System and method for differential measurement of fluid level in sample receptacle

Abstract

To provide a system and method for differential measurement of a fluid level in a suitable sample receptacle.SOLUTION: Automated systems and methods determine a level of fluid relative to a rim of a sample receptacle defining an open top of the sample receptacle. The systems and methods utilize a distance sensor to measure a distance between the rim of the sample receptacle and a surface of a fluid sample contained in the sample receptacle, where at least one of the sensor and the sample receptacle is moved relative to the other to enable the sensor to obtain a sequence of discrete measurements of distances between the sensor and the rim of the sample receptacle and between the sensor and the surface of the fluid sample. A controller processes an output signal from the sensor to determine a level of a fluid relative to the rim of the sample receptacle. A derivative of a sequence of discrete measurements may be used to identify the rim and the fluid surface in the output signal.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 015,129, filed April 24, 2020, the disclosure of which is incorporated herein by reference.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to automated analytical system methods, and more particularly to automated systems and methods for measuring differential fluid levels in sample tubes. [Background technology]

[0003] Automated analytical systems for handling and analyzing various kinds of fluid samples (also called fluid specimens) are widely used in clinical diagnostics and medical research. The fluid sample can be any type of sample or specimen type, such as whole blood, serum, plasma, interstitial fluid, sputum, urine, feces, semen, mucus, pus, tissue, food, environmental, industrial, etc. For example, a large number of automated systems are available for performing assays on biological fluid samples to detect and / or quantify the presence or amount of antigens, cellular abnormalities, disease states, and / or disease-associated pathogens, such as parasites, fungi, bacteria, and viruses, present in the sample. In general, diagnostic assays are based either on the detection of antigens or antibodies (immunoassays), or the detection of nucleic acids belonging to the organism or virus of interest (nucleic acid-based assays). There are also automated systems for performing genetic tests on biological fluids to identify genes present in the sample, e.g., to detect disease-associated mutations.

[0004] Automated analytical systems typically have various stations, which may include sample preparation "prep" stations, analysis stations, storage stations, and / or transport mechanisms for preparing and analyzing samples contained in sample containers. For example, sample containers may be test tubes, vials, etc. Most, if not all, stations typically have associated sample container handling mechanisms (e.g., pick-and-place robots) and / or fluid handling mechanisms for manipulating sample containers, samples, reagent vessels, and reagents, such as robots, fluid aspirating and dispensing devices, etc. Transport mechanisms may include robots, conveyors, and other devices for moving sample containers and other materials between stations. The components of the automated system are controlled by a controller, including one or more computerized controllers, which control the operation of each of the components to coordinate and coordinate the components involved in performing one or more assays on multiple samples contained in sample containers.

[0005] When handling sample containers in an automated analytical system, it is important to ensure that the biological fluid sample within the sample container does not spill or splash out of the container. Spilling and / or splashing of the fluid sample can result in cross-contamination of samples or contamination of the system itself that may require cleaning and / or other maintenance, and can pose a hazard to personnel operating the system. Summary of the Invention [Means for solving the problem]

[0006] The present disclosure is directed to an automated system and method for processing a fluid sample contained in a sample vessel having a rim that defines the open top of the sample vessel. The automated system and method measures and determines one or more dimensional aspects of the fluid sample and the sample vessel, including the level of the fluid contained in the sample vessel relative to the rim of the sample vessel, the amount of the fluid sample contained in the sample vessel, and / or other physical dimensions of the sample vessel. The level of the fluid contained in the sample vessel relative to the rim of the sample vessel is sometimes referred to as the "headspace" of the fluid sample in the sample vessel. In other words, the "headspace" is the distance between the top surface of the fluid and the rim of the sample vessel. The headspace may also be determined from one or more locations of the top surface of the fluid, or from the entire top surface of the fluid (e.g., a profile).

[0007] In general, an automated fluid handling system includes robots, conveyors, and / or other electromechanical devices for transporting fluid samples contained in sample vessels around the system, as well as robots and / or other sample vessel handling mechanisms (e.g., pick-and-place robots, carriages, etc.) for manipulating sample vessels within stations of the system. The automated manipulation and transport of sample vessels by the automated analysis system, as well as any other movement, are collectively referred to as "handling" of sample vessels. An automated fluid handling system may utilize a sample vessel holder to hold the sample vessels while they are handled on the system, or the system may handle the sample vessels themselves, or the system may include a combination of handling sample vessels in the sample vessel holders and removing the sample vessels from their respective holders and handling the sample vessels directly. Handling of sample vessels containing their respective fluid samples by the automated system causes the sample vessels, and thus the fluid samples, to move relative to their respective sample vessels. For example, acceleration of the sample vessels, including translation and / or rotation (e.g., tilting), may cause the fluid samples to move within the sample vessels. If the sample vessel is filled near the top rim of the sample vessel, this movement can cause the fluid sample to splash or spill out of the sample vessel.

[0008] As discussed above, it is often desirable to prevent spillage and / or splashing of fluid samples from sample containers during automated movement of the sample containers on an automated fluid sample processing system to prevent cross-contamination of the samples and / or contamination of personnel in the vicinity of the system and the samples. This may be particularly true for automated analytical systems, such as diagnostic systems used to perform diagnostic assays and / or genetic testing of patient samples, where cross-contamination may cause false positives in the patient's diagnosis. Although the systems and methods disclosed herein are particularly useful when implemented in automated analytical systems, the present disclosure is not limited to automated analytical systems and may be utilized in any automated system and method for processing fluid samples contained in sample containers.

[0009] Thus, an automated system and method may check the fluid level in a sample container to determine if the fluid level against the rim of the sample container is above an acceptable level and isolate the sample container if the level is too high. However, if the measurement of the level of the fluid in the sample container is determined by simply measuring only the surface of the fluid, the tolerance stack of the automated mechanical system for handling the sample container, and the tolerance of the sample container, may lead to a measurement uncertainty of + / - 3.5 mm or more. A "tolerance stack" or "stackup" is the combination of tolerances associated with the components of an assembly. In design, the worst case scenario is typically considered to be the sum of the expected tolerances of the system. In practice, due to statistical variations, the actual tolerances are typically less than the worst case scenario.

[0010] This uncertainty can result in sample containers being erroneously measured as having unacceptable fluid levels (e.g., too high and prone to spillage, or too low to be viable as an assay, etc.) As a result, sample containers may be unnecessarily quarantined, thereby affecting processing times and overall throughput, as well as placing additional strain on laboratory personnel who must remove the containers to determine whether they are in fact overfilled.

[0011] In one particularly advantageous aspect of the present disclosure, the disclosed system and method removes measurement uncertainties caused by tolerance stacking in automated mechanical systems and sample vessels. The present disclosure eliminates mechanical tolerance stacking by performing precise differential measurements in which a sensor measures the distance from a particular point (such as the sensor location) to both the fluid surface and the rim of the sample vessel, and determines the fluid level relative to the rim based on the measurements of both features. Additionally, multiple measurements of the fluid surface and rim may also be taken and filtered and / or averaged to further refine the measurements before determining the fluid level based on the difference in the measurements.

[0012] In one embodiment, the system and method of the present disclosure are directed to an automated fluid sample processing system capable of determining head space. In one aspect, the system and method can utilize the determined level of fluid in the sample container to prevent or at least minimize spillage and / or splashing of the fluid sample from the sample container during handling of the sample container on the system by ensuring that the sample containers on the system have respective fluid levels within a predetermined range or below a predetermined level. In another aspect, the fluid level can be measured at the start of processing of the sample container by the automated fluid processing system, and the system can be configured to isolate sample containers having fluid levels that are outside of an acceptable range or above an acceptable level, which would otherwise risk spilling or splashing the sample from the container. In other words, sample containers that are overfilled with fluid sample are immediately isolated for corrective action before they can contaminate the system.

[0013] Accordingly, one embodiment of the present disclosure is directed to an automated system for detecting the level of a fluid sample contained in a sample container. The automated system may also be configured to process multiple sample containers. The sample container has a closed bottom and a container wall extending from the closed bottom to a rim that defines an open top of the sample container. In one aspect, the sample container may be a sample vial, such as a test tube. The sample container may also be any other suitable fluid container having an acceptable shape and size.

[0014] The system includes a sensor for periodically measuring a distance between the sensor and (i) one or more surfaces of the sample vessel and (ii) a surface of a fluid contained within the sample vessel, respectively. The measurements include measuring a distance between the sensor and (i) a rim of the sample vessel and (ii) a surface of a fluid contained within the sample vessel. For example, the sensor may be an ultrasonic sensor, a laser sensor, or other suitable distance measuring sensor for measuring distance.

[0015] At least one of the sensor and the sample vessel is controllably movable relative to the other to allow the sensor to obtain a series of discrete surface distance measurements between the sensor and respective surfaces of the sample vessel and the fluid contained therein. For example, one or both of the sensor and the sample vessel holder are controllably movable to perform a linear scan across the rim of the sample vessel and the surface of the fluid, thereby allowing the sensor to obtain measurements at different locations of the rim and top surface of the fluid during the scan. In one aspect, the linear scan can utilize continuous relative motion while the sensor obtains measurements, and in another aspect, the linear scan can utilize intermittent relative motion, where the motion is intermittently stopped for the sensor to obtain measurements. A controller is operably coupled to the sensor and configured to receive and process an output signal from the sensor including a digital representation of the series of individual surface distance measurements. The output signal may further include a sensor position relative to the sample vessel, where each sensor position is associated with one of the individual surface distance measurements.

[0016] The controller processes the output signal from the sensor to determine the relative level of the fluid contained within the sample vessel relative to the rim, or headspace, of the sample vessel.

[0017] In another aspect, the sensor is supported by a linear translator that moves the sensor relative to the sample vessel, or the sensor may be fixedly mounted relative to the sample vessel, in which case the sample vessel is moved, such as with a conveyor or other robotic arm, to move the sample vessel relative to the sensor.

[0018] In another aspect, the sensor is attached to a vertical linear translator that moves the sensor vertically relative to the sample vessel. The sensor may have limitations on the distance from the measurement surface that the sensor can measure or be more accurate at, so the vertical linear translator allows the sensor to take such limitations into account by moving the sensor to a predetermined position from the rim of the sample vessel. This vertical adjustment of the sensor also allows the automated system to measure the fluid level of different sample vessels having different heights. For example, if the sensor is designed to be within a maximum (and / or minimum) distance from the measurement surface, the vertical linear translator can adjust the vertical position of the sensor to be within a maximum (and / or minimum) distance of the rim of the sample vessel, and the vertical position can be adjusted based on the height of the sample vessel. As an example, if 100 mm and 75 mm high sample tubes are utilized, the sensor is adjusted to be lower for the 75 mm sample tube than for the 100 mm sample tube, because the bottom of the sample vessel sits at the same depth in the recess of the respective sample vessel holder.

[0019] As another feature, the sensor can be disposed at an input station for loading sample vessels onto the system. The input station can include a vessel rack configured to hold a plurality of sample vessels and a gripper robot configured to retrieve sample vessels from the rack.

[0020] In yet another aspect, the automated system may also include a detector configured to determine one or more physical characteristics of the sample vessel, such as the height, diameter, shape, and / or the presence or absence of a cap on the sample vessel. The detector may be any suitable detector, such as a laser or an imaging device.

[0021] In yet another aspect, the controller may be configured to determine the volume of fluid contained within the sample vessel based on at least one of one or more physical characteristics of the sample vessel and the level of fluid contained within the sample vessel. For example, the physical characteristics may include the height and diameter of the sample vessel, and thus the controller may determine the volume of fluid based on the height and diameter of the sample vessel and the fluid level (e.g., the volume of fluid is the total volume of the sample vessel minus the volume of the vessel above the fluid level). If the shape of the bottom of the sample vessel is other than flat, the shape of the bottom of the vessel is another physical characteristic that may be considered in determining the volume of fluid in the sample vessel.

[0022] In one aspect, the automated system may also include a respective sample vessel holder for supporting the sample vessel such that an upper portion of the vessel wall terminating in the rim rests on the sample vessel holder. The automated system may be configured to transport the sample vessel holder (and any associated sample vessels) within the automated system.

[0023] In a further feature, the sample vessel holder may include a recess configured to seat a closed bottom of the sample vessel, and / or the sample vessel may be a generally cylindrical puck with the recess formed in a base of the puck. In another aspect, the vessel holder may include a plurality of fingers extending upwardly from the puck, the fingers configured to support the sample vessel in a generally vertical orientation.

[0024] In yet another aspect, the automated system also includes an automated conveyor configured to transport the sample vessel holders between respective stations of the system. For example, the stations may include an analyzer configured to perform an analytical procedure using a fluid, such as a molecular assay or other suitable assay. In such a case, the sensor may be configured to obtain a series of discrete surface distance measurements while the sample vessel holders are supported by the conveyor.

[0025] In yet another feature, the controller may also be configured to determine an orientation of the sample vessel relative to the sample vessel holder from the output signal of the sensor. For example, the sample vessel may be tilted relative to a vertical axis of the sample vessel holder. The orientation may include a tilt angle of the sample vessel relative to the vertical axis of the sample vessel holder. An excessive tilt angle may be an error condition, and the system may be configured to transport the sample vessel from the sample vessel holder to the segregation area if the tilt angle is greater than a predetermined tilt angle.

[0026] In yet another aspect, the series of individual surface distance measurements may include (i) a plurality of distance measurements between the sensor and a first portion of the rim (first rim measurements), and (ii) a plurality of distance measurements between the sensor and a second portion of the rim (second rim measurements), and the controller may be configured to determine a tilt angle of the sample container relative to a vertical axis of the sample container holder from a difference between the first rim measurements and the second rim measurements.

[0027] In another aspect, the series of discrete measurements of distance includes multiple distance measurements between the sensor and one or more surfaces of the sample vessel, including multiple distance measurements between the sensor and the rim (referred to as "rim measurements"), and multiple distance measurements between the sensor and a surface of the fluid (referred to as "fluid measurements"). Additionally, the controller may be configured to utilize the multiple rim measurements and the multiple fluid measurements to determine a fluid level in the sample vessel relative to the rim. For example, the controller may be configured to determine an average rim distance based on the multiple rim measurements, determine an average fluid distance based on the multiple fluid measurements, and determine the fluid level as the difference between the average fluid distance and the average rim distance.

[0028] In yet another aspect, the controller may be configured to identify which of the individual surface distance measurements in the series of measurements are rim measurements and which of the individual surface distance measurements in the series are fluid measurements. In one method, the controller is configured to identify one or more edges of the rim by analyzing the rate of change of distance in the series of measurements. For example, the controller may identify the edge of the rim as the measurement corresponding to a peak in the rate of change, and measurements between the peaks are either rim or fluid measurements. Alternatively, the controller may determine which measurements are rim and fluid measurements by identifying measurements for which the rate of change of distance in the series of measurements is within a threshold window (i.e., below a maximum absolute value).

[0029] In yet another aspect, the controller may also be configured to determine which measurements in the series of measurements correspond to each of the first portion of the rim (i.e., the rim measurement of the first portion of the rim), the top surface of the fluid, and the second portion of the rim opposite the first portion of the rim (i.e., the rim measurement of the second portion of the rim). The controller may make these determinations utilizing the edge finding techniques described above. The controller may then determine the fluid level based on the average of the rim measurement for the first portion of the rim, the rim measurement for the second portion of the rim, and the fluid measurement. In other words, the controller determines the average of the rim measurement for the first portion of the rim, the average of the rim measurement for the second portion of the rim, and the average of the fluid measurement. The controller is further configured to determine the fluid level as the average of the average of the rim measurement for the first portion of the rim and the average of the rim measurement for the second portion of the rim minus the average distance to the top surface of the fluid.

[0030] In yet another aspect, the system may be configured to (i) transport the sample container to an isolation area if the level of fluid contained within the sample container relative to the rim is determined to be outside a predetermined range or above a predetermined level, and (ii) release the sample container for subsequent processing on the system, including performing an assay using the fluid, if the level of fluid contained within the sample container relative to the rim is determined to be within a predetermined range or below a predetermined level.

[0031] Another embodiment of the present disclosure is directed to a method for detecting the level of a fluid sample contained in a sample vessel. The sample vessel has a closed bottom and a vessel wall extending from the closed bottom to a rim that defines an open top of the sample vessel. The method may be performed on an automated system as described herein, or other suitable system. The method includes obtaining a series of discrete measurements of the distance between the sensor and (i) one or more surfaces of the sample vessel, and (ii) the surface of the fluid contained in the sample vessel, by periodically measuring the distance between the sensor and (i) one or more surfaces of the sample vessel, and (ii) the surface of the fluid contained in the sample vessel, including measuring the distance between the sensor and the rim of the sample vessel while moving at least one of the sensor and the sample vessel relative to the other.

[0032] An output signal from the sensor, which comprises a digital representation of a series of discrete surface distance measurements, is processed to determine the level of fluid contained within the sample vessel relative to the rim of the sample vessel (ie, the fluid level or headspace).

[0033] In yet another aspect of the method, the sensor can be attached to a linear translator that moves the sensor relative to the sample vessel to obtain the series of discrete surface distance measurements, hi another aspect, the sensor can be fixedly mounted relative to the sample vessel, whereby the sample vessel moves relative to the sensor during the step of obtaining the series of measurements.

[0034] In another aspect, a method includes inserting a sample vessel into a sample vessel holder configured to support the sample vessel in a generally upright orientation such that an upper portion of the vessel wall terminating in a rim rests on the sample vessel holder.

[0035] In another aspect, inserting the sample vessel into the sample vessel holder may include seating the closed bottom of the sample vessel in a recess in the sample vessel holder. The sample vessel holder may be a generally cylindrical puck, and the recess may be formed in a base of the puck. Additionally, the vessel holder may further include a plurality of fingers extending upwardly from the puck, the fingers configured to support the sample vessel in a generally vertical orientation.

[0036] In yet another aspect, the sample vessel holder can be positioned on an automated conveyor during the step of inserting the sample vessel into the sample vessel holder. The conveyor can be configured to transport the sample vessel holder between respective stations of the sample processing system. The stations can include an analyzer configured to perform an analytical procedure with the fluid, such as a molecular assay or other suitable assay. Additionally, a series of measurements can be obtained while the sample vessel holder is positioned on the automated conveyor.

[0037] In another aspect, prior to the step of inserting the sample vessel into the sample vessel holder, the method includes loading a vessel rack holding the sample vessels into an input station of the sample processing system, where the vessel rack is configured to hold a plurality of sample vessels. After loading the sample rack into the input station, the method may further include removing the sample vessels from the sample vessel rack with a gripper robot and performing the inserting step with the gripper robot. In yet another aspect, the sensor may be disposed at the input station.

[0038] In yet another aspect, processing the output signal also includes determining an orientation of the sample vessel relative to the sample vessel holder. For example, the orientation can be a tilt angle of the sample vessel relative to a vertical axis of the sample vessel holder. In another feature, the method further includes transporting the sample vessel to a segregation area if the tilt angle is greater than a predetermined tilt angle.

[0039] In yet another aspect, the series of individual surface distance measurements may include (i) a plurality of distance measurements between the sensor and a first portion of the rim (first rim measurements), and (ii) a plurality of distance measurements between the sensor and a second portion of the rim (second rim measurements), and the method may further include determining an angle of inclination of the sample container relative to a vertical axis of the sample container holder from a difference between the first rim measurements and the second rim measurements.

[0040] In another aspect of the method, the sensor is an ultrasonic sensor.

[0041] In another aspect, the method further includes determining one or more physical characteristics of the sample vessel. For example, the physical characteristics may include one or more of height, diameter, shape, and / or presence or absence of a cap. In another aspect, the one or more physical characteristics are determined using a laser, an imaging device, and / or other suitable detector.

[0042] In yet another aspect, the step of processing the output signal further includes determining a volume of fluid contained within the sample vessel based on one or more physical characteristics of the sample vessel and the level of fluid contained within the sample vessel.

[0043] In another aspect, the method also typically includes reading machine-readable indicia on the sample vessel while the sample vessel is in position to obtain the series of discrete surface distance measurements.

[0044] In another aspect, the method further includes transporting the sample vessel to a quarantine area if the level of fluid contained within the sample vessel is determined to be outside of or above a predetermined range. Additionally, the method may also include releasing the sample vessel for processing if the level of fluid contained within the sample vessel is determined to be within or below a predetermined range.

[0045] In another feature, the method includes adjusting a vertical position of the sensor using a vertical translator that supports the sensor during the step of obtaining the series of surface distance measurements to position the sensor within a predetermined distance or measurement range from the rim of the sample container.

[0046] In another aspect of the method, the series of measurements is taken by the sensor at a rate of 10 to 20 measurements per second. In another aspect, the series of measurements is taken by moving the sensor and the sample container holder relative to one another at a rate of 2.5 mm / sec to 10 mm / sec.

[0047] In another aspect, the method further includes, after the step of processing the output signal, transporting the sample container to an analyzer, removing an aliquot of fluid from the sample container and transferring the aliquot to a reaction vessel contained within the analyzer, and performing an analytical procedure with the aliquot of fluid. The analytical procedure may be a molecular assay or other suitable assay. In another aspect, the sample container may be a sample tube.

[0048] Thus, the present disclosure provides automated systems and methods for processing a fluid sample in a sample vessel and measuring and determining one or more dimensional characteristics of the fluid sample and the sample vessel, such as the fluid level, the physical dimensions of the sample vessel, and / or the volume of the fluid sample. The present specification also provides, for example, the following: (Item 1) 1. An automated system for detecting a level of a fluid contained in a sample vessel, the sample vessel having a closed bottom and a vessel wall extending from the closed bottom to a rim defining an open top of the sample vessel, the system comprising: a sensor for periodically measuring distances between the sensor and (i) one or more surfaces of the sample vessel and (ii) a surface of a fluid contained within the sample vessel, the sensor including measuring a distance between the sensor and the rim of the sample vessel, wherein at least one of the sensor and the sample vessel is controllably movable relative to the other such that the sensor is able to obtain a series of discrete surface distance measurements of the distances between the sensor and (i) the one or more surfaces of the sample vessel and (ii) the surface of the fluid contained within the sample vessel; a controller operably coupled to the sensor and configured to receive and process an output signal from the sensor including a digital representation of the series of individual surface distance measurements, thereby determining a level of the fluid contained within the sample vessel relative to the rim of the sample vessel; , an automated system. (Item 2) 2. The system of claim 1, wherein the output signal further includes a sensor position relative to the sample vessel, each sensor position being associated with one of the individual surface distance measurements. (Item 3) 3. The system of claim 1 or 2, wherein the sensor is supported by a linear translator that moves the sensor relative to the sample vessel. (Item 4) 3. The system of claim 1 or 2, wherein the sensor is fixedly attached to the sample vessel. (Item 5) 2. The system of claim 1, wherein one or both of the sensor and the sample vessel are controllably movable to perform a linear scan across the rim of the sample vessel and the surface of the fluid, thereby enabling the sensor to obtain measurements at different locations on the rim and top surface of the fluid during the scan. (Item 6) Item 6. The system of item 5, wherein the linear scanning utilizes continuous relative motion while the sensors acquire the measurements. (Item 7) 6. The system of claim 5, wherein the linear scanning utilizes intermittent relative motion, the motion being stopped intermittently for the sensor to take measurements. (Item 8) the sensor is disposed at an input station for loading the sample vessel onto the system; the input station includes a vessel rack configured to hold a plurality of sample vessels and a gripper robot configured to remove the sample vessels from the rack. 8. The system according to any one of items 1 to 7. (Item 9) 9. The system of claim 8, wherein the input station further comprises a detector system configured to determine one or more physical properties of the sample vessel. (Item 10) 10. The system of claim 9, wherein the one or more physical characteristics of the sample vessel include at least one of a height, a diameter, a shape, and the presence or absence of a cap secured to an upper end of the sample vessel. (Item 11) 11. The system of claim 9 or 10, wherein the detector system comprises at least one of a laser and an imaging device. (Item 12) 12. The system of any one of claims 9 to 11, wherein the controller is further programmed to determine a volume of the fluid contained in the sample vessel based on at least one of the one or more physical characteristics of the sample vessel and the level of the fluid contained in the sample vessel. (Item 13) 13. The system of any one of claims 1 to 12, wherein the sensor is an ultrasonic sensor. (Item 14) 14. The system of any one of items 1 to 13, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and one or more surfaces of the sample vessel, including a plurality of distance measurements between the sensor and the rim (rim measurements), and (ii) a plurality of distance measurements between the sensor and a surface of the fluid (fluid measurements). (Item 15) Item 15. The system of item 14, wherein the controller is configured to determine a level of the fluid contained in the sample vessel relative to the rim based on an average of the rim measurements and an average of the fluid measurements. (Item 16) 16. The system of any one of claims 1 to 15, wherein the controller is configured to determine which measurements in the series of individual surface distance measurements correspond to each of a first portion of the rim, a top surface of the fluid, and a second portion of the rim opposite the first portion of the rim. (Item 17) Item 17. The system of item 16, wherein the controller is configured to determine which measurements in the series of individual surface distance measurements correspond to each of a first portion of the rim, a top surface of the fluid, and a second portion of the rim opposite the first portion of the rim using an edge finding technique, the edge finding technique including: (a) analyzing the rate of change of distance in the series of individual surface distance measurements and identifying an edge of the rim as a measurement corresponding to a peak in the rate of change and identifying measurements between the peaks as rim measurements or fluid measurements; or (b) identifying measurements for which the rate of change of distance in the series of individual surface distance measurements is within a threshold window. (Item 18) 18. The system of any one of claims 1 to 17, further comprising a sample vessel holder for supporting the sample vessel such that an upper portion of the vessel wall ending in the rim is positioned above the sample vessel holder. (Item 19) Item 19. The system of item 18, wherein the sample vessel holder comprises a recess configured to seat the closed bottom of the sample vessel. (Item 20) 20. The system of claim 19, wherein the sample vessel holder is a generally cylindrical puck, and the recess is formed in a base of the puck. (Item 21) 21. The system of claim 20, wherein the vessel holder further comprises a plurality of fingers extending upwardly from the puck, the fingers being configured to support the sample vessels in a substantially vertical orientation. (Item 22) 22. The system of any one of items 18 to 21, further comprising an automated conveyor configured to transport the sample vessel holders between each station of the system. (Item 23) 23. The system of claim 22, wherein at least one of the stations is an analyzer configured to perform an analytical procedure using the fluid. (Item 24) 24. The system of claim 23, wherein the analytical procedure is a molecular assay. (Item 25) 25. The system of any one of claims 22 to 24, wherein the sensor is configured to obtain the series of individual surface distance measurements while the sample vessel holder is supported by the conveyor. (Item 26) 26. The system of any one of items 18 to 25, wherein the controller is further programmed to determine an orientation of the sample vessel relative to the sample vessel holder from the output signal. (Item 27) 27. The system of claim 26, wherein the orientation includes a tilt angle of the sample vessel relative to a vertical axis of the sample vessel holder. (Item 28) 28. The system of claim 27, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and a first portion of the rim (first rim measurements), and (ii) a plurality of distance measurements between the sensor and a second portion of the rim (second rim measurements), and the controller is further programmed to determine an angle of inclination of the sample vessel relative to a vertical axis of the sample vessel holder from a difference between the first rim measurements and the second rim measurements. (Item 29) 30. The system of claim 27 or 28, wherein the system is configured to transport the sample vessel from the sample vessel holder to an isolation area if the tilt angle is greater than a predetermined tilt angle. (Item 30) Item 16. The system of item 14 or 15, wherein the controller is configured to identify the individual surface distance measurements as either rim measurements or fluid surface measurements by analyzing the rate of change of measurements in the series of individual surface distance measurements to find measurements that correspond to an edge of the rim. (Item 31) Item 31. The system of item 30, wherein if the rate of change exceeds a threshold, the rate of change is indicative of an edge of the rim. (Item 32) 32. The system of any one of items 1 to 31, wherein the system is configured to (i) transport the sample vessel to an isolation area if the level of the fluid contained in the sample vessel relative to the rim is determined to be outside a predetermined range or above a predetermined level, and (ii) release the sample vessel for subsequent processing on the system, including performing an assay using the fluid, if the level of the fluid contained in the sample vessel relative to the rim is determined to be within a predetermined range or below a predetermined level. (Item 33) 33. The system of any one of the preceding claims, wherein the sample vessel is a test tube. [Brief description of the drawings]

[0049] The foregoing and other aspects of the embodiments will be described in further detail with reference to the accompanying drawings, in which like reference numerals refer to like elements and the description of like elements shall apply to all relevant described embodiments.

[0050] [Figure 1]FIG. 1 is a schematic diagram of an exemplary automated system for processing a fluid sample contained in a sample vessel.

[0051] [Figure 2A] FIG. 2A is a side view of an exemplary sample vessel in the form of a sample tube and cap.

[0052] [Figure 2B] FIG. 2B is a cross-sectional view of the sample container of FIG. 2A.

[0053] [Diagram 3] FIG. 3 is a front perspective view of an exemplary sample vessel holder.

[0054] [Figure 4] FIG. 4 is a schematic diagram of an exemplary input station of the automated system of FIG.

[0055] [Diagram 5] FIG. 5 is a rear perspective view of the exemplary input station identified in FIG. 1 showing the sample container detector system and the fluid measurement system.

[0056] [Figure 6] FIG. 6 is a rear perspective view of the input station of FIG. 5 showing a sample container within the fluid measurement system.

[0057] [Figure 7] 7 is a rear perspective view of the input station of FIG. 6 showing a distance sensor of the fluid level measurement system in position to make a distance measurement.

[0058] [Figure 8] FIG. 8 is a diagram depicting a method for determining a fluid level relative to a rim of a sample vessel using the automated system of FIG. 1 in an exemplary embodiment.

[0059] [Figure 9]FIG. 9 depicts an algorithm for determining fluid level relative to the rim of a sample vessel using the automated system of FIG. 1 in an exemplary embodiment.

[0060] [Figure 10] FIG. 10 is a diagram depicting an algorithm for determining a fluid level relative to the rim of a sample vessel using the automated system of FIG. 1 in another exemplary embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0061] Unless otherwise defined, all technical terms, notations, and other scientific or technical terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs.All patents, applications, published applications and other publications referenced herein are incorporated by reference in their entirety.If the definitions set forth in this disclosure are contrary to or otherwise inconsistent with the definitions in these references, the definitions set forth in this disclosure shall prevail over the definitions incorporated herein by reference.None of the references set forth or referenced herein are admitted to be prior art to this disclosure.

[0062] References herein to "one embodiment," "an embodiment," "an additional embodiment," "an exemplary embodiment," "some aspects," "further aspects," "aspects," and the like indicate that the described embodiment may include a particular feature, structure, or characteristic, but not all embodiments necessarily include the particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Furthermore, when a particular feature, structure, or characteristic is described in connection with an embodiment, such feature, structure, or characteristic is also described in connection with other embodiments, whether or not explicitly described. As used herein, "a" or "an" means "at least one" or "one or more."

[0063] As used herein, the term "sample" refers to any material suspected of containing at least one analyte of interest. The analyte of interest may be, for example, a nucleic acid, a protein, a prion, a chemical, etc. The material may come from any source, including an animal, an industrial process, the environment, a water source, a food, or a solid surface (e.g., a surface in a medical facility). Materials obtained from animals may include, for example, blood or blood products, urine, mucus, sputum, saliva, semen, tears, pus, feces, nasopharyngeal or urogenital samples, and other bodily fluids or materials obtained using a swab or other collection device. The term "sample" is understood to mean a specimen in its original form or at any stage of processing.

[0064] As used herein, the term "vessel" refers to any type of fluid container including, for example, a tube, vial, cuvette, cartridge, microtiter plate, etc., configured to contain a sample or another fluid (collectively referred to herein as fluid). Non-limiting examples of illustrative vessels include, for example, Aptima® urine specimen transport tubes, Aptima® specimen transfer tubes, BD Vacutainer®, etc.

[0065] As used herein, the term "gripper robot" refers to an electromechanical device, such as a pick-and-place device, that moves containers in the X, Y, and / or Z directions.

[0066] As used herein, the term "conveyor" refers to a mechanical device for transporting items (e.g., containers) from one location to another along a defined path. Non-limiting examples of exemplary conveyors include robots, belts (e.g., moving belts, tracks, rails, shuttles / carriages that move on belts, etc.), magnetic devices, gear systems, cable systems, vacuum systems, autonomous wheeled vehicles, etc.

[0067] As used herein, the term "assay" refers to a procedure for detecting and / or quantifying an analyte in a sample. A sample containing or suspected to contain an analyte is contacted with one or more reagents and subjected to conditions that permit the production of a detectable signal that provides information about whether the analyte is present or the amount (e.g., mass or concentration) of the analyte in the sample.

[0068] As used herein, the term "analyzer" refers to an automated instrument capable of performing one or more steps of an assay, including determining the presence or absence of one or more analytes suspected to be present in a fluid sample.

[0069] As used herein, the term "analyte" refers to a molecule present or suspected to be present in a sample and that is the target of detection in an assay. Typical types of analytes include biopolymers such as nucleic acids, polypeptides, and prions.

[0070] As used herein, the term "molecular assay" refers to a procedure for specifically detecting and / or quantifying a target molecule, such as a target nucleic acid. A sample containing or suspected to contain a target molecule is contacted with one or more reagents, including at least one reagent specific for the target molecule, and subjected to conditions that allow the generation of a detectable signal that provides information about whether the target molecule is present. For example, when the molecular assay is a polymerase chain reaction (PCR), the reagents include primers specific for the target, and the generation of the detectable signal can be achieved, at least in part, by providing a labeled probe that hybridizes to the amplicon generated by the primers in the presence of the target. Alternatively, the reagents can include an intercalating dye for detecting the formation of double-stranded nucleic acid.

[0071] As used herein, the term "reagent" refers to any substance or combination of substances that participate in a molecular assay, other than the sample materials and the products of the assay. Exemplary reagents include nucleotides, enzymes, primers, probes, and salts.

[0072] FIG. 1 shows a schematic diagram of an automated system 100 for processing a fluid sample 102 (see FIG. 2) contained in a sample container 104. In this exemplary embodiment, the automated system 100 is configured to process a plurality of sample containers 104. The automated system 100 includes a plurality of stations 106, including an input station 106a, an output station 106b, a decapping station 106c, a sample preparation station 106d, one or more analyzer stations 106e (although two analyzer stations 106e are shown, any suitable number of analyzer stations 106e, including only one, may be employed in the automated system 100), a capping station 106g, and a storage station 106h. The automated system 100 may have any different number and types of stations 106 suitable for the intended use of the system 100, including having two or more of each type of station 106. The automated system 100 also includes an automated conveyor system 108 that connects each of the stations 106 and is configured to transport sample containers 104 between the stations 106. Exemplary conveyor systems include those described in U.S. Patent Nos. 9,766,258 and 9,776,811.

[0073] In the illustrated embodiment, the automated system 100 is configured to utilize a sample tube 104 (e.g., a test tube) as the sample vessel 104. An exemplary sample tube 104 is illustrated in FIGS. 2A and 2B. The sample tube 104 is a cylindrical tube having a closed bottom 110 and a cylindrical vessel wall 112 extending from the closed bottom 110 to a rim 114. The rim 114 defines an open top 116 of the sample tube 104. The sample tube 104 may have a threaded top 109 for connecting a cap 107 having a thread. The sample vessel 104 may be any suitable fluid sample vessel having a closed bottom and a rim defining an open top. For example, the sample vessel 104 may be any other suitable fluid vessel having a suitable shape and size. The sample tube 104 contains a fluid sample 102 having a top surface 103.

[0074] The automated system 100 utilizes a sample vessel holder 118 to hold and transport the sample vessels 104 around the system 100. FIG. 3 illustrates an exemplary sample vessel holder 118. The sample vessel holder 118 is in the form of a generally cylindrical puck 120 having a cylindrical base 122. Exemplary pucks are described in U.S. Provisional Application No. 62 / 891,728 and U.S. Patent Application No. 17 / 003,754. The base 122 of the puck 120 has a recess 125 in which the closed bottom 110 of the sample vessel 104 rests. The base 122 may also have one or more grooves 123 configured to receive and slide along a pair of opposing rails of the conveyor track 119. The puck 120 also has a number of fingers 124 extending upwardly from the base 122 configured to support the sample vessels 104 in a vertical orientation. The fingers 124 are arranged in a circular pattern to match the cylindrical shape of the sample vessels 104. The fingers 124 extend to a point below the rim 114 of the sample vessels 104 such that a top 126 of the sample vessels 104, including the rim 114, is above and exposed on the fingers 124. The tops 128 of the fingers 124 taper inwardly from the top to provide a guide for inserting the sample vessels 104 between the fingers 124 of the puck 120. The tapered tops 128 also facilitate flexing of the fingers 124 as the sample vessels 104 are inserted into the sample vessel holders 118. The input station 106a includes a sample vessel handling system 130a configured to retrieve sample vessels 104 from a sample vessel rack 111 supporting a plurality of sample vessels 104 and transfer them to respective sample vessel holders 118.

[0075] The automated system 100 includes a computerized controller 105 that controls the operation of each of the components involved in processing the fluid sample 102 contained in the sample container 104, including, for example, determining the level of the fluid sample 102 in the sample container 104, determining whether to quarantine the sample container 104, and / or performing one or more analytical procedures on the fluid sample 102. The controller 105 may include a main controller 105i and one or more subsystem controllers. For example, each station 106 may have a corresponding subsystem controller 105 for control of the respective station 106 and coordination with the main controller 105i and the other subsystem controllers 105. Thus, the input station 106a has an input station controller 105a, the output station 106b has an output station controller 105b, the decapping station 106c has a decapping station controller 105c, the sample preparation station 106d has a sample preparation station controller 105d, the first analyzer station 106e has a first analyzer station controller 105e1, the second analyzer station 106e has a second analyzer station controller 105e2, the capping station 106g has a capping station controller 105g, the storage station has a storage station controller 105h, and the conveyor system 108 has a conveyor controller 105j. The main controller 105i may be configured to handle high level routing logic for each sample 102. In other words, it may only indicate a path or workflow through the system 100, such as a path that includes station 106a, station 106c, at least one station 106e, station 106g, and station 106h.The conveyor controllers 105j may be configured to manage all of the details of how to physically route each fluid sample 102 (and the sample vessels 104 containing the respective fluid samples 102) to all of the stations 106 as directed by the main controller 105i. The individual controllers 105 within the stations 106 are at the lowest level and monitor and control all components of their respective stations, including sensors, motors, actuators, etc.

[0076] The stations 106 and the conveyor system 108 are configured to handle and transport the sample vessel holders 118, and the sample vessels 104 received in the sample vessel holders 118 (collectively referred to as loaded sample vessel holders 118), around the automated system 100. The conveyor system 108 transports the loaded sample vessel holders 118 between the stations 106 of the automated system 100. The automated conveyor system 108 is controlled by a conveyor controller 105j.

[0077] The conveyor system 108 may be any device for conveying or facilitating transport of the loaded sample vessel holders 118 between the stations 106 along a defined path. In the embodiment shown, the conveyor system 108 includes a conveyor track 119 and a conveyor controller 105j. The conveyor system 108 employs a conveyor track 119 that includes a main conveyor line 184, a number of branch lines 182 associated with each station 106, and one or more recirculation loops including return lines 184a, 184b. The conveyor system 108 may be formed of any other suitable conveyor, such as a robot, a belt (e.g., a moving belt, a shuttle / carriage moving on a track, rails, etc.), a magnetic device, a gear system, a cable system, a vacuum system, an automated wheeled vehicle, or other system for controllably transporting the loaded sample vessel holders 118 between the stations 106.

[0078] The main conveyor line 184 serves as the primary line for transporting the loaded sample vessel holders 118 between the different stations 106 of the automated system 100. In the embodiment shown, the main conveyor line 184 has a closed geometric shape (e.g., rectangular) that facilitates unidirectional movement of the loaded sample vessel holders 118. In alternative embodiments, the main conveyor line 184 may be linear and / or bidirectional.

[0079] Each of the branch lines 182 can be used as a buffer queue to receive and queue one or more loaded sample vessel holders 118 to be processed at a particular station 106. The return lines 184a, 184b form a closed inner loop that allows the loaded sample vessel holders 118 to circulate while they are waiting to access one or more of the stations 106. For example, if the branch line 182 of a station 106 has a full queue of loaded sample vessel holders 118, a loaded sample vessel holder 118 waiting to be processed at such station 106 can be circulated on the inner loop 184a or 184b until the queue of the branch line 182 has available space.

[0080] The conveyor controller 105j is configured to control the functions of the conveyor system 108, such as the transport of the loaded sample vessel holders 118 between the stations 106 of the automated system 100. The main controller 105i may communicate with the conveyor controllers 105j and instruct the conveyor controllers 105j on the path along which each sample vessel holder 118 is routed. Thus, the conveyor controllers 105j may control the stations 106 to which the loaded sample vessel holders 118 are transported and which stations 106 are bypassed by the loaded sample vessel holders 118. The conveyor controllers 105j may communicate directly with each of the individual station controllers 105 and manage the workflow path of each sample vessel holder 118.

[0081] Each station 106 is configured to receive, handle, and move sample vessel holders 118 and / or sample vessels 104 within the respective station 106. For example, at least some of the stations 106 may include a respective sample vessel handling system 130 for moving and / or manipulating the sample vessel holders 118 and / or sample vessels 104 within the respective station 106. The vessel handling system 130 may include a gripper robot, such as a pick-and-place device, or other type of transporter(s).

[0082] Generally speaking, the input station 106a serves to receive and load sample containers 104 containing fluid samples 102 onto the automated system 100. The input station 106a is configured to receive container racks 111, each of which supports a plurality of sample containers 104 containing fluid samples 102, and to load the sample containers 104 onto the conveyor system 108. The container racks 111 may be configured to hold any suitable number of sample containers 104, such as 50-500, 10-100, 10-50, etc. per rack 111. The input station 106a is described in more detail below.

[0083] Each analyzer station 106e is configured to process a fluid sample 102 contained in a sample container 104 by performing an analytical test on at least an aliquot of the sample. Such tests may include molecular tests (e.g., nucleic acid-based assays), sequencing assays, immunoassays, chemical analyses, and the like. Non-limiting examples of such analyzer stations 106e include automated analyzers such as, for example, the TIGRIS®, PANTHER®, and PANTHER FUSION® systems sold by Hologic, Inc. of Marlborough, Massachusetts. In the illustrated embodiment, each analyzer station 106e may be configured to receive a sample container 104 via automated loading (using a conveyor system 108) or manual loading via a sample bay (not shown). An example of automated loading of sample containers is described in U.S. Provisional Application No. 62 / 951,019.

[0084] The analyzer station 106e may be specialized or redundant to allow for a higher throughput of analytical tasks on the fluid sample 102 contained in the sample container 104. Typically, the analyzer station 106e extracts a liquid or liquefied fluid sample 102 from the sample container 104 and combines the fluid sample 102 with reagents in a reaction vessel, such as a cuvette, tube, vial, microtiter plate, etc., which may then be sealed, capped, or otherwise closed. After combining the sample with the reagents, the contents of the reaction vessel are exposed to a set of test conditions.

[0085] The sample preparation station 106d is configured to prepare the fluid sample 102 contained in the sample container 104 for testing at one or more of the analyzer stations 106e. For example, the sample preparation station 106d may be an aliquot module configured to transfer a portion of the fluid sample 102 from one type of sample container (e.g., a container having a different shape than the sample container 104) to another type of sample container (e.g., the sample container 104) for use by at least one of the analyzer stations 106 and perform tests on the transferred fluid sample 102. An exemplary aliquot module is described in U.S. Pat. No. 9,335,336. The sample preparation station 106 may also combine the fluid sample 102 (or a portion thereof) with a reagent from another container (e.g., a bulk reagent container) to prepare the fluid sample 102 for testing at at least one of the analyzer stations 106. Thus, the sample preparation station 106d may include one or more pipettors (not shown) for aspirating and dispensing the fluid sample 102 and / or reagents. A non-limiting example of a sample preparation station 106d is the TOMCAT® instrument sold by Hologic, Inc. of Marlborough, Massachusetts.

[0086] The storage station 106h is configured to automatically load, store, and unload sample containers 104, such as completed sample containers 104 (i.e., sample containers 104 containing fluid samples 102 for which a workflow has been completed) and / or sample containers 104 containing fluid samples 102 to be tested at a low frequency until there is a sufficient number of fluid samples 102 for testing. The storage station 106h is configured to handle and store a plurality of container racks 111 (or other container racks configured to hold a plurality of sample containers 104). Some racks 111 may be filled to capacity with sample containers 104, while other racks may have openings to receive additional sample containers 104 to be stored in the storage station 106h. The sample container handling system 130h of the storage station 106h is configured to transfer such sample containers 104 from the sample container holders 118 on the conveyor system 108 to the container racks 111 in the storage system 106h for storage. The sample vessel handling system 130h is also configured to transfer the stored sample vessels 104 from the vessel racks 111 in the storage system 106 to the sample vessel holders 118 to load the sample vessels 104 onto the conveyor system 108 for further processing. Exemplary storage stations, as well as other functions of the automated system for processing fluid samples, are disclosed in U.S. Provisional Application No. 63 / 014,624, filed April 23, 2020. The decapping station 106c is configured to remove the caps 107 from the sample vessels 104 (one example is shown in FIG. 2A) prior to processing the fluid sample 102 contained therein. Examples of suitable decapping stations are described in U.S. Patent Nos. 6,321,619 and 7,152,504. In the illustrated embodiment, the decapping station 106c is located along the conveyor 108 in front of the sample preparation station 106d and the analyzer station 106e.The decapping station 106c may be capable of removing different types of caps from capped sample vessels 104, and in some embodiments, the decapping station 106c may be capable of removing only a single type of cap 107 from a sample vessel 104. In the latter case, multiple decapping stations 106c may be provided along the conveyor system 108, each capable of removing a different type of cap 107 from a capped sample vessel 104. In addition, sample vessels 104 may have pierceable caps (not shown), and such sample vessels 104 may be transported directly to the sample preparation station 106d and / or analyzer station 106e for processing, bypassing or passing the decapping station 106c.

[0087] The capping station 106g is configured to place a cap 107 (e.g., a replacement cap or stopper) on the open-ended sample container 104, for example after extracting a fluid sample from the sample container 104 at the analyzer station 106e. Examples of suitable capping stations are described in U.S. Patent Nos. 6,321,619 and 7,152,504. In the illustrated embodiment, the capping station 106g is located along the conveyor system 108 between the analysis station 106e on one side and the storage station 106h and the output station 106b on the other side. The capping station 106g may be capable of placing different types of caps 107 on the open-ended sample container 104, and in some embodiments, the capping station 106g may be capable of coupling only a single type of cap 107 to the open-ended sample container 104. In the latter case, multiple capping stations 106g may be provided along the conveyor system 108, each capable of placing a different type of cap 107 on the open-ended sample vessels 104. Sample vessels 104 may have pierceable caps (not shown), and such sample vessels 104 may bypass or pass through the capping station 106g on their way to the storage station 106h or output station 106b.

[0088] The output station 106b is configured to receive the sample containers 104 and remove them from the conveyor system 108. For example, the sample containers 104 may be unloaded after their fluid samples 102 have been processed on the automated system 100, or because the sample containers 104 have been rejected, or for any other reason. The output station 106b is configured to retrieve the sample containers 104 from their respective sample container holders 118 on the conveyor system 108 and place the sample containers 104 in a container rack 111 (or other container holder) using the sample container handling system 130b of the output station 106b. Once the rack 111 is sufficiently filled with sample containers 104, the rack 111 may be removed from the output station 106, thereby removing the sample containers 104 from the automated system 100.

[0089] With reference to Figures 1, 4 and 5, the input station 106a will now be described in more detail. The input station 106a is configured to load sample vessels 104 containing fluid samples 102 into the automated system 100. In the embodiment shown, the sample vessels 104 containing fluid samples 102 are loaded into vessel racks 111 configured to hold a plurality of sample vessels 104. The vessel racks 111 may be configured to hold any suitable number of sample vessels 104, such as 50-500, 10-100, 10-50, etc. per rack 111. The vessel racks 111 are loaded into the input station 106a (e.g., manually or using a robotic system, not shown). The input station 106a has an input station controller 105a that controls the operation of the input station 106a. Once the sample vessels 104 are removed from the vessel racks 111 of the input station 106a, they are inserted into the sample vessel holders 118 of the sample vessel detector system 134. The sample container is characterized to determine sample container characteristics of the sample container 104, which are used to generate sample container data. For example, the input station 106a may determine the height, shape, diameter, bottom profile, head space (if not capped), and barcode ID of the sample container. The sample container data may be sent to the conveyor controller 105j, which may convey the sample container data to the main controller 105i for instructions. The main controller 105i may determine an open test order for the sample container 104, and the main controller 105i may send routing instructions for the sample container 104 to the conveyor controller 105j.

[0090] The input station controller 105a is operatively coupled to the components of the input station 106a to receive data signals of the components, process the data signals, and control operation of the input station 106a based on the data signals.

[0091] The input station sample vessel handling system 130a of the input station 106a includes a gripper robot 131 configured to remove sample vessels 104 from the vessel racks 111 and insert each sample vessel 104 into a respective sample vessel holder 118. The gripper robot 131 may be any suitable robot, such as a pick-and-place robot, for removing sample vessels 104 from the vessel racks 111 and inserting them into the sample vessel holders 118.

[0092] As shown in FIGS. 4-7, the input station 106a has a sample container detector system 134 configured to determine one or more physical characteristics of the sample container 104. The sample container detector system 134 includes one or more suitable detectors 136, preferably including at least one high-resolution detector with sub-millimeter resolution capability. The at least one high-resolution detector 136 can be a wide laser measurement sensor (e.g., Omron ZX-GT Smart Sensor), a 2D laser profiler, an imaging device (e.g., CCD sensor-based camera or CMOS sensor camera), or a single-point distance measurement sensor (e.g., Keyence CL-3000 series confocal displacement sensor). When the detector system 134 includes a high-resolution detector 136, the high-resolution detector can be in addition to or instead of an array of optical sensors 140. Unlike an array of optical sensors 140, the high-resolution detector 136 can be used to detect the shape of the sample container 104 or to determine the dimensions of the sample container 104.

[0093] The sample vessel detector system 134 may be positioned and configured to detect physical characteristics of the sample vessels 104 before the sample vessels 104 are inserted into the sample vessel holder 118 or after the sample vessels 104 are inserted into the sample vessel holder 118. For example, in the former case, the gripper robot 131 of the input station 106a may retrieve the sample vessels from a vessel rack and move the sample vessels 104 into a detection zone of the detector(s) 136, and the detector(s) 136 are activated to detect one or more physical characteristics of the sample vessels 104. In the latter case, the loaded sample vessel holder 118 is moved into the detection zone of the detector(s) 136, and the detector(s) 136 are activated to detect one or more physical characteristics of the sample vessels 104. 4, in one embodiment, the detector 136 includes an array of vertically aligned optical sensors 140, and the sample container 104 is disposed in a detection zone of the array of optical sensors 140 to detect the height of the sample container 104. The optical sensors 140a, 140b, and 140c may be reflective sensors with integrated emitter / receivers, reflective fiber optic sensors, and the like. By determining which of the optical sensors 140a, 140b, and 140c are blocked by the bottom portion of the sample container 104 when the sample container 104 is inserted into the detection zone of the array of optical sensors 140, the sample container detector system 134 can determine the height of the sample container 104 from among several different expected heights.

[0094] By knowing the height of the sample container 104, the corresponding volume capacity of the sample container 104 can also be known. As an example, to determine the volume capacity of the sample container 104 from three different sizes of sample containers 104, the sample container detector system 134 can distinguish between a large test tube (e.g., a 100 mL test tube), a medium test tube (e.g., a 75 mL test tube), and a small test tube (e.g., a 50 mL test tube). To do this, the sample container detector system 134 determines which of the optical sensors 140a, 140b, 140c are blocked by the bottom portion of the sample container 104 when the gripper robot 131 inserts the sample container 104 into the detection zone of the array of optical sensors 140. If only the first optical sensor 140a is blocked by the bottom portion of the sample container 104, the sample container detector system 134 determines that the sample container 104 is a small test tube. If the optical sensors 140a, 140b are obstructed by the bottom of the sample container 104 and the optical sensor 140c is not obstructed, the sample container detector system 134 determines that the sample container 104 is a medium test tube. If all three optical sensors 140a, 140b, 140c are obstructed by the bottom of the sample container 104, the sample container detector system 134 determines that the sample container 104 is a large test tube. The array of optical sensors 140 can be configured to determine the size (i.e., volume capacity) of any desired number "n" of different sized sample containers 104 by utilizing n-1 optical sensors 140, where each sized sample container has a different length.

[0095] When a wide laser measurement sensor is used as the detector(s) 136, the gripper robot 131 retrieves the sample container 104 from the sample container rack 111 located at the input station 106a, moves the sample container 104 laterally to a position above the sample container detector system 134, and then vertically lowers the sample container 104 into the detection zone of the wide laser measurement sensor. While in the detection zone, the wide laser measurement sensor may detect the shape of the sample container 104 and / or determine its dimensions. The process is similar to that of an imaging device, except that the sample container 104 is positioned within the field of view of an imaging device (e.g., a camera), and the imaging device captures an image of the sample container 104. The sample container detector system 134 may analyze the image and then determine the shape and / or dimensions of the sample container 104. The sample container detector system 134 can use information about the shape and / or dimensions of the sample container 104 to determine the type of sample container 104 (e.g., a 50 mL, 75 mL, or 100 mL tube), which is an indication of the volume capacity of the tube. The sample container detector system 134 can also be used to determine other characteristics of the sample container 104 filled with the fluid sample 102, as described herein.

[0096] In the case of a single point distance measurement sensor, the sensor is scanned across the sample vessel 104 to measure its diameter and / or other characteristics.

[0097] The sample vessel detector system 134 may include one or more cap detectors 135 (positioned to detect caps 107 associated with different sized sample vessels 104) to determine the presence or absence of a cap by determining whether the sample tube 104 has a cap 107 secured to its open top 116. The cap detectors 135 may be reflective fiber optic sensors or other suitable sensors. The sample vessel detector system 134 may also be configured to send an output signal to the controller 105 representative of the cap status of the sample tube 104.

[0098] The sample container detector system 134 may also include a reader 137 configured to read machine-readable indicia 139 (see FIG. 2B), such as a bar code, machine-readable text, or the like, on the sample container 104. Alternatively, the reader 137 may be located on (or otherwise associated with) the fluid level measurement system 144 of the input station 106a.

[0099] The fluid level measurement system 144 includes a distance sensor 146 configured to measure a distance from the sensor to a feature. The distance sensor 146 may be an ultrasonic sensor, such as a Series 9 ultrasonic sensor available from Baumer Electric, Hummelstraße 17, 8501 Frauenfeld, Switzerland, a laser sensor, or other suitable sensor. The distance sensor 146 may have a beam columnator 147, directed vertically downward to measure a vertical distance from the distance sensor 146 to a surface, such as the rim 114 of a sample container 104 (known or determined to not have a cap secured to the open end 116 of the sample container 104), the top surface 103 of the fluid sample 102, or other desired surface. The distance sensor 146 is highly accurate, preferably having a resolution of 0.3 mm or less, more preferably having a resolution of 0.1 mm or less. This distance sensor 146 is also fast, preferably having a response time of 10 milliseconds or less, more preferably having a response time of 7 milliseconds or less, and even more preferably having a response time of 5 milliseconds or less. Thus, the distance sensor 146 can take multiple measurements over a short period of time, including periodically measuring the distance to the measurement surface (i.e., the rim 114 of the sample container 104 and the surface 103 of the fluid sample 102) as the distance sensor 146 is controllably moved relative to the sample container 104, or as the sample container 104 is controllably moved relative to the distance sensor 146, to obtain a series of individual measurements of the distance between the distance sensor 146 and the measurement surface. For example, the series of measurements can be obtained by the distance sensor 146 at a rate of 10-20 measurements per second, 10-100 measurements per second, at least 10 measurements per second, or at least 50 measurements per second. The fast response time of the distance sensor 146 also allows the distance sensor 146 to be moved at a relatively fast speed of 2.5 mm / sec to 10 mm / sec relative to the sample container 104, such that the distance sensor 146 can quickly obtain a series of measurements of the distance to the rim 114 and the fluid surface 103, such as in less than 10 seconds, less than 7.5 seconds, or less than 5 seconds.

[0100] Measurements may also be taken by stopping the distance sensor 146 at a particular location as the distance sensor 146 is moved laterally over the sample container 104 or as the sample container 104 is moved laterally relative to the distance sensor 146. For each particular location, several distance measurements are taken and averaged. This process may be performed by scanning all or any portion of the sample container 104 and fluid surface 103 sufficient to calculate the headspace 117 (e.g., taking a half profile).

[0101] The fluid level measurement system 144 also includes a sensor interface 148 operably coupled to the distance sensor 146. The sensor interface 148 may be a digital or analog interface for communicating a representation of the surface distance measurement to the input station controller 105a. The distance sensor 146 and / or the sensor interface 148 provide an output signal representative of the distance measurement received by the input station controller 105a and / or the main controller 105i. The output signal may be a digital or analog representation.

[0102] In the embodiment of FIGS. 1, 4 and 5, the input station controller 105a is configured to controllably move the distance sensor 146 while the sample container 104 (and / or the corresponding sample container holder 118) is stationary. In this embodiment, the distance sensor 146 is supported by a horizontal linear translator 150. The horizontal linear translator 150 may be a linear stage that controllably moves the distance sensor 146 relative to the stationary sample container 104 and provides a horizontal stage position signal representative of the horizontal position of the stage 150. Thus, the horizontal position of the distance sensor 146 may be determined from the horizontal stage position signal. The horizontal linear translator 150 is operably coupled to the input station controller 105a, which controllably actuates the horizontal linear translator 150 and receives the horizontal stage position signal. The input station controller 105a is configured to process the horizontal stage position signal to determine the horizontal position of the distance sensor 146.

[0103] To accurately position and orient the sample container 104 to perform a measurement scan of the sample container 104 and the fluid sample 102, the fluid level measurement system 144 may also include a container clamp 152 configured to grip the sample container 104 and center the sample container 104 in the measurement location. The container clamp 152 positions the center of the sample container 104 on the scanning axis 154 of the distance sensor 146 and the horizontal linear translator 150. This ensures that the distance sensor 146 consistently measures the sample container 104 along the center of the sample container 104. For example, in the case of sample tubes 104, the distance sensor 146 scans along the diameter of each sample tube 104, as shown in FIGS. 2A-2B. The container clamp 152 is configured to vertically orient the sample container 104 such that the central axis 157 of the sample container 104 is approximately vertical during the measurement scan. Nonetheless, if the vessel clamp 152 improperly grips (or does not grip) the sample vessel 104, it is possible that the sample vessel 104 may be tilted at an angle to the vertical when it is received within the sample vessel holder 118. Because of this possibility, as described herein, a measurement scan may be performed using the distance sensor 146 to (i) determine the level of the fluid sample 102 relative to the rim 114 and / or (ii) determine the angle of tilt of the sample vessel 104.

[0104] The input station controller 105a is configured to operate the horizontal linear translator 150 to position and move the distance sensor 146 along a scan axis 154 over one or more surfaces of the sample container 104, including the rim 114, and the top surface 103 of the fluid sample 102. As the distance sensor 146 is moved, the controller receives horizontal stage position signals representative of the position of the distance sensor 146. Simultaneously, the input station controller 105a operates the distance sensor 146 to obtain a series of individual measurements between the distance sensor 146 and one or more surfaces of the sample container 104 and the top surface 103 of the fluid sample 102. The distance sensor 146 and / or the sensor interface 148 output output signals representative of the series of individual measurements. The input station controller 105a receives and processes the horizontal stage position signals and the output signals to determine the level of the fluid sample 102 relative to the rim 114 of the sample container 104, as further described herein.

[0105] The distance sensor 146 may also be supported by a vertical linear translator stage 156, which is operated by a stage motor 155 to move the distance sensor 146 vertically relative to the sample container 104. The vertical linear translator 156 adjusts the position of the distance sensor 146 so that the distance sensor 146 is positioned within the distance measurement range of the distance sensor 146. For example, the distance sensor 146 may have limitations on the distance from a measurement surface at which the distance sensor can measure or be more accurate. As an example, a Series 9 ultrasonic sensor available from Baumer Electric has a measurement range from about 3 mm to about 150 mm. The vertical linear translator 156 may also be a linear stage that controllably moves the distance sensor 146 vertically relative to the stationary sample container 104 and provides a vertical stage position signal representative of the vertical position of the stage. Thus, the vertical position of the distance sensor 146 may be determined from the vertical stage position signal. The vertical linear translator 156 is operatively coupled to a controller 105 a that controllably operates the vertical linear translator 156 .

[0106] Thus, the vertical linear translator 156 allows the automated system 100 to accommodate different sized sample containers 104 by adjusting the vertical position of the distance sensor 146 to a predetermined distance from the rim 114 of the sample container 104. As described herein, the sample container detector system 134 can determine the type, size and / or shape of the sample container 104. Once the system 100 determines the characteristic of the sample container 104 to be measured, the vertical linear translator 156 can be operated to adjust the vertical position of the distance sensor 146 to a predetermined position that vertically positions the distance sensor 146 within the range of measurement by the distance sensor of the rim 114 of the sample container 104 as well as the expected surface 103 of the fluid sample 102. In the above example with sample tubes 104 having heights of 100 mm and 75 mm, for example, the vertical linear translator is adjusted to position the distance sensor 146 lower for the 75 mm sample tubes than for the 100 mm sample tubes because the bottoms 110 of the sample containers 104 are seated at the same position (i.e., height relative to the conveyor track 119) within the recesses 124 of their respective sample container holders 118.

[0107] Alternatively, the distance sensor 146 may be mounted in a fixed horizontal position relative to the sample container 104, and the sample container 104 is moved relative to the distance sensor 146 to obtain a series of distance measurements. For example, the sample container 104 may be positioned on a conveyor system 108, which moves a sample conveyor relative to the fixed distance sensor 146 while the distance sensor 146 obtains a series of distance measurements.

[0108] The sample container detector system 134 is in communication with the input station controller 105 a and sends an output signal representative of a physical characteristic of the sample container 104 to the input station controller 105 a.

[0109] The input station controller 105a is configured to receive and process output signals representing distance measurements from the fluid level measurement system 144 to determine the level of the fluid 102 in the sample container 104 relative to the rim 114. In the embodiment shown, the input station controller 105a receives and processes the output signals of the fluid level measurement system 144, although another controller 105, such as the main controller 105i, may be configured to do so. The input station controller 105a has a fluid level software application 158 for analyzing the output signals of the distance measurements to determine the level of the fluid 102 relative to the rim 114. Each of the distance measurements referred to herein is measured by a distance sensor 146, which provides an output signal representing the distance between the measured feature and the distance sensor 146.

[0110] In one embodiment, the fluid level software application 158 is configured to determine the fluid level relative to the rim 114 by the difference between a distance measurement to the top surface 103 of the fluid 102 (referred to as the “fluid measurement”) and a distance measurement to the rim 114 of the sample container 104 (referred to as the “rim measurement”).

[0111] 8, in another embodiment, the fluid level software application 158 is configured to determine the fluid level relative to the rim 114 using an average of multiple fluid measurements and an average of multiple rim measurements. As described herein, the automated system 100 is configured to obtain a series of individual surface distance measurements, including multiple fluid measurements (at different locations on the top surface 103) and multiple rim measurements (at different locations on the rim 114), by controllably moving at least one of the distance sensor 146 or the sample vessel 104 relative to the other while the distance sensor 146 periodically measures a distance between the sensor 146 and (i) one or more surfaces of the sample vessel 104, and (ii) the surface 103 of the fluid 102 contained within the sample vessel. The controller 105a receives the series of fluid measurements and rim measurements. Also, while the distance sensor 146 or the sample container 104 is being moved relative to the other (or while both the distance sensor 146 and the sample container 104 are moving relative to each other) and while the series of individual measurements are being taken, the controller 105a receives the horizontal stage position signal and the output signal of the distance sensor 146. The controller 105a associates each distance measurement with a sensor position such that the controller 105 can generate a distance measurement profile 160 of the measurements. FIG. 8 shows an exemplary distance measurement profile 160 that plots distance measurements versus measurement position. As shown in FIG. 8, the distance sensor 146 begins scanning at a position to the left of the open top 116 of the sample container 104 and takes a number of measurements 162 shown on the left side of the profile 160. As the distance sensor 146 moves to the right relative to the sample container 104 (the direction in which the distance sensor 146 moves is not important), the distance sensor 146 takes a number of first rim measurements 164 for a first side of the rim 114. Moving further to the right, the distance sensor 146 takes a number of fluid measurements 166. Continuing to the right, the distance sensor 146 takes a number of second rim measurements 168 about a second side of the rim 114 opposite the first side of the rim 114.

[0112] The fluid level software application 158 is configured to determine the relative fluid level 117 (also referred to as the relative fluid level 117 or "headspace 117") by determining an average of the first and second rim measurements 164, 168 and an average of the fluid measurements 166. The fluid level software application 158 determines the relative fluid level 117 as the average of the fluid measurements minus the average of the rim measurements.

[0113] Note that in FIG. 8, the first rim measurement 164 actually starts on the left side of the first side of the rim 114 and ends on the right side of the first side of the rim 114. Similarly, the second rim measurement 168 actually starts on the left side of the second side of the rim 114 and ends on the right side of the second side of the rim 114. The fluid measurement 166 starts on the right side of the far left edge of the fluid surface 103 and ends on the left side of the far right edge of the fluid surface 103. The reason that some of the data points of the measurements 164, 168, 166 do not exactly coincide with the horizontal axis location of the respective surfaces 114 and 103 along the horizontal axis is because ultrasonic sensors emit sound waves that propagate in a cone of increasing diameter from the sensor emitter. Any surface that falls into the cone of sound waves will be interpreted by the sensor as an object and detected for measurement. 8, as the sensor approaches the first and second sides of the rim 114 from the left, the rim will be detected by the sensor before the horizontal axis position of the sensor actually coincides with the rim 114 on the first or second side, producing a first rim measurement 164 and a second rim measurement 168, respectively. As the sensor moves to the right past the first and second sides of the rim 114, the rim will be detected by the sensor after the horizontal axis position of the sensor actually coincides with the rim 114 on the first or second side, producing a first rim measurement 164 and a second rim measurement 168, respectively.

[0114] The fluid level software application 158 may also be configured to identify whether a measurement in a series of individual measurements is a rim measurement or a fluid measurement. FIG. 9 illustrates a derivative filtering method programmed into the fluid level software application 158. In this method, the fluid level software application 158 determines the rate of change 170 of the measurements in the series of individual measurements (the derivative of the profile 160). The application 158 then identifies a peak 172 in the rate of change 170. The peak 172 identifies an edge of the rim 114 such that a measurement between a first peak 172a and a second peak 172b corresponds to a first rim measurement 164 for a first side of the rim 114, a measurement between a second peak 172b and a third peak 172c corresponds to a fluid measurement 166, and a measurement between a third peak 172c and a fourth peak 172d corresponds to a second rim measurement to a second side of the rim 114. As discussed above, the relative fluid level 117 is the difference between the average of the fluid measurements 166 and the average of the rim measurements 164,168.

[0115] The relative fluid level 117 may also be determined using faster scanning and less measurement data by measuring only one of the first side of the rim 114 or the second side of the rim 114. In such a case, the relative fluid level 117 is the average of the fluid measurements 166 minus the average of the first rim measurements 164, or the average of the fluid measurements 166 minus the average of the second rim measurements 168.

[0116] FIG. 10 illustrates yet another algorithm of the fluid level software application 158 for determining whether a measurement in a series of individual measurements is a rim measurement or a fluid measurement. This algorithm is similar to the algorithm shown in FIG. 9 in that the fluid level software application 158 determines the rate of change 170 of the measurement (the derivative of the profile 160) in the series of individual measurements. The algorithm utilizes predefined positive derivative thresholds 174 and negative derivative thresholds 176 and determines which measurements 162 are between the positive derivative threshold 174 and the negative derivative threshold 176. The algorithm then determines which of these measurements between the thresholds 174 and 176 correspond to the first rim measurement 164, the fluid measurement 166, and the second rim measurement 168 in the same manner as the algorithm of FIG. 9. In other words, the measurements between the first peak 172a and the second peak 172b are between the thresholds 174 and 176 and correspond to the first rim measurement 164 for the first side of the rim 114. The measurement between the second peak 172b and the third peak 172c is between the thresholds 174 and 176 and corresponds to the fluid measurement 166. And the measurement between the third peak 172c and the fourth peak 172d is between the thresholds 174 and 176 and corresponds to the second rim measurement to the second side of the rim 114. As discussed above, the relative fluid level 117 is the difference between the average of the fluid measurements 166 and the average of the rim measurements 164, 168.

[0117] The fluid level software application 158 may also be configured to determine the angle of inclination of the central axis 157 of the sample vessel 104 relative to the vertical axis of the sample vessel holder 118 based on the series of measurements. In one method, the software application 158 determines the difference between the height of a first side of the rim 114 and the height of a second side of the rim 114. In other words, the software application 158 determines the difference between (a) the distance between the distance sensor 146 and the first side of the rim 114 and (b) the distance between the distance sensor 146 and the second side of the rim 114. The software application 158 may determine this difference based on an average of the first rim measurements 164 and an average of the second rim measurements 168 or other suitable methodology. The software application 158 may also determine which measurements are the first rim measurements 164 and which measurements are the second rim measurements 168 using the methods described above. The tilt angle of the central axis 157 of the sample container 104 can be calculated based on the difference in height between the first side of the rim 114 and the second side of the rim 114, and the distance between the two heights (e.g., the diameter of the rim 114). Thus, as an example, the tilt angle of the central axis 157 from vertical can be calculated as arc cos[(difference in height between the first side of the rim and the second side of the rim) / (diameter of the rim)].

[0118] The input station controller 105a is further configured to determine whether the relative fluid level 117 of the sample vessel 104 is outside a predetermined range or above a predetermined set level. The term "above" in this context means that the level of fluid is higher than a predetermined, programmed, or set level. Furthermore, the input station controller 105a, the input station 106a, and / or the automated system 100 may be configured to quarantine the sample vessel 104 if the relative fluid level 117 of the sample vessel 104 is determined to be outside or above a predetermined level. For example, as shown in FIG. 4, the input station 106a has a quarantine area 190 in which the gripper robot 131 of the input station 106a places sample vessels 104 that need to be quarantined. For example, a predetermined maximum level of the relative fluid level 117 may be set (i.e., a minimum head space) to reduce the risk of spilling or splashing of the fluid sample 102 from the sample vessel 104, which may contaminate other sample vessels 104 or components of the system 100. If the input station controller 105a determines that the relative fluid level 117 of the sample vessel 104 is above a maximum level, the gripper robot 131 retrieves the sample vessel 104 from the fluid measurement system 144 and places the sample vessel 104 in a dedicated sample vessel rack 111 located in an isolation area 190 of the input station 106a. Similarly, a predetermined minimum level of the relative fluid level 117 may be set to ensure, for example, that there is enough fluid sample 102 in the sample vessel 104 for processing on an automated system (e.g., to perform one or more tests at one or more of the analyzer stations 106e). If the input station controller 105a determines that the relative fluid level 117 of the sample vessel 104 falls below the minimum level, the sample vessel 104 can be moved to the dedicated sample vessel rack 111 located in the isolation area 190 in the same manner as a sample vessel 104 having a relative fluid level 117 above a maximum level. A dedicated sample vessel rack 111 may be positioned for manual removal from the quarantine area of ​​input station 106a.

[0119] The input station controller 106a may also be configured to release the sample vessel 104 for processing on the automated system 100 if the relative fluid level 117 is determined to be within a predetermined range or below a predetermined level. For example, the input station controller 105a may be configured to release the sample vessel if the relative fluid level 117 is determined to be below a predetermined maximum level for the relative fluid level 117.

[0120] The input station controller 105a may also be configured to quarantine the sample vessel if the tilt angle is determined to be outside a predetermined range of tilt angles or above a predetermined tilt angle. For example, the input station controller 105a may be programmed to quarantine the sample vessel if the tilt angle is determined to be greater than 2°, greater than 5°, or greater than 10°.

[0121] The input station controller 105a may also be configured to release the sample vessel if the tilt angle is determined to be within a predetermined range of tilt angles or to exceed a predetermined tilt angle. For example, the input station controller 105a may be programmed to release the sample vessel 104 if the tilt angle is determined to be less than 2°, less than 5°, or less than 10°.

[0122] Embodiment

[0123] One or more of the following features and advantages may be included in or attained by the embodiments described herein.

[0124] Embodiment 1. An automated system for detecting a level of a fluid contained in a sample vessel, the sample vessel having a closed bottom and a vessel wall extending from the closed bottom to a rim defining an open top of the sample vessel, the system including a sensor for periodically measuring distances between the sensor and (i) one or more surfaces of the sample vessel and (ii) a surface of a fluid contained within the sample vessel, the sensor including measuring a distance between the sensor and the rim of the sample vessel, wherein at least one of the sensor and the sample vessel is controllably movable relative to the other such that the sensor is capable of obtaining a series of discrete surface distance measurements of distances between the sensor and (i) one or more surfaces of the sample vessel and (ii) a surface of a fluid contained within the sample vessel; and a controller operably coupled to the sensor and configured to receive and process output signals from the sensor including digital representations of the series of discrete surface distance measurements, thereby determining a level of a fluid contained within the sample vessel relative to the rim of the sample vessel.

[0125] Embodiment 2. The system of embodiment 1, wherein the output signal further includes a sensor position relative to the sample container, each sensor position being associated with one of the individual surface distance measurements.

[0126] Embodiment 3. The system of embodiment 1 or 2, wherein the sensor is supported by a linear translator that moves the sensor relative to the sample vessel.

[0127] Embodiment 4. The system of embodiment 1 or 2, wherein the sensor is fixedly attached relative to the sample vessel.

[0128] Embodiment 5. A system as described in embodiment 1, wherein one or both of the sensor and the sample vessel are controllably movable to perform a linear scan across the rim and surface of the fluid of the sample vessel, thereby enabling the sensor to obtain measurements at different locations on the rim and top surface of the fluid during the scan.

[0129] Embodiment 6. The system of embodiment 5, wherein linear scanning utilizes continuous relative motion while the sensors acquire measurements.

[0130] Embodiment 7. The system of embodiment 5, wherein the linear scanning utilizes intermittent relative motion, and the motion is stopped intermittently for the sensor to take measurements.

[0131] Embodiment 8. A system described in any one of embodiments 1 to 7, wherein the sensor is disposed at an input station for loading sample containers onto the system, the input station comprising a container rack configured to hold a plurality of sample containers, and a gripper robot configured to remove sample containers from the rack.

[0132] Embodiment 9. The system of embodiment 8, wherein the input station further comprises a detector system configured to determine one or more physical characteristics of the sample container.

[0133] Embodiment 10. The system of embodiment 9, wherein the one or more physical characteristics of the sample vessel include at least one of height, diameter, shape, and the presence or absence of a cap secured to the upper end of the sample vessel.

[0134] Embodiment 11. A system as described in embodiment 9 or 10, wherein the detector system comprises at least one of a laser and an imaging device.

[0135] Embodiment 12. A system as described in any one of embodiments 9 to 11, wherein the controller is further programmed to determine a volume of fluid contained within the sample vessel based on at least one of one or more physical characteristics of the sample vessel and the level of fluid contained within the sample vessel.

[0136] Embodiment 13. A system described in any one of embodiments 1 to 12, wherein the sensor is an ultrasonic sensor.

[0137] Embodiment 14. A system as described in any one of embodiments 1 to 13, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and one or more surfaces of the sample container, including a plurality of distance measurements between the sensor and the rim (rim measurements), and (ii) a plurality of distance measurements between the sensor and a surface of the fluid (fluid measurements).

[0138] Embodiment 15. The system of embodiment 14, wherein the controller is configured to determine a level of fluid contained within the sample vessel relative to the rim based on an average of the rim measurements and an average of the fluid measurements.

[0139] Embodiment 16. A system described in any one of embodiments 1 to 15, wherein the controller is configured to determine which measurements in the series of individual surface distance measurements correspond to each of a first portion of the rim, a top surface of the fluid, and a second portion of the rim opposite the first portion of the rim.

[0140] Embodiment 17. The system of embodiment 16, wherein the controller is configured to determine which measurements in the series of individual surface distance measurements correspond to each of a first portion of the rim, a top surface of the fluid, and a second portion of the rim opposite the first portion of the rim using an edge finding technique, the edge finding technique including: (a) analyzing the rate of change of distance in the series of individual surface distance measurements and identifying an edge of the rim as a measurement corresponding to a peak in the rate of change and identifying measurements between the peaks as rim measurements or fluid measurements; or (b) identifying measurements for which the rate of change of distance in the series of individual surface distance measurements is within a threshold window.

[0141] Embodiment 18. A system described in any one of embodiments 1 to 17, further comprising a sample vessel holder for supporting a sample vessel such that an upper portion of the vessel wall ending in a rim is positioned above the sample vessel holder.

[0142] Embodiment 19. The system of embodiment 18, wherein the sample vessel holder comprises a recess configured to seat the closed bottom of the sample vessel.

[0143] Embodiment 20. A system as described in embodiment 19, wherein the sample vessel holder is a generally cylindrical puck and the recess is formed in the base of the puck.

[0144] Embodiment 21. A system as described in embodiment 20, wherein the vessel holder further comprises a plurality of fingers extending upwardly from the puck, the fingers being configured to support the sample vessel in a substantially vertical orientation.

[0145] Embodiment 22. A system described in any one of embodiments 18 to 21, further comprising an automated conveyor configured to transport sample vessel holders between each station of the system.

[0146] Embodiment 23. The system of embodiment 22, wherein at least one of the stations is an analyzer configured to perform an analytical procedure using a fluid.

[0147] Embodiment 24. The system of embodiment 23, wherein the analytical procedure is a molecular assay.

[0148] Embodiment 25. A system described in any one of embodiments 22 to 24, wherein the sensor is configured to obtain a series of individual surface distance measurements while the sample container holder is supported by the conveyor.

[0149] Embodiment 26. A system described in any one of embodiments 18 to 25, wherein the controller is further programmed to determine an orientation of the sample vessel relative to the sample vessel holder from the output signal.

[0150] Embodiment 27. The system of embodiment 26, wherein the orientation includes a tilt angle of the sample vessel relative to a vertical axis of the sample vessel holder.

[0151] Embodiment 28. The system of embodiment 27, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and a first portion of the rim (first rim measurements), and (ii) a plurality of distance measurements between the sensor and a second portion of the rim (second rim measurements), and the controller is further programmed to determine an inclination angle of the sample container relative to a vertical axis of the sample container holder from a difference between the first rim measurements and the second rim measurements.

[0152] Embodiment 29. A system as described in embodiment 27 or 28, wherein the system is configured to transport the sample vessel from the sample vessel holder to the isolation area when the tilt angle is greater than a predetermined tilt angle.

[0153] Embodiment 30. A system as described in embodiment 14 or 15, wherein the controller is configured to identify individual surface distance measurements as either rim measurements or fluid surface measurements by analyzing the rate of change of the measurements in a series of individual surface distance measurements to find a measurement that corresponds to an edge of the rim.

[0154] Embodiment 31. The system of embodiment 30, wherein if the rate of change exceeds a threshold, the rate of change indicates a rim edge.

[0155] Embodiment 32. A system as described in any one of embodiments 1 to 31, wherein the system is configured to (i) transport the sample container to an isolation area if the level of fluid contained in the sample container relative to the rim is determined to be outside a predetermined range or above a predetermined level, and (ii) release the sample container for subsequent processing on the system, including performing an assay using the fluid, if the level of fluid contained in the sample container relative to the rim is determined to be within a predetermined range or below a predetermined level.

[0156] Embodiment 33. A system according to any one of embodiments 1 to 32, wherein the sample container is a test tube.

[0157] Embodiment 34. A method for detecting a level of a fluid contained in a sample vessel, the sample vessel having a closed bottom and a vessel wall extending from the closed bottom to a rim defining an open top of the sample vessel, the method comprising: (a) measuring a distance between the sensor and the rim of the sample vessel while moving at least one of the sensor and the sample vessel holder relative to the other, periodically measuring the distance between the sensor and (i) one or more surfaces of the sample vessel supported by the sample vessel holder, and (ii) a surface of a fluid contained in the sample vessel, respectively, to obtain a series of individual surface distance measurements of the distances between (i) the sensor and one or more surfaces of the sample vessel and (ii) the sensor and the surface of the fluid contained in the sample vessel; and (b) determining the level of the fluid contained in the sample vessel relative to the rim of the sample vessel by processing an output signal from the sensor comprising a digital representation of the series of individual surface distance measurements.

[0158] Embodiment 35. The method of embodiment 34, wherein the sensor is attached to a linear translator that moves the sensor relative to the sample container to obtain a series of discrete surface distance measurements.

[0159] Embodiment 36. The method of embodiment 34, wherein the sensor is fixedly attached relative to the sample vessel, and the sample vessel moves relative to the sensor during step (a).

[0160] Embodiment 37. A method according to any one of embodiments 34 to 36, further comprising, prior to step (c) inserting the sample vessel into a sample vessel holder, the sample vessel holder being configured to support the sample vessel in a substantially upright orientation, whereby an upper portion of the vessel wall ending in the rim rests on the sample vessel holder.

[0161] Embodiment 38. The method of embodiment 37, wherein step (c) includes seating the closed bottom of the sample vessel in a recess of the sample vessel holder.

[0162] Embodiment 39. The method of embodiment 37, wherein the sample vessel holder is a generally cylindrical puck and the recess is formed in the base of the puck.

[0163] Embodiment 40. The method of embodiment 39, wherein the vessel holder further includes a plurality of fingers extending upwardly from the puck, the fingers being configured to support the sample vessels in a substantially vertical orientation.

[0164] Embodiment 41. A method according to any one of embodiments 37 to 40, wherein the sample container holder is positioned on an automated conveyor during step (a), and the conveyor is configured to transport the sample container holder between respective stations of the sample processing system.

[0165] Embodiment 42. The method of embodiment 41, wherein at least one of the stations is an analyzer.

[0166] Embodiment 43. The method of embodiment 42, wherein the analyzer is configured to perform a fluid-based molecular assay.

[0167] Embodiment 44. The method of any one of embodiments 37 to 43, further comprising, prior to step (c), loading the sample vessel into an input station of the sample processing system in a vessel rack configured to hold a plurality of sample vessels.

[0168] Embodiment 45. The method of embodiment 44, further comprising removing the sample container from the sample container rack using a gripper robot and performing step (c) using the gripper robot.

[0169] Embodiment 46. The method of embodiment 44 or 45, wherein the sensor is disposed in the input station.

[0170] Embodiment 47. The method of any one of embodiments 34 to 46, wherein the sensor is an ultrasonic sensor.

[0171] Embodiment 48. The method of any one of embodiments 34 to 47, further comprising determining one or more physical characteristics of the sample container prior to step (a).

[0172] Embodiment 49. The method of embodiment 48, wherein the one or more physical characteristics of the sample vessel include at least one of height, diameter, shape, and the presence or absence of a cap secured to the upper end of the sample vessel.

[0173] Embodiment 50. The method of embodiment 48 or 49, wherein the one or more physical properties are determined using at least one of a laser and an imaging device.

[0174] Embodiment 51. The method of embodiment 49 or 50, wherein processing the output signal further includes determining a volume of fluid contained within the sample vessel based on one or more physical characteristics of the sample vessel and the level of fluid contained within the sample vessel.

[0175] Embodiment 52. The method of any one of embodiments 34 to 51, further comprising reading a machine-readable indicia on the sample container while the sample container is in position to obtain the series of individual surface distance measurements.

[0176] Embodiment 53. The method of any one of embodiments 34 to 52, further comprising transporting the sample container to an isolation area if it is determined that the level of fluid contained within the sample container is outside a predetermined range or above a predetermined level.

[0177] Embodiment 54. The method of any one of embodiments 34 to 52, further comprising releasing the sample vessel for processing if the level of fluid contained within the sample vessel is determined to be within a predetermined range or below a predetermined level.

[0178] Embodiment 55. The method of any one of embodiments 34 to 54, further comprising, during step (a), adjusting the vertical position of the sensor using a vertical translator supporting the sensor to position the sensor within a predetermined measurement range from the rim of the sample container.

[0179] Embodiment 56. A method according to any one of embodiments 34 to 55, wherein the series of individual surface distance measurements is obtained by the sensor at a measurement rate of 10 to 20 measurements per second.

[0180] Embodiment 57. The method of any one of embodiments 34 to 56, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and one or more surfaces of the sample container, including a plurality of distance measurements between the sensor and the rim (rim measurements), and (ii) a plurality of distance measurements between the sensor and a surface of the fluid (fluid measurements).

[0181] Embodiment 58. The method of embodiment 57, wherein step (b) includes determining a level of fluid contained within the sample container relative to the rim based on an average of the rim measurements and an average of the fluid measurements.

[0182] Embodiment 59. The method of any one of embodiments 34 to 58, further comprising processing the output signal to determine which measurements in the series of individual surface distance measurements correspond to each of the first portion of the rim, the top surface of the fluid, and the second portion of the rim opposite the first portion of the rim by (a) analyzing the rate of change of distance in the series of individual surface distance measurements and identifying the edge of the rim as the measurement corresponding to a peak in the rate of change and identifying the measurements between the peaks as rim measurements or fluid measurements, or (b) identifying measurements for which the rate of change of distance in the series of individual surface distance measurements is within a threshold window.

[0183] Embodiment 60. The method of any one of embodiments 37 to 46, further comprising determining an orientation of the sample vessel relative to the sample vessel holder from the output signal.

[0184] Embodiment 61. The method of embodiment 60, wherein the orientation includes a tilt angle of the sample vessel relative to a vertical axis of the sample vessel holder.

[0185] Embodiment 62. The method of embodiment 61, wherein the series of individual surface distance measurements includes (i) a plurality of distance measurements between the sensor and a first portion of the rim (first rim measurements), and (ii) a plurality of distance measurements between the sensor and a second portion of the rim (second rim measurements), and the method further includes determining an inclination angle of the sample container relative to a vertical axis of the sample container holder from a difference between the first rim measurements and the second rim measurements.

[0186] Embodiment 63. The method of embodiment 61 or 62, further comprising transporting the sample vessel from the sample vessel holder to an isolation area if the tilt angle is greater than a predetermined tilt angle.

[0187] Embodiment 64. The method of any one of embodiments 34 to 63, further comprising transporting the sample container to an analyzer after step (b), removing an aliquot of fluid from the sample container and transferring the aliquot to a reaction vessel contained within the analyzer, and performing an analytical procedure using the aliquot of fluid.

[0188] Embodiment 65. The method of embodiment 64, wherein the analytical procedure is a molecular assay.

[0189] Embodiment 66 The method of any one of embodiments 34 to 65, wherein the sample vessel is a sample tube.

[0190] Although specific embodiments have been shown and described, the above description is not intended to limit the scope of these embodiments. Although embodiments and variations of many aspects of the present disclosure have been disclosed and described herein, such disclosure is provided for the purpose of description and example only. Thus, various changes and modifications may be made without departing from the scope of the claims. For example, not all of the components described in the embodiments are required, and the disclosure may include any suitable combination of the components described, and the overall shape and relative size of the disclosed components may be changed. Thus, the embodiments are intended to illustrate alternatives, modifications, and equivalents that may fall within the scope of the claims. The present disclosure is therefore not to be limited, except by the following claims and their equivalents.

Claims

[Claim 1] The invention described in this specification.

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