A computer-implemented method for operating an automated sample workcell
Abstract
Method implemented by computer to operate an automated sample work cell (100), the work cell comprising a sample conveyor (109) that connects at least one centrifuge (108) to a sample inlet station (107), the method comprising: - reception of (200) samples (104, 105, 106) by the sample input station (107), - assignment (201) to each sample of a centrifugation parameter (101, 102, 103); - transport (202) of each sample from the sample inlet station (107) to at least one centrifuge (108); - comparison (203) of the centrifugation parameters (101, 102, 103) of the samples loaded or to be loaded in the centrifuge and determine the centrifugation parameter of higher centrifugation intensity, the method being characterized by: - the loading (204) of the samples in the centrifuge (108), the loaded samples comprising samples with different centrifugation parameters, - the centrifugation (205) of the loaded samples according to a centrifugation protocol comprising the centrifugation parameter of higher centrifugation intensity.
Term
3.5 yearsto projected expiry
Projected expiry 1 April 2030, counted from filing; an application has no term until it is granted.
- Priority and filed
- Published
- Today
- Projected expiry
12 claims: 4 independent, 8 dependent
- 1ES 2 583 643 T3 REIVINDICACIONES 1. Método implementado por ordenador para operar una celda de trabajo de muestras automatizada (100), comprendiendo la celda de trabajo un transportador de muestras (109) que conecta por lo menos una centrífuga (108) a una estación de entrada de muestras (107), comprendiendo el método:- recepción de (200) muestras (104, 105, 106) por la estación de entrada de muestras (107), - asignación (201) a cada muestra de un parámetro de centrifugación (101, 102, 103);- transporte (202) de cada muestra desde la estación de entrada de muestras (107) a por lo menos una centrífuga (108);- comparación (203) de los parámetros de centrifugación (101, 102, 103) de las muestras cargadas o que deben cargarse en la centrífuga y determinar el parámetro de centrifugación de intensidad de centrifugación más elevada, estando caracterizado el método por: - la carga (204) de las muestras en la centrífuga (108), comprendiendo las muestras cargadas muestras con diferentes parámetros de centrifugación, - la centrifugación (205) de las muestras cargadas de acuerdo con un protocolo de centrifugación que comprende el parámetro de centrifugación de intensidad de centrifugación más elevada.
- 2Método implementado por ordenador según la reivindicación 1, en el que la etapa de carga (204) de las muestras en la centrífuga comprende las sub-etapas de:- recogida (400) de muestras con un primer parámetro de centrifugación en un primer área de retención, - recogida (401) de muestras con un segundo parámetro de centrifugación en un segundo área de retención, - determinación (402) de si se satisface una condición de terminación para la recogida de muestras en el primer y segundo áreas de retención, - carga (403), si se satisface la condición de terminación, de las muestras recogidas en el primer área de retención en la centrífuga, - llenado (404) de los vasos de centrífuga no ocupados con muestras del segundo área de retención.
- 3Método implementado por ordenador según la reivindicación 2, en el que la condición de terminación se selecciona de entre el grupo que consiste de:- la recogida de un número predefinido de muestras con el primer parámetro de centrifugación en el primer área de retención, - la incidencia de un tiempo particular del día, - el transcurso de un periodo de tiempo predefinido desde la recogida de las muestras y - la recepción de una orden para llevar a cabo la centrifugación con las muestras recogidas hasta el momento.
- 4Método implementado por ordenador según la reivindicación 2 o 3, en el que las muestras con el primer parámetro de centrifugación son muestras que aparecen en menor cantidad que las muestras con el segundo parámetro de centrifugación.
- 5Método implementado por ordenador según la reivindicación 2 o 3, en el que las muestras en el primer área de retención son muestras a las que se ha asignado un parámetro de centrifugación de intensidad de centrifugación más elevada que la asignada a las muestras en el segundo área de retención.
- 6Método implementado por ordenador según cualquiera de las reivindicaciones 1 a 5, en el que el parámetro de centrifugación de intensidad de centrifugación más elevada es para muestras para las que la solicitud de análisis de la coagulación fue recibido por la celda de trabajo de muestras automatizada.
- 7Método implementado por ordenador según cualquiera de las reivindicaciones 1 a 6, en el que las muestras a las que no se ha asignado el parámetro de centrifugación de intensidad de centrifugación más elevada pero que se centrifugan conjuntamente con muestras a las que se ha asignado un parámetro de centrifugación de intensidad de centrifugación máxima se seleccionan de entre el grupo que consiste de:- muestras de suero, - muestras de plasma y - muestras de orina.
- 8Método implementado por ordenador según cualquiera de las reivindicaciones 1 a 7, en el que la asignación de un parámetro de centrifugación a cada una de las muestras se lleva a cabo mediante un motor de reglas. ES 2 583 643 T3
- 9Método implementado por ordenador según cualquiera de las reivindicaciones 1 a 5, en el que la etapa de carga de las muestras en la centrífuga comprende las sub-etapas de:- determinar si existen muestras entre las muestras recibidas que son incompatibles con el parámetro de centrifugación de intensidad más elevada, en el que una muestra es incompatible con el parámetro de centrifugación de intensidad más elevada en el caso de que la centrifugación de dicha muestra con un protocolo de centrifugación que comprende dicho parámetro de centrifugación de intensidad más elevada resultaría en una reducción de la calidad de los resultados generados con dicha muestra, - bloquear la carga de las muestras incompatibles con el parámetro de centrifugación de intensidad de centrifugación más elevada en la centrífuga conjuntamente con las muestras a las que se ha asignado el parámetro de intensidad de centrifugación más elevada.
- 10Celda de trabajo de muestra automatizada, que comprende:- una estación de entrada de muestras para cargar muestras en la celda de trabajo de muestra, - un módulo de asignación de parámetros para asignar un parámetro de centrifugación a cada muestra, - un controlador para comparar los parámetros de centrifugación de las muestras cargadas o que deben cargarse en la centrífuga conjuntamente y para determinar, como resultado de la comparación, el parámetro de centrifugación de intensidad de centrifugación más elevada, - siendo por lo menos una centrífuga operable para centrifugar las muestras cargadas de acuerdo con un protocolo de centrifugación según el parámetro de centrifugación de intensidad de centrifugación más elevada, - un transportador de muestras para transportar muestras desde la estación de entrada de muestras a la centrífuga o centrífugas y para cargar muestras en la centrífuga o centrífugas, estando caracterizada la celda de trabajo de muestra automatizada por que: comprende las muestras cargadas con diferentes parámetros de centrifugación, en el que las muestras cargadas se centrifugan con el protocolo de centrifugación según el parámetro de centrifugación de intensidad de centrifugación más elevada.
- 11Celda de trabajo de muestra automatizada (100) según la reivindicación 10, que comprende además:- un primer área de retención (318) para recoger muestras de un primer parámetro de centrifugación, en el que las muestras del primer tipo son muestras a las que se ha asignado un primer parámetro de centrifugación de intensidad de centrifugación más elevada, y - un segundo área de retención (319) para recoger muestras a las que se ha asignado un segundo parámetro de centrifugación, en el que las muestras (104, 105, 106) del primer parámetro de centrifugación son transferidas automáticamente por el transportador de muestras (109) a la centrífuga o centrífugas (108) tras satisfacerse una condición de terminación, y en el que los vasos de centrífuga no ocupados (304) se llenan con muestras del segundo parámetro de centrifugación.
- 12Celda de trabajo de muestra automatizada (100) según cualquiera de las reivindicaciones 10 a 11, que además comprende por lo menos un analizador, en el que el transportador de muestras (109), tras la centrifugación de las muestras del primer tipo de muestra y muestras de otros tipos en la centrífuga o centrífugas según un protocolo de centrifugación que comprende el parámetro de centrifugación de la intensidad de centrifugación más elevada, es operable para la transferencia automática de las muestras a por lo menos un analizador.
Independent claims12
185 paragraphs in 8 sections, as filed
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DESCRIPTION
Computer-implemented method of operating an automated sample work cell
Field of the invention
The invention relates to a computer-implemented method and an automated sample work cell that allows samples to be centrifuged after assigning different centrifugation parameters in the same centrifuge.
Background and prior art
In analytical laboratories, in private clinical laboratories, a multitude of analyzes of biological samples are carried out in order to determine the physiological and biochemical states of patients indicative of a disease, nutritional habits, pharmacological efficacy or organ function.
The biological samples used in such analyzes can be several different biological fluids, such as blood, urine, cerebrospinal fluid, saliva, etc. These original biological samples can be further processed prior to analysis. Often the sample is filled into a vial that already contains substances such as, for example, citrate buffer, EDTA buffer, and / or liquids that form a barrier during centrifugation.
Before an analysis of a biological sample can be carried out, it is usually necessary to perform a set of pre-analytical steps on the biological sample, such as sample discharge from a sample introduction station, dilution or concentration of the sample, the covering or uncapping of the sample, the division into aliquots of the same, the complementation of the same with various buffers, media and substances, or centrifugation of the sample or an aliquot thereof to separate its constituents. For safety reasons, as well as for reasons of analytical quality, reproducibly and efficiently, an increasing number of such 'preanalytical' steps and procedures are automatically performed by automated sample work cell systems, also known as 'automated preanalytical systems'.
Document No. WO 2007 / 018897A2 describes a method for processing chemical and coagulation assays automatically in a laboratory work cell system comprising multiple analyzers and a centrifuge. For the centrifuge, a current centrifuge operating protocol was established. Patient samples were sorted at the entry station of an automated clinical work cell system and treated differently based on their pre-run centrifugation requirements. In the event that a sample did not present centrifugation requirements corresponding to the currently established centrifugation operating protocol, the sample was held at the entry station until the centrifuge operating protocol had been appropriately modified. After completing the modification of the centrifuge operating protocol, the sample was loaded into the centrifuge and centrifuged according to the new operating protocol. In the event that a sample had centrifugation requirements consistent with the currently established centrifuge operating protocol, the sample was loaded into the centrifuge, centrifuged according to the established centrifuge operating protocol, and sent to an appropriate analyzer. Therefore, the method disclosed in WO 2007 / 018897A2 automated the task of adopting centrifuge operating protocols according to the requirements of the current set of samples to be analyzed. The disadvantage of such a method is that only samples that require the same centrifugation protocol can be centrifuged simultaneously in a centrifuge.
US 2000 / 50037502A1 describes a method for automatically operating a sample handling system to carry out tests on various patient samples by comparing the tests to be carried out with a set of rules defined for the test. . A set of analyzers that is part of the sample handling system is subdivided into analyzers that meet the defined rules for the assay and analyzers that do not meet the defined set of rules for the assay. If necessary, at least one analyzer is adapted to comply with the rules defined for an assay to be carried out on a group of patient samples. The patient samples are then delivered to the analyzer that meets the defined rules for the assay.
Document No. WO 2007/018897 A2 describes a method for automatically providing sample sorting at the entrance station of a clinical laboratory work cell and allowing only those samples that have centrifugation requirements that are satisfied by the currently established operating protocols of the centrifuge are processed by a centrifuge and an analyzer associated with said work cell.
US 2008/0190857 A1 describes an apparatus and a method of forming a solid fibrin mesh. The apparatus includes a centrifuge having a housing, an actuator, a wheel, and a flange. The housing includes a recessed area and a base that can rest on a surface. The wheel engages the actuator and extends into the recessed area and is adapted to contact a first end of a container.
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The flange extends into the recessed area in front of the wheel and defines an adjustable distance between the wheel and the flange. The flange is adapted to contact a second end of the container and the actuator is operable to rotate the container.
US 2008/0182742 A1 discloses a centrifuge including a plurality of centrifuge discs. Each disc has an anchor to attach a container. The container contains the liquid for centrifugation. The centrifuge further includes a disc motor positioned to engage and rotate the discs, and a controller to control which discs are coupled or uncoupled from the disc motor and the length of time each disc is spun.
US 2005/0037502 A1 discloses a method for automatically operating a sample handling system and associated analyzers to carry out tests on several patient samples by comparing the tests to be carried out with a set of rules defined for the test, the subdivision of analyzers into analyzers that comply with the defined rules for the assay and analyzers that do not comply with the set of defined rules for the assay; then, the operation of the system for the supply of patient samples to the analyzers that comply or operate the system, so that at least one analyzer complies with the rules defined for the assay and supply of patient samples to said analyzer.
US Patent No. 6390965 B1 describes a centrifugal separator having a cylindrical-bottomed main rotor body and rack configured with a plurality of rack parts along the inner circumferential surface of the main rotor body, said rack parts being linked together and being able to move in radial directions of the main rotor body, so that by rotating the main rotor body, the rack parts are pressed against the inner circumferential surface of the main rotor body and are held in this position by the centrifugal forces associated with the rotation of the main rotor body.
Document No. WO 89/06162 describes an improved method for predicting the success of two additional therapies that is based on estimating the minimum effective concentration of a therapeutic agent that achieves in vitro kill of most tumor cells. The method includes an assay and apparatus for simultaneously analyzing a series of dilutions of a therapeutic agent using a 90% cell kill as an index of the effective cytotoxic concentration of the agent. Document No. US5865718A describes a system and a method for operating one or more centrifuges using a database of protocol records.
The user can search the database for the necessary centrifugation protocol for a particular specimen or type of separation desired. Although that invention and others have increased the degree of automation of sample handling workflows, some aspects of sample processing are still not flexible enough for many clinical diagnostic tasks, particularly with regard to centrifugation of samples that require different centrifugation protocols. Consequently, the centrifugation times of the preanalytical systems of the state of the art are excessively long, the number of processed samples is excessively low, or a multitude of centrifuges is necessary to guarantee a rapid processing of samples that require different protocols of centrifugation by means of the use of multiple centrifuges in parallel, which significantly increases the costs of preanalytical systems.
Summary description of the invention
The invention relates to a computer-implemented method and working cell system that allows the centrifugation of samples with different centrifugation parameters in a centrifuge as claimed in the respective independent claims. Embodiments of the invention are provided in the dependent claims.
The option of centrifuging samples that have different centrifugation requirements is particularly advantageous, as no dedicated centrifuge is required for each particular centrifugation protocol. This reduces the number of centrifuges required and thus also reduces the cost of the complete sample work cell system. Compared to working cell systems that use only one centrifuge that sequentially centrifuges samples with different centrifugation requirements and that are often not loaded to full capacity, the time required to centrifuge all samples according to the invention is reduced.
Sample work cell systems are often highly complex systems comprising a multitude of different laboratory apparatus connected with one or multiple conveyors. The sample work cell systems may comprise, in addition to preanalytical sample processing units, such as centrifuges, capping and uncapping units or aliquoting units. Samples can be transported automatically or manually from a preanalytical system to an analyzer. A variety of analyzers are known in the art that differ from each other, for example, in the types of reagents.
ES 2 583 643 T3 used, the number and type of biological samples that can be analyzed in a unit of time, the analytical approach, etc.
A typical, but not the only example in which the limitations of state-of-the-art work cell systems are overcome with embodiments of the invention is the centrifugation of patient samples, in particular whole blood samples, with centrifuges. of a clinical work cell system in order to specifically prepare the sample for a desired blood type analysis.
Blood flows throughout the body, transporting nutrients to the organs, as well as waste products to the excretory systems. For these reasons, many medical conditions have an effect on blood components, and blood tests are the most commonly performed clinical tests. Most routine tests are performed on plasma or serum samples rather than whole blood samples because the cellular components of the blood interfere with some analytical tests. Serum and plasma can be frozen or chilled and therefore can be stored for several days or weeks for later analysis. Therefore, it is common practice to centrifuge whole blood samples in order to obtain plasma or serum by separating it from blood cells before storing or analyzing the plasma or serum.
Blood plasma is the liquid component of blood, not presenting blood cells. It is made up mainly of water and contains dissolved proteins, glucose, clotting factors, mineral ions and hormones. Blood plasma is prepared by centrifuging whole blood samples containing anticoagulant substances in a centrifuge until the blood plasma is separated from the blood cells at the bottom of the tube.
Blood serum is blood plasma without fibrinogen or the other clotting factors. It includes all proteins not used in blood clotting and all electrolytes, antibodies, antigens, hormones, as well as exogenous substances such as drugs.
Blood serum is commonly used for a wide variety of tests, such as antibody detection tests, blood typing, or DNA testing in a forensic laboratory. Tests are laboratory procedures that characterize a parameter of a biological sample, for example its opacity, or of an analyte in the sample. An analyte is a component of a sample that must be analyzed, for example molecules of various sizes, ions, proteins, metabolites, and the like. The information collected can be further used to assess the impact of drug administration on the body or on particular tissues or to make a diagnosis. The determination of analytes and their concentrations in a biological sample is often referred to, in the context of the analysis of blood samples, as clinical chemistry. The characterization of the cellular components of blood samples is called 'clinical hematology', while laboratory tests that evaluate an individual's clotting mechanism are called 'coagulation tests'.
Clotting of a blood sample may make clinical chemistry analysis impossible or result in the generation of erroneous measurement values. Therefore, clotting is prevented for such types of tests by adding anticoagulant substances to blood samples immediately after they are obtained from the patient. Such substances include sodium citrate, EDTA, heparin, and others. Some vials used to collect whole blood samples already contain such anticoagulant substances.
In the event that serum is to be obtained from a whole blood sample, the sample tube may comprise substances that initiate and accelerate clotting, so-called 'clotting activators', which accelerate the clotting of fibrinogen, blood cells and other clotting factors. Said blood components can be separated after completion of the coagulation process, by centrifugation.
Because the sample tubes used to collect blood often contain additional substances, such as clot activators or anticoagulant substances, which have an impact on sample processing, a mixture of sample tube types can cause make a blood sample unusable for testing. To avoid errors in sample collection and handling, the color of sample caps from many manufacturers is uniformly coded according to a fixed color scheme, and sample tubes are supplied by tube manufacturers already adapted to the specifications. Preanalytical and analytical requirements of a particular test, for example a clinical chemistry test or a hematology or coagulation test. Commonly, manufacturers of laboratory test sample tubes provide their customers with information on recommended centrifugation protocols, considering the recommended centrifugation protocol as the optimal centrifugation protocol to prepare a sample for a desired analysis.
Table 1 lists a set of sample types I-VII, each sample type comprising a tube for samples of a particular material, which contains a particular set of substances and which has been optimized for the
ES 2 583 643 T3 sample preparation according to the requirements of an analysis or a set of analyzes. Table 2 lists the recommended centrifugation parameters for each type of sample tube by a manufacturer.
A centrifugation protocol is a set of instructions that controls the operation of a centrifuge according to a set of centrifugation parameters.
A centrifugation parameter according to embodiments of the present invention may be, but is not limited to, centrifugal force, centrifugation time, acceleration time, up ramp time, deceleration time, and temperature in a centrifuge.
A centrifugation parameter is assigned to the samples according to the present invention. Said centrifugation parameter specifies at least one operating parameter of a centrifuge. In the event that a particular centrifuge is configured, for example to run at a specific speed, the intensity of the centrifugation can be modified by selecting different durations of the centrifugation (for example 5 minutes for samples undergoing analysis of clinical chemistry and 10 minutes for a sample for the coagulation test). In many practical cases, a particular centrifugation parameter would, however, require a centrifugation protocol comprising a speed or force and a duration. The centrifugation protocol may further comprise ramping up the centrifugation speed or even centrifugation at different speeds with the same loaded samples.
A centrifuge operates according to a particular centrifugation protocol by rotating a rotor containing the sample at a particular speed, resulting in a particular centrifugal force for the particular time at a particular temperature as specified by the centrifugation parameters of the centrifugation protocol.
The most important centrifugation parameters that determine the intensity of the centrifugation are the centrifugation time and the centrifugation speed. In the context of centrifugation of samples in a laboratory, the terms 'centrifugation speed' and 'centrifugal force' are often used synonymously, since centrifugal force can be calculated from a given centrifugation speed and vice versa. A centrifugal force is exerted on a body in the event that said body, for example a biological sample in a centrifuge beaker of a centrifuge, moves in a circular path (spins around a fixed axis). Centrifugal force pushes the body away from the center of the circular path. The higher the centrifugation speed of the centrifuge, usually measured in revolutions per minute, rpm, or meters per second, the higher the centrifugal force exerted on the centrifuged body. The unit rpm indicates the number of revolutions made by a centrifuge per unit of time, for example in one minute. The centrifugation speed measured in meters per second indicates the length of the path traveled by a centrifuged sample following a circle around the axis of the centrifuge, where the radius of said circle is typically the radius of the centrifuge rotor or the distance between the sample beaker and the centrifuge shaft. The magnitude of the centrifugal force F given a particular speed of centrifugation v is given by the formula F = mv Ir, where m is the mass of the body, for example a sample, [kg], v is the speed of the body [ meters per second] and r is the radius [meters] of the centrifuge. Alternatively, F = mw r, where ω is the angular velocity.
Coagulation assays require a higher centrifugation intensity than clinical chemistry assay because the number of cells or particles remaining in plasma that is acceptable for coagulation assay is smaller than for coagulation assay. clinical chemistry.
The centrifugation intensity is a value that is determined mainly from the centrifugation time and the centrifugal force or a combination of both parameters. According to the present invention it is not necessary to determine an exact centrifugation intensity, since it is only important to compare the centrifugation intensities of the samples loaded or to be loaded into the centrifuge.
The centrifugation parameter of the highest centrifugation intensity is determined by comparing with each other all the centrifugation parameters assigned to each sample loaded into the working cell. Therefore, the 'highest centrifugation intensity centrifugation parameter' is determined by comparing all the centrifugation parameters assigned to the samples loaded or to be loaded into the working cell system against each other.
A centrifugation parameter of maximum centrifugation intensity is the centrifugation time of that same sample to which the longest centrifugation time of all the samples to be centrifuged has been assigned, provided that the centrifugal forces of said samples are equal. Similarly, a maximum centrifugation intensity centrifugation protocol is the centrifugation protocol based on centrifugation parameters of the same sample to which the longest centrifugation time of all the samples to be centrifuged has been assigned, with the condition of that the centrifugal forces of said samples are equal.
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A centrifugation parameter of maximum centrifugation intensity is the centrifugal force of the same sample to which the longest centrifugation time of all the samples to be centrifuged has been assigned, provided that the centrifugation times of said samples are equal. Similarly, a maximum centrifugation intensity centrifugation protocol is the centrifugation protocol based on centrifugation parameters of the same sample to which the highest centrifugal force of all the samples to be centrifuged has been assigned, provided that the centrifugation times of said samples are equal.
In the event that a first sample of the samples to be centrifuged has been assigned a longer centrifugation time than a second sample, while the second sample has been assigned a higher centrifugal force value, It must be determined experimentally which of these parameters should be considered the highest centrifugation intensity parameter and which centrifugation parameters constitute the highest centrifugation intensity centrifugation protocol. Alternatively, the person skilled in the art may decide based on his or her specialized knowledge, which centrifugation parameter should be considered the highest centrifugation intensity parameter.
In the context of blood sample analysis, in preferred embodiments of the invention, the centrifugation time acts as the highest centrifugation intensity parameter and determines the centrifugation protocol according to which serum samples and coagulation samples they are spun together within a single centrifuge. Consequently, serum samples are centrifuged for a longer time if they are loaded into a centrifuge together with coagulation samples. However, the total time to renew the work cell system is reduced.
The moment in time in which the comparison between centrifugation parameters of different samples is executed depends on the performance of the invention.
According to some embodiments of the invention, the comparison between samples is performed after loading the sample into a centrifuge. According to further embodiments, the comparison is performed during the procedure of loading the samples into the centrifuge of the work cell system. Such embodiments are particularly advantageous in that it can be pre-checked and thus ensured that all samples loaded into the sample work cell are compatible with the higher centrifugation intensity centrifugation protocol.
According to further embodiments of the invention, the comparison between centrifugation parameters assigned to the samples loaded into the working cells is carried out before loading the samples into the centrifuge. Such embodiments are advantageous in scenarios where samples must be directed to different buffer areas or where samples incompatible with a centrifugation parameter of maximum centrifugation intensity of other samples must be prevented from being loaded into the centrifuge together with the others. samples.
Table 1:
<td>sample: tube type</td><td>Added substances</td><td>sample type (depending on the type of analysis required for the sample)</td><td>Possible analyzes</td>
<td>I</td><td>Contains a clot activator. The clot activator accelerates clotting.</td><td>Serum sample</td><td>Clinical serum chemistry (determination of the level of glucose / ions / proteins, etc.); routine blood donor screening; diagnostic tests for infectious diseases</td>
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<td>II</td><td>Contains a coagulation activator and gel. Gel density between the density of blood serum and that of blood cells. The gel helps separate serum and blood cells after centrifugation. The gel prevents the exchange of substances between the blood cell and the serum.</td><td>Serum sample</td><td>Clinical chemistry of serum (determination of glucose / ion / protein level, etc.); immunology; routine screening of blood donors; diagnostic tests for infectious diseases</td>
<td>III</td><td>Contains anticoagulant EDTA. EDTAK2 does not distort blood cells and is therefore the anticoagulant of choice for hematology testing.</td><td>Hematological samples (whole blood)</td><td>Blood cell hematology clinical exams; routine screening of blood donors;</td>
<td>IV</td><td>Contains anticoagulants: heparin, lithium, sodium heparin and gel. The density of the gel is between the density of blood plasma and that of blood cells. The gel helps separate plasma and blood cells after centrifugation. The gel prevents the exchange of substances between the blood cell and the plasma.</td><td>Plasma sample</td><td>Clinical chemistry of plasma (determination of the level of glucose / ions / proteins, etc.); immunology; routine screening of blood donors; diagnostic tests for infectious diseases; some elements of hemorrheology</td>
<td>V</td><td>Contains thrombin, a rapid clotting activator</td><td>STAT serum sample</td><td>STAT Serum Rapid Test</td>
<td>SAW</td><td>Contains citrate anticoagulants. Citrate binds to calcium in the blood sample.</td><td>Plasma-citrate sample</td><td>Clotting tests: The addition of calcium allows the blood to clot again; determining, for example, clotting time; platelet function tests</td>
<td>VII</td><td>Urine tubes</td><td>Urine sample</td><td>Chemical analysis of urine samples</td>
Table 2:
<td>sample tube type</td><td>Recommended / optimal centrifugation parameters</td>
<td>II</td><td>Centrifugal force: 2,000xg; centrifugation time: 5 min</td>
<td>IV</td><td>Centrifugal force: 2,000xg; centrifugation time: 5 min</td>
<td>SAW</td><td>Centrifugal force: 3,000xg; centrifugation time: 10 min</td>
<td>VII</td><td>Centrifugal force: 1,200xg; centrifugation time: 10 min</td>
Typically, a clinical laboratory must carry out a multitude of analytical tests on a multitude of blood samples collected in different types of sample tubes according to different optimal centrifugation protocols each day, in which the sequence and number of requests for analysis and, in relation to them, the required centrifugation protocol is not previously known. In addition, there may be samples that require very urgent processing and analysis. Consequently, their analysis is of vital importance for a patient, the so-called 'STAT' samples. Therefore, in a clinical laboratory associated with, for example, a hospital, the design of an optimal work cell system that is capable of centrifuging
ES 2 583 643 T3 flexibly any type of sample according to its respective optimal centrifugation protocol for a particular analysis that is also operable to process STAT samples in a preferential way is a highly complex task. The solution provided by current state-of-the-art systems is to physically separate the samples according to their recommended centrifugation protocols and direct each class of samples to different centrifuges. For each of these centrifuges, a different centrifugation protocol must be established. Such an approach greatly increases the number of centrifuges required. Other systems sequentially process different classes of sample, in which the established centrifugation protocol is modified by loading the samples with a different recommended centrifugation protocol into the centrifuge. This is also suboptimal, because the case of a particular type of sample assigned to a particular centrifugation protocol and corresponding to a particular type of analysis is only rarely required, the centrifuge may not be filled to full capacity, whereas Samples requiring other centrifugation protocols may have to be collected in a holding area.
Although Table 1 lists a set of tube types, the type of a sample is not determined or characterized by the tube in which it is contained, but rather by the type of analysis required to run for the sample. Accordingly, a serum sample is a blood sample for which clinical chemistry or immunology analysis is required and from which serum must be prepared prior to such required analysis. A plasma sample is a blood sample for which clinical chemistry or immunology analysis is required and from which plasma must be prepared prior to such required analysis. A coagulation sample is a blood sample for which a coagulation test is required. A STAT serum sample is a blood sample for which a rapid clinical chemistry or immunology analysis is required and for which the preparation of serum from the sample is required in a very short time. In some cases, blood samples are collected from a patient after specifying a test request or knowing that a particular test request for a particular type of test will be requested in the future. In accordance with the foregoing, blood is collected in specially adapted sample tubes to prepare serum or plasma for the required type of analysis. However, it may happen that the same type of tube is used for different types of sample. In any case, the centrifugation parameter assigned to a biological sample depends on the type of analysis required. In a laboratory where the type of tube is a clear indicator of the type of analytical procedure required for a sample, the type of tube can also be used in embodiments of the invention to determine which centrifugation parameter should be assigned to a sample.
In the event that a sample is centrifuged for a longer time or with a higher centrifugal force than is generally recommended to prepare a sample for a particular type of analysis, the quality of the analysis result may be adversely affected. One possible reason is that the cell membranes of blood cells can be damaged, resulting in hemolysis, an effect that negatively interferes with various analytical tests. It may also happen that the gel barrier of the vials used to separate the serum / plasma from the clot / cells is destroyed by a higher intensity centrifugation.
The present invention is based on the unexpected observation that for various types of sample and sample tubes, a deviation from the recommended centrifugation protocol within a particular range of values does not have negative consequences on the quality of the analysis results obtained with such samples. Furthermore, it has been found that sample tubes for lower centrifugation intensity can also be used for higher centrifugation intensities without the tubes being destroyed.
In particular, the observation that a centrifugal force such as that used for coagulation samples does not have a negative effect on the quality of the analysis of other types of analysis allows the creation of an improved system of work cells that allows the centrifugation of multiple samples for use in different analyzes and requiring different centrifugation protocols in a single centrifuge.
Although the principles of the present invention are described below in the context of blood sample analysis, the stated embodiments are merely illustrative of the principles and applications of the present invention. Therefore, it should be understood that numerous modifications can be made with respect to the type of biological sample to be centrifuged (urine, saliva, cerebrospinal fluid, etc.), with respect to the centrifugation parameters applicable to a particular type of sample and regarding the type of analytical test for which a sample is centrifuged in a working cell.
Work cell systems according to embodiments of the invention can reduce the overall time required to prepare samples for analysis. Such work cell systems make it possible to avoid situations whereby a centrifuge not loaded to full capacity is used to centrifuge samples with a particular set of centrifugation parameters, while other samples that have been assigned another recommended set of centrifugation parameters. centrifugation are collected in a holding area of the working cell. According to such embodiments, a centrifuge having only a few of its vessels occupied by samples requiring a higher intensity centrifugation protocol can be filled to capacity with samples requiring a lower intensity centrifugation protocol.
ES 2 583 643 T3
According to other embodiments of the invention, a centrifuge in which only a few of its centrifuge cups are occupied by samples requiring a low intensity centrifugation protocol can be filled to capacity with samples requiring a low intensity centrifugation protocol. higher centrifugation.
According to embodiments of the invention, a centrifuge in which only a fraction of its vessels is filled with coagulation samples (type IV sample tube) can be filled to capacity with blood samples for use in other analytical tests, for example example clinical chemistry analysis. Coagulation samples are generally not requested as often as clinical chemistry tests. Therefore, an option to load samples of other types into centrifuges with an established protocol of coagulation samples of higher centrifugation intensity is a feature of significant practical relevance and economic impact.
According to a further beneficial aspect of the invention, the number of centrifuges required can be reduced by centrifuging the samples to which different centrifugation protocols have been assigned in a single centrifuge according to the highest intensity centrifugation protocol.
Some embodiments of the invention provide an automated sample work cell system featuring a sample conveyor connecting at least one centrifuge to a sample inlet station. The term 'conveyor' in the context of the present application refers to any type of conveyor belt, robotic arm, or device that is operable to transport samples from the sample inlet station to the centrifuge and load the samples into the centrifuge. centrifuge.
According to some embodiments of the invention, the sample inlet station is an integral part of the centrifuges of the work cell system. According to such embodiments, the conveyor is a component of the centrifuge that transports the sample from the sample inlet station of the centrifuge to the vessels of the centrifuge.
Each sample is labeled with a unique identifier, for example a barcode, matrix code, or a combination of a unique sample rack code and a unique sample position within that sample rack. In a first stage, the sample input station receives samples to be prepared for a particular requested analysis. A centrifugation parameter is assigned to each of the received samples. Similarly, the allocation can be done, depending on the embodiment of the invention, on the work cell with a different work cell component or can be done on the sample beforehand (before loading the sample into the work cell) . According to preferred embodiments of the invention, the centrifugation parameter is assigned to the samples prior to loading them into the work cell system at the time a request for analysis is entered into a data management system. The system then automatically assigns a centrifugation parameter based on one or more specific analytical tests in the test request. For example, in the event that a coagulation assay is required, the data management system will assign centrifugation parameters adapted to prepare a sample for coagulation analysis to the required sample or samples.
In a request for tests for a particular patient, clinical, immunological and coagulation tests are often specified. Typically blood is then drawn from the patient and filled into different sample tubes, for example one tube for clinical chemistry and immunological tests and one for coagulation tests. Occasionally these tubes are all labeled with the same patient-specific barcode. Accordingly, the analytical system in this case would need to distinguish these tubes from the same patient, which can be done by, for example, the type of tube (including the tube closure) or a marking on the tubes. The data management system will then assign the centrifugation parameters to the tubes according to the analytical tests to be performed.
Alternatively, the assignment of centrifugation parameters can also be carried out manually, for example by the operator of the sample work cells.
According to some embodiments of the invention, the assignment is carried out automatically by a 'parameter assignment module' upon receipt of the samples by the input station of the work cell system. The mapping module can be implemented in the form of a rule engine or equivalent computing implementation method. Each mapping can be stored, for example, as entry in a database that connects a sample identifier with one or multiple sample parameters.
The assignment of centrifugation parameters to a sample may depend on the information contained in an analysis request (i.e., an order, a request to run an analysis of a particular type on a particular sample) received by the cell system. job. A request for analysis can be entered manually, for example in the form of submitting an electronic or paper form. An analysis request can be entered directly into the work cell system through a human interface
ES 2 583 643 T3 machine, for example a touch screen or by means of a remote computer connected to the laboratory intranet. The request for analysis according to some embodiments of the invention is controlled and transferred to the work cell system by an intermediate laboratory support or a laboratory computer system.
Assigning centrifugation parameters to a sample can also depend on information read from a sample label or sample cap.
According to other embodiments of the invention, the color of the sample cap or sample label, for example a barcode, can be read and used as an indicator of the centrifugation parameter to be assigned to the sample. The parameter assignment module checks whether the data contained in an analysis request or sample label satisfies a particular condition and assigns the centrifugation parameter depending on that condition. For example, a condition applied to a test request could comprise the condition that the requested test type is equal to a particular test type, eg 'coagulation test'. In the event that the condition is satisfied, a 'coagulation analysis' is requested for a sample from a particular patient, the required sample from said patient is assigned a set of centrifugation parameters comprising a centrifugal force of 3,000 xg and a centrifugation time of 10 minutes. Similarly, the condition could be applied to data obtained from the label of a sample, for example the type of sample. In the event that the condition of a sample received as a 'urine sample' type is satisfied, one or multiple centrifugation parameters will be assigned to the received sample.
The step of assigning a centrifugation parameter to a sample comprises, according to embodiments of the invention, the step of determining whether a sample has already been centrifuged or not. This information can be retrieved from the laboratory information system (SIL) that operates the work cell system, from the software module that is part of the laboratory's intermediate support, or from a stand-alone software application for managing data associated with processing and analysis of biological samples. This check ensures that a sample is not unnecessarily centrifuged a second time and helps to save centrifugation resources.
According to further embodiments of the invention, multiple centrifugation parameters can be assigned to a sample, for example a particular centrifugation time and a particular centrifugal force. To simplify the matter, most of the examples provided below refer to assigning a centrifugation parameter to a sample.
According to preferred embodiments, the assigned centrifugation parameter is obtained from the set of centrifugation parameters recommended by the manufacturer of the sample tubes used, it is based on the technical knowledge of the laboratory, on knowledge in textbooks or on knowledge obtained from scientific journals. and techniques. Typically, the assigned centrifugation protocol is considered optimal for a particular sample or analysis, ensuring that the desired analysis can be carried out on the centrifuged sample components and that it will return valid results. Optimal centrifugation parameters further ensure that the centrifugation time is no longer than necessary to prepare a sample for a particular analysis, saving energy and avoiding unnecessarily long centrifugation times.
In the next stage, the received samples are automatically transported by the conveyor to the centrifuge or centrifuges of the working cell system.
A controller, for example a software or firmware component of the work cell, compares the centrifugation parameters that have been assigned to each of the samples. Under typical usage scenarios, samples loaded into the centrifuge have been assigned different centrifugation parameters. The controller determines, as a result of the comparison, the spin parameter of highest spin intensity. The controller can be implemented as an integral component of the work cell system, as a stand-alone software application, or as a software module embedded in the intermediate support or SIL of the laboratory operating the work cell system.
Finally, the samples are loaded into the centrifuge and centrifuged with the centrifugation protocol according to the highest intensity centrifugation parameter.
For example, the samples received by the sample entry station could be whole blood samples to prepare serum for clinical chemistry assigned a centrifugal force of 2,000xg and a centrifugation time of 5 minutes, blood samples Complete to prepare plasma in Type IV sample tubes assigned a centrifugal force of 2,000xg and 5 minutes, and cogulation samples assigned a centrifugal force of 3,000xg and 10 minutes. The controller determines that the centrifugation parameters centrifugation time = 10 min. 'and' centrifugal force = 3,000xg assigned to coagulation samples determine the highest intensity centrifugation protocol.
In the case where only samples to which the same centrifugation parameters have been assigned are to be centrifuged, all samples are centrifuged according to their assigned centrifugation parameters.
ES 2 583 643 T3
According to some embodiments of the invention, the highest intensity centrifugation centrifugation protocol comprises a centrifugal force of 3,000xg and a centrifugation duration of 10 minutes, the centrifugation parameters of said protocol having been assigned to coagulation samples.
According to some embodiments of the invention, the highest centrifugation intensity centrifugation protocol comprises a centrifugal force of 2,000xg and a centrifugation duration of 5 minutes, having assigned the centrifugation parameters of said protocol to serum or plasma samples to clinical chemistry analysis.
According to some embodiments of the invention, the highest intensity centrifugation centrifugation protocol comprises a centrifugal force of 1,200xg and a centrifugation duration of 10 minutes, the centrifugation parameters of said protocol having been assigned to urine samples.
According to some embodiments of the invention, the samples are loaded into the centrifuge in the order that they are received by the sample inlet station or according to the order in which they are transported to the centrifuge (s) of the sample work cell system by the transporter. After the centrifuge is loaded to capacity, it receives an explicit centrifugation order or after a specified period of time has elapsed, the centrifuge is operated according to the centrifugation protocol according to the highest intensity centrifugation parameter of the samples loaded into the centrifuge. .
According to further embodiments of the invention, the sample working cell system further comprises at least a first and a second holding area for collecting samples to which different sets of centrifugation parameters have been assigned or which differ from each other with with respect to its average incidence frequency. Samples that have been assigned a centrifugation parameter that specifies a high centrifugation intensity are collected in a first retention area, while all other samples that have been assigned centrifugation parameters of a lower centrifugation intensity are collected in at least a second holding area. According to further embodiments of the invention, the criteria that determine which holding area a sample is sent to are: the type of sample (urine or blood, tube type II or VII, etc.), the degree of urgency of a sample (STAT samples are very urgent and the STAT status can be indicated by the color of the tube or tube cap, the barcode label or a specific input section, etc.), the average amount of a particular type of sample, the average frequency of receipt of a request for a particular preanalytical procedure, and the like. According to preferred embodiments of the invention, the STAT status of a sample is determined by parameters contained in the request for analysis.
For example, in the event that the work cell system receives STAT samples, they are collected in the first holding area. Other samples collected in the second holding area are used to fill unoccupied cups in the centrifuge.
According to some further embodiments, samples whose sample type or corresponding preanalytical procedure is requested on average less frequently are collected in the first holding area. Samples that have been collected in the first holding area are loaded into at least one centrifuge of the sample work cell system after a termination condition is satisfied. Said termination condition may be the elapse of a specified period of time, the occurrence of a specified time of day, the collection of a specified number of samples in the first or second holding area, an explicit centrifugation order, and so on. Only in the event that the centrifuge has not been loaded to capacity with the samples collected in the first holding area, samples from the second holding area are transferred to the unoccupied centrifuge cups. After loading the centrifuge to capacity or after loading the collected samples into the second holding area in the centrifuge, the centrifuge is started according to the centrifugation protocol comprising the highest intensity centrifugation parameter.
The termination condition for STAT samples may differ from other samples: the minimum number of STAT samples to be collected in the first holding area may be less than for other samples and the period of time that must elapse before starting the sample. centrifugation can be shorter.
With respect to the example provided above, the coagulation samples are collected in the first retention area because they have been assigned a higher intensity centrifugation parameter than clinical chemistry analysis samples. In most laboratories, coagulation samples are also processed less frequently than clinical chemistry samples (type I and II sample tubes). These clinical chemistry samples are collected in the second holding area. After a completion condition is satisfied, the coagulation samples are loaded by a conveyor from the first holding area in the centrifuge. In the event that the centrifuge cups remain unoccupied, the clinical chemistry samples are transferred from the second holding area to the unoccupied centrifuge cups.
The examples listed above are examples where the samples contained in different sample types as listed in Table 2 (Type II tube for clinical chemistry, Type IV tube for some items
ES 2 583 643 T3 of haemorrheology, type VI tube for coagulation tests, type VII tube for analysis of urine samples) can be centrifuged together according to the highest intensity centrifugation parameters; in this case, 3,000xg and 10 minutes, as assigned to coagulation samples. In various laboratories there may be types of sample and types of analysis according to which the centrifugation of the sample to be analyzed at high intensity would invalidate the result of the analysis or make it impossible to carry out the desired analysis of said sample. For example, EDTA-blood samples collected in type III sample tubes can be used to examine blood cells, for example their shape and number per unit volume. For this type of analysis, a centrifugation would make it impossible to carry out said analysis.
According to further embodiments of the invention, the controller determines the existence of samples in the set of samples received by the work cell that are incompatible with the higher intensity centrifugation parameter assigned to some of the received samples. A sample is incompatible with the highest centrifugation parameter in the event that a centrifugation of said sample following a centrifugation protocol specified by said centrifugation parameter results in the invalidation or deterioration of the quality of the analysis results that are obtained. would obtain from said samples or make it impossible to perform the desired analysis on said samples. In the event that the controller detects samples that are incompatible with the highest intensity centrifugation parameter, the loading of those samples into the centrifuge is blocked. Depending on the embodiment of the invention, the sample or multiple samples the load of which has been blocked in the centrifuge (s) together with the samples to which incompatible centrifugation parameters have been assigned are collected in a third holding area. Such samples are later referred to as 'incompatible' samples. After the samples assigned a higher intensity centrifugation parameter and samples not adversely affected by a centrifugation with that higher centrifugation intensity parameter have completed the centrifugation, a centrifugation is set in the centrifuge. new centrifugation protocol, the 'incompatible' samples are transferred from the third holding area to the centrifuge and spun according to the centrifugation parameters assigned to the incompatible samples.
According to further embodiments, said 'incompatible' samples are not collected in a third holding area but instead are transferred to a second centrifuge of the work cell system. A centrifugation protocol specified by the centrifugation parameters assigned to the 'incompatible' samples is established in the second centrifuge and centrifugation is started according to the established protocol.
Embodiments of the invention provide an improved work cell system in which samples to which different centrifugation parameters have been assigned do not need to be separated manually or automatically. In contrast, samples assigned different centrifugation parameters can be spun together within at least one centrifuge of the working cell system according to the highest intensity centrifugation protocol of the samples loaded into the system. of work cells. The highest spin intensity protocol is determined and set in the centrifuge (s) automatically. As a result, fewer centrifuges are required, work cell system costs are reduced, and processing of samples assigned different centrifugation protocols is facilitated and accelerated.
According to further embodiments of the invention, the work cell system is operable to determine its workload or to receive workload information from a user of the system, for example the operator. In the event that the system workload is low and the work cell system comprises a sufficient number of centrifuges, the work cell directs the samples to which different centrifugation parameters have been assigned to different centrifuges presenting different established centrifugation protocols. In the case of high workload, samples assigned different sets of centrifugation parameters are spun together according to the highest centrifugation intensity centrifugation protocol. Samples can be loaded sequentially into the centrifuge (s) or by collecting samples of different types from different holding areas initially and then loading the centrifuge preferably with samples from the first holding area.
After centrifuging the samples according to any of the embodiments indicated above, they can be automatically or manually transferred to an analyzer, or they can be further processed in one or more pre-analytical steps, for example by uncapping the sample tubes, removing aliquots of the centrifuged sample for subsequent analysis. and, in some cases, also centrifuging the aliquot.
Some additional embodiments of the invention are particularly suitable for use in laboratories where a multitude of samples must be centrifuged and for which compatible centrifugation parameters have not necessarily been assigned. Such embodiments operate based on the logical classification of the samples based on their assigned centrifugation parameters. After sorting the samples into sample subsets, multiple sample subsets are pooled together if they have compatible centrifugation parameters. Finally, the logical classes of samples are physically separated. The subsets of samples to which compatible centrifugation parameters have been assigned are spun together in a first
ES 2 583 643 T3 centrifuge, while samples assigned different centrifugation parameters in parallel in a second centrifuge or in the first centrifuge after completing the first run of the centrifuge. Said embodiments are described in detail below.
Some additional examples that are not part of the invention provide classes of compatible centrifugation parameters for particular analyzes, for example in the form of database tables. Table 3 provides an example of centrifugation parameter sets that are optimal for preparing a biological sample for a particular test or group of tests.
Table 3
<td>Analysis type</td><td>Centrifugation parameter ID</td><td>Centrifugation parameter (optional) for a particular analysis</td>
<td>Clinical chemistry analysis of serum samples</td><td>TO</td><td>Centrifugal force: 2,000 g</td>
<td>clinical chemistry analysis of plasma samples</td><td>TO</td><td>Centrifugal force: 2,000 g</td>
<td>Coagulation tests</td><td>B</td><td>Centrifugal force: 3,000 g</td>
<td>clinical chemistry analysis of urine samples</td><td>C</td><td>Centrifugal force: 1,200 g</td>
<td>Hematological analysis</td><td>D</td><td>No centrifugation</td>
<td>Separation of red blood cells and white blood cells</td><td>AND</td><td>Centrifugal force: 10,000 g</td>
Table 4
<td>Class IDs of compatible sets of centrifugation parameters</td><td>Upper centrifugation parameter</td><td>Subordinate centrifugation parameter</td>
<td>I</td><td>B</td><td>A, C</td>
<td>II</td><td>TO</td><td>C</td>
Table 4 provides classes I and II of compatible centrifugation parameters. Each class I-II comprises exactly one higher centrifugation parameter and one or more lower centrifugation parameters. A centrifugation parameter can be a higher parameter in one class (parameter A in class II) and be a subordinate parameter of other classes (parameter A in class I). In the event that a centrifuge is loaded only with samples to which the same centrifugation parameter has been assigned, for example only with serum or plasma samples for clinical chemistry analysis according to parameter A, the centrifugation protocol carried out on these samples is based on parameter A. In the event that samples to which multiple different parameters have been assigned are to be centrifuged, only the samples assigned compatible centrifugation parameters will be loaded together into a centrifuge and then centrifuged with the highest centrifugation parameter of the class of compatible centrifugation parameters.
For example, if multiple samples have to be centrifuged to which different parameters A, B and C have been assigned, these samples will be loaded together into the centrifuge and centrifuged according to the centrifugation parameter B, which is the set of parameters of Class I superior centrifugation.
In the case where the set of samples to be centrifuged comprises samples to which parameter A or C has been assigned, the set of samples to be centrifuged is loaded into the centrifuge and centrifuged according to parameter A.
In the event that the set of samples received by the sample entry station includes samples whose centrifugation parameter is incompatible with the centrifugation parameter assigned to other samples, for example samples for hematological analysis to which the parameter has been assigned centrifugation D which is specific that no centrifugation should be performed, the loading of said samples and the centrifugation of the same together with other samples is blocked.
The working cell system according to said examples operates as follows: initially the input station receives samples to be centrifuged. The parameter assignment module assigns a set of centrifugation parameters optimal for the type of analysis to be run on a sample to each sample. The assignment may depend on the data contained in an analysis request or data specified on the sample label. What is considered an 'optimal' centrifugation parameter can vary between different laboratories. The samples are then logically classified into subsets of samples according to the centrifugation parameters assigned to the samples. Each subset of samples comprises at least one sample. In the next step it is determined which subsets of the received samples correspond to a centrifugation parameter belonging to a class of compatible centrifugation parameters. I only know
ES 2 583 643 T3 transfer those subsets of samples to the centrifuge whose centrifugation parameter belongs to a class of parameters compatible with centrifugation. In the case that subsets of samples can be assigned to different classes of compatible centrifugation parameters, said class of compatible centrifugation parameters comprising the largest number of samples is used. In the event that all received samples have been assigned the same centrifugation parameter, this parameter is considered to be a higher centrifugation parameter. Finally, a centrifugation protocol is established in the centrifuge according to the upper parameter of the class of compatible centrifugation parameters determined in the previous step of loading samples with compatible centrifugation parameters in the centrifuge. All subsets of samples assigned centrifugation parameters belonging to a class of compatible centrifugation parameters are then transferred to the centrifuge and centrifuged according to the highest centrifugation parameter of that class.
According to the preferred examples, the highest centrifugation parameter is the highest centrifugation intensity centrifugation parameter within a class of compatible centrifugation parameters.
According to some additional examples that are not part of the invention, the subset of samples to which the upper centrifugation parameter has been assigned is collected in a first holding area, while the subsets of samples to which a parameter has been assigned of subordinate centrifugation are collected in a second retention area. In the next stage, the samples from the first holding area are transferred to the centrifuge. In the event that the centrifuge vessels are left unoccupied, they are filled in the next step with samples from the second retention area provided that said samples are compatible with the higher centrifugation parameter. Finally, centrifugation is carried out according to the upper centrifugation parameter.
Brief description of the drawings
Embodiments of the invention are explained below in greater detail by way of example, with reference only to the drawings, in which:
Figure 1 is a block diagram of a sample working cell, Figure 2 is a flow chart of a method for centrifuging samples with different centrifugation parameters in a centrifuge, Figure 3a illustrates the loading of samples with different parameters centrifugation in a centrifuge in the same order as that received by the sample inlet station, Figure 3b illustrates the loading by groups of samples with different centrifugation parameters in a centrifuge, Figure 4 is a flow chart of a method for centrifuging samples, the method comprising collecting samples in a first and a second holding area , and Fig. 5 is a flow chart of a method for centrifuging samples together in a centrifuge according to compatible centrifugation parameter classes.
Detailed description
FIG. 1 is a block diagram of a sample work cell system 100 in accordance with one embodiment of the invention. The work cell system 100 comprises a sample inlet station 107, at least one centrifuge 108, a sample conveyor 109 for automatically transporting biological samples
104, 105, 106, from a sample inlet station 107 to at least one centrifuge 108. Some embodiments of sample work cell 100 may further comprise one or more additional centrifuges 110 that also connect to the sample inlet station. samples 107 via conveyor 109. After receiving a sample from the sample input station 107, the parameter assignment module 112 assigns each sample 104, 106, and 106 a centrifugation parameter 101, 102, 103. For example, sample 104 is assigned the centrifugation parameter 103 and sample 106 is assigned the centrifugation parameter 101. The allocation may depend on the data contained in the request for analysis (ie, an order) or the information specified on the label 113 attached to each sample. The label can be a unique sample code, for example a barcode or matrix code, etc., or a combination of unique codes from a sample rack in combination with a sample location within that rack. The controller 111 can be operated to compare the centrifugation parameter 101, 102, 103 that has been assigned to each sample 104,
105, 106 and to determine the centrifugation protocol with the highest centrifugation intensity of all the samples received by the sample inlet station 107. After loading the samples into the centrifuge 108, the samples were
ES 2 583 643 T3 centrifuge according to the highest centrifugation intensity assigned to any of the samples loaded into centrifuge 108.
Figure 2 is a flow chart of a method for centrifuging samples with different centrifugation parameters in a single centrifuge 108. In step 200, the input station 107 receives biological samples. In step 201, the parameter assignment module 112 assigns each sample a centrifugation parameter. The centrifugation parameter can be centrifugal force, centrifugation time (ie duration), centrifuge temperature, and the like. In step 202, the samples are transported from the sample inlet station 107 to the centrifuge or centrifuges 108. The controller 111 compares in step 203 the centrifugation parameters of the samples received in step 200 and determines the centrifugation parameter higher intensity. Depending on the embodiment of the invention, the samples may be located inside or outside the centrifuge at the time of comparison. In step 204, the samples are loaded into the centrifuge, where different centrifugation parameters have been assigned to the loaded samples. Finally, the loaded samples are centrifuged in step 205 according to a maximum intensity centrifugation protocol.
Figure 3a illustrates the loading of samples with different centrifugation parameters into a centrifuge in the order in which they have been received by the sample inlet station 107. On the left side of Figure 3a, a series of biological samples are illustrated in the order in which the samples in the series have been loaded into the sample entry station 107. The first sample loaded into the sample entry station is sample 303, followed by sample 302. The last sample to be loaded into the sample inlet station according to figure 3a is sample 300. Sample tubes with a black cap 301, 303 represent samples to which maximum intensity centrifugation parameters have been assigned, for example samples coagulation. Samples with a white cap 300, 302 represent samples to which lower centrifugation intensity centrifugation parameters have been assigned, for example serum samples. Centrifuge 108 is illustrated on the right hand side of Figure 3a in plan view. Dotted line circles (eg 304) represent unoccupied centrifuge cups. The first sample 303 to be loaded into the sample inlet station 107 is also the first sample to be loaded into the centrifuge 108, into the vessel 305. The next sample 302 is loaded into the vessel 309. The last sample 300 received by the Sample inlet station is loaded into sample cup 307. Loading of samples into the centrifuge is carried out according to the illustrated embodiment, in clockwise order starting from position 306. Centrifuge beakers loaded with serum samples 307, 309 are indicated as white circles with a thick black border.
Centrifuge cups loaded with coagulation samples 308, 305 are indicated as black circles. Centrifuge 108 starts centrifugation after a specific period of time has elapsed, at a particular time of day, after all vessels in the centrifuge have been filled, or after receiving an explicit centrifugation start signal. The maximum intensity centrifugation parameter is determined by controller 111 by comparing the centrifugation parameters of all samples. Finally, the centrifuge 108 has been started according to a maximum intensity centrifugation protocol.
Figure 3b illustrates the loading by groups of samples with different centrifugation parameters in a centrifuge. Similar to the embodiment illustrated in Figure 3a, samples 310 to 317 can be received by the sample inlet station 107 in an order arbitrary. They can be received sequentially or they can be received in the form of one or multiple sample racks. Nineteen serum samples, eg 313, 317, are illustrated as sample tubes with white caps. Six coagulation samples are illustrated: 310, 311, 312, 314, 315 and 316, as sample tubes with black caps. The coagulation samples have been assigned a centrifugation parameter of maximum intensity. According to the embodiment illustrated in Figure 3b, samples assigned a centrifugation protocol with maximum centrifugation intensity are collected in a first retention area 318. Other samples, for example serum samples, are collected in a second holding area 319. After a specific period of time has elapsed, at a particular time of day, after a specified number of samples have been collected in the first or second areas retention or upon receipt of an explicit centrifugation start signal, all samples that have been collected in the first retention area 318 are loaded into centrifuge 108. The centrifuge vessels occupied by the six coagulation samples are illustrated as black circles 323 to 328 of centrifuge 108. In the next step 321, the empty vessels of centrifuge 108 are filled with samples that have been collected in the second sample area. retention 319. The centrifuge 108 illustrated in Figure 3b is filled to capacity with six coagulation samples and 10 serum samples. The centrifuge vessels occupied by a serum sample 329, 330 are illustrated as white circles with thick black borders. The remaining nine serum samples can be transferred to a second centrifuge 110 or kept in the second holding area 319 until the next run of centrifuge 108.
Figure 4 is a flow chart of a method for centrifuging samples, the method comprising collecting samples from first and second retention areas. Steps 200-203 are carried out as indicated for Figure 2. In step 400, the samples assigned a first centrifugation parameter are collected in the first holding area 318. Samples to which other centrifugation parameters have been assigned are collected in a second retention area 319 according to step 401. In the case of
As a termination condition 402 is satisfied, as many sample tubes from the first holding area are loaded into centrifuge 108 as are present and depending on the availability of centrifuge vessels. In step 404, the unoccupied vessels of the centrifuge 108 are filled by loading the sample tubes from the second holding area 319 into the centrifuge. Controller 111 determines the maximum intensity centrifugation parameter and establishes a corresponding centrifugation protocol for centrifuge 108. In the event that no coagulation sample has been loaded into the workflow system, centrifuge 108 starts at step 205 according to the centrifugation parameter that has been assigned to the serum samples. Only in the case that coagulation samples are also loaded into the centrifuge 108, the serum samples as well as the coagulation samples are centrifuged according to the centrifugation parameter assigned to the coagulation samples. The centrifugation parameter that has been assigned to the coagulation samples has a higher centrifugation intensity than the centrifugation parameter assigned to the serum samples. The termination signal according to decision 402 can be the elapse of a specific period of time, a particular time of day, the collection of a predefined number of samples in the holding area I or II, or the receipt of an explicit start signal. centrifugation.
Figure 5 is a flow chart of a method according to an example that is not part of the invention. Said method is used to centrifuge samples together in a centrifuge according to the classes of compatible sets of centrifugation parameters. In step 200, the entry station 100 and 700 of the workflow system 100 receives multiple biological samples. In step 201, each sample is assigned a centrifugation parameter. In step 500, the workflow system provides classes of compatible centrifugation parameters, wherein each class of compatible centrifugation parameters comprises a higher centrifugation parameter and at least one lower centrifugation parameter. The supported centrifugation parameter classes can be provided, for example, by a relational database, by the configuration file, or can be hard-coded in a software module application. In step 501, the samples that have been loaded into the work cell system in step 200 are logically classified into subsets of samples according to the centrifugation parameter assigned to them. All samples assigned to the same subset of samples share the same set of conjugation parameters. In step 502, said subsets of samples are selectively loaded into the centrifuge or centrifuges 108 to which compatible centrifugation parameters have been assigned to each other according to a class of compatible centrifugation parameters as illustrated in, for example, Table 4. In step 503, the samples that have been loaded into the centrifuge are spun according to the highest centrifugation parameter of the class of compatible centrifugation parameters used to transfer the sample to the centrifuge in step 502. In the case that only samples are received to which the sample input station 107 has assigned the same centrifugation parameter, the centrifugation parameter that has been assigned to said samples by the parameter assignment module is considered the parameter of top centrifugation.
According to preferred examples, the upper centrifugation parameter of each class of compatible centrifugation parameters specifies a centrifugation protocol with a higher centrifugation intensity than the centrifugation protocol specified by any of the subordinate centrifugation parameters of that class.
Reference number list
<td> 100</td><td>Sample work cell</td>
<td> 101</td><td>Centrifugation parameters</td>
<td> 102</td><td>Centrifugation parameters</td>
<td> 103</td><td>Centrifugation parameter</td>
<td> 104</td><td>Biological sample</td>
<td> 105</td><td>Biological sample</td>
<td> 106</td><td>Biological sample</td>
<td> 107</td><td>Sample entry station</td>
<td> 108</td><td>Centrifuge</td>
<td> 110</td><td>Second centrifuge</td>
<td> 111</td><td>Controller</td>
<td> 112</td><td>Parameter assignment module</td>
<td> 113</td><td>Hashtag</td>
<td> 200-205</td><td>Stages</td>
<td> 300</td><td>Serum sample</td>
<td> 301</td><td>Coagulation sample</td>
<td> 302</td><td>Serum sample</td>
<td> 303</td><td>Coagulation sample</td>
<td> 304</td><td>Centrifuge bowl not occupied</td>
<td> 305</td><td>Centrifuge vessel occupied by coagulation sample 303</td>
<td> 306</td><td>Sample loading start</td>
<td> 307</td><td>Centrifuge beaker filled with 300 serum sample</td>
ES 2 583 643 T3
Centrifuge vessel filled with coagulation sample 301
Centrifuge vessel filled with serum sample 302 Coagulation samples
Serum sample
Coagulation samples
Serum sample
Sample retention area I
Sample retention area II
Stage: Loading samples from holding area 318
Stage: Empty glass filling
Centrifuge beaker
Centrifuge vessels occupied by coagulation sample
Centrifuge vessels occupied by serum sample
Stage
Decision
Stages
Stages
Contents8
Numbers
- Publication
- 2583643
- Application
- 10158946
Titles2
- Spanish
- Método implementado por ordenador para operar una celda de trabajo para muestras automatizada
- English
- Computer-implemented method to operate an automated sample work cell
Classification
- CPC, 6
- B04B13/00
- B04B2011/046
- G01N35/0092
- G01N35/0095
- G01N2035/0094
- Y10T436/111666
- IPC, 3
- B04B11 04
- B04B13 00
- G01N35 00