Multi-point filtered liquid level detection method and apparatus

Abstract

A method of detecting a level of a liquid in a well of a container. The method includes finding an expected liquid level of the liquid in the well of the container, measuring and recording a measured liquid level of the liquid in the well, changing the level of the liquid in the well based on an expected amount of the liquid to be added or removed, and calculating a next expected liquid level based at least in part on a multipoint filtering. Apparatus for performing the method are provided as other aspects.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 088,934, filed October 7, 2020, entitled “MULTI-POINTFILTERING LIQUID LEVELDETECTION METHOD S AND APPARATUS”, the disclosure of which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] The present invention generally relates to methods and apparatus configured to determine a liquid level associated with the aspiration of a liquid (such as when a reagent liquid is aspirated from a well of a container). Background Technology

[0004] In diagnostic laboratories, fully automated analyzers can reduce the number of trained technicians required to perform the analysis in tests that measure various chemical components of bodily fluids obtained from patients (such as whole blood, serum, plasma, interstitial fluid, cerebrospinal fluid, urine, etc.), improve test accuracy, and reduce the cost per test.

[0005] Typically, automated analyzers include automated aspiration and dispensing devices configured to aspirate liquid (e.g., liquid reagent) from a well in a container and dispense that liquid into a vessel (e.g., a cuvette). The aspiration and dispensing devices typically include pipettes (otherwise referred to herein as “probes”) mounted on a robotic mechanism (such as a robotic bench or robotic arm) to allow defined movement of the probe and to perform the aspiration and dispensing functions, thereby allowing liquid (e.g., reagent) to be transferred to the vessel. Separate probes can be used for sample and reagent aspiration and dispensing operations to avoid cross-contamination.

[0006] During the aspiration operation, a robotic mechanism under controller can position the probe above the well in the reagent container and then lower the probe into the well until it is partially immersed in the liquid reagent to the desired well depth. The depth to which the probe descends below the top liquid surface in the well is called the "well depth (WD)". A pump or other aspiration device is then activated to draw a portion of the reagent liquid from the container into the interior of the probe. The probe is then retracted from the container while still containing the reagent liquid, allowing the reagent liquid to be transferred to a reaction vessel for testing.

[0007] In addition to pumping liquid reagents from the well, it may be desirable to determine the location of the top surface of the reagent liquid contained in the well. For example, knowing the location of the top liquid surface can help avoid pumping in air. Similarly, knowing the location of the top liquid surface in the well can help position the probe at the appropriate well depth. Typically, the top liquid surface is located using a probe in which a capacitive sensor is embedded. When the liquid surface is contacted, the change in the electrical signal is detected by the capacitive measurement circuitry. However, in some instances, the measurement may be erroneous. For example, level detection may occasionally be triggered above the top liquid surface, or in some instances, it may not trigger at all.

[0008] Therefore, there is a need for a method and apparatus for more accurately determining the position of the top liquid surface. Summary of the Invention

[0009] Liquid level detection in reagent supply containers is used in many types of diagnostic devices, such as clinical chemistry analyzers and immunoassay instruments (both referred to herein as "analysts"). For example, liquid level detection can be used to detect the top surface level of reagent liquid in a well. Although the examples provided herein pertain to detecting the liquid surface of reagent liquid in a well of a reagent container, such detection methods and apparatus can also be used to detect the liquid level (top surface position) of other liquids, such as process water (e.g., deionized water), waste liquid, or even cleaning liquid.

[0010] In some embodiments, a capacitive level detection system is used to determine the liquid level and to position a probe in the liquid based on where the capacitive level detection system detects the surface level. However, such a capacitive level detection system can be prone to error if it fires incorrectly, such as in the presence of foam or static charge, or fails to fire when it should. In some embodiments, liquid level detection using a capacitive sensor embodied in a probe coupled to and movable by a robotic arm may be prone to incorrect triggering. For example, the positioning system of the robot that causes the probe movement may malfunction, such as due to a position sensor error, a broken wire, or other component failure. As a result, the test may be aborted and possibly rescheduled, resulting in wasted time. Furthermore, reagent containers (such as reagent packs comprising multiple wells) are sometimes incorrectly unloaded due to erroneous liquid level readings, which may result in the discarding of reagent packs still containing usable reagents. Therefore, such erroneous liquid level readings can increase reagent costs due to premature reagent pack replacement.

[0011] The accuracy of detection sensors can be affected by a number of additional factors, including hardware failure, environmental conditions, or anomalies in the container. While capacitive level detection systems may be preferred for a wide range of applications, they can also be susceptible to such effects. When used for aspiration, erroneous level detection signals can cause the probe to be outside the correct aspiration position, resulting in inaccuracies in the volume of liquid transferred, such as excessive contamination of the probe's outer surface with reagent liquid due to aspirated air or foam, or because the probe may be inserted too deeply into the well. This excessive contamination of the probe exterior is referred to herein as "carryover." Carryover may drip from the probe, but is typically rinsed away from the probe exterior at the analyzer's rinsing station before dispensing reagent liquid.

[0012] In some cases, liquid levels are unpredictable, essentially random. However, in many cases, such as within reagent containers, liquid levels exhibit some predictability based on their historical surface level position. In these cases, an improved liquid level detection method is provided. This improved method uses historical knowledge of the liquid level in the well, along with an estimate of the volume removed by each pumping over a time period, to determine the expected liquid level to be encountered before each pumping operation. Specifically, the method uses actual measured surface position values ​​and a multi-point filtering technique to determine the current liquid level. For example, the multi-point filtering technique can use the normalized liquid level output of the liquid level sensor and proportional control as feedback to generate the next expected liquid level with specific corrections, thereby correcting the expected liquid level based on the measured liquid level at the liquid surface and a correction factor based on the gain value.

[0013] In some embodiments, this allows filtering of the actual liquid level output readings of the liquid level sensor so that spurious readings can be detected and minimized, thereby minimizing or preventing erroneous responses. In some embodiments, a pre-filter may be provided that clearly removes outlier liquid level values ​​(outliers) before a multi-point filter is applied, thereby further improving resilience to incorrect liquid level sensor readings.

[0014] If, at any time, the method determines that an erroneous signal or an unexpected change in the liquid level has indeed occurred (as determined by monitoring the actual liquid level), then the next expected liquid level predicted by the probe is adjusted (e.g., adjusted downwards) so that the next aspiration is likely to occur within the liquid, thereby allowing normal aspiration operations to continue. In some embodiments, a correction limit may be employed to limit the adjustment (excursion) of the next liquid level from the theoretical liquid level.

[0015] The methods and apparatus embodiments of this disclosure can be used to aspirate reagent liquids from reagent containers; however, the methods and apparatus described herein can be employed to detect and / or track liquid levels in any type of container, where changes in the liquid level are semi-predictable, such as when the liquid level change is based on the volume of liquid used in the test.

[0016] Therefore, in a first embodiment, a method for detecting the level of a liquid in a well is provided. The method includes: determining a desired liquid level in the well; ramping a probe into the well containing the liquid to a depth of the well; measuring and recording the measured liquid level of the liquid based on the ramp; and calculating the next desired liquid level based at least in part on multi-point filtering.

[0017] According to other embodiments, a liquid level detection device is provided. The liquid level detection device includes: a liquid level sensor configured to obtain a liquid level measurement result of liquid in a well; and a processor configured to receive the liquid level and calculate a next expected liquid level based on a multi-point filtering module. In some embodiments, a probe is configured to aspirate the liquid.

[0018] In yet another embodiment of the method, a method for detecting the level of liquid in a well is provided. The method includes: finding a desired liquid level in the well of a container; measuring and recording the measured liquid level in the well; changing the liquid level in the well based on desired liquid to be added or removed, such as changing it based on a test; and calculating the next desired liquid level based at least in part on multi-point filtering.

[0019] Other aspects, features, and advantages of this disclosure will become apparent from the following detailed description by illustrating several exemplary embodiments—including the best mode for carrying out the invention. This disclosure may also have other and different embodiments, and certain details thereof may be modified in various ways without departing from the scope of this disclosure. Therefore, the drawings and description are to be considered illustrative in nature and not restrictive. This disclosure is intended to cover all modifications, equivalents, and substitutions falling within the scope of the claims and their equivalents. Attached Figure Description

[0020] This disclosure will be better understood by referring to the detailed description obtained in conjunction with the following accompanying drawings. The drawings are not necessarily drawn to scale. Throughout this document, the same numerals are used to denote the same elements.

[0021] Figure 1 The illustration shows a schematic diagram of a suction device including liquid level measurement according to an embodiment of the present disclosure.

[0022] Figure 2A decision flowchart is illustrated, which illustrates a method for detecting the liquid level in a well of a container according to an embodiment of the present disclosure.

[0023] Figure 3A A decision flowchart is illustrated, which illustrates a method for calculating the next expected liquid level using multi-point filtering and error correction according to embodiments of the present disclosure.

[0024] Figure 3B A flowchart illustrating a method for multi-point filtering according to embodiments of the present disclosure is shown.

[0025] Figures 4A-4D A data plot is illustrated, which illustrates a multi-point filtering method according to an embodiment of the present disclosure.

[0026] Figure 5A The illustration shows a graphical representation of the liquid level during continuous aspiration according to an embodiment of the present disclosure.

[0027] Figure 5B The illustration shows a portion of a suction device including a liquid level measuring device according to an embodiment of the present disclosure, the liquid level measuring device being inserted into a well of a bulk reagent container.

[0028] Figure 6 A flowchart is shown illustrating a method for determining the position of the top liquid surface in a detection well according to an embodiment.

[0029] Figure 7 Another flowchart is shown, illustrating a method for detecting the liquid level in a well of a container according to an embodiment of the present disclosure.

[0030] Figure 8 Another flowchart is shown, illustrating a method for detecting the liquid level in a well according to an embodiment. Detailed Implementation

[0031] Given the aforementioned difficulties, there is an unmet need for accurately determining the position of the top liquid surface (e.g., in the liquid aspiration of liquid reagents) as part of an analysis performed by an analyzer on biological fluids (biofluids) to determine the presence and concentration of analytes or other components of interest in the biological fluid. In particular, the apparatus and methods described herein can be practical for use in analyzers configured to perform analyte measurements, assays, immunoassays, or other tests in which biological fluids and liquid reagents are aspirated and dispensed, and in which accurate measurement of the liquid level is desirable.

[0032] In one aspect, embodiments of this disclosure provide methods and apparatus that can significantly reduce errors in determining the top liquid surface level in a container of liquids (such as reagent liquids). In particular, embodiments of this disclosure can accurately determine the liquid level by filtering a normalized liquid level reading using a multi-point filter. Although this disclosure utilizes the example of detecting the position of the top liquid surface of a liquid reagent, it can also be used and is applicable to accurately determining the position of other liquids used in an analyzer, such as process water, waste liquid in a waste reservoir that must be emptied from time to time, and cleaning solutions used to clean pipettes and / or test tubes.

[0033] In particular, the inventors herein have discovered that in suction devices comprising a suction pump, a probe, and a robotic device for moving the probe, erroneous measurements can occur, which then contaminate the next liquid surface level, potentially leading to incorrect calculations of the top surface level. For example, it is desirable for the probe to be positioned a few millimeters (e.g., 2 mm to 6 mm) below the top surface of the reagent liquid to minimize carryout. However, if the measured liquid level is incorrect, such as being calculated too low compared to the actual position, the probe will be commanded to dive too deep into the well, and the amount of carryout may be excessive. Furthermore, the liquid reagent may be prematurely removed by controller command. If the calculated liquid level is too high compared to the actual position, the probe may aspirate air or foam. Therefore, accurate liquid level accounting is desirable for proper operation on multiple suctions and to ensure adequate use of the reagent in the well.

[0034] Therefore, according to embodiments, the methods and apparatus described herein provide improved accuracy for liquid level detection. Reference will be made herein to... Figure 1-8 These and other aspects and features are used to describe embodiments of the method and apparatus.

[0035] Now for reference Figure 1The illustration shows a first embodiment of a suction device 100 including a liquid level detection device 101 according to the present disclosure. The suction device 100 may include any suitable robot 102 configured to move a probe 104 as needed to aspirate liquids, such as liquid reagent 107R. Liquid reagent 107R may also be dispensed by the suction device 100. The robot 102 is adapted to perform movement of the probe 104 in one or more coordinate directions (such as X, Y (in and out of paper) and / or Z). The robot 102 may include a robot component 105 (e.g., a robot arm, cantilever, frame, etc.), to which the probe 104 may be mounted for movement. The robot component 105, which may be a robot arm as shown, may be swung about a fixed axis 112A by operation of a rotary actuator 112 to provide, for example, horizontal movement capability in the XY plane. Optionally or additionally, vertical movement of probe 104 along the vertical Z-axis can be imparted by the operation of a suitable vertical actuator 109, such as a linear actuator of robot 102, which can be coupled to probe 104. The vertical actuator 109 can be operable to lower probe 104 into and out of container 107 (e.g., reagent container), container 107 having one or more wells 107W comprising volumes of liquid reagent 107R, such that at least some can be aspirated and transferred to and dispensed into reactor dish 113 along with biological liquid samples 108S contained in sample container 108. Sample 108S can be blood, serum, plasma, cerebrospinal fluid, cerebrospinal fluid, interstitial fluid, urine, etc. Other fluids can be aspirated and dispensed. Additionally or alternatively, actuators 106, such as linear actuators, can be provided to impart movement along the X-axis. Each of the actuators 106, 109, and 112 can be appropriately actuated under the control of the position control module 114 of the controller 115 to impart the desired motion to the probe 104 in one-dimensional, two-dimensional, or three-dimensional space.

[0036] Each of actuators 106, 109, and 112 can be configured and operable to move probe 104 from container 107 to reactor dish 113 (e.g., test tube). Sample 108S can be aspirated from sample container 108 and dispensed into reactor dish 113 using a separate probe (not shown) or the same probe after interventional cleaning. Aspirator device 100 can be provided to aspirate a desired liquid (e.g., liquid reagent 107R) into the interior of probe 104. The aspirated volume can be up to about 100 μL, but in some embodiments it can be less than about 25 μL.

[0037] The aspirator device 100 may include a pump 122, such as a piston-type pump that can be driven by a suitable motor (not shown). Other types of pumps may also be used. The pump 122 is configured to aspirate liquid reagent 107R into probe 104 at a suction rate over a predetermined time period, which generates a pressure signal from pressure sensor 130 in line 134. The suction rate achievable by the aspirator device 100 ranges from about 20 μL / s to about 500 μL / s. The pump 122 may be fluidly coupled to probe 104 via a flexible tube 125, such as a portion of a hollow Teflon tube or other suitable flexible conduit. The flexible tube 125 and probe 104 are filled with a backing liquid 126 (e.g., purified water) to provide a suitable liquid backing, thereby enabling the generation of a suitable vacuum pressure to perform aspiration of the liquid (e.g., liquid reagent 107R) into the internal channels of probe 104 for transfer to reactor dish 113.

[0038] The suction control module 128 of controller 115 can be configured and operable to control pump 122 to draw (e.g., aspirate) a desired amount of liquid (e.g., liquid reagent 107R) into the interior of probe 104. The suction control module 128 of controller 115 can also control dispensing operations performed by suction device 100. Suction device 100 may include other conventional components, such as one or more valves, one or more accumulators, distributors, or other hydraulic components (not shown), to perform liquid suction and dispensing. Any suitable device for suctioning liquid into probe 104 can be used. For example, suction and dispensing systems that can be used are described in, for example, U.S. Patents 7,867,769; 7,634,378; 7,477,997; 7,186,378; 7,150,190; and 6,370,942.

[0039] According to embodiments, a complete cycle of aspiration of a liquid (e.g., liquid reagent 107R) can be completed in less than about 300 ms, or even less than about 200 ms, or in some embodiments in even less than about 100 ms. In some embodiments, the aspiration cycle can be completed between about 40 ms and about 200 ms. Other aspiration durations may be used.

[0040] According to one or more embodiments, the suction verification module 129 can also be used to verify the effectiveness of liquid suction. For example, the suction verification module 129 can determine the presence of air in the probe 104 during suction by determining whether a low viscosity error exists. If suction is performed and certain pre-established pressure parameters are not met, a low viscosity error is registered. A low viscosity error indicates that air, rather than liquid, is being suctioned. In another example, the suction verification module 129 can determine the presence of blockages or other obstructions in the probe 104.

[0041] More specifically, the suction pressure in the flexible tube 125 can be measured by pressure sensor 130. Pressure sensor 130 is operable and configured to provide a raw pressure signal in line 134. Pressure sensor 130 can be located at any suitable location along the flexible tube 125, or adjacent to pump 122 or probe 104. Sensor conditioning can be provided to condition the raw pressure signal in line 134, as is typically the case. This sensor conditioning may include, for example, a suitable amplifier, an A / D converter, and a suitable anti-aliasing filter.

[0042] According to embodiments of this disclosure, as referenced Figure 1 and Figure 2 As explained, the suction device 100 further includes a liquid level detection module 131. The liquid level detection module 131 is configured to accurately determine the level of the top liquid surface 107T of the liquid reagent 107R in the well 107W. The liquid level detection module 131 may include a liquid level sensor. The liquid level sensor 133 may be, for example, a capacitive sensor integrated with the probe 104, such that when the probe tip contacts the top liquid surface 107T of the liquid reagent 107R, an electrical signal is generated, carried by the line 135 and identified by the liquid level circuit 136 (e.g., a capacitive level circuit) of the liquid level detection module 131. Capacitive liquid level sensors and capacitive level circuits are described, for example, in US4,977,786, US5,550,059, US7,150,190, and US9,863,905. However, it should be recognized that other types of liquid level sensors and liquid level circuits can be used, such as optical sensors, ultrasonic sensors, conductivity or resistance sensors, etc.

[0043] The liquid level detection module 131 further includes a multi-point liquid level filter module 138. The multi-point liquid level filter module 138 may include a method 200 that retrieves and processes multiple liquid level readings from memory 140, such as in a processor 142 of the controller 115. For example, in some embodiments, a currently measured liquid level value and two or more previously obtained liquid level measurements may be used. In particular, the multi-point liquid level filter module 138 may include a digital filter, wherein the filtering occurs in software within the controller 115.

[0044] Now refer to Figure 2 This describes the operations and filtering performed by the multi-point liquid level filter module 138. Figure 2 The diagram illustrates a flowchart of the various actions performed according to method 200 when determining the liquid level of well 107W containing liquid reagent 107R. Method 200 is initiated when controller 115 determines that aspiration from well 107W will occur, such as the initiation of an ordered test at an analyzer having samples received for testing at that analyzer. From the start of the aspiration sequence at box 202, method 200 may determine at box 204 whether this aspiration is the first aspiration. If the answer is yes, the well is assumed to be full, and in box 206, the expected well level (synonymous with the top liquid surface position) is assigned as the theoretical well level. The theoretical liquid level is the level at which a particular reagent 107R is contained from the plant, i.e., the plant fill level. This value is typically controlled relatively tightly.

[0045] According to method 200, if the answer at box 204 is no, then in box 208, the expected well fluid level is assigned as the last (last) expected well fluid level, which is stored in memory 140 after filtering according to method 200. Therefore, in either the "yes" or "no" case, the next expected well fluid level is provided, which is either the theoretical well fluid level or the last expected well fluid level. Next, in box 210, the probe 104 is tilted to the well depth WD by the action of robot 102. During operation, during suction, robot 102 can position probe 104 above container 107 and lower probe 104. Under the control of position control module 114, the descent into container 107 can be generated by the action of vertical actuator 109 until probe 104 reaches the desired well depth WD therein.

[0046] When at well depth WD, method 200 may optionally test to see if well 107W is empty. For example, empty is determined by the expected liquid level a few millimeters above the bottom of container 107. Therefore, in block 212, method 200 determines whether well 107W is empty. If well 107W is empty (yes), then in block 214, an empty error can be issued to the operator, allowing pumping from a new well 107W to begin or container 107 to be replaced. If the well is not empty (no), then in block 216, the actual liquid level is measured and recorded. The actual liquid level is the liquid level measured when probe 104 is tilted downwards. For example, when probe 104 contacts the top liquid surface 107S, liquid level circuit 136 detects a change, such as a change in capacitance from liquid level sensor 133. This level is recorded as the actual liquid level in memory 140.

[0047] Next, in box 218, a volume of liquid reagent 107R is drawn into probe 104 for use in performing the test. The aspirator device 100 can be operated via a signal from the aspiration control module 128 to draw off a predetermined volume of liquid reagent 107R for a specific test into the internal channel of probe 104. When pump 122 is operated, the liquid level of liquid reagent 107R in container 107 attempts to be drawn down (aspirated). When it is determined, as measured by the aspiration control module 128, that the desired volume of liquid 107R has been contained within probe 104, pump 122 can be stopped, preventing further aspiration of liquid reagent 107R. This can be determined by a suitable feedback sensor (not shown) on the motor driving pump 122, and thus provides feedback on the position of pump 122. Any suitable position feedback can be provided.

[0048] Optionally, in block 220, it may be desirable to further determine whether the suction has been successful, such as by performing a suction quality verification. During the suction process, a representative raw suction pressure (e.g., the measured suction pressure) in line 134 can be measured via pressure sensor 130. This raw measured pressure in line 134 can be converted (A / D), regulated, and filtered by the suction verification module 129 to provide a regulated pressure signal. By examining this regulated pressure signal, it is possible to accurately determine the suction quality, and in particular, whether air has been suctioned. Suction verification can be performed by any known method, such as those described in US7,477,997, US7,867,789, US7,926,325, US2015 / 0276534, and US2016 / 0258972.

[0049] For example, in some embodiments, to verify the effectiveness (e.g., quality) of the suction in block 220, a regulated pressure signal is compared at evaluation points along a regulated pressure trajectory relating to the suction. At the desired evaluation point, the regulated pressure signal is compared to a pre-established threshold. If the regulated pressure signal is above the pre-established threshold, the suction can be considered successful. If the regulated pressure signal has a value below the pre-established threshold, the suction can be considered unsuccessful or incomplete. This may indicate that some air has been suctioned.

[0050] Refer again Figure 2 Following suction in box 218, the suction device 100 searches for a liquid level sensing transition (LLS transition) in box 222. Determining the presence of an LLS transition in box 222 involves... Figure 1 The liquid level detection module 131 uses a liquid level circuit 136 to check the signal in line 135. For example, a voltage spike above a predefined voltage value sensed by the liquid level circuit 136 when probe 104 is lowered can indicate a positive (yes) presence of an LLS transition. If no LLS transition is detected in block 222 (no), the suction quality verification from block 220 is used, and then it is determined in block 224 whether low viscosity has occurred. Low viscosity in block 224 means a viscosity much lower than expected, such as a lower-than-expected value in line 134, or a pressure reading below a predetermined threshold. The indication of low viscosity in block 224 (yes) indicates that not only was no LLS transition detected, but air may have been suctioned. In this example, in block 226, the test is aborted, and in block 230, the next expected liquid level is assigned as the current expected level stored in memory 140 minus ΔH. In this case, ΔH is the theoretical change in liquid level height based on the theoretical amount of reagent liquid 107L required for the current test.

[0051] If no LLS transition is found in box 222 and no low viscosity is detected in box 224, it is assumed that aspiration has occurred, but the liquid level sensor 133, liquid level circuit 136, or line 135 has failed. In this case, the LLS sensing event can be logged as an error in box 228. However, in this case, the correction is set to 0, and the next expected liquid level is calculated based on multi-point filtering in box 232, as fully described in Figure 3. After calculating the next expected liquid level based on multi-point filtering in box 232, the next expected liquid level is recorded in memory 140 in box 234. Method 200 then continues at box 208 for the next aspiration of the new test.

[0052] The details of the multi-point filtering employed by method 200 in block 232 will now be described with reference to Figure 3. First, in block 336, the actual measured liquid level is obtained from memory 140. This measured liquid level is in block 216 ( Figure 2 The tilt of the probe 104 to the well depth WD in box 210 is recorded. When the liquid level sensor 133 and liquid level circuit 136 of the liquid surface detection module 131 sense the top liquid surface 107S of the liquid reagent 107R, the position of the probe tip of the probe 104 from the position control module 114 is previously recorded.

[0053] Next, optionally, pre-filtering can be applied to determine whether the actual measured liquid level is meaningful. Pre-filtering in block 338 includes performing pre-filtering to remove outliers before applying multi-point filtering. Specifically, in block 338, it is determined whether the measured liquid level is within the pre-established pre-filter window set in block 340. Figure 5A As best shown in the diagram, the pre-filter window can be established and set in box 340, as shown in the measured LL. n The preset +Y value above the value. Optionally, this preset value can be provided, for example, by summing all theoretical changes in ΔH for previous pumping for well 107W and allowing for + / - tolerances in its vicinity. Other means can be used to preset the pre-filter window in box 340. If it is found in box 338 that the measured liquid level n is not in the pre-filter window set in box 340 (No), then a zero correction is assigned in box 342, which will be described later herein. If it is determined in box 338 that the measured liquid level n is in the pre-filter window set in box 340 (Yes), then multi-point filtering is used to filter the measured liquid level n in box 344.

[0054] Regarding this article Figures 4A-4D To further describe the multi-point filtering in box 344. Liquid levels will be abbreviated as LL in this document. Similarly, multiple liquid levels will be abbreviated as LL in this document. Specifically, Figure 4A The diagram illustrates both the theoretical LL value of well 107W with a dotted line trajectory 440 and the actual measured LL value of well 107W for a series of tests with a solid line trajectory 442. Figure 4B The dataset of normalized theoretical LL values ​​for well 107W is illustrated as a dotted line trajectory 440N. Similarly, normalized measured LL data for well 107W across multiple tests are shown as a solid line trajectory 442N. The entire dataset is shown. However, this method calculates the normalized LL for each new test data point on a point-by-point basis. The LL values ​​are normalized for each test n according to the normalization equation, which is as follows:

[0055] Normalized LLn =Measured LL n -TheoryLL n

[0056] Figure 4C The diagram illustrates the dotted line trajectory 440NF, which shows the normalized and filtered theoretical liquid level for a series of tests. Figure 4C The figure also illustrates the solid line trajectory 442NF of the normalized and filtered dataset of actual measurements that have been normalized and filtered for a series of tests.

[0057] More specifically, multi-point filtering of the test data in Figure 3B This is best shown in the image. For example... Figure 3B As shown, the multi-point filtering in block 344 involves first normalizing the measured LL for test n in block 346 according to the equation above. The running tally of the theoretical LL for each test can be maintained in memory 140. Next, in block 348, the normalized and filtered LL is calculated. n Normalized and filtered LL n The multi-point filter can be based on a normalized data point n and multiple previous m-1 normalized data points, where m is 3 or more, 10 or more, 15 or more normalized measured LL data points. The m data points can be obtained consecutively along with point n. In some embodiments, the multi-point filter is a median filter. Specifically, instead of directly using the value of n, the median filter uses the median of all the previous m normalized liquid level measurements, including the latest n value, as the new median. This new median is as follows: Figure 4C The normalized, filtered LL values ​​are shown. Therefore, this filtering effectively minimizes the impact of erroneous LL measurements. As shown, data point n is at the end of the set of intermediate data points from previous tests. The median of the m data points is shown as a set of a fixed number of m data points, where m can be set empirically. In some embodiments, m can be in the range of, for example, 3 to 40, or even between 5 and 20. In some embodiments, instead of using a median filter, a pattern filter can be used, where the pattern values ​​of the m data points are used, or an average filter can be used, where the average of the m data points is used, although a median filter is the most desirable.

[0058] Next, in box 350, the normalized and filtered LL... n Denormalization is performed to obtain the filtered LL. n Value. Denormalization is performed based on the following equation:

[0059] Filtered LLn =Filtered and normalized LL n +TheoryLL n

[0060] Figure 4D The diagram illustrates the denormalized data obtained by adding back the theoretical values. Therefore, the dotted line trajectory 440F illustrates the denormalized theoretical LL for a series of tested wells 107W. Similarly, the solid line trajectory 442F illustrates the denormalized and filtered measured LL for a series of tested wells 107W.

[0061] Refer again Figure 3A After performing multi-point filtering in box 344, the method can determine the error in box 352. The error can be calculated as follows:

[0062] Error = FLL n -Expected LL n

[0063] Once the error is determined, the error correction to be applied can be determined in box 354. The error correction can be determined as follows:

[0064] Error correction = gain x error

[0065] Gain can be a constant value determined experimentally. For example, gain can have values ​​from 0.05 to 1.5, or even from 0.05 to 0.5. If applied to significantly different container systems, such as when monitoring liquid levels in large-volume containers, both the number of points in the median filter and the gain can vary outside the above ranges because they are functions of the number of data points with respect to the rate of change of liquid level.

[0066] Next, calculate the next expected LL. n+1 Value. Next expected LL n+1 It can be calculated as follows:

[0067] Next expected LL n+1 =Expected LL n -(Test LL change + Carry-out LL change) + Error correction

[0068] Therefore, the next expected LL n+1The value can be based at least in part on multi-point filtering, but additionally on error correction. The test LL change is based on a reduction in LL, which is based on the volume of liquid reagent 107R aspirated for test n. In a general sense, carryover is an accounting for expected losses in LL, such as losses in LL due to reagent carryover on probe 104, or even losses in LL due to evaporation. In the case of probe carryover, the carryover LL change (carryover) is based on the amount of change in LL due to carryover of liquid reagent 107R on the outside of probe 104, which can be based on moving probe 104 to well depth WD (see...). Figure 1 The process involves multiple extractions and washes, with the average carryover from each extraction determined experimentally. The evaporation carryover can also be determined experimentally. Therefore, in some embodiments, the carryover may include both reagent carryover and / or evaporation carryover. Thus, the next expected LL is calculated. n+1 The value can be considered for the items to be taken out.

[0069] Once the next expected LL n+1 Once the value is calculated, it can be compared to the adjustment limit in box 358 to test the next expected LL. n+1 Value. The adjustment limit 440L can be set to a value for n that is X mm below the theoretical value 440F (e.g., 5-10 mm below), such as... Figure 4D As shown in the diagram. Therefore, in box 358, if the next expected LL... n+1 If the value is less than the adjustment limit of 440L (yes), then the next expected LL will be placed in box 360. n+1 Set it to be the limit of adjustment for n+1. Then... Figure 2 The limit value is recorded in box 234. Alternatively, if in box 358, the next expected LL... n+1 If not less than the adjustment limit of 440L (No), then in Figure 2 Record the next expected LL in box 234 n+1 For illustrative purposes, in Figure 3A Box 234 was copied.

[0070] Figure 5AA plot 570 of the LL (Limited Least Hour) for continuous aspiration is illustrated graphically, showing what happens when certain anomalies are encountered. As can be seen, the actual measured value 571 is shown as a diamond. The normalized, median-filtered trajectory 542 is shown as a solid line. An upper pre-filter 572 with a pre-filter limit is shown, which can be empirically set, for example, as a value +Y above the normalized and filtered LL value for this test. Therefore, points such as LL value 574 are ignored by the median filter, and the expected LL is simply adjusted downward by ΔH plus the carryover. The upper pre-filter 572 mitigates significant LL sensing noise or foaming caused by pulling the expected LL from the liquid reagent 107R.

[0071] although Figure 5A The diagram shows a single upper pre-filter limit set at +Y, but the upper pre-filter 572 can have multiple pre-filter limit levels, such as after access to well 107W begins at 580, allowing a wider range of +Y pre-filter limits for multiple evacuations to allow for greater fill variations in well 107W. Similarly, after adjustments have been made due to air evacuation (e.g., at point 582), a wider pre-filter limit value of +Y can be allowed for multiple evacuations. Therefore, the upper pre-filter 572 includes pre-filter limits that can be adjusted based on the state of container 107. For example, the container may be full, such as when container 107 is initially accessed, or the container may be in a state such that air has just been evacuated, as after point 582. Additional pre-filter limits (not shown) can be set at a preset position above the bottom of well 107W.

[0072] Additionally, a lower normalized adjustment limit 578 is shown, which prevents spurious pressure errors from pushing the probe 104 too deep. No value of the normalized expected LL can exceed this normalized adjustment limit 578. This adjustment limit can be set to any desired liquid level X, where X can be, for example, 5 mm to 10 mm.

[0073] As can be seen from the test starting at point 580, there is no previously measured LL value, so the expected LL and the theoretical normalized value are the same. In some embodiments, the median filter can be pre-filled with enough zeros to fill approximately half of the filter (e.g., 8 zeros for a 15-point median filter). The median filter will then not function until the 9th point, and then the median filter can begin to operate and adjust to the expected filtered LL value of 542. Of course, the median filter can be loaded with fewer zeros, causing the median filter to start responding with a small number of suckers. However, this comes at the cost of less noise suppression capability. Alternatively, more zeros can be pre-filled in the median filter, causing the filter to respond after a larger number of suckers and resulting in better noise suppression.

[0074] An illustration of an air suction event is also shown at LL measurement result 582. When air suction is determined, probe 104 is adjusted downwards to a new position with an X / 2 or other suitable value for the next suction, such that the tip of probe 104 is approximately X / 2 below LL. Furthermore, the pre-filter value 572 is reset, for example, to a value at Y above the normalized, filtered LL. Similarly, the expected LL and the theoretical LL are the same until three data points (LL measurements) are included in the median filter, after which the median filter can begin adjusting for the next expected L.

[0075] Figure 5B A schematic diagram of a portion of a suction device 100, including a liquid level measuring device and a liquid level sensor 133, is illustrated, which are inserted into a well 507W of a bulk container 507. The method 200 described herein, with slight modifications, is equally applicable to accurately measuring the liquid level of a bulk volume liquid 507B contained in the bulk container 507. Method 800 can suppress errors caused by fluctuations or splashes on the bulk volume liquid 507B due to liquid movement or vibration. Furthermore, in this document… Figure 8 The method 800 described herein is equally applicable to accurately measuring the liquid level in a process water container (e.g., deionized water), a cleaning liquid container (e.g., cleaning liquid), a waste container (e.g., waste liquid), or any other container with a changing (e.g., decreasing or increasing) liquid level, whether it is introduced and aspirated by probe 104 or dispensed by probe 104. In these examples, method 800 can suppress errors due to fluctuations or splashes on a large volume of liquid 507B caused by the entry or exit of liquid, such as when valve 509 is opened or closed, or when waste liquid is poured in.

[0076] Now for reference Figure 6The illustration depicts a broad method of this disclosure. Method 600 includes: in 602, determining the expected liquid level (e.g., liquid reagent 107R) in a well (e.g., well 107W, 507W). If this is the first test, the liquid level is the theoretical LL. After obtaining at least three readings, the expected LL is the filtered LL stored in memory 140. n+1 Method 600 further includes: in block 604, tilting a probe (e.g., probe 104) into a well (e.g., well 107W, 507W) containing the liquid (e.g., liquid reagent 107R) to a well depth (WD). Method 600 includes: in block 606, measuring and recording, based on the tilting, the measured liquid level (e.g., the measured LL) of the liquid (e.g., liquid reagent 107R). n ); and in box 608, the next expected liquid level (e.g., the next expected LL) is calculated at least in part based on multi-point filtering. n+1 However, this calculation can also include error correction, i.e., a combination of multi-point filtering and error correction. Multi-point filtering in Figure 3B It is described in the text. (Reference) Figure 3A A combination of multi-point filtering and error correction is shown and described. In some embodiments, method 600 includes: in block 610, aspirating a volume of the liquid for testing, and in block 612, dispensing the volume of the liquid into a reactor dish (e.g., reactor dish 113).

[0077] In some embodiments, such as in the example using a large-volume container 507, as Figure 5B As shown, a large volume of liquid 507B can be added to or subtracted from the large volume container 507 without using probe 104. For example, the large volume of liquid 507B can be added or subtracted through a fixed port formed in the side or bottom of the large volume container 507 or through a spout opening. For example, a fixed port with a valve is shown as a dotted line because valve 509 can be used to extract the large volume of liquid 507B from the large volume container 507 for use, such as in testing. Similarly, waste liquid from a recently completed test can be added. Furthermore, a cleaning solution can be extracted, for example, using valve 509 and used in testing. Using a method including multi-point filtering, the liquid level in the large volume container 507 can be more accurately determined.

[0078] In this example, an LL sensor will be included to detect the liquid level LL at the top liquid surface. Any suitable LL sensor can be used. The LL sensor can be a fixed sensing device, such as a float on a sensor stalk, a capacitive sensor, or even a precision scale that measures and converts weight to obtain the measured LL. In this case, the scale will also be considered an LL sensor. Methods 700 and 800 can be used to more accurately determine the next expected liquid level (e.g., the next expected LL). n+1 This provides a more accurate estimate of the liquid level over time.

[0079] Now for reference Figure 7 A method 700 is provided for detecting the level of liquid (e.g., process liquid, cleaning liquid, or waste liquid) in a well 507W of a container (e.g., a large-volume container 507). Method 700 is related to... Figure 2 The method is the same as described in method 200, except that non-essential aspects are removed, and the liquid is removed or added by dispensing into a nozzle or by adding or removing through a port located on the side or bottom of the bulk container 507. Similar to Figure 2 In contrast, except for box 718, the same numbers are used for the same boxes, which require changing the level of the fluid in a well with a desired level change, such as based on a test rather than by pumping using probe 104.

[0080] Therefore, in a broad sense, such as Figure 8As shown, the method includes: in block 802, finding the expected liquid level (e.g., expected LL) of liquid (e.g., large volume liquid 507B) in a well (e.g., well 507W) of a container (e.g., large volume container 507). Method 800 includes: in block 804, measuring and recording the measured liquid level (e.g., large volume liquid 507B) of liquid (e.g., well 507W). According to method 800, block 806 includes: changing the liquid level in the well based on the expected liquid to be added or removed. The expected amount of liquid to be added or removed may be based on test requirements. For example, the test may require a defined amount or process liquid for testing. Similarly, if the liquid is a cleaning liquid, a defined amount of cleaning liquid may be used for cleaning operations. If the liquid is waste liquid, for each test, there may be a defined volume of waste liquid, which is the expected amount of waste liquid added to well 507W. The test can be a test of a biological fluid as described herein, and a bulk volume of liquid 507B is used in the test in a defined amount. Therefore, if the bulk volume of liquid 507B is a process fluid or a cleaning fluid, a defined target volume needs to be used for each test. As in the previous methods, method 800 involves, in block 808, calculating the next expected liquid level (e.g., the next expected LL) based at least in part on multi-point filtering. n+1 This multi-point filter is in Figure 3B This is described in the text. Besides multi-point filtering, error correction can also be used, such as... Figure 3A As shown in boxes 352 to 356. A pre-filter window and adjustment limits can also be used, as shown in boxes 340, 338 and 342 and boxes 358 and 360, respectively.

[0081] With some exemplary embodiments already shown, those skilled in the art will recognize that many variations are possible that still fall within the scope of this disclosure. Therefore, it is intended to limit this disclosure, as indicated only by the scope of the claims and their equivalents.

Claims

1. A method for detecting the liquid level in a well, comprising: Locate the expected liquid level of the liquid in the well; Tilt the probe into the well containing the fluid to the well depth; The measured liquid level of the liquid is measured and recorded based on the tilt. as well as The next expected liquid level is calculated, at least in part, based on multi-point filtering; The calculation of the next expected liquid level includes: The normalized measured liquid level is obtained by subtracting the theoretical liquid level from the measured liquid level. A medium filter is applied to the normalized liquid level value and several previously obtained normalized liquid level values ​​to obtain a filtered liquid level value. The error is calculated based on the difference between the filtered liquid level value and the expected liquid level; and The next expected liquid level is calculated based on the previous expected liquid level, the liquid level change caused by the suction operation, and the error.

2. The method of claim 1, wherein the calculation of the next expected liquid level is further based on an applied error correction.

3. The method of claim 2, wherein the error correction is equal to the error multiplied by the gain.

4. The method of claim 1, wherein the calculation of the next expected liquid level further includes taking into account the carryover material.

5. The method of claim 1, wherein the median filter uses the median derived from three or more measured level values.

6. The method of claim 5, wherein the median filter uses the median of 10 or more consecutively obtained values.

7. The method of claim 5, wherein the median filter uses the median of 15 or more consecutively obtained values.

8. The method of claim 1, wherein the multi-point filtering is implemented using a mode filter or an average value filter.

9. The method of claim 1, further comprising pre-filtering to remove outliers before applying the multi-point filtering.

10. The method of claim 9, wherein the pre-filtering includes a pre-filter limit that is adjusted based on the state of the container containing the liquid.

11. The method of claim 1, further comprising employing an adjustment limit to restrict any adjustment of the next expected liquid level from the next theoretical liquid level.

12. The method of claim 1, further comprising aspirating a volume of the liquid designated for testing prior to the calculation.

13. The method of claim 1, wherein the liquid in the well is a reagent liquid.

14. The method of claim 1, wherein the liquid in the well is water, waste liquid, or cleaning liquid.

15. The method of claim 1, further comprising performing aspiration quality verification after aspiration.

16. The method of claim 15, further comprising adjusting the probe position downwards by means of adjustment when the suction quality verification detects that air has been drawn in.

17. The method of claim 1, wherein the measurement of the liquid level occurs during the tilting process.

18. A method for detecting the liquid level in a well, comprising: Locate the expected liquid level of the liquid in the well of the container; Measure and record the measured liquid level of the liquid in the well; The level of the fluid in the well is changed based on the expected amount of the fluid to be added or removed; as well as The calculation of the next expected liquid level is based at least in part on multi-point filtering. The calculation of the next expected liquid level includes: The normalized measured liquid level is obtained by subtracting the theoretical liquid level from the measured liquid level. A medium filter is applied to the normalized liquid level value and several previously obtained normalized liquid level values ​​to obtain a filtered liquid level value. The error is calculated based on the difference between the filtered liquid level value and the expected liquid level; and The next expected liquid level is calculated based on the previous expected liquid level, the liquid level change caused by the suction operation, and the error.

19. A liquid level detection device, comprising: A liquid level sensor, configured to obtain liquid level measurements of the liquid in a well; as well as A processor configured to receive the liquid level measurement result and calculate the next expected liquid level using the method of any one of claims 1 to 18.

20. The liquid level detection device of claim 19, comprising a probe configured to aspirate the liquid.

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