Method, system, and computer readable medium for operating and monitoring the cleaning of a sample processing instrument - Patents.com

Abstract

What is provided is a method for operating and cleaning a sample processing instrument, comprising the steps of directing, performed by a control device, a first sample containing a first particle through a flow cell in the sample processing instrument, processing the first sample, cleaning the flow cell of the sample processing instrument with a cleaning agent, measuring an amount of carryover in the flow cell after cleaning, the carryover amount comprising a measurement value related to an amount of the first particle remaining in a measurement area of ​​the flow cell, comparing the measured amount of carryover to a predetermined target value, the target value corresponding to a value indicative of a cleaning requirement, and determining whether the cleaning requirement is met based on the comparison.

Description

[Technical field]

[0001] The present disclosure relates to methods or systems for operating and cleaning a sample processing instrument, and to a sample processing instrument, such as a flow cytometer sorter or analyzer, that includes the system. [Background technology]

[0002] This section provides only background information related to the present disclosure, which is not necessarily prior art.

[0003] Sample processing instruments are typically configured to analyze liquid samples containing small suspended particles (e.g., biological particles such as extracellular vesicles, non-biological particles such as beads) or cells, and / or to separate particles or cells therein. Sample processing instruments generally process multiple samples, and after a sample is processed, it needs to be cleaned to avoid inaccurate processing results for the next sample.

[0004] Some sample processing instruments are known to be cleaned using a sheath fluid. However, sheath fluids are not necessarily suitable for all types of samples. In other words, some samples may not be cleaned well. If a separate cleaning agent is used to clean the sample processing instrument, it may be necessary to manually load the cleaning agent into the sample processing instrument, for example in a semi-automatic loader. This may significantly reduce the cleaning efficiency.

[0005] In addition, it is not easy for users to accurately monitor and learn the cleaning results on conventional sample processing instruments, which is a disadvantage for the detection of samples, especially samples containing small particles (e.g., nanoparticles) that are not easily cleaned. Summary of the Invention [Means for solving the problem]

[0006] This section provides a general overview of the disclosure and is not an exhaustive disclosure of its entire scope or all of its features.

[0007] It is an object of the present disclosure to provide a method and system that is capable of automatically running and cleaning a sample processing instrument between different samples processed by the sample processing instrument.

[0008] Another object of the present application is to provide a method that allows automatic and continuous monitoring of the cleaning of a sample processing device.

[0009] Yet another object of the present application is to provide a convenient method for a user to operate and intuitively monitor the cleaning of a sample processing instrument.

[0010] According to an aspect of the present application, there is provided a method for operating and monitoring cleaning of a sample processing instrument, the method including the steps of: directing a first sample through a flow cell in the sample processing instrument, performed by a control device, the first sample comprising a first particle; processing the first sample; cleaning the flow cell of the sample processing instrument with a cleaning agent; measuring an amount of carryover in the flow cell after cleaning, the carryover amount comprising a measurement value associated with an amount of the first particle remaining in a measurement area of ​​the flow cell; comparing the measured amount of carryover to a predetermined target value, the target value corresponding to a value indicative of a cleaning requirement; and determining whether the cleaning requirement is met based on the comparison.

[0011] In some embodiments according to the present application, the method further includes repeating the cleaning step when it is determined that the cleaning requirements are not met, and stopping the cleaning process when it is determined that the cleaning requirements are met or when the number of cleanings has reached a maximum threshold.

[0012] In some embodiments according to the present application, the target value is input by a user.

[0013] In some embodiments according to the present application, the cleaning step includes selecting a cleaning agent from a plurality of cleaning agents configured to clean the flow cell.

[0014] In some embodiments according to the present application, at least one of the cleaning agents comprises a sheath liquid.

[0015] In some embodiments according to the present application, the measuring step includes pumping a monitor solution through a flow cell and measuring light scattered from within the flow cell, the measured light corresponding to an amount of carryover within the flow cell.

[0016] In some embodiments according to the present application, the monitoring solution is different from the cleaning agent. In some embodiments, the monitoring solution is water. In other embodiments, the monitoring solution is a buffer solution.

[0017] In some embodiments according to the present application, the measuring step comprises measuring a carryover count and / or monitoring the volume of the monitoring solution.

[0018] In some embodiments according to the present application, the amount of carryover may be a count of carryover particles. In some embodiments, the count of carryover particles and / or the volume of the monitoring solution is the total count of carryover particles and / or the total volume of the monitoring solution measured during the monitoring period, or the count of carryover particles and / or the volume of the monitoring solution measured at a predetermined interval during the monitoring period.

[0019] In some embodiments according to the present application, the method further includes a step of calculating, by the control device, a value representing the relationship of the carryover amount to the monitoring solution (e.g., a value of the concentration of carryover in the monitoring solution) and / or a value representing the relationship of the carryover amount after cleaning and the amount of the first particles in the sample before cleaning (e.g., a value of the ratio of carryover to particles) based on the measured carryover amount.

[0020] In some embodiments according to the present application, the method further includes calculating a ratio of the amount of carryover after cleaning to the amount of the first particle detected in the first sample or a ratio of the concentration of carryover measured after cleaning to the concentration of the first particle in the first sample.

[0021] In some embodiments according to the present application, the method further includes, following a determination that the cleaning requirements have been met, directing a second sample through the sample processing apparatus and processing the second sample.

[0022] In some embodiments according to the present application, the second sample is directed through the sample processing instrument automatically by the control device in response to determining that the cleaning requirements have been met.

[0023] In some embodiments according to the present application, the first particle comprises a biological nanoparticle.

[0024] In some embodiments according to the present application, the sample processing instrument is a flow cytometer, and processing the first sample includes determining one or more properties of a first particle in the first sample by directing an optical beam towards a flow cell and measuring light emitted or scattered from within the flow cell.

[0025] In some embodiments according to the present application, the method further comprises providing a user interface operated by the user to display information to the user.

[0026] In some embodiments according to the present application, prior to cleaning, an operation window is displayed on the user interface for the user to operate, the operation window comprising at least one of an option for selecting a process to be performed, a dialog box for inputting parameters and / or target values ​​associated with the selected option, and a field for setting cleaning standards for cleaning / monitoring the flow cell after a particular sample has been processed (e.g., one or more particular samples may be selected and specific cleaning standards may be defined for the particular samples, as described below with respect to FIG. 17).

[0027] In some embodiments according to the present application, during cleaning or measurement, a status window is displayed on the user interface, and the running status is displayed on the status window.

[0028] In some embodiments according to the present application, after the measurement, a result viewing window is displayed on the user interface, and the execution results are displayed on the result viewing window.

[0029] In some embodiments according to the present application, the measured amount of carryover is displayed in real time on a user interface.

[0030] In some embodiments according to the present application, control buttons are provided on the user interface window to control the next activity.

[0031] According to another aspect of the present application, there is provided a method for operating and monitoring cleaning of a sample processing instrument, the method comprising: displaying, by a computing system associated with the sample processing instrument, on a user interface, a menu comprising at least one next activity element; displaying, on the user interface, a parameter setting element in response to a user selection of the at least one next activity element, the parameter setting element being configured to set a target carryover amount in a flow cell of the sample processing instrument; receiving user input at the parameter setting element, the user input defining the target carryover amount; receiving carryover data corresponding to a measurement value of particles present in a monitoring solution in the flow cell; deriving an actual carryover amount according to the received carryover data; and displaying, on the user interface, one or more monitoring elements representing the measured carryover amount, the actual carryover amount, and / or the target carryover amount.

[0032] In some embodiments according to the present application, the method further includes determining a cleaning level by comparing the actual carryover amount to a target carryover amount and displaying, on a user interface, the cleaning level having a first level indicating that the cleaning requirement is met and a second level indicating that the cleaning requirement is not met.

[0033] In some embodiments according to the present application, the method further includes repeating the cleaning cycle and then the monitoring cycle when the second level is determined until a maximum cleaning cycle is reached. Receiving user input includes inputting parameters associated with the cleaning cycle and the monitoring cycle in a parameter setting element, the parameters comprising a maximum cleaning cycle.

[0034] In some embodiments according to the present application, the method further includes displaying the status of the cleaning cycle and the monitoring cycle on a user interface.

[0035] In some embodiments according to the present application, the status of the cleaning cycle and the monitoring cycle comprises the running process of the cleaning cycle, the number of cleaning cycles that have been performed, and the running process of the monitoring cycle.

[0036] In some embodiments according to the present application, the monitoring element comprises a graph showing the measured carryover data.

[0037] In some embodiments according to the present application, the graph comprises a histogram, a scatter dot plot, a density plot, a pseudocolor plot, or a contour plot.

[0038] In some embodiments according to the present application, the graph shows carryover signal strength versus carryover counts.

[0039] In some embodiments according to the present application, the parameter setting element is further configured to set cleaning standards for cleaning / monitoring the flow cell after a particular sample has been processed (e.g., one or more particular samples may be selected and specific cleaning standards may be defined for cleaning the particular samples, as described below with respect to FIG. 17).

[0040] In some embodiments according to the present application, the parameter setting elements comprise dialog boxes, text fields, slider elements, drop-down lists, and / or radio buttons.

[0041] In some embodiments according to the present application, the method further includes a step of displaying, on the user interface, an applicable sample setting element in response to a user selection of at least one next activity element, the applicable sample setting element being configured to define samples to be monitored using the same user input in the parameter setting element, and a step of receiving user input in the applicable sample setting element for defining samples to which the same user input in the parameter setting element is applied.

[0042] In some embodiments according to the present application, the actual carryover amount and the target carryover amount, respectively, are presented in the text, in graphs, and / or in tables.

[0043] In some embodiments according to the present application, the actual carryover amount and the target carryover amount are presented in the same graph or table.

[0044] In some embodiments according to the present application, the method further includes storing the monitoring data for each sample and displaying, on a user interface, the monitoring data for the one or more samples in response to a user request for one or more samples by at least one next activity element.

[0045] In some embodiments according to the present application, the target carryover amount comprises at least one of a target carryover count, a target carryover rate, a target carryover concentration, and a target percentage of the carryover concentration, and the actual carryover amount accordingly comprises at least one of an actual carryover count, an actual carryover rate, an actual carryover concentration, and an actual percentage of the carryover concentration.

[0046] In some embodiments according to the present application, the method further comprises displaying on the user interface control elements for starting, stopping, interrupting, cancelling and repeating the method or steps of the method.

[0047] In some embodiments according to the present application, the control element comprises a control button.

[0048] According to an aspect of the present application, a system for operating and monitoring cleaning of a sample processing instrument is provided, the system comprising a fluid pipeline communicating a fluid source with a flow cell of the sample processing instrument, a pump arranged within the fluid pipeline, and a control device configured to: direct a first sample through the flow cell in the sample processing instrument, the first sample including a first particle; control the pump to process the first sample, pump a cleaning agent through the fluid pipeline to clean the flow cell, and pump a monitoring solution through the fluid pipeline; measure a carryover amount in the cleaned flow cell, the carryover amount comprising a measurement value associated with an amount of the first particle remaining within a measurement area of ​​the flow cell; compare the measured carryover amount to a predetermined target value, the target value corresponding to a value indicative of a cleaning requirement, and determine whether the cleaning requirement is met based on the comparison.

[0049] In some embodiments according to the present application, the control device is further configured to repeatedly clean the flow cell when it is determined that the cleaning requirements are not met, and to stop the cleaning process when it is determined that the cleaning requirements are met or when the number of cleanings has reached a maximum threshold.

[0050] In some embodiments according to the present application, the system further comprises a switching device configured to allow the pump to selectively fluidly communicate with a sample needle or a sample source of a fluid source fitted within the flow cell.

[0051] In some embodiments according to the present application, the switching device comprises a three-way valve including a first port connected to the pump, a second port connected to the sample needle, and a third port connected to the sample source, the three-way valve being switched between a first position that allows the pump to communicate with the sample needle and a second position that allows the pump to communicate with the sample source.

[0052] In some embodiments according to the present application, the pump is in communication with at least two cleaning agents.

[0053] In some embodiments according to the present application, the at least two cleaning agents include a sheath fluid.

[0054] In some embodiments according to the present application, the pump includes a first pump for pumping the sheath fluid and a second pump for selectively pumping other cleaning agents and a monitoring solution.

[0055] In some embodiments according to the present application, the monitoring solution is water, hi other embodiments, the monitoring solution is a buffer solution.

[0056] According to another aspect of the present application, there is provided a sample processing instrument comprising the cleaning system described above.

[0057] According to another aspect of the present application, a computer readable medium is provided having stored thereon a program executed by a processor of a control device (e.g., on an associated personal computing device, on a dedicated device, etc.) to implement the methods described above.

[0058] The above and other objects, features, and advantages of the present disclosure will be more fully understood through the detailed description and drawings given to illustrate, rather than limit, the present disclosure. [Brief description of the drawings]

[0059] The features and advantages of one or more embodiments of the present disclosure will be more readily understood from the following description taken in conjunction with the accompanying drawings.

[0060] [Figure 1] FIG. 1 is a functional block diagram of a sample processing instrument.

[0061] [Diagram 2] FIG. 2 is a schematic diagram of a portion of a system according to an embodiment of the present application.

[0062] [Diagram 3] FIG. 3 is a schematic diagram showing the sampling process of the system of FIG.

[0063] [Figure 4] 4-6 are schematic diagrams illustrating that the system of FIG. 2 performs cleaning using a cleaning agent other than a sheath liquid. [Diagram 5] 4-6 are schematic diagrams illustrating that the system of FIG. 2 performs cleaning using a cleaning agent other than a sheath liquid. [Figure 6] 4-6 are schematic diagrams illustrating that the system of FIG. 2 performs cleaning using a cleaning agent other than a sheath liquid.

[0064] [Figure 7] 7-9 are schematic diagrams illustrating the system of FIG. 2 using a sheath fluid to perform cleaning. [Figure 8] 7-9 are schematic diagrams illustrating the system of FIG. 2 using a sheath fluid to perform cleaning. [Figure 9] 7-9 are schematic diagrams illustrating the system of FIG. 2 using a sheath fluid to perform cleaning.

[0065] [Figure 10] FIG. 10 is a schematic diagram of a portion of a system according to another embodiment of the present application.

[0066] [Figure 11] FIG. 11 is a schematic diagram of a portion of a system according to yet another embodiment of the present application.

[0067] [Figure 12] FIG. 12 is a schematic flow chart of a method for cleaning a sample processing instrument according to an embodiment of the present application.

[0068] [Figure 13] FIG. 13 is a schematic flow chart of a method for cleaning a sample processing instrument according to another embodiment of the present application.

[0069] [Figure 14] FIG. 14 is a schematic diagram of a user interface for monitoring the cleaning of a sample processing instrument, according to an embodiment of the present application.

[0070] [Figure 15] FIG. 15 is a schematic diagram of an embodiment of a menu of a user interface.

[0071] [Figure 16] FIG. 16 is a schematic diagram of an embodiment of a parameter setting element of a user interface.

[0072] [Figure 17] FIG. 17 is a schematic diagram of an embodiment of an applicable sample settings element of a user interface.

[0073] [Figure 18A] 18A-18E are schematic diagrams of various embodiments of monitoring elements of a user interface. [Figure 18B] 18A-18E are schematic diagrams of various embodiments of monitoring elements of a user interface. [Figure 18C] 18A-18E are schematic diagrams of various embodiments of monitoring elements of a user interface. [Figure 18D]18A-18E are schematic diagrams of various embodiments of monitoring elements of a user interface. [Figure 18E] 18A-18E are schematic diagrams of various embodiments of monitoring elements of a user interface.

[0074] [Figure 19] FIG. 19 is a schematic diagram of an embodiment of a view historical data element.

[0075] [Figure 20] FIG. 20 is a schematic diagram of a cleaning / monitoring user interface integrated within a sample processing user interface according to another embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0076] Detailed Description of the Preferred Embodiments The present application will be described in detail hereinafter with exemplary embodiments with reference to the accompanying drawings. In the several drawings, similar reference numerals indicate similar parts and components. The following detailed description of the present application is for illustrative purposes only and is in no way intended to limit the present application and its application or use. The embodiments described herein are not exhaustive and are merely some of several possible embodiments. The exemplary embodiments may be implemented in many different forms and should not be interpreted as limiting the scope of the present application. In some exemplary embodiments, well-known processes, well-known device structures, and well-known technologies may not be described in detail.

[0077] Before at least one embodiment of the present application is described in detail, it is to be understood that the present application is not limited in its application to the details of construction and arrangement of components set forth in the following description or illustrated in the drawings. The present invention is applicable to other embodiments and combinations of the disclosed embodiments that can be practiced or carried out in various ways. In addition, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0078] Unless specifically stated otherwise, and as will be apparent from the discussion below, discussions utilizing terms such as "controlling," "processing," "calculating," "determining," "deriving," or the like throughout this specification will be understood to refer to the actions and / or processes of a computer or computing system or similar electronic computing device that manipulates and / or converts data represented as physical quantities, such as electrons, in the registers and / or memory of the computing system to other data that is similarly represented as physical quantities in the memories, registers, or other such information storage, transmission, or display devices of the computing system.

[0079] The sample processing instrument according to the present disclosure will be described by taking a flow cytometer as an example. The flow cytometer is used to detect particles in a sample and determine one or more characteristics of the particles. However, it should be understood that the sample processing instrument according to the present disclosure is not limited to a flow cytometer, but can be any other suitable instrument for processing biological or non-biological samples. In some embodiments, the sample processing instrument can be a cell or particle sorter.

[0080] The sample processing instrument according to the present disclosure is suitable for automatically performing a cleaning process during processing different samples, automatically performing a cleaning process using different cleaning agents, and automatically performing a monitoring process of measuring the cleaning results after the cleaning process. The system may additionally automatically determine the next action according to the measurement results. In addition, the system may provide the user with an interface to allow the user to easily operate and intuitively observe the monitoring and cleaning process. The main functional parts of the sample processing instrument 1 will be described below with reference to FIG. 1. The sample processed (e.g., analyzed or sorted) by the sample processing instrument 1 may contain biological particles such as exosomes or extracellular vesicles or non-biological particles such as beads. Although the disclosed system is optimized for detecting and measuring particles at the nano level (e.g., nanoparticles, nanobeads, exosomes), the disclosed system can also be used for larger particles.

[0081] 1 is a functional block diagram of a sample processing instrument 1. As shown in FIG. 1, the sample processing instrument 1 includes a fluidics component 10, a flow cell 20, a sample processing unit 30, and a control unit 40.

[0082] The fluidics components 10 are configured to supply various fluids to and eject fluids out of the flow cell 20. The fluids described herein may include samples to be analyzed, sorted, or otherwise processed, sheath fluids, cleaning agents, waste fluids, and the like. The fluidics components 10 may include various pumps, valves, pressure regulating devices, sensors, etc. for delivering or ejecting fluids.

[0083] Various fluids, particularly sample and sheath fluids, are delivered to a flow cell 20. Referring to FIG. 2, the flow cell 20 includes two opposite sheath ports 21 and 22 through which the sheath fluid is delivered to a chamber 25 of the flow cell 20. The flow cell 20 further includes a sample needle 23 disposed therein, through which the sample is transported into the chamber 25. Within the chamber 25, the sample is encased in the sheath fluid and then flows through a cuvette 26 for processing. The cuvette 26 forms a processing area for the sample. For example, an optical detection device focuses a light beam within the processing area of ​​the cuvette 26. In the case where particles in the sample pass through the processing area of ​​the cuvette 26, the properties of the particles are determined by measuring the light scattered or emitted from the particles.

[0084] The sample processing unit 30 processes the sample encased in the sheath fluid flowing through the cuvette 26. For example, the sample processing unit 30 may measure properties of particles / cells in the sample and quantify particles / cells having particular properties, and / or the sample processing unit 30 may sort particles / cells in the sample based on their properties. The sample processing unit 30 may include a variety of optical, electrical, and / or mechanical devices according to the goal of the sample processing.

[0085] The control unit 40 controls the operation of the entire sample processing instrument 1. The various functions, actions or steps of the various systems, devices, components or methods of the sample processing instrument according to the present application are controlled by the control unit 40. The control unit 40 will be described in detail below.

[0086] Examples of fluidic components according to embodiments of the present application will be described below with reference to Figures 2-9, which show a portion of a system 100 including fluidics for controlling the flow of different fluids. As explained above, the fluidic system 100 is used to supply various fluids to the flow cell 20 and to pump fluids out of the flow cell 20. To this end, the fluidic system 100 includes fluidic pipelines that connect various fluid sources to the flow cell 20.

[0087] These fluid sources may include a sample source 101, a sheath source (not shown), a waste reservoir, and other solution sources. The sample source 101 is used to supply a sample. Generally, the sample source 101 includes multiple sample containers, such as well plates, test tubes, and the like, containing different samples. The sheath fluid is stored in the sheath source. The sheath liquid is a matrix liquid that helps the sample flow to be detected normally, and functions to wrap around the sample flow and keep it centered in the nozzle, ensuring the accuracy of detection while preventing particles in the sample flow from approaching the nozzle wall and clogging the nozzle. In addition, the sheath fluid may also be used as a cleaning agent to clean the sample processing equipment (especially the flow cell and the fluid pipeline). The other solution sources include a fluid container 103 that stores other cleaning agents (e.g., water or another special cleaning solution) rather than a sheath fluid, and a separate container (not shown) that stores a monitoring solution (e.g., water or a buffer solution) for measuring the cleaning result of the sample processing equipment. The waste reservoir is used to collect waste liquids after sample processing and cleaning of the sample processing equipment.

[0088] Referring to FIG. 2, the fluid pipelines include sample pipelines 111, 112, and 113 that connect the sample source 101 to the sample needle 23, a sheath pipeline 117 for connecting a sheath source (not shown) to the sheath ports 21 and 22 of the flow cell 20, a waste pipeline 116 for connecting the flow cell 20 to a waste reservoir (not shown), sheath cleaning pipelines 153 and 154 for transporting sheath fluid for cleaning, and cleaning agent pipelines 142 and 144 for transporting cleaning agents for cleaning.

[0089] Various pumps for pumping various fluids may be provided in the fluid pipeline. In the example shown in FIG. 2, there is a sample pump 121 for pumping the sample, a sheath pump 125 for pumping a sheath liquid for cleaning, and a cleaning pump 123 for pumping a cleaning agent. In the example of FIG. 2, the sample pump 121, the sheath pump 125, and the cleaning pump 123 are all piston pumps. However, it should be understood that the system disclosed in the present application is not limited to the specific example shown in the drawings, as long as it can achieve the functions described herein. For example, the type of pump may be varied. In another embodiment shown in FIG. 10, the sheath pump 125 and the cleaning pump 123 may be other types of pumps, such as peristaltic pumps. Similarly, the sample pump 121 may also employ any other suitable type of pump, for example, a peristaltic pump. In some embodiments, the number of pumps may be changed. In the example shown in FIG. 11, the sheath pump is omitted.

[0090] Various switching devices may be provided in the fluid pipeline, for example, to switch the flow direction of the fluid or to control the on / off state of the fluid. The switching devices may include various types of valves. As shown in FIG. 2, the switching devices include three-way valves 131 and 132 and on / off valves 141, 151, and 152.

[0091] The three-way valve 132 is configured to selectively communicate the sample pipelines 111-113 with different pumps (e.g., sample pump 121 or cleaning pump 123) to aspirate or pump different fluids (e.g., sample or cleaning agent) to the flow cell 20 or the sample source 101. In the example of FIG. 2, the three-way valve 132 includes a first port 1321 connected to the sample pipeline 113, a second port 1322 connected to the sample pump 121, and a third port 1323 connected to the cleaning pump 123. In the case where the first port 1321 is switched to communicate with the second port 1322, the sample pump 121 is enabled to aspirate sample from the sample source 101 when the sample pipeline 113 is connected to the sample pipeline 111, or to pump fluids (e.g., sample or sheath fluid) to the flow cell 20 when the sample pipeline 113 is connected to the sample pipeline 112. That is, the system may enable the sample pump 121 to aspirate sample from the sample source 101 by switching valve 132 to connect the sample pump 121 to the sample pipeline 113, and by switching valve 131 to connect the sample pipeline 113 to the sample pipeline 111 (sample or sheath fluid may alternatively be sent to the flow cell 20 by switching valve 131 to connect the sample pipeline 113 to the sample pipeline 112). The system may enable the cleaning pump 123 to aspirate cleaning agent from the fluid container 103 and pump it to the flow cell 20 by switching valve 132 to connect the sample pipeline 113 to the sample pipeline 112, and by switching valve 131 to connect the sample pipeline 113 to the sample pipeline 112 (cleaning agent may alternatively be sent to the sample source 101 by switching valve 131 to connect the sample pipeline 113 to the sample pipeline 111).

[0092] The three-way valve 131 is configured to selectively communicate a pump (e.g., sample pump 121 or cleaning pump 123) with the sample source 101 or the flow cell 20 to selectively aspirate or pump a fluid (e.g., sample or cleaning agent) into the flow cell 20 or the sample source 101. In the example of FIG. 2, the three-way valve 131 is provided between the sample pipelines 111, 112, and 113 to selectively communicate the sample pipeline 113 with the sample pipeline 111 or the sample pipeline 112. The three-way valve 131 has a first port 1311 connected to the sample pump 121 or the cleaning pump 123 via the three-way valve 132, a second port 1312 connected to the sample needle 23, and a third port 1313 connected to the sample source 101. The system may allow fluid in sample pipeline 113 (e.g., sample pumped by sample pump 121 or cleaning agent pumped by cleaning pump 123) to be transported into flow cell 20 by switching valve 131 to connect sample pipeline 113 to sample pipeline 112, or alternatively, allow fluid to be aspirated / pumped into sample source 101 by switching valve 131 to connect sample pipeline 113 to sample pipeline 111.

[0093] Three-way valves 131 and 132 make it possible, for example, to selectively pump a sample to flow cell 20 for analyzing the sample, or to pump a cleaning agent to sample source 101 or flow cell 20 for cleaning sample pipelines 111-113 or flow cell 20.

[0094] The cleaning pump 123 is connected to the third port 1323 of the three-way valve 132 via a cleaning agent pipeline 144 and to the fluid container 103 via a cleaning agent pipeline 142. An on / off valve 141 may be provided in the cleaning agent pipeline 142 to control the on / off state of the cleaning agent pipeline 142. When cleaning agent is to be sucked, the on / off valve 141 is in a closed state to allow communication of the cleaning agent pipeline 142. When cleaning agent does not need to be sucked, the on / off valve 141 is in an open state to interrupt communication of the cleaning agent pipeline 142.

[0095] The sheath pump 125 is arranged between the sheath pipeline 117 connected to the sheath source and the sample pump 121 to deliver sheath fluid to the sample source 101 or the flow cell 20 via the sample pump 121 to clean the sample pipelines 111-113 or the flow cell 20 with the sheath fluid. The sheath pump 125 is connected to the sheath pipeline 117 (or the sheath source) via a sheath cleaning pipeline 153 and to the sample pump 121 via a sheath cleaning pipeline 154. An on / off valve 151 may be provided in the sheath cleaning pipeline 153 to control the on / off state of the sheath cleaning pipeline 153. In the case where the sheath fluid is aspirated for cleaning, the on / off valve 151 is in a closed (i.e., on) state to allow communication of the sheath cleaning pipeline 153. In the case where there is no need to aspirate sheath fluid, the on / off valve 151 is in an open (i.e., off) state to interrupt communication of the sheath cleaning pipeline 153. Further, an on / off valve 152 may be provided in the sheath cleaning pipeline 154 to control the on / off state of the sheath cleaning pipeline 154. In the case where sheath fluid is pumped, the on / off valve 152 is in a closed (i.e., on) state to allow communication of the sheath cleaning pipeline 154. In the case where there is no need to pump sheath fluid, the on / off valve 152 is in an open (i.e., off) state to interrupt communication of the sheath cleaning pipeline 154.

[0096] It should be understood that the system according to the present application is not limited to the specific embodiment shown in FIG. 2 and may be modified according to actual requirements. For example, in the system 200 shown in FIG. 10, the sheath pump 225 and the cleaning pump 223 may be peristaltic pumps, and the on / off valves may be omitted in the sheath cleaning pipelines 253 and 254 and the cleaning agent pipeline 142 accordingly. In the system 300 shown in FIG. 11, the sheath pump is omitted, and instead, only the on / off valve 351 is provided in the sheath cleaning pipeline 353 between the sheath pipeline 317 (or sheath source) and the sample pump 321. It should be understood that the system according to the present application is not limited to having the components described above. For example, it may also have a filter (e.g., the filter 119 for filtering the sheath fluid as shown in FIG. 2), a sensor for sensing temperature or pressure, a regulator for adjusting temperature or pressure, and the like.

[0097] The process of transporting a sample through the fluidic system 100 during sample processing will be described below with reference to FIGS.

[0098] As shown in FIG. 2, when a sample is to be processed, three-way valve 132 is switched so that sample pump 121 is connected to sample pipeline 113, and three-way valve 131 is switched so that sample pipeline 113 is connected to sample pipeline 111, whereby sample is drawn from sample source 101 into sample pipeline 113 by sample pump 121 (e.g., the piston of sample pump 121 moves downward).

[0099] Then, as shown in FIG. 3, the three-way valve 131 is switched to connect the sample pipeline 113 to the sample pipeline 112, and the sample in the sample pipeline 113 is pumped into the flow cell 20 by the sample pump 121 (e.g., the piston of the sample pump 121 moves upward) for processing (e.g., detection or sorting, etc.).

[0100] During sample processing, the sample pump 121 is constantly connected to the sample pipeline 113, and the three-way valve 131 is repeatedly switched between the second port 1312 and the third port 1313, repeatedly performing the process of aspirating and pumping the sample until the sample processing is completed.

[0101] The process of cleaning the sample pipelines 111-113 and the flow cell 20 by the fluid system 100 using a cleaning agent will be described below with reference to FIGS.

[0102] As shown in FIG. 4, when the sample processing instrument is to be cleaned with a cleaning agent, the on / off valve 141 is closed to communicate the cleaning agent pipeline 142, thereby allowing the cleaning pump 123 to draw the cleaning agent from the fluid container 103.

[0103] 5, the on / off valve 141 is switched to an open state and the three-way valve 132 is switched to connect the cleaning agent pipeline 144 to the sample pipeline 113 and pump the cleaning agent into the sample pipeline 113. At this moment, the three-way valve 131 may be in a state in which the sample pipeline 113 is connected to either the sample pipeline 112 or the sample pipeline 111.

[0104] 5, in the case where sample pipeline 113 is connected to sample pipeline 111, cleaning agent is pumped through sample pipeline 111, thereby cleaning sample pipelines 113 and 111. On / off valve 141 is then repeatedly closed and opened to suck or pump cleaning agent until sample pipeline 111 is cleaned.

[0105] 6, in the case where sample pipeline 113 is connected to sample pipeline 112, cleaning agent is pumped through sample pipeline 112 and flow cell 20, thereby cleaning sample pipelines 113 and 112 and flow cell 20. On / off valve 141 is then repeatedly closed or opened to suck or pump cleaning agent until sample pipeline 112 and flow cell 20 are cleaned.

[0106] The process of cleaning the sample pipelines 111-113 and the flow cell 20 by the fluid system 100 using a sheath liquid will be described below with reference to FIGS.

[0107] As shown in FIG. 7, when the sample processing instrument is to be cleaned with sheath liquid, the on / off valve 151 is closed to allow communication of the sheath cleaning pipeline 153, thereby allowing the sheath pump 125 to aspirate sheath liquid from a sheath source (not shown).

[0108] 8, on / off valve 151 is opened, on / off valve 152 is closed, and three-way valve 132 is switched such that first port 1321 communicates with second port 1322 to pump sheath fluid into sample pipeline 113 via sample pump 121. Three-way valve 131 may be in a state in which sample pipeline 113 is connected to either sample pipeline 112 or sample pipeline 111.

[0109] 8, in the case where sample pipeline 113 is connected to sample pipeline 111, sheath fluid is pumped through sample pipeline 111, thereby clearing sample pipelines 113 and 111. On / off valves 151 and 152 are then alternately closed or open to aspirate or pump sheath fluid until the sample pipeline is cleared.

[0110] 9, in the case where sample pipeline 113 is connected to sample pipeline 112, sheath fluid is pumped through sample pipeline 112 and flow cell 20, thereby cleaning sample pipelines 113 and 112 and flow cell 20. On / off valves 151 and 152 are then alternately closed or open to aspirate or pump sheath fluid until the sample pipeline and flow cell 20 are cleaned.

[0111] In addition to the sample processing and cleaning processes described above, the system may also be used to monitor the cleaning of sample processing equipment.

[0112] In some embodiments, the sample source 101 may be filled with a monitoring solution (e.g., water, buffer) instead of a sample between analyses of two different samples. For example, a first sample in the sample source 101 may be analyzed by the system 100, the system 100 may be cleaned with a cleaning agent from the fluid container 103, and then the sample source 101 may be switched for a different sample source 101 filled with a monitoring solution to monitor the flow cell 20 for the presence of carryover. In some cases, the monitoring solution and the cleaning agent may be the same fluid, e.g., water.

[0113] In some embodiments, the cleaning agent may be the monitoring solution, in which case the fluid container 103 may be used as a source of the monitoring solution and the cleaning agent. In this case, the process of pumping the monitoring solution through the flow cell 20 during the monitoring process may be similar to the process of pumping the cleaning agent through the flow cell 20 during the cleaning process.

[0114] In some embodiments, a separate fluid container (i.e., a container other than the sample source 101 and the fluid container 103) may be provided to contain the monitoring solution. In this case, the same pump as the other fluids or an additional pump may be used to pump the monitoring solution through the flow cell 20. The fluid pipeline for the monitoring solution may be integrated into other fluid pipelines, such as the sheath cleaning pipeline, or may be an independent fluid pipeline from the fluid container containing the monitoring solution to the flow cell 20. Similarly, the sheath cleaning pipeline may also be formed as an independent fluid pipeline from the sheath source to the flow cell 20 and sample pipeline, i.e., it does not pass through the sample pump 121.

[0115] As explained above, the structure of the disclosed systems and their fluidic components is not limited to the specific embodiment described and shown above, and can be varied as long as it can realize an automatic cleaning / monitoring process or an automatic cleaning process using different cleaning agents. Furthermore, since the structure of the disclosed systems can be changed, the method of operation of the disclosed systems can be changed accordingly.

[0116] In the following, a method 500 for cleaning and monitoring a sample processing instrument 1 using the above-referenced disclosed system according to an embodiment of the present application will be described with reference to FIG.

[0117] The sample processing instrument 1 first pumps a first sample containing a first particle through the pipeline of the system through the flow cell 20 and processes the first sample, e.g., detects or sorts the first particle. The first particle is, for example, a biological nanoparticle. After the first sample is processed, there may be a need to process a second sample. For accurate results, the flow cell 20 and one or more pipelines of the system may need to be washed between successive samples to prevent particles from the first sample from affecting the results of the processing of the second sample. Generally, it is difficult to remove these remaining particles, referred to herein as carryover, especially when the particles are of small size. Therefore, to ensure accurate processing of the second sample, the sample processing instrument 1 (especially the sample pipeline and the flow cell) must be properly cleaned.

[0118] According to the first sample (particularly the first particle), a suitable cleaning agent (e.g., sheath fluid, water, and / or any other suitable cleaning solution), cleaning parameters (e.g., duration of one cleaning cycle, number of cleaning cycles, maximum number of cleaning cycles, etc.), monitoring solution (e.g., water), and / or monitoring parameters can be selected or set. The monitoring parameters may include a parameter associated with the solution being monitored (e.g., delivery time or volume, etc.), a population associated with the particle being monitored or the monitoring parameter (e.g., monitoring criteria indicating that the cleaning requirements are met). The monitoring criteria may be embodied in various forms, for example, target carryover counts in a given time, target carryover concentration / concentration percentage, target carryover rate (number / second), etc. An exemplary setting of the cleaning parameters and monitoring parameters and criteria can be seen in FIG. 16.

[0119] Then, in step S51, the sample processing instrument 1 is cleaned by the selected cleaning agent according to the set cleaning parameters. In a cleaning cycle, the selected cleaning agents may be one, two or more. Correspondingly, cleaning parameters may be set for each cleaning agent. The cleaning parameters may be determined based on experimental data, historical data or empirical data. After the cleaning cycle or a predetermined number of cleaning cycles, proceed to step S52.

[0120] In step S52, the monitor solution is pumped by the fluidics components through the flow cell 20. The sample processing instrument 1 then analyzes the flow cell 20 containing the monitor solution for a monitoring period (see step S53).

[0121] In step S53, measurements related to carryover or monitoring solution during the monitoring period are obtained, for example, the amount of carryover (first particles) and / or the flow rate of the monitoring solution. The flow rate of the monitoring solution may be measured by one or more sensors. For example, for a sample processing instrument 1 that is a flow cytometer, the measurements may be performed by measuring the light scattered from the flow cell 20 in response to one or more laser beams being directed at the flow cell 20. In this embodiment, the carryover (first particles remaining in the flow cell 20) may be counted by an optical detection system, for example, based on the detected light scattered or emitted from the particles. In the same monitoring time, the smaller the amount of carryover (e.g., the count or approximate count of the number of carryover particles remaining in the flow cell 20 during the monitoring period), the better the cleaning result. Naturally, the longer the monitoring time, the higher the amount of carryover detected. If the measurements are not sufficient to indicate the cleaning level, proceed to step S54.

[0122] In step S54, a value that accurately indicates the cleaning level may be calculated based on the measurements obtained in step S53. For example, the value may be a carryover rate (number / second) (the number of carryover particles detected during monitoring divided by the monitoring time), a carryover concentration (number / microliter) (the number of carryover particles detected during monitoring divided by the volume of the monitoring solution), or a carryover concentration percentage (the ratio of the carryover concentration to the concentration of the first particle in the first sample). It should be understood that if the measurements obtained in step S53 are sufficient to indicate the cleaning level, step S54 may be omitted.

[0123] In step S55, the calculated value in step S54 or the measured value in step S53 (e.g., if step S54 is omitted) may be compared to a target value as a monitoring standard. If the measured or calculated value (actual value) is less than or equal to the target value, this indicates that the cleaning requirement is met, and proceed to step S56. If the measured or calculated value (actual value) is greater than the target value, this indicates that the cleaning requirement is not met, and then proceed to step S57. In some embodiments, the target value may be based on the type of first sample, second sample, or processing occurring. For example, different samples or different sample processing / analysis may have different target values.

[0124] In step S56, because the cleaning requirements have been met, the cleaning process is stopped and the next sample is ready to be processed. Optionally, in step S56, the user may be notified that the cleaning requirements have been met. The second sample may then be automatically transported through the flow cell and processed in the flow cell.

[0125] In step S57, it is further determined whether a maximum cleaning limit has been reached, for example a set maximum cleaning duration limit (e.g. a maximum limit on the total amount of time spent in one or more cleaning cycles) or a maximum cleaning cycle number limit (e.g. a maximum limit imposed on the number of cleaning cycles performed). In some embodiments, the maximum cleaning limit may be set by a user. In some embodiments, the maximum cleaning limit may be based on the type of first sample, second sample, or processing occurring. For example, different samples or different sample processing / analysis may have different maximum cleaning limits. If the maximum cleaning limit has not been reached, return to step S51 and continue the cleaning process until the cleaning requirements are met or the maximum cleaning limit is reached. If the maximum cleaning limit has been reached, proceed to step S58.

[0126] In step S58, the cleaning process is stopped. Optionally, in step S58, a message or warning may be issued to the user so that the user may take appropriate measures, such as troubleshooting.

[0127] 13 is a schematic flow chart of a method 600 for cleaning a sample processing instrument according to another embodiment of the present application. Steps S61, S62, S64-S68 of the method 600 are identical to steps S51, S52, S54-S58 of the method 500, and therefore will not be described in detail. The method 600 differs from the method 500 in step S63. A total measurement value during a monitoring period is obtained in step S53 of the method 500, while measurements are obtained at predetermined intervals in step S63 of the method 600. The predetermined intervals here include consecutive predetermined intervals and superimposed predetermined intervals. The consecutive predetermined intervals means, for example, obtaining measurements from 0 to 5 seconds, measurements from 5 to 10 seconds, measurements from 10 to 15 seconds, etc., assuming that the predetermined interval is 5 seconds. The superimposed predetermined interval means, for example, taking a measurement value from 0 to 5 seconds, a measurement value from 1 to 6 seconds, and a measurement value from 2 to 7 seconds, assuming the predetermined interval is 5 seconds, etc. Thus, the calculated values ​​within the predetermined interval are taken in step S64.

[0128] In method 600, once a cleaning requirement is found to be met, the monitoring process may be immediately stopped. Thus, compared to method 500, method 600 allows a user to learn the information that a cleaning requirement has been met more quickly.

[0129] It should be understood that the method according to the present application is not limited to the above-mentioned methods 500 and 600, and may be modified according to requirements. For example, the method of obtaining measurements may be modified, and the setting parameters may be modified. For example, in step S55 or S65, both the measured values ​​and the calculated values ​​may be used to determine whether the cleaning requirements are met. Also, the steps of the method may not necessarily be performed in the order described, and may be permuted in order or performed simultaneously without inconsistency. In addition, the method may omit certain steps or add additional steps.

[0130] To facilitate user actions and obtain information, the methods of the present application may be implemented using a user interface, which will be described below with reference to Figures 14-20.

[0131] With reference to FIG. 14, the user interface 800 may include a menu 810, a parameter setting element 820, a monitoring element 840, an applicable sample settings element 830, a view historical data element 850, and a control element 860. The menu 810 may include one or more next activity elements that allow a user to interact with the sample processing instrument by configuring the processing of samples and cleaning of the sample processing instrument or monitoring such processing or cleaning. The next activity elements will be described in detail below with reference to FIG. 15. The parameter setting element 820, the monitoring element 840, the applicable sample settings element 830, and the view historical data element 850 may be displayed on the user interface in response to a selection or operation of the corresponding next activity element of the menu 810 such that the user may input information or such information is displayed to the user. The parameter setting element 820 is used to receive user input related to cleaning, monitoring, and carryover (which will be described in detail below with reference to FIG. 16). The monitoring element 840 is configured to display information related to cleaning or monitoring status, monitoring data, monitoring results, monitoring standards, etc. to the user (this will be described in detail below with reference to Figures 18A-18E). The applicable sample settings element 830 includes the sample to be monitored, and the user may select the sample to which the settings in the parameter settings element 820 are applied so that the sample processing instrument may automatically and sequentially process multiple samples (this will be described in detail below with reference to Figure 17). The historical data viewing element 850 may retrieve or display historical monitoring data according to a user request (this will be described in detail below with reference to Figure 19). The control element 860 allows the user to control or view the content of various elements displayed on the user interface.

[0132] As shown in FIG. 14, the menu 810, the parameter setting element 820, the applicable sample settings element 830, the monitoring element 840, the view historical data element 850, and the control element 860 may be displayed simultaneously on one screen, for example, in corresponding boxes. It should be understood that the user interface according to the present application should not be limited to the specific example shown in FIG. 14, and may be changed as required. In some embodiments, any subset of these interface elements may be displayed simultaneously on the user interface. For example, in some cases, only the menu 810 and the parameter setting element 820 may be displayed simultaneously on the user interface 800. In some embodiments, the interface elements displayed on the user interface may be selected based on user input. For example, the user may select the applicable sample settings element 830, and in response, the user interface may show an expanded applicable sample settings element 830 and not show any of the other interface elements (or only show a subset thereof). For example, the view historical data element 850 is optional. Furthermore, the layout of various elements on the user interface may be changed. The content and display form of each element may also be changed as desired.

[0133] Hereinafter, elements of the user interface will be described with reference to specific examples shown in the figures. These examples are for illustrative purposes only and are not limitations on the present application.

[0134] Figure 15 shows an example of a menu 810. As shown in Figure 15, the menu 810 may display several different next activity elements, including "Set parameters," "Set applicable samples," "Run cleaning / monitoring," and "View monitoring reports."

[0135] The menu 810 allows the user to select among different next activity elements. For example, the user may select the "Parameter Settings" next activity element of the menu 810. In response, parameter setting elements 820 may be displayed on the user interface for user input. In some examples, the parameter setting elements may be shown in the form of separate windows (e.g., pop-up windows), which may also be referred to herein as operation windows or setting windows. The parameter setting elements may include setting cleaning parameters, setting monitoring parameters, and setting target carryover amounts.

[0136] FIG. 16 shows an example of a parameter setting element 820. As shown in FIG. 16, the setting of the cleaning parameters includes the cleaning time of the cleaning cycle and the maximum number of cleaning cycles. The setting of the monitoring parameters includes the delivery time of the monitoring solution. In some examples, the target carryover amount may be a target count (or approximate count) of carryover particles, a target carryover rate (quantification of the carryover particles that are acceptable / desired to be in the flow cell over a period of time (e.g., per second) when the monitoring solution should be flowed through the flow channel), a target carryover concentration (representing a desired concentration of carryover particles in the volume of the monitoring solution that should be in the flow cell), etc. In addition, in the example of FIG. 16, the setting of the population to which the sample to be monitored belongs is also included. It should be understood that the parameter setting may be changed according to requirements and is not limited to the specific example shown in the figure. For example, in the parameter setting element, options for running the program (e.g., "no cleaning", "clean only", "clean and monitor" as shown in FIG. 20) may also be set for the user to select. 16, the user inputs and selections are in the form of text fields or drop-down lists, however, the settings may also be entered in any other suitable manner, for example, dialog boxes, radio buttons, slider elements, etc.

[0137] After the user clicks on the activity element "Set Applicable Samples" of the menu 810, the applicable sample settings element 830 is displayed on the user interface. FIG. 17 shows an example of the applicable sample settings element 830. As shown in FIG. 17, all samples to be monitored are shown in the applicable sample settings element 830. The samples may be differentiated by the name of the vessel containing the sample. There is a radio button in front of each sample for the user to select. The applicable sample settings element 830 allows the user to have different acceptable cleaning standards following the processing of different samples (e.g., samples to be run in succession) by, for example, letting the user set different target carryover amounts for different samples (e.g., via the example element 820 shown in FIG. 16, as described in more detail above). For example, the user may have three samples to be run in succession through the sample processing instrument (e.g., sample 1 followed by sample 2 followed by sample 3). In this example, as illustrated in FIG. 17, a user may set a cleaning standard by selecting sample 1 and sample 2 by checking their respective boxes in element 830 and setting a desired target carryover amount for both sample 1 and sample 2 (e.g., setting a target carryover rate and a target concentration via element 820). The user may then select sample 3 by checking its respective boxes (while the boxes for sample 1 and sample 2 are unchecked) and set a cleaning standard for sample 3 in a similar manner. As another example, a user may set cleaning standards for one sample (e.g., sample 1) and then copy those cleaning standards to one or more different samples (e.g., sample 2) to similar effect. In some examples, the sample processing instrument may automatically process each of the different samples sequentially and automatically based on the pre-set cleaning standards selected for each different sample.For example, samples 1-3 may be automatically and sequentially processed with the desired cleaning cycles performed according to their pre-set cleaning standards, thereby improving the efficiency of the sample processing instrument. That is, the user may not need to manually monitor and provide manual input during the processing of these different samples. It is understood that the display of samples is not limited to the specific example shown in FIG. 17, but may be presented in any other suitable manner or for the user to select or input.

[0138] After the user clicks on the next activity element of "Perform Cleaning / Monitoring" in the menu 810, the cleaning / monitoring process is started according to the settings or selections in Figures 16 and 17. A monitoring element 840 is displayed on the user interface. The monitoring element 840 may display the cleaning / monitoring status, measured carryover amount, target carryover amount, and the like to the user.

[0139] The monitoring element 840 may be shown in one or more windows or modules according to various stages of cleaning / monitoring. Content related to the entire monitoring period may be always displayed on the user interface, and content related to each stage of cleaning / monitoring may be displayed in a separate window (e.g., a pop-up window). It should be understood that the display content and display form of the monitoring element 840 is not limited to the specific example described herein or shown in the figures, and may be modified. For example, the status of the cleaning / monitoring process may be displayed in a separate status window, or the final result of the monitoring may be displayed in a separate browser window.

[0140] Figures 18A-18E show various embodiments of monitoring element 840. The embodiments of Figures 18A-18E differ in the content displayed and the form of the carryover display according to various stages of the method.

[0141] FIG. 18A shows a monitoring element 841, in which the status of the cleaning process includes the cleaning progress and the number of cleaning cycles. The carryover measurement data during the monitoring process represents the carryover data measured during the entire monitoring process, shown in FIG. 18A in the form of a histogram G1, where the abscissa represents the intensity of the carryover signal (e.g., light signal) and the ordinate represents the carryover (particle) count. The histogram G1 shows the measurement data of the entire monitoring process, and therefore it can be displayed at all times on the user interface, such as the top left of FIG. 18A. In this histogram G1, the longer the monitoring time, the higher the carryover (particle) count. It should be understood that the measurement data can be displayed in any other suitable graph, for example, a scatter dot plot, a density plot, a pseudocolor plot, a grayscale plot, and / or a contour plot, as required. It should be understood that the carryover measurement data can also be shown in any other suitable form other than a graph. In some cases, the measured carryover data may be used to determine whether a desired level of cleaning has been achieved (e.g., from a determination that the measured carryover is below a desired threshold). In some examples, the measured amount of carryover may be expressed in terms of, for example, a count or estimated count of carryover particles present in the flow cell, a carryover rate (a quantification of the carryover particles as detected in the flow cell over a period of time (e.g., per second) as the monitor solution is flowed through the flow channel), and / or a concentration of carryover (representing the concentration of carryover particles in the volume of monitor solution that is in the flow cell). In some examples, the measured amount of carryover may be a derived value based solely on carryover data measured by the system (e.g., a value derived by applying one or more formulas or functions to the measured carryover data).The measured carryover amount is shown in text form in Figure 18A as the carryover rate (detection of carryover particles per second as the monitoring solution is flowed through the flow channel) and the concentration of carryover, where the cleaning / monitoring status, measured carryover amount, and target carryover amount are displayed in separate pop-up windows.

[0142] Figure 18B shows a monitoring element 842. The difference between the monitoring element 842 of Figure 18B and the monitoring element of Figure 18A is that the measured carryover amount and the set target carryover amount are also shown in the form of the part of Figure 18B labeled as G2. Through the part G2, it can be intuitively seen whether the cleaning level meets the requirement. In Figure 18B, the measured carryover amount exceeds the target carryover amount, and therefore the cleaning standard has not yet been reached.

[0143] Figure 18C shows a monitoring element 843. The monitoring element 843 of Figure 18C differs from the monitoring element 842 of Figure 18B in that it also shows monitoring results, for example, monitoring results after a cleaning cycle. Specifically, in Figure 18C, the user is provided with information indicating that the monitoring results have not been met and that a new cleaning cycle may be initiated in 3 seconds.

[0144] Figure 18D shows a monitoring element 844. The difference between monitoring element 844 of Figure 18D and monitoring element 843 of Figure 18C is that the monitoring result indicates that the cleanliness standard is being met.

[0145] Figure 18E shows a monitoring element 845. The difference between the monitoring element 845 of Figure 18E and the monitoring element 844 of Figure 18D is that the measured carryover amount and the set target carryover amount are shown in the form of a table. The measured carryover amount and the set target carryover amount are displayed in the same table, allowing the user to intuitively determine whether the cleaning standard is being met.

[0146] It should be understood that the measured actual carryover amounts and target carryover amounts are not limited to being displayed in text (as shown in FIG. 18A), graphs (as shown in FIGS. 18B-18D), and tables (as shown in FIG. 18E), but may be presented in any other suitable form.

[0147] After the user clicks on the next activity element of "View monitoring report" in the menu 810, the report may be displayed on an interface such as a view historical data element 850. The view historical data element 850 includes the historical data being monitored. FIG. 19 shows an example of the view historical data element 850. Through the view historical data element 850, it is convenient for the user to query the historical monitoring data at any time. The display content of the view historical data element 850 may be determined according to the user requirements.

[0148] The user interface described with reference to Figures 14-19 may be integrated into a user interface for sample processing, as shown in Figure 20. In the embodiment shown in Figure 20, an option for "Post-processing cleaning and monitoring operation" may also be provided in the setting window. This option is for the user to select before processing the sample. Once the user selects this option in the setting window, cleaning and monitoring are automatically performed after processing the sample without waiting for user's command or setting. In addition, in the embodiment shown in Figure 20, other program options, such as "no cleaning", "cleaning only", "cleaning and monitoring", may also be provided in the setting window. Although not shown in Figure 20, it should be understood that the program options may then also include an option specifying that only monitoring should be performed (e.g., an option specifying "monitoring only").

[0149] Depending on user requirements, control elements may be displayed in the user interface or various elements, including, for example, but not limited to, "switch on," "start," "stop," "pause," "repeat," "close," "apply," "cancel," etc. The control elements may be in the form of one or more control buttons, for example, as shown at the bottom of the windows in Figures 16-19.

[0150] The above system or method may be implemented by the control unit 40. The control unit 40 in this application may include a processor implemented as a computer or computing system. The method of operating and cleaning a sample processing instrument and the method of monitoring cleaning of a sample processing instrument described herein may be implemented by one or more computer programs executed by a processor of a computer. The computer program includes processor-executable instructions stored on a non-transitory tangible computer-readable medium. The computer program may also include stored data. Non-limiting examples of non-transitory tangible computer-readable media are non-volatile memory, magnetic storage devices, and optical storage devices.

[0151] The term computer-readable medium does not include transient electrical or electromagnetic signals propagated with a medium (such as on a carrier), and the term computer-readable medium may therefore be considered tangible and non-transient. Non-limiting examples of non-transient tangible computer-readable media are non-volatile memory (such as flash memory, erasable programmable read-only memory, or masked read-only memory), volatile memory (such as static random access memory circuits or dynamic random access memory), magnetic storage media (such as analog or digital magnetic tape or hard drives), and optical storage media (such as CDs, DVDs, or Blu-ray® disks).

[0152] Although the present application has been described with reference to exemplary embodiments, it should be understood that the present application is not limited to the specific embodiments described and illustrated herein. Those skilled in the art can make various modifications to the exemplary embodiments without departing from the scope defined by the claims. Provided that no contradiction exists, the features in the various embodiments can be combined with each other. Alternatively, certain features in the embodiments can also be omitted.

Claims

1. 1. A method for operating and monitoring the cleaning of a sample processing instrument, said method comprising steps carried out by a control device, said steps comprising: directing a first sample through a flow cell in the sample processing device, the first sample including a first particle; processing the first sample; cleaning the flow cell of the sample processing device with a cleaning agent; measuring the amount of carryover in the flow cell after the cleaning, the amount of carryover comprising a measurement related to the amount of the first particles remaining in a measurement region of the flow cell; comparing the measured carryover amount to a predetermined target value, the target value corresponding to a value indicative of a cleaning requirement, the target value being input by a user; determining whether the cleaning requirements are met based on the comparison; and A method comprising:

2. repeating the cleaning step when it is determined that the cleaning requirements have not been met; automatically stopping the cleaning process when it is determined that the cleaning requirements have been met or when a maximum threshold number of cleaning cycles has been reached; The method of claim 1 further comprising:

3. The method of claim 1 , wherein the target value is input by a user.

4. The cleaning step includes: selecting the cleaning agent from a plurality of cleaning agents configured to clean the flow cell; The method of claim 1.

5. The measuring step includes: pumping a monitoring solution through the flow cell; directing an optical beam towards the flow cell; measuring light scattered from within the flow cell, the measured light corresponding to the amount of carryover within the flow cell; The method of claim 1 , comprising:

6. The method of claim 5 , wherein the monitor solution is different from the cleaning agent.

7. 6. The method of claim 5, wherein the carryover amount comprises a count of the first particles, a carryover rate of the first particles, or a concentration of the first particles in the flow cell.

8. 5. The method of claim 4, further comprising calculating, by the control device, based on the measured carryover amount, at least one of: 1) a value representing the relevance of the carryover amount to the monitoring solution; and 2) a value representing the relevance of the carryover amount after cleaning and the amount of the first particle in the sample before cleaning.

9. following a determination that the cleaning requirements have been met, directing a second sample through the sample processing device; processing the second sample; The method of claim 1 further comprising:

10. 10. The method of claim 9, wherein the second sample is directed through the sample processing instrument automatically by the control device in response to the determination that the cleaning requirement has been met.

11. 10. The method of claim 1, wherein the sample processing instrument is a flow cytometer, and processing the first sample comprises determining one or more properties of the first particle in the first sample by directing an optical beam toward the flow cell and measuring light emitted or scattered from within the flow cell.

12. 1. A system for operating and monitoring the cleaning of a sample processing instrument, comprising: a fluid pipeline connecting a fluid source to a flow cell of the sample processing device; a pump arranged in the fluid pipeline; A control device comprising: directing a first sample through the flow cell in the sample processing device, the first sample including a first particle; processing the first sample; controlling the pump to pump a cleaning agent through the fluid pipeline to clean the flow cell and to pump a monitoring solution through the fluid pipeline; measuring a carryover amount in the cleaned flow cell, the carryover amount comprising a measurement value related to an amount of the first particles remaining in a measurement region of the flow cell; comparing the measured carryover amount to a predetermined target value, the target value corresponding to a value indicative of a cleaning requirement; determining whether the cleaning requirements have been met based on the comparison; and a control device configured to: A system comprising:

13. 13. The system of claim 12, wherein the control device is further configured to repeatedly clean the flow cell when it is determined that the cleaning requirements are not met, and to stop the cleaning process when it is determined that the cleaning requirements are met or when a maximum threshold number of cleaning cycles is reached.

14. 13. The system of claim 12, further comprising a switching device configured to enable the pump to selectively fluidly communicate with a sample needle fitted within the flow cell or a sample source of the fluid source.

15. 15. The system of claim 14, wherein the switching device comprises a three-way valve including a first port connected to the pump, a second port connected to the sample needle, and a third port connected to the sample source, the three-way valve being switched between a first position that allows the pump to communicate with the sample needle and a second position that allows the pump to communicate with the sample source.

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