastermix..
The NSC is used to detect contamination as the samples pass through the entire process from the receiving stage OP10 through to the testing stage 0P40. The control is contained inside a sample tube and added by the operator in the receiving stage OP10.
The PC and NTC are prepared offline in a 96 well plate, which is then sealed with a foil seal and maintained at a temperature of 4°C. The control plate is loaded onto a manual plate position inside the working envelope of the liquid handler 2208. This position is provided by a cooler 2213, 2214 operating at a temperature of 4 °C. At a pre-defined time interval, the liquid handler 2208 pierces and transfers PC and NTC into the test tube strips 402.
\Mien the test tube blocks 401 are have been processed and are ready to proceed to the testing stage 0P40, they are presented to an output area 2701 by the robotic arm 2210. The output area 2701, and corresponding access window 2302, are illustrated in Figure 27. The location of the access window 2302 is also shown in Figure 28. The output area 2701 comprises two chilled plate positions on a linear actuator. When the test tube blocks 401 have been transferred to the output area 2701, a user 2301 presses a button to call the linear actuator closer. The user 2301 then closes the lids of the test tubes in the test tube block 401 while they are still inside the laminar airflow inside the enclosure 105, before the user 2301 transfers the test tube block 401, via the access window 2302, for subsequent processing at the testing stage OP40.
In this example, the enclosure 105 of the second sample processing stage 0P30 is provided with a laminar downflow hood. The hood has an inlet grille along one side with disposable pre-filters. Two fan modules are provided, each with one centrifugal impellor driven by speed controllable EC type motor. A perforated equalization grid is provided to 'even out' the air as it enters HEPA filters below. Two HEPA (H14) filters are provided. A remote control panel may be provided, containing apparatus and interfaces for operating the unit, including a power on indication, a fan run indication, an airflow fail indication, an on/off button, an alarm mute, and a filter pressure drop indication gauge.
The robotic arm used in the second sample processing stage may be the same type of robotic arm 505 used in the receiving stage OP10, or may be the same type of robotic arm 1013 used in the first sample processing stage 0P20, and so will not be described in detail again here. The robotic arm 2210 may be provided with a gripper end effector as shown in Figure 20 and described above.
As for the first sample processing stage 0P20, the second sample processing stage 0P30 may be provided with waste bins in a similar configuration, which will not be described again in detail here.
Testing stage (0P40) The testing stage 0P40 will now be described in more detail, with reference to Figures 29 to 31.
Figure 29 shows a simplified block diagram of the testing stage 0P40. The testing stage 0P40 comprises a system PC 3101 that is connected to sample testing machines 3103, 3104 via an ethernet switch 3102. The system PC 3101 is also connected to a push button control system 3105 via the ethernet switch 3102. In this example, the system PC 3101 is also connected to other system PCs 3107 via an ethernet switch 3106.
An overview of the testing stage 0P40 is shown in Figure 30. A test tube block 401 from the second sample processing stage is first placed onto a centrifuge at a centrifuge station 2903 by a user and spun. Once the centrifuge process is complete, the test tube strips are then loaded into one of the testing machines 3103, 3104 for testing of the samples. In other words, the third receptacle 402 is for insertion into a testing machine 3103, 3104 to perform the test on the sample.
The base portions 403 of the test tube blocks 401 that held the test tube strips 402 are placed in a bleach solution bath for cleaning and reuse.
The testing machine may be a Genie testing machine to perform analysis of the samples. In this example, the test is a LAMP test, and the testing machine is configured to detect the presence of SARS-CoV-2 virus in the sample (saliva), and output an indication of whether the virus is present in the sample.
Upon completion of the sample analysis by the testing machine 3103, 3104, the test result is output, and the user removes the test tube strip 402 from the testing machine for disposal. The test result may be output to a remote database. The test result is also output to the receiving stage OP10 so that the robotic arm 505 of the receiving stage OP10 can sort the returned samples, as described above.
The testing stage 0P40 is provided with a push button control system 3105 for control of the apparatus in the testing stage OP40. Green push button switches are supplied next to each piece of instrumentation, to provide feedback to control software that a manual action has been completed. Instructions for a user at the testing stage 40 may be provided visually on display monitors 2902a, 2902b. Figure 31 shows an example of a user interface 3700 that indicates an action 3701 to be performed at the testing stage 0P40. The interface also indicates 3702 one or more items of PPE that should be worn by the user whilst performing the action 3701.
The apparatus in the testing stage 0P40 are positively located using locator feet or physically mounted to the worksurface to aid positional repeatability and to allow instruments to be removed and replaced for servicing requirements. In this example, the two testing machines 3103, 3104 are two Genie HT machines that are positioned either side of a waste outlet 3109 to provide improved user access and improved process flow. The centrifuge may be sunken into the worktop surface for ergonomic purposes. A waste bin on the Genie workbench may be configured to retract from the rear of the bench to minimise disruption while the bin is exchanged. The waste bin includes a sensor configured to detect when the bin requires changing.
Further implementational details As described above, the receiving stage OP10, first sample processing stage 0P20, second sample processing stage 0P30 and testing stage 0P40 may form an automated LAMP Preparation system that receives saliva samples and process them to test them for existence of COVID 19. This process starts with tubes of saliva being received in the post and transferred into the receiving stage OP10, and ends with the generation of positive/negative test results at the testing stage 0P40, that are linked back to the original samples by using barcodes that are provided on the outside of the sample tubes, and on the various other receptacles that are used in the sampling processing line 100.
The rate limiting step of the sample processing line 100 is the Genie testing machine. Advantageously, the configuration of the sample processing line 100 enables the utilisation of the Genie testing machines to be maintained close to 100%. Availability at the Genie testing machine drives the rest of the system -each process is driven by availability in the subsequent stage.
The system is designed to run with minimal human interaction over an 8 hour shift. It is expected that the testing stage 0P40 will have a takt time of 28 minutes, assuming the human operators keep up with the throughput of the system. If the operator is able to remain on takt, in an 8-hour shift, then approximately 16 cycles of the system can be run, allowing some time for initial setup of the system.
Exemplary methods Receiving Stage OP10 Figure 32 shows a method that may be performed in the above described receiving stage OP10.
In step S310, an RFID tag on a clamped rack of samples is read.
In step S311, a database is queried to obtain test results for the samples in the rack. In step S312, a tube is obtained from the rack.
In step 5313, the tube is transferred (sorted) to a location based on the corresponding obtained test result.
Steps 5312 and 5312 are executed 24 times before proceeding to step 5314 (in order to remove all of the 24 tubes from the rack).
In step S314 the clamped rack is released.
First Sample Processing Stage 0P20 Figures 33 and 34 shows a method that may be performed in the above-described first sample processing stage 0P20.
Steps 5320, 5321, S323, S325, S327 and S328 may be performed using the first type robotic arm. Steps S322 and S326 may be performed using the liquid dispenser/heater. The remaining steps of Figure 33 may be performed using the second type of robotic arm.
In step S320, a microplate is placed on a Multidrop.
In step S321, two tipboxes are placed on the liquid handler.
In step S322, RapiLyse is dispensed.
In step S323, a microplate is placed on the liquid handler.
Step S324 is shown in Figure 34.
In step S324a, a tube rack is clamped in position.
In step 5324b, 4 tubes from the rack are loaded into the decapper.
In step S324c, the tubes are spun to scan the barcodes and de-cap the tubes.
In step S324d, two tips are obtained from the tipbox.
Step S324e comprises checking that tips are present, aspirating from the tube, and confirming successful aspiration.
Step S324f comprises dispensing into a microplate Step S324g comprises dropping the tips.
Steps 324h to S324k are the same as steps 324d to S324g.
Step S324L comprises re-capping the tubes and returning the tubes to the block. Step 5324m comprises releasing the tube rack.
Step S325 comprises getting the microplate from the liquid handler, sealing the plate, and placing the microplate on the heated nest.
Step S326 comprises heating the microplate.
Step S327 comprises unloading empty tipboxes from the liquid handler.
Step S328 comprises getting the microplate from the heated nest and putting the microplate on a shuttle for subsequent transfer to the second sample processing stage 01P30.
Second Sample Processing Stage 0P30 Figures 35 and 36 show a method that may be performed at the above-described second sample-processing stage. As indicated in the figure, some steps or groups of steps are executed multiple times.
Step S341 comprises obtaining Genie Block strips, and placing the strips on the cooled nest Step S342 comprises obtaining a microplate from the shuttle and putting the microplate on the liquid handler.
Step S343 comprises obtaining two tipboxes and putting the tipboxes on the liquid handler Step S344 comprises obtaining the Genie Block from the cooled nest and putting the Genie Block in the liquid handler.
Step S345 is the same as step S341. Step S346 is the same as step 5344.
Step S347 comprises moving a plate into the liquid handler.
Step S348 comprising obtaining tips and transferring reaction mix to the strips.
Step S349 comprises dropping tips.
Step S350 is shown in Figure 36. Step S350a comprises obtaining tips. Step S350b comprises aspirating from a sealed plate and dispensing into a Genie strip. Step S350c comprises dropping tips.
Step S351 comprises moving the Genie Block out of the liquid handler.
Steps S352, S353, S354 and S355 are the same as steps 5347, S348, S349 and S351, respectively.
Step S356 comprises obtaining the Genie Block from the liquid handler and putting the Genie block on a cooled nest position.
Step S357 comprises obtaining the fipbox from the liquid handler and putting the tipbox in a waste bin.
Step S358 comprises obtaining the microplate from the liquid handler and putting the microplate in a waste bin.
Testing Stage 0P40 Figure 37 shows a method that may be performed at the above-described testing stage 0P40.
Step 5360 comprises pressing a foot pedal at the second sample processing stage OP30.
Step S361 comprises closing Genie strips by hand.
Step S362 comprises placing the Genie Block on a closer tool.
Step S363 comprises closing lids using a closing tool.
Step S364 comprises spinning strips on a microfuge.
Step S365 comprises visually inspecting the strips.
Step S366 comprises unloading the completed strips.
Step S367 comprises loading strips to be processed.
Step S368 comprises scanning a barcode on the Genie drawer.
Step S369 comprises scanning a barcode on the Genie strip. Database interactions Software running at the receiving stage OP10, the first sample processing stage 0P20, the second sample processing stage 0P30, and the testing stage 0P40 may have access to a local database (e.g. SQL database) storing sample information.
The database may contain a table. The system PCs of the receiving stage OP10, the first sample processing stage 0P20, the second sample processing stage 0P30 and the testing stage 0P40 may be used to read entries from the database and write entries to the database. Examples of information that may be stored in the database are set out below: * 'Id' -unique ID of the record in the database * 'SampleId' -Barcode of the sample as printed on the sample tube received from the receiving stage OP10 * 'PlateId' -Barcode of the 96-well plate used in the first sample processing stage 0P20 * locationInPlate' -1 to 96 index of the sample within the 96-well plate * Rackld' -Barcode of the tube rack containing the sample tube * LocationInRack' -1 to 48 index of a sample tube within the rack * 13lockld' -Barcode of the Genie block containing the sample * tocationInBlock' -1 to 3 index of a sample within a block (first, second or third strip on the block) * Stripld' -Barcode of the Genie strip containing the sample * locationInStrip' -1-8 index of a sample within a block (A1-A8) * 'Result' -Positive, Negative, Investigate (field values: POS, NEG, INV) * SentToLims' -Flag True once a sample has been sent to LANTERN server.
* Machine ID' -Identifier for the system, e.g. serial number There may also be additional table fields for indicating when some manual steps at the testing stage 0P40 are completed, and to log system information such as batch IDs. The batch IDs for Lysis buffer, Mastermix, positive control and negative control can be recorded by the scanning of a barcode.
The system may interact with the external 'LANTERN' database, or a suitable similar database for storing test results. Upon the completion of the Genie testing, the system may push information to the LANTERN database via the corresponding API. This information is formed by the database logging the location of the sample within the various pieces of labware as it moves through the sample processing line 100, and coupling this information with the barcode scanned when the sample tube entered the first sample processing stage 0P20.
Further exemplary methods Figure 38 shows method steps that may be performed at the receiving stage OP10 and at the first sample processing stage 0P20. 'FIFO' indicates a first-in first-out arrangement. The steps shown in boxes with dashed lines are performed manually by a user (in a 'manual process'), and the steps shown in boxes with solid lines are performed automatically by apparatus On an 'automatic process').
Step 5381 comprising loading boxes of samples to a flow rack.
Step S382 comprises picking a sample pack box and scanning the sample pack.
Step S383 comprises inspecting the sample tube for leaks. Rejected or queried tubes may be placed into a separate sample box.
Step 5384 comprises unbagging the sample tube using an opener, and racking the sample tube.
Step S385 comprises a robot picking up the sample tube.
Step S386 comprises scanning a barcode on the sample tube using a barcode reader.
Figures 39 and 40 show method steps that may be performed at the first sample processing stage 0P20. The steps shown in boxes with dashed lines are performed manually by a user (in a 'manual process'), and the steps shown in boxes with solid lines are performed automatically by apparatus On an 'automatic process').
Step S391 comprises de-lidding a sample tube using a robot at a de-lid station.
Step 3392 comprises placing the sample in a liquid handler. A plate carousel and a bulk liquid dispenser may be used in this step.
Step S393 comprises feeding in a filled lysis buffer plate.
Step S394 comprises feeding in a 200 pL tip rack.
Step S395 comprises selecting a tip using a robot.
Step S396 comprises aspirating from the sample using a robot.
Step S397 comprises loading a carousel with 96-well plates.
Step S398 comprises selecting a 96-well plate. The 96-well plate may be selected from a plate carousel.
Step S399 comprising bulk filling a lysis buffer plate.
Step S400 comprises loading a carousel with tip racks. The tip racks may be loaded from a tip carousel.
Step S401 comprises selecting a tip rack.
Step S403 comprises dispensing the sample to a 96 well plate. Step S404 comprises ejecting the tip.
Step S405 comprises a robot moving the sample tube out.
Step S406 comprises a robot re-lidding the sample.
Step S407 comprises a robot replacing the sample in the sample rack. Step S408 comprises sealing the 96-well plate with foil.
Figure 41 shows method steps that may be performed at the first sample processing stage 0P20 and at the second sample processing stage 0P30. The steps shown in boxes with dashed lines are performed manually by a user (in a 'manual process), and the steps shown in boxes with solid lines are performed automatically by apparatus On an 'automatic process').
Step S409 comprises deactivating the sample with heat.
Step S410 comprises deactivating the sample with heat using a plate heater.
Step S411 comprises moving a plate to the second sample processing stage 0P30.
Step S412 comprises loading a pre-prepared Master Mix plate from a carousel.
Step S413 comprises loading a pre-prepared positive control plate.
Step S414 comprises loading a pre-pared negative control plate.
Step S415 comprises preparing the Master Mix plate.
Step S416 comprises preparing the positive control plate.
Step S417 comprises preparing the negative control plate.
Figure 42 shows method steps that may be performed at the second sample processing stage 0P30. The steps shown in boxes with dashed lines are performed manually by a user (in a 'manual process'), and the steps shown in boxes with solid lines are performed automatically by apparatus On an 'automatic process').
Step 5418 comprises loading Genie blocks to the liquid handler. Step S419 comprises loading a 50 pl tip box to liquid handler. Step S420 comprises loading a 200 pl tip box to liquid handler. Step S421 comprises aliquoting Master Mix to Genie strips.
Step S422 comprises aliquoting positive control to a Genie strip (1 in 96).
Step S423 comprises aliquoting negative control to a Genie strip (1 in 96). Step S424 comprises loading a carousel with Genie blocks.
Step S425 comprises loading a carousel with tip boxes.
Step S426 comprises loading a carousel with tip boxes.
Step S427 comprises aliquoting Master Mix to a yellow plate and sealing.
Step S428 comprises loading the master mix plate to a yellow position.
Step S429 comprises aliquoting a positive control to a red plate and sealing.
Step S430 comprises loading the positive control plate to a red position.
Step S431 comprises aliquoting a negative control to a green plate and sealing.
Step S432 comprises loading the negative control plate to a green position.
Figure 43 shows method steps that may be performed at the second sample processing stage 0P30 and at the testing stage 0P40. The steps shown in boxes with dashed lines are performed manually by a user On a 'manual process), and the steps shown in boxes with solid lines are performed automatically by apparatus (in an 'automatic process').
Step S433 comprises aliquoting the lysed sample to a Genie strip using a liquid handler Step S434 comprises moving a filled Genie block to an exit position using a robot.
Step S435 comprises manually closing lids on Genie strips.
Step S436 comprises closing lids on a strip closing device. Step S437 comprises centrifuging strips using a centrifuge. Step S438 comprises loading strip to a Genie HT.
Figure 44 shows method steps that may be performed at the testing stage 0P40.
The steps shown in boxes with dashed lines are performed manually by a user (in a manual process'), and the steps shown in boxes with solid lines are performed automatically by apparatus On an 'automatic process').
Step S439 comprises scanning a strip into Genie HT. Step S440 comprises running Genie HT.
Step S441 comprises unloading the Genie machine.
Step S442 comprises processing test results using a computer and or a human-machine interface (HMI). At this stage, the test results may be output (e.g. to an external server).
Step S443 comprises ejecting Genie strips to waste.
Step S444 comprises recovering positive and inconclusive samples.
Figure 45 shows method steps that may be performed at the receiving stage OP10 and at the first sample processing stage 0P20.
Step S450 comprises performing pre-shift checks at the receiving stage OP10.
Step S451 comprises performing pre-shift cleaning at the receiving stage OP10. Step S452 comprises running and processing.
Step S453 comprises generating a quality control decision.
Step S454 comprises performing pre-shift checks at the first sample processing stage 0P20.
Step S455 comprises performing pre-shift cleaning at the first sample processing stage 0P20.
Step S456 comprises running and processing.
Step S457 comprises loading Rapi Lyse.
Step S458 comprising running a programme. Step S458 proceeds to step S462 shown in Figure 46.
Figure 46 shows method steps that may be performed at the second sample processing stage 0P30 and at the testing stage 0P40.
Step S460 comprises performing pre-shift checks at the second sample processing stage 0P30.
Step S461 comprises performing pre-shift cleaning at the second sample processing stage 0P30.
Step S462 comprises running and processing.
Step S463 comprises loading Mastermix.
Step S464 comprises running a programme.
Step S465 comprises performing pre-shift checks at the testing stage 0P40. Step S466 comprises performing pre-shift cleaning at the testing stage 0P40. Step S467 comprises running and processing.
Step S468 comprises generating a LAMP test result.
Step S469 comprises releasing the test result.
Step 5470 comprises repeating a test. The method proceeds from step 5470 to the Rack step of the receiving stage OP10 shown in Figure 45.
Modifications and Alternatives As those skilled in the art will appreciate, a number of modifications and alternatives can be made to the above examples and variations whilst still benefiting from the inventions embodied therein.
Whilst the sample processing line 100 has been described as comprising a number of discrete stages 0P10, 0P20, 0P30, 0P40, it will be appreciated that the funcfionalities of each stage may be built into the sample processing line 100 as a whole, and that the stages need not necessarily be discernible as discrete entities.
In the above description, the sample processing line 100 (and in particular, the testing stage 0P40) has been referred to with reference to performing tests for detecting the presence of COVID 19. However, it will be appreciated that the sample processing line 100 may be configured for processing samples for any other suitable test.
In the above description, the system PCs and controllers may comprise a number of discrete software modules. However, it will be appreciated that the functionality performed by part or all of the software may be performed using one or more dedicated hardware circuits for example using one or more dedicated integrated circuits such as an application specific integrated circuit (ASIC) or the like. The use of software modules is, nevertheless, preferred as it facilitates the updating of the system.
In the above description, some of the steps performed at the testing stage 0P40 have been described as manual steps performed by a user (for example, the insertion of the test strips into the testing machine 3101, 3104). Alternatively, the testing stage OP may be fully automated. For example, the testing stage 0P40 may comprise one or more robotic arms for inserting samples into testing machines. Similarly, in the above description, some of the steps of transferring of samples and apparatus between each of the receiving stage OP10, first sample processing stage 0P20, second sample processing stage 0P30 and testing stage 0P40 have been described as manual transfers performed by a user. Alternatively, these transfer steps may be fully automated, for example using one or more conveyors or robotic arms.
It will be appreciated that the system PCs and controllers referred to in the present disclosure may comprise any suitable controller such as, for example an analogue or digital controller. Each controller may comprise any suitable form of processing circuitry including (but not limited to), for example: one or more hardware implemented computer processors; microprocessors; central processing units (CPUs); arithmetic logic units (ALUs); input/output (10) circuits; internal memories / caches (program and/or data); processing registers; communication buses (e.g. control, data and/or address buses); direct memory access (DMA) functions; hardware or software implemented counters, pointers and/or timers; and/or the like.
Various other modifications will be apparent to those skilled in the art and will not be described in further detail here.

Claims (35)

  1. CLAIMS1. A sample processing line comprising: a receiving stage configured for receiving a sample in a first receptacle; a first transfer means configured for transferring the sample from the receiving stage to a first sample processing stage, wherein the first sample processing stage is configured for transferring a portion of the sample from the first receptacle to a second receptacle; a second sample processing stage configured for: receiving the sample in the second receptacle from the first sample processing stage; dispensing a reagent into a third receptacle; and dispensing at least a portion of the sample from the second receptacle into the third receptacle; and a testing stage configured for: receiving the sample in the third receptacle from the second sample processing stage, and performing a test on the sample.
  2. 2. The sample processing line according to claim 1, wherein the sample processing line further comprises a second transfer means configured for returning the sample in the first receptacle from the first sample processing stage to the receiving stage, after the portion of the sample has been transferred to the second receptacle.
  3. 3. The sample processing line according to claim 2, wherein one or both of the first transfer means and the second transfer means comprises a conveyor.
  4. 4. The sample processing line according to claim 2 or 3, wherein the receiving stage comprises sorting apparatus configured for sorting the samples that are returned to the receiving stage.
  5. 5. The sample processing line according to claim 4, wherein the sorting apparatus comprises a robotic arm.
  6. The sample processing line according to claim 4 or 5, wherein the sorting apparatus is configured for sorting a sample that is returned to the receiving stage based on a corresponding test result from the testing stage.
  7. The sample processing line according to any one of claims 4 to 6, wherein the sorting apparatus is configured for sorting a sample that is returned to the receiving stage based on at least one of an indication output from the first sample processing stage or an indication output from the second sample processing stage.
  8. 8. The sample processing line according to any one of claims 4 to 7, wherein the sorting apparatus is configured for transferring a sample that is returned to the receiving stage to a waste output, based on a corresponding negative test result output from the testing stage for the sample.
  9. 9. The sample processing line according to any one of claims 4 to 8, wherein the sorting apparatus is configured for sorting a sample that is returned to the receiving stage for subsequent re-testing of the sample, based on a corresponding first positive test output from the testing stage for the sample.
  10. 10. The sample processing line according to any one of claims 4 to 9, wherein: the sorting apparatus is configured for sorting a sample that is returned to the receiving stage based on an indication output from the first sample processing stage or based on an indication output from the second sample processing stage; and wherein the sorting apparatus is configured to output an indication to a user of a processing step to be performed at the receiving stage based on the indication output from the first sample processing stage or the indication output from the second sample processing stage.
  11. 11. The sample processing line according to claim 10, wherein the indication to the user comprises at least one of: an indication that a user should manually remove a lid from the first receptacle that contains the sample, based on an indication from the first sample processing stage of a failure to remove the lid from the first receptacle; or an indication that a user should manually check the amount of the sample in the first receptacle, based on an indication from the first sample processing stage of a failure in an extraction the sample from the first receptacle; or an indication that a user should manually check an identifying mark or number provided on the first receptacle, based on an indication from the first sample processing stage of a failure to identify the sample.
  12. 12. The sample processing line according to any preceding claim, wherein the sample is a sample of saliva.
  13. 13. The sample processing line according to any preceding claim, wherein the test is a loop-mediated isothermal amplification, LAMP, test.
  14. 14. The sample processing line according to any preceding claim, wherein the first sample processing stage is configured for: removing a lid from the first receptacle; extracting a portion the sample from the first receptacle; and transferring the extracted portion of the sample to the second receptacle.
  15. 15. The sample processing line according to claim 14 wherein the first sample processing stage is configured for extracting the portion of the sample from the first receptacle by aspiration.
  16. 16. The sample processing line according to claim 14 or 15, wherein the first sample processing stage comprises a vision system configured for verifying that the portion the sample has been extracted from the first receptacle.
  17. 17. The sample processing line according to any one of claims 14 to 16, wherein the first sample processing stage is configured for attaching a lid to the first receptacle after the portion of the sample has been extracted from the first receptacle.
  18. 18. The sample processing line according to any one of claims 14 to 17, wherein the first sample processing stage is configured for sealing the second receptacle before transfer of the second receptacle to the second sample processing stage.
  19. 19. The sample processing line according to any preceding claim, wherein the first sample processing stage is configured for dispensing a buffer solution into the second receptacle.
  20. 20. The sample processing line according to claim 19, wherein the buffer solution is a lysis buffer solution.
  21. 21. The sample processing line according to claim 19 or 20, wherein the first sample processing stage is configured for storing the buffer solution at a temperature of around 4 °C before it is dispensed into the second receptacle.
  22. 22. The sample processing line according to any preceding claim, wherein the first sample processing stage is configured for heating the sample in the second receptacle.
  23. 23. The sample processing line according to claim 22, wherein the first sample processing stage is configured for heating the sample in the second receptacle to a predetermined sterilisation temperature to deactivate a virus in the sample.
  24. 24. The sample processing line according to claim 22 or 23, wherein the first sample processing stage is configured for heating the sample in the second receptacle to a temperature of approximately 80 °C.
  25. 25. The sample processing line according to any preceding claim, wherein the second sample processing stage is configured for cooling the sample in the third receptacle.
  26. 26. The sample processing line according to any preceding claim, wherein the second sample processing stage is configured for cooling the sample received from the first sample processing stage to be within a threshold range of a first predetermined temperature.
  27. 27. The sample processing line according to claim 26, wherein the second sample processing stage is configured for maintaining the cooled sample within the threshold range of the first predetermined temperature until the sample is output to the testing stage.
  28. 28. The sample processing line according to claim 26 or 27, wherein the first predetermined temperature is 4 °C.
  29. 29. The sample processing line according to any preceding claim, wherein the second sample processing stage is configured for maintaining the temperature of the reagent in the second sample processing stage to be within a threshold range of a second predetermined temperature.
  30. 30. The sample processing line according to claim 29, wherein the second predetermined temperature is 4 °C.
  31. 31. The sample processing line according to any preceding claim, wherein the first receptacle is a tube or vial.
  32. 32. The sample processing line according to any preceding claim, wherein the second receptacle is a well of a well plate.
  33. 33. The sample processing line according to any preceding claim, wherein the third receptacle is a test tube, or a tube of a test tube strip.
  34. 34. The sample processing line according to claim 33, wherein the third receptacle is for insertion into a testing machine to perform the test on the sample.
  35. 35. A method for processing a sample using a sample processing line according to any preceding claim, the method comprising: receiving, at the receiving stage, a sample in the first receptacle; transferring the sample from the receiving stage to the first sample processing stage, and transferring a portion of the sample from the first receptacle to the second receptacle at the first sample processing stage; receiving, at the second sample processing stage, the sample in the second receptacle from the first sample processing stage; dispensing, at the second sample processing stage, a reagent into the third receptacle; and dispensing, at the second sample processing stage, at least a portion of the sample from the second receptacle into the third receptacle; receiving, at the testing stage, the sample in the third receptacle from the second sample processing stage, and performing, at the testing stage, a test on the sample.
GB2204030.7A 2022-03-22 2022-03-22 Sample processing line Pending GB2616869A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2418493A1 (en) * 2009-04-09 2012-02-15 Hitachi High-Technologies Corporation Autoanalyzer and dispensing apparatus
WO2015057877A1 (en) * 2013-10-17 2015-04-23 Siemens Helathcare Diagnostics Inc. Compact high volume analytical instrument architecture

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2418493A1 (en) * 2009-04-09 2012-02-15 Hitachi High-Technologies Corporation Autoanalyzer and dispensing apparatus
WO2015057877A1 (en) * 2013-10-17 2015-04-23 Siemens Helathcare Diagnostics Inc. Compact high volume analytical instrument architecture

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