阅读说明：本技术 用于分析生物样本的实验室系统 (Laboratory system for analyzing biological samples ) 是由 A.比瑞尔 M.马兹勒 A.彼得 O.兰白克 于 2019-08-28 设计创作，主要内容包括：一种用于分析生物样本的实验室系统(1),其包括多个实验室仪器(10PRE、10POST、10AI),该多个实验室仪器被配置成接收和标识生物样本,并且向实验室控制单元(20)查询指示要在生物样本上实施的处理步骤的处理命令,其中实验室控制单元(20)被配置成针对有效查询序列模式来验证来自该多个实验室仪器(10PRE、10POST、10AI)的查询序列。(A laboratory system (1) for analyzing a biological sample, comprising a plurality of laboratory instruments (10PRE, 10POST, 10AI) configured to receive and identify the biological sample and to query a laboratory control unit (20) for process commands indicating process steps to be performed on the biological sample, wherein the laboratory control unit (20) is configured to validate query sequences from the plurality of laboratory instruments (10PRE, 10POST, 10AI) against valid query sequence patterns.)

1. A laboratory system (1) for analyzing a biological sample, the laboratory system (1) comprising:

-a plurality of laboratory instruments (10PRE, 10POST, 10AI), wherein:

○ at least one of the plurality of laboratory instruments (10PRE, 10POST, 10AI) is configured to receive a biological sample and identify the biological sample by reading a sample identifier ID from an identifier tag (32) attached to a sample container (30) holding the biological sample using an identifier tag reader (12);

○ at least one of the plurality of laboratory instruments (10PRE, 10POST, 10AI) is configured to send a process command query to the laboratory control unit (20) asking for a process command indicating one or more process steps to be performed on the biological sample, the query including the sample identifier ID;

○ at least one of the plurality of laboratory instruments (10PRE, 10POST, 10AI) is configured to process the biological sample according to a processing command from the laboratory control unit (20);

-the laboratory control unit (20) communicatively connected to the plurality of laboratory instruments (10PRE, 10POST, 10AI) and a database (22), the laboratory control unit (20) being configured to:

○ sending process commands to the querying laboratory instrument (10PRE, 10POST, 10AI), the process commands being generated based on one or more test commands in the database (22) corresponding to respective sample identifiers ID;

○ validating the query sequences from the plurality of laboratory instruments (10PRE, 10POST, 10AI) against a valid query sequence pattern, and

○ if the inquiry sequence from the plurality of laboratory instruments (10PRE, 10POST, 10AI) does not match the valid inquiry sequence pattern, generating an alert/error signal indicating at least one unsuccessful reading of the identifier tag (32) by one of the plurality of laboratory instruments (10PRE, 10POST, 10AI),

thereby identifying the particular sample that failed identification.

2. Laboratory system (1) for analyzing biological samples according to claim 1, wherein the plurality of laboratory instruments (10PRE, 10POST, 10AI) comprises:

-one or more PRE-analytical laboratory instruments (10PRE), wherein the query for processing commands by one or more PRE-analytical laboratory instruments (10PRE) to the laboratory control unit (20) comprises: next target query; and/or

-one or more analytical laboratory instruments (10AI) comprising an analysis unit (18), the analysis unit (18) being configured to carry out an analytical test to measure the presence and/or concentration of at least one analyte in the biological sample, wherein the query for a processing command by the analytical laboratory instrument (10AI) to the laboratory control unit (20) comprises the following test query: the test query pertains to one or more analytical tests to be performed on the biological sample based on a sample identifier, ID, of the biological sample; and/or

-one or more POST-analytical laboratory instruments (10POST) comprising a storage unit (19), the POST-analytical laboratory instruments (10AI) being configured to store sample containers (30) into the storage unit (19) or retrieve the sample containers (30) from the storage unit (19), wherein a query for a processing command by one or more POST-analytical laboratory instruments (10POST) to the laboratory control unit (20) comprises a container to be stored into the storage unit (19) or retrieved from the storage unit (19),

wherein the content of the first and second substances,

-the laboratory control unit (20) is configured to:

○ retrieve a list of test commands from the database (22) based on the sample identifier ID, the list of test commands comprising one or more test commands, each test command indicating one or more process steps to be performed on the biological sample, and

○ when queried by the analytical instrument (10AI), sending a test command to the querying analytical instrument (10AI) based on the sample identifier ID;

○ when queried by a PRE-analysis laboratory instrument (10PRE), sending data indicating a next target instrument for the biological sample based on the sample identifier ID of the biological sample and the list of test commands;

○ when queried by a POST-analysis laboratory instrument (10POST), sending data indicative of a sample container (30) to be retrieved from the storage unit (18);

-the valid query sequence pattern comprises the following validity conditions: i.e. the next target query must be followed by a test query, wherein no test query after the next target query indicates that the sample identifier ID cannot be read from the identifier tag (32) by the next target analysis laboratory instrument (10AI) identified in said next target query; and/or

-the valid query sequence pattern comprises the following validity conditions: i.e. the query of the container to be retrieved must be followed by a test query, wherein no test query after the query of the container to be retrieved indicates a failure to read the sample identifier ID from the identifier tag (32) by one of said laboratory instruments (10PRE, 10POST, 10 AI).

3. A laboratory system (1) for analyzing biological samples according to claim 2, wherein:

-the laboratory system (1) further comprises a sample transport system (50), the sample transport system (50) being configured to: transporting one or more sample carriers (40) from a first laboratory instrument (10PRE, 10POST, 10AI) of the plurality of laboratory instruments (10PRE, 10POST, 10AI) to a second laboratory instrument (10PRE, 10POST, 10AI) of the plurality of laboratory instruments (10PRE, 10POST) in accordance with data indicative of a next target instrument; and/or

-one or more PRE-analysis laboratory instruments (10PRE) comprising a sample container sorting unit (14), the sample container sorting unit (14) being configured to sort sample containers (30) holding biological samples into sample carriers (40), each sample Carrier (40) being identified by means of a Carrier identifier (Carrier-ID) of a Carrier label (42) attached to the sample Carrier (40), the PRE-analysis laboratory instrument (10PRE) being further configured to send a signal to the laboratory control unit (20) to associate one or more sample Identifiers (ID) of the sorted sample containers (30) with one or more sample Carrier identifiers (Carrier-ID) of one or more corresponding sample carriers (40); and/or

-one or more PRE-analysis laboratory instruments (10PRE) comprise an aliquoting unit (16), the aliquoting unit (16) being configured to prepare one or more aliquots of a biological sample from one or more sample containers (30), and to provide each of the aliquots with a sample identifier ID on an identifier tag (32) by means of an identifier tag writer (60); and/or

-one or more analytical laboratory instruments (10AI) are further configured to read the Carrier identifier (Carrier-ID) from the Carrier tag (42) and to send the Carrier identifier (Carrier-ID) to the laboratory control unit (20) following the test query; and/or

-the laboratory control unit (20) is configured to: generating a warning/error signal if the Carrier identifier (Carrier-ID) and the sample identifier ID of the test query do not match the association made by the PRE-analysis laboratory instrument (10PRE) at the time of sorting.

4. Laboratory system (1) for analyzing biological samples according to one of the claims 1 to 3, wherein the control unit (20) is configured to: one or more sample identifiers that cannot be read by one or more analytical laboratory instruments (10AI) are identified by correlating the number of one or more test queries received for each sample identifier with the number of test commands identified for the one or more respective sample identifiers so as to avoid the test commands remaining open for a long period of time, wherein the test commands are open if the analytical laboratory instrument (10AI) does not process the corresponding biological sample in accordance with the test commands.

5. Laboratory system (1) for analyzing biological samples according to one of the claims 1 to 4, wherein one or more of the plurality of laboratory instruments (10PRE, 10POST, 10AI) are configured to: sending one or more quality signals to the laboratory control unit (20), the quality signals being indicative of the quality of the identifier tags (32) of the one or more sample containers obtained by the identifier tag reader (12).

6. Laboratory system (1) for analyzing biological samples according to claim 5, wherein the laboratory control unit (20) is configured to:

-determining a degradation of the identifier tag reader (12) based on a sequence of two or more signals indicative of degraded tag quality, the sequence corresponding to readings of a plurality of identifier tags (32) by the same identifier tag reader (12); and/or

-determining a degradation of the identifier tag writer (60) based on a sequence of two or more signals indicative of degraded tag quality, the sequence corresponding to a reading of an identifier tag (32) originating from one specific supplier and/or written by one specific identifier tag writer (60); and/or

-determining whether a label quality corresponding to one or more identifier labels (32) is below a critical label quality threshold, and labeling one or more analysis results obtained by processing one or more biological samples held in one or more sample containers (30) with one or more respective identifier labels (32).

7. Laboratory system (1) for analyzing biological samples according to claim 5 or 6, wherein the laboratory control unit (20) is configured to:

-instructing the laboratory instrument (10PRE, 10POST, 10AI) to process the biological sample in the sample container (30) with the respective identifier tag (32) according to a processing command sent to the laboratory instrument (10PRE, 10POST, 10AI) in the following cases:

○, the label quality corresponding to the one or more identifier labels (32) is above a critical label quality threshold, based on the one or more quality signals, or

○ the identifier tag (32) comprising a sample identifier code of a security type, and

○, the data read from the identifier tag (32) being consistent with the data in the database (20);

-instructing the laboratory instrument (10PRE, 10POST, 10AI) to stop any processing of the biological sample and/or to prompt a user to decide whether to stop or continue processing of one or more biological samples held in one or more sample containers (30) with one or more respective identifier tags (32) and/or to output the sample containers (30) to a wrong orientation and/or to flag one or more analysis results obtained by processing one or more biological samples held in one or more sample containers (30) with one or more respective identifier tags (32) if:

○, based on the one or more quality signals, the tag quality corresponding to the one or more identifier tags (32) is below a critical tag quality threshold, and

○ the identifier tag (12) does not include a sample identifier code of a security type, or the data read from the identifier tag (32) is inconsistent with the data in the database (20).

8. A method (1) for operating a laboratory system for analyzing a biological sample, comprising the steps of:

-receiving the biological sample by one or more of a plurality of laboratory instruments (10PRE, 10POST, 10AI) and identifying the biological sample using its identifier tag reader (12) to read a sample identifier ID from an identifier tag (32) attached to a sample container (30) holding the biological sample;

-sending a process command query by one or more of a plurality of laboratory instruments (10PRE, 10POST, 10AI) to a laboratory control unit (20) asking for a process command indicating one or more process steps to be performed on the biological sample, the query comprising the sample identifier ID;

-sending, by a laboratory control unit (20), a process command to a laboratory instrument (10PRE, 10POST, 10AI) that is being queried, the process command being generated based on one or more test commands in the database (22) corresponding to respective sample identifiers ID;

-processing the biological sample by at least one of the plurality of laboratory instruments (10PRE, 10POST, 10AI) according to a processing command from the laboratory control unit (20); and

-verifying, by the control unit (20), a query sequence from the plurality of laboratory instruments (10PRE, 10POST, 10AI) against a valid query sequence pattern, and generating an alert/error signal indicating at least one unsuccessful reading of an identifier tag (32) by one of the plurality of laboratory instruments (10PRE, 10POST, 10AI) if the query sequence from the plurality of laboratory instruments (10PRE, 10POST, 10AI) does not match the valid query sequence pattern,

-thereby identifying the specific sample that failed the identification.

9. The method of claim 8, further comprising one or more of the following steps:

-one or more PRE-analysis laboratory instruments (10PRE) querying the control unit (20) for a next target instrument for a biological sample;

-the control unit (20), when queried by a PRE-analysis laboratory instrument (10PRE), sending data indicative of a next target instrument for the biological sample based on a sample identifier, ID, of the biological sample;

-transporting, by a sample transport system (50), one or more sample carriers (40) holding sample containers (30) from a first laboratory instrument (10PRE, 10POST, 10AI) of the plurality of laboratory instruments (10PRE, 10POST) to a second laboratory instrument (10PRE, 10POST, 10AI) according to data indicative of the next target instrument;

-one or more analytical laboratory instruments (10AI) query the control unit (20) about one or more analytical tests to be carried out on the biological sample based on the sample identifier ID of the biological sample;

-when queried by an analytical instrument (10AI), the control unit (20) sends a test command to the plurality of analytical instruments (10AI) based on the sample identifier ID and the querying analytical instrument (10 AI);

-performing an analytical test on the biological sample by one or more analytical laboratory instruments (10AI) in response to the test command;

-one or more POST-analysis laboratory instruments (10POST) query the control unit (20) about the container to be retrieved;

-the control unit (20) sending data indicative of sample containers (30) to be stored or retrieved from the storage unit (18) when queried by a POST-analysis laboratory instrument (10 POST);

-storing the sample container (30) or retrieving the sample container (30) from a storage unit (19) of the POST-analysis laboratory instrument (10POST) according to data indicative of the sample container (30) to be stored or retrieved from the storage unit (18).

10. The method of claim 9, further comprising: one or more sample identifiers that cannot be read by one or more analytical laboratory instruments (10AI) are identified by correlating the number of one or more test queries received for each sample identifier with the number of test commands identified for the one or more respective sample identifiers so as to avoid the test commands remaining open for a long period of time, wherein the test commands are open if the analytical laboratory instrument (10AI) does not process the corresponding biological sample in accordance with the test commands.

11. The method according to one of claims 8 to 10, further comprising the step of: one or more of the plurality of laboratory instruments (10PRE, 10POST, 10AI) send one or more tag quality signals to the laboratory control unit (20), the tag quality signals being indicative of the tag quality of the identifier tags (32) of the one or more sample containers obtained by the identifier tag reader (12).

12. The method of claim 11, further comprising one or more of the following steps:

-determining a degradation of the identifier tag reader (12) based on a sequence of two or more signals indicative of degraded tag quality, the sequence corresponding to readings of a plurality of identifier tags (32) by the same identifier tag reader (12); and/or

-determining a degradation of the identifier tag writer (60) based on a sequence of two or more signals indicative of degraded tag quality, the sequence corresponding to a reading of an identifier tag (32) originating from one specific supplier and/or written by one specific identifier tag writer (60); and/or

-determining whether a label quality corresponding to one or more identifier labels (32) is below a critical label quality threshold, and labeling one or more analysis results obtained by processing one or more biological samples held in one or more sample containers (30) with one or more respective identifier labels (32).

13. The method according to claim 11 or 12, further comprising the step of:

-instructing the laboratory instrument (10PRE, 10POST, 10AI) to process the biological sample in the sample container (30) with the respective identifier tag (32) according to a processing command sent to the laboratory instrument (10PRE, 10POST, 10AI) in the following cases:

○, the label quality corresponding to the one or more identifier labels (32) is above a critical label quality threshold, based on the one or more quality signals, or

○, the identifier tag (32) being of a secure type, and the data read from the identifier tag (32) being consistent with data in the database (20);

-instructing the laboratory instrument (10PRE, 10POST, 10AI) to stop any processing of the biological sample in the sample container (30) with the respective identifier tag (32) and/or to prompt a user to decide whether to stop or continue processing of the one or more biological samples held in the one or more sample containers (30) with the one or more respective identifier tags (32) and/or to output the sample container (30) to a wrong orientation and/or to flag one or more analysis results obtained by processing the one or more biological samples held in the one or more sample containers (30) with the one or more respective identifier tags (32) if:

○, based on the one or more quality signals, the tag quality corresponding to the one or more identifier tags (32) is below a critical tag quality threshold, and

○ the identifier tag (12) is not of a secure type, or the data read from the identifier tag (32) is inconsistent with the data in the database (20).

14. A computer program product comprising instructions which, when executed by a control unit (20) of a laboratory system (1), cause the laboratory system (1) to carry out the steps of any of the methods of claims 8 to 13.

Technical Field

The present application relates to a laboratory system for analyzing a biological sample, a method for operating a laboratory system, or a computer program product for a control unit of a laboratory system.

Background

In vitro diagnostic tests have a significant impact on clinical decision making, providing critical information to physicians. In analytical laboratories, in particular in clinical laboratories, a large number of analyses are performed on a sample by an analysis system in order to determine the physiological state of a patient.

To ensure that healthcare professionals can rely on analyzing test results to diagnose and treat patients, the integrity of the test results is critical. One key aspect of the integrity of the test results is the association of the biological sample being tested with the correct patient (who the sample is). This is typically accomplished by associating a sample ID with each biological sample. To allow identification of the biological sample, the corresponding sample ID is typically encoded as a bar code that is printed on a label attached to the sample tube holding the biological sample, or in the case of a tissue sample, on a label attached to a slide.

Since the sample ID is the only item that allows to associate the analytical test result with the correct patient, any error in handling the sample ID(s) may result in a so-called sample mismatch. Sample mismatch is one of the adverse events (even if not the most severe adverse event) in the analysis laboratory, as it may lead to test result(s) attributed to the wrong patient, which may lead to a wrong diagnosis/treatment of the patient. Thus, prior art analytical laboratories implement various fault protection mechanisms to avoid and detect any errors in identifying samples.

Such fault protection mechanisms include: a secure barcode (a barcode with some degree of read error tolerance and/or detection, such as a checksum number), a rescan barcode, etc. is used.

However, the more strictly such failsafe mechanisms are set, the higher the amount of manual labor, as any time an error or even a little chance of error is identified, the corresponding sample is marked for manual error handling. On the other hand, less stringent fault protection rules may result in read errors not being detected.

Furthermore, known read error detection methods only allow detection of instruments, or identifier readers that cannot read the sample identifier. However, since the sample identifier cannot be read, it is not possible to determine which particular sample cannot be identified. In an automated laboratory system, if one of several instruments fails to identify a sample and the sample is then transported to the next instrument, this may lead to a situation in which the scheduled analytical test is skipped (not performed). Failure to identify the sample is ignored and no potentially critical analytical test is performed. In certain cases, the sample may even become contaminated if a more sensitive test is missed, followed by a less sensitive test.

Accordingly, there is a need for a laboratory system, and alternatively a method of operating a laboratory system, that allows for early detection of tag quality degradation and allows for determination of biological sample(s) that cannot be identified by one or more laboratory instruments.

Disclosure of Invention

Disclosed herein is a laboratory system for analyzing biological samples, a method for operating a laboratory system, and correspondingly a computer program product for a control unit of a laboratory system, which address the above-identified need by monitoring and verifying a query made by a laboratory instrument, a sequence of queries relating to processing steps to be carried out on a biological sample received by the respective instrument.

The laboratory system disclosed herein comprises: a plurality of laboratory instruments communicatively connected to the control unit and the database. At least one of the plurality of laboratory instruments is configured to: a biological sample is received and identified by reading a sample identifier ID from an identifier tag attached to a sample container holding the biological sample using an identifier tag reader. Further, at least one of the plurality of laboratory instruments is configured to: a process command query is sent to the laboratory control unit, asking for a process command indicating one or more process steps to be performed on the biological sample, the query including the sample identifier ID. Also, at least one of the plurality of laboratory instruments is configured to: the biological sample is processed according to a processing command from the laboratory control unit.

The laboratory control unit is configured to:

-sending a process command to the querying laboratory instrument, the process command being generated based on one or more test commands in the database corresponding to the respective sample identifier ID;

-validating query sequences from a plurality of laboratory instruments against a valid query sequence pattern; and

-generating an alert/error signal if the query sequence from the plurality of laboratory instruments does not match the valid query sequence pattern, the alert/error signal indicating at least one unsuccessful read of the identifier tag by one of the plurality of laboratory instruments.

Correspondingly, the disclosed method comprises the steps of:

-receiving a biological sample by one or more of the plurality of laboratory instruments and identifying the biological sample by reading a sample identifier ID from an identifier tag attached to a sample container holding the biological sample using its identifier tag reader;

-sending, by one or more of the plurality of laboratory instruments, a process command query to the laboratory control unit, thereby querying a process command indicating one or more process steps to be performed on the biological sample, the query comprising the sample identifier ID;

-sending, by the laboratory control unit, a process command to the querying laboratory instrument, the process command being generated based on one or more test commands in the database corresponding to the respective sample identifier ID;

-verifying, by the control unit, the query sequences from the plurality of laboratory instruments against the valid query sequence pattern, and, if the query sequences from the plurality of laboratory instruments do not match the valid query sequence pattern, generating an alert/error signal indicating at least one unsuccessful reading of the identifier tag by one of the plurality of laboratory instruments.

In other words, the sequence of inquiry messages from the instrument is monitored by the control unit and verified to check whether there is a deviation from the expected sequence (pattern) indicating that at least one instrument "missed" the identification of the sample.

The system and method disclosed herein is advantageous because it allows for the identification of specific samples that are failed to be identified, in addition to detecting that a sample identification error has occurred.

Particular embodiments disclosed herein further include:

-determining a degradation of the identifier tag reader(s) based on a sequence of two or more signals indicative of degraded tag quality; and/or

-determining a degradation of the identifier tag writer(s) based on a sequence of two or more signals indicative of degraded tag quality; and/or

-if the tag quality corresponding to the identifier tag(s) is below a critical tag quality threshold, labeling the analysis result(s) obtained by processing the biological sample(s) held in the sample container(s).

Such embodiments are advantageous as they enable prediction of impending failure(s) of tag reader(s) or writer (s)/supplier(s), allowing for predictive maintenance thereof to avoid further degradation and thus read errors. Furthermore, if the tag quality corresponding to the identifier tag(s) is below a critical tag quality threshold, marking the analysis result(s) corresponding to the sample container(s) enables auditing of such conditions, thereby providing a higher level of certainty while avoiding complete discarding of valid analysis results (if the marked results are issued after auditing).

An identifier tag writer or supplier that is able to identify degradation (errors) of low quality identifier tags is advantageous for root cause analysis if read errors occur.

Drawings

Further features and advantages of the disclosed method/apparatus/system will be described in detail below by way of description and with reference to the following drawings:

FIG. 1 is a highly schematic block diagram of an embodiment of the disclosed laboratory system;

FIG. 2 is a flow chart illustrating a first embodiment of the method disclosed herein;

FIG. 3 is a swim lane diagram of an embodiment of the disclosed method;

FIG. 4 is a flow chart illustrating a further embodiment of the method disclosed herein;

FIG. 5 is a highly schematic block diagram of an embodiment of a pre-analytical laboratory instrument of the disclosed laboratory system;

FIG. 6 is a highly schematic block diagram of a further embodiment of a pre-analytical laboratory instrument of the disclosed laboratory system;

FIG. 7 is a highly schematic block diagram of an embodiment of an analytical laboratory instrument of the disclosed laboratory system;

FIG. 8 is a highly schematic block diagram of an embodiment of a post-analytical laboratory instrument of the disclosed laboratory system.

Detailed Description

Certain terms will be used in this patent application, and the statements of this patent application should not be construed as limited to the specific terms chosen, but rather as related to the general concepts behind the specific terms.

The term "laboratory instrument" as used herein encompasses any instrument or instrument component operable to perform one or more process steps/workflow steps on one or more biological samples and/or one or more reagents. Thus, the expression "processing step" refers to a physically performed processing step such as centrifugation, aliquotation (aliquotation), sample analysis, and the like. The term "instrument" covers pre-analytical instruments, post-analytical instruments and also analytical instruments.

The term "pre-analytical instrument" as used herein encompasses any device or device component configured to perform one or more pre-analytical processing steps/workflow steps, including but not limited to: centrifugation, resuspension (e.g., by mixing or vortexing), capping, decapping, recapping, sorting, tube type identification, sample quality determination, and/or aliquoting steps. The processing step may also include adding chemicals or buffers to the sample, concentrating the sample, incubating the sample, and the like.

The term "analyzer"/"analytical instrument" as used herein encompasses any device or device component configured to obtain a measurement. The analyzer is operable to determine parameter values of the sample or components thereof via various chemical, biological, physical, optical or other technical processes. The analyzer may be operable to measure said parameter of the sample or of the at least one analyte and return the obtained measurement. The list of possible analysis results returned by the analyzer includes, but is not limited to: a concentration of an analyte in the sample, a digital (yes or no) result indicative of the presence of the analyte in the sample (corresponding to a concentration above a detection level), an optical parameter, a DNA or RNA sequence, data obtained from mass spectrometry of proteins or metabolites, and various types of physical or chemical parameters. The analysis instrument may comprise units to assist in the pipetting, dosing (dosing) and mixing of samples and/or reagents. The analyzer may include: a reagent holding unit for holding a reagent to carry out an assay. The reagents may be arranged, for example, in the form of containers or cassettes containing individual reagents or groups of reagents placed in appropriate receptacles or orientations within a storage chamber or conveyor. It may comprise a consumable supply unit. The analyzer may include: process and detection system whose workflow is optimized for certain types of analysis. Examples of such analyzers are clinical chemistry analyzers, coagulation chemistry analyzers, immunochemical analyzers, urine analyzers, nucleic acid analyzers, which are used to detect the results of, or monitor the progress of, a chemical or biological reaction. The term "analyte" is a component of the sample to be analyzed, such as molecules of various sizes, ions, proteins, metabolites, and the like. The information collected on the analyte can be used to assess the effect of drug administration on the organism or on specific tissues, or to make a diagnosis. Thus, "analyte" is a general term for a substance for which information about the presence and/or concentration is intended. Examples of analytes are e.g. glucose, coagulation parameters, endogenous proteins (e.g. proteins released from the myocardium), metabolites, nucleic acids, etc.

The term "post-analytical instrument" as used herein encompasses any device or device component configured to carry out one or more post-analytical processing steps/workflow steps, including but not limited to: sample unloading, shipping, recapping, decapping, temporary storage/buffering, archiving (with or without refrigeration), retrieval, and/or disposal.

The term "communication network" as used herein encompasses any type of wireless network, such as WIFI, GSM, UMTS, or other wireless digital network or cable-based network (such as ethernet), among others. In particular, the communication network may implement the Internet Protocol (IP). For example, a communication network includes a combination of cable-based networks and wireless networks.

The term "control unit" as used herein encompasses any physical or virtual processing device that is configurable to control a laboratory instrument and/or a system comprising one or more laboratory instruments in such a way that workflow(s) and workflow step(s) are performed by the laboratory instrument/system. The control unit may for example instruct the laboratory instrument/system to perform the workflow (s)/workflow step(s) before, after and/or during the analysis. The control unit may receive information from the data management unit about which steps need to be carried out with a certain sample. In some embodiments, the control unit may be integral with the data management unit, may be included by the server computer, and/or may be part of one laboratory instrument, or even distributed across multiple instruments of a laboratory system. For example, the control unit may be embodied as a programmable logic controller running a computer readable program provided with instructions to carry out operations.

A "data management unit" or "database" is a computing unit for storing and managing data. This may involve data relating to the biological sample(s) to be processed by the automated system. The data management unit may be connected to an LIS (laboratory information system) and/or a HIS (hospital information system). The data management unit may be a unit within the laboratory instrument or a unit co-located with the laboratory instrument. It may be part of the control unit. Alternatively, the database may be a cell remote locator. For example, it may be embodied in computers connected via a communication network.

The terms "sample," "patient sample," and "biological sample" refer to material(s) that may contain an analyte of interest. A patient sample may be derived from any biological source, such as a physiological fluid, including blood, saliva, ocular lens fluid, cerebral spinal fluid, sweat, urine, stool, semen, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cultured cells, and the like. Patient samples may be pre-treated prior to use, such as to prepare plasma from blood, dilute viscous fluids, lyse, and the like. The treatment methods may involve filtration, distillation, concentration, inactivation of interfering components, and addition of reagents. The patient sample may be used directly as obtained from the source or used to modify the characteristics of the sample after pre-processing. In some embodiments, the initial solid or semi-solid biological material may be rendered liquid by dissolving or suspending it with a suitable liquid medium. In some embodiments, the sample may be suspected of containing an antigen or nucleic acid.

The terms "sample container" and "sample tube" refer to any individual container used for storing, transporting, and/or processing a sample. In particular, the term refers without limitation to a piece of laboratory glass or plastic, optionally comprising a cover on its upper end.

The term "sample carrier" as used herein refers to any kind of holder configured to receive one or more sample tubes and configured to be used for transporting the sample tube(s). The sample carrier may be of two main types, a single holder and a sample rack. A "single holder" is one type of sample carrier configured to receive and transport a single sample tube. Typically, a single holder is provided as an ice-ball puck (i.e., a flat cylindrical object with an opening to receive and retain a single sample tube). A "sample rack" is a type of sample carrier, typically made of plastic and/or metal, which is adapted to receive, hold and transport sample tubes, e.g. 5 or more sample tubes arranged in one or more rows. There may be holes, windows or slits to enable visual or optical inspection or reading of the sample tube, or of a sample in the sample tube, or of indicia present on the sample tube held in the sample rack, such as a bar code.

The term "identification tag" as used herein refers to an optical and/or radio frequency based identifier that allows the identifier tag to be uniquely identified by a corresponding identification tag reader. "identification tag" shall include, but is not limited to, a bar code, a QR code, or an RFID tag.

The term "RFID tag" as used herein refers to an active or passive RFID tag that contains information. An RFID tag or transponder (transponder) comprising: a coil or antenna and some information stored on the RFID chip, which can be read and/or written by an RFID reader. Correspondingly, the RFID tag may be read-only or read/write, and information associated with the RFID tag may be hard-coded into the RFID tag at the time of manufacture or at some later time.

The term "RFID reader" as used herein includes: a device that can read information from and/or write information to the RFID tag. In general, an RFID reader may include a coil or antenna and circuitry for transmitting and receiving signals with the coil or antenna. The RFID reader antenna generates an electromagnetic field, thereby transferring energy to the tag. Depending on the design of the tag, part of the energy delivered to the tag will be reflected to the reader in order to provide information about the tag back to the reader. Some RFID systems may be used to read data from and optionally write data to RFID tags. The RFID reader may generate signals spanning distances from less than one centimeter to greater than fifty meters, depending on the frequency and power of the signals generated at the RFID reader antenna.

"test commands" as used herein includes any data object, computer-loadable data structure, modulated data representing such data indicative of one or more analytical tests to be performed on a particular biological sample. For example, the test command may be a file or entry in a database. For example, if the test command includes or is stored in association with an identifier of an analytical test to be performed on a particular sample, the test command may indicate the analytical test.

The term "barcode quality" as used herein refers to any data object that indicates the quality of a barcode. In particular, barcode quality refers to barcode quality as specified by ISO/IEC international standard 15416 for one-dimensional barcodes, or ISO/IEC 15415 for two-dimensional barcodes.

Specific embodiments of the disclosed method/system will be described below with reference to the accompanying drawings.

As shown in fig. 1, the laboratory system 1 comprises a plurality of laboratory instruments 10PRE, 10POST, 10AI, a laboratory control unit 20, which laboratory control unit 20 is communicatively connected to the plurality of laboratory instruments 10PRE, 10POST, 10AI and a database 22.

At least one of the plurality of laboratory instruments 10PRE, 10POST, 10AI is configured to: a biological sample is received and identified by reading a sample identifier ID from an identifier tag 32 attached to a sample container 30 holding the biological sample using an identifier tag reader. After identifying the biological sample, the laboratory instrument 10PRE, 10POST, 10AI sends a process command query to the laboratory control unit 20, asking for a process command indicating one or more process steps to be carried out on the biological sample, the query including the sample identifier ID. In other words, when the instrument receives a sample, it "asks" the control unit what to do with the sample. Upon receiving back a processing command from the control unit 20, the laboratory instruments 10PRE, 10POST, 10AI are configured to process the biological sample. The processing of the sample includes pre-analysis, analysis and post-analysis processing steps.

According to particular embodiments disclosed herein, the identifier tag(s) 32 is a barcode, the identifier tag reader is a barcode reader, and the identifier tag writer is a barcode printer.

Fig. 1 shows a particular embodiment of the disclosed laboratory system 1, which includes a PRE-analysis laboratory instrument 10PRE, an analysis laboratory instrument 10AI, a POST-analysis laboratory instrument 10POST, interconnected by a sample transport system 50.

Details of PRE-analysis laboratory instrument 10PRE, analysis laboratory instrument 10AI, and POST-analysis laboratory instrument 10POST will be described in detail with reference to fig. 5 to 8.

The sample transport system 50, as its name implies, is configured to: sample carrier(s) 40 holding one or more sample containers 30 are transported from a first laboratory instrument 10PRE, 10POST, 10AI of the plurality of laboratory instruments 10PRE, 10POST to a second laboratory instrument 10PRE, 10POST, 10AI (and vice versa) in accordance with data indicative of a next target instrument. According to embodiments disclosed herein, the sample transport system 50 is a one-dimensional conveyor belt based system, a two-dimensional transport system (such as a magnetic sample carrier transport system), or a combination thereof.

Turning now to FIG. 2, the functionality of the disclosed system or the steps of the disclosed method will be described. In step 102, a sample is received by one or more of the laboratory instruments 10PRE, 10POST, 10AI and identified by means of the identifier tag reader 12 reading a sample identifier ID from an identifier tag 32 attached to a sample container 30 holding the biological sample. According to various embodiments disclosed herein, more than one or even all of the laboratory instruments 10PRE, 10POST, 10AI identify a biological sample. According to other embodiments disclosed herein, particularly in particular embodiments that include an automated sample transport system 50, only one instrument, particularly PRE-analysis laboratory instrument 10PRE, needs to identify a biological sample, while all other laboratory instruments 10PRE, 10POST, 10AI are notified by the control unit 20 as to which sample they are to receive via the sample transport system 50.

In step 104, the laboratory instrument 10PRE, 10POST, 10AI sends a process command query to the control unit 20, thereby interrogating a process command indicating one or more process steps to be performed on the biological sample, the query including the sample identifier ID. In other words, the laboratory instruments 10PRE, 10POST, 10AI ask the control unit 20 what to do with the sample they just identify. In response to being queried, in step 106, laboratory control unit 20 sends back to the querying laboratory instrument 10PRE, 10POST, 10AI a process command generated based on one or more test commands in database 22 corresponding to the respective sample identifier ID. In other words, the control unit 20 checks what test commands have been identified (register) for the sample and sends the corresponding test commands back to the querying instrument(s).

In a subsequent step 1, the laboratory instruments 10PRE, 10POST, 10AI process the biological sample(s) according to the processing commands received from the control unit 20.

As illustrated on the flowchart of fig. 2, the sequence of steps 102 to 110 is repeated a plurality of times (depending on the particular sample processing workflow) by a plurality of laboratory instruments 10PRE, 10POST, 10 AI. In step 120 (in parallel with the sequence of steps 102 to 110), the control unit 20 verifies the query sequences from the plurality of laboratory instruments 10PRE, 10POST, 10AI against the valid query sequence pattern. A query sequence is considered valid if it relates to a sample processing workflow of the biological sample consistent with the test commands in the database 22.

If the polling sequences from the plurality of laboratory instruments 10PRE, 10POST, 10AI do not match the valid polling sequence pattern, a warning/error signal is generated by the control unit in step 122, which warning/error signal indicates an unsuccessful reading of at least one of the identifier tags 32 by one of the plurality of laboratory instruments 10PRE, 10POST, 10 AI.

When using the prior art method, it is not possible to distinguish which is the unreadable sample identifier, according to a further embodiment disclosed herein, the control unit 20 is configured to: the particular sample identifier(s) that cannot be read by one or more analytical laboratory instruments 10AI are identified by correlating the number of test queries received for each sample identifier with the number of test commands identified for the respective sample identifier(s) so as to avoid test commands that remain open for a long period of time if the analytical laboratory instrument 10AI does not process the corresponding biological sample in accordance with the test commands. This provides a significant advantage over known methods in that manual intervention (e.g., to manually identify the sample container) is greatly reduced. As an additional safety precaution, according to certain embodiments disclosed herein, test results corresponding to biological samples whose identifiers cannot be read by laboratory instruments 10PRE, 10POST, 10AI, but can be inferred (reduced) by control unit 20 are flagged so that manual review can be performed and/or for audit trail reasons.

The validation of the query sequence continues when the query sequences from the plurality of laboratory instruments 10PRE, 10POST, 10AI match the valid query sequence pattern.

Fig. 3 shows a lane diagram of a further embodiment of the disclosed method performed by the laboratory system 1, which laboratory system 1 comprises at least one PRE-analytical laboratory instrument 10PRE, an analytical laboratory instrument 10AI and a sample transport system 50. In a first sequence of steps 102 to 1, PRE-analysis laboratory instrument 10PRE first receives a biological sample, prepares the sample, and sends the sample to analysis laboratory instrument 10AI via sample transport system 50 according to a processing command that includes the next target instrument. In a second sequence of steps 102 to 1, analytical laboratory instrument 10AI receives and identifies a biological sample, sends a test query to control unit 20 in step 104, and processes the sample in accordance with the test command sent by control unit 20 in step 106 in step 110.

From all the time (i.e. in parallel), the control unit 20 monitors the queries from all the instruments 10PRE, 10AI and verifies the query sequence. In the example depicted on fig. 3, the valid query sequence pattern includes the following validity conditions: the next target query must be followed by a test query. No test query after the next target query indicates that the next target analysis laboratory instrument 10AI identified in the next target query failed to read the sample identifier ID from the identifier tag 32. In other words, if the instrument has already queried for the next target instrument, and then no query has been received as to what test to perform on the sample, then a conclusion may be drawn that the next target instrument cannot identify the sample. Otherwise, the next target instrument will ask what test it is going to perform.

Fig. 4 shows a flow chart of a further embodiment of the disclosure, wherein one or more of the plurality of laboratory instruments 10PRE, 10POST, 10AI sends in step 105 a quality signal(s) to the laboratory control unit 20, which quality signal(s) indicates the quality of the identifier tag 32 of the sample container(s) obtained by the identifier tag reader 12. For example, in the case of a barcode, the quality signal(s) indicate the quality of the barcode as specified by ISO/IEC international standard 15415 or 15416. As illustrated on the flow chart, if the tag quality (corresponding to the identifier tag(s) 32) is below the critical tag quality threshold, based on the quality signal(s), the control unit 20 instructs the laboratory instrument 10PRE, 10POST, 10AI to process the biological sample only if: the sample identifier code on the identifier tag 32 is of a secure type and the sample data read from the identifier tag 32 is consistent with the sample data in the database 20. If the code implements an error tolerance, such as a checksum, the identifier code is of a secure type. The data read from the identifier tag 32 includes, but is not limited to, a sample identifier ID, a sample type, a sample collection date, and the like. This data is then compared with corresponding data in a database. If the data read from the identifier tag 32 is consistent with the database 22, it can be safely concluded that no errors have occurred in reading the identifier tag 32, even if the quality signal from the identifier tag reader 12 indicates a low tag quality. On the other hand, if the tag quality corresponding to the identifier tag(s) 32 is below the critical tag quality threshold, and the sample identifier code on the identifier tag 12 is not of a secure type, or the data read from the identifier tag 32 is inconsistent with the data in the database 20, the control unit 20 will:

instructing the laboratory instruments 10PRE, 10POST, 10AI to stop any processing of the biological sample in the sample container 30 with the respective identifier tag 32; and/or

Prompting the user to decide (e.g., by means of a user interface prompt, configuration settings, etc.) whether to stop or continue processing the biological sample(s) held in the sample container(s) 30 with the respective identifier tag(s) 32; and/or

Instruct the laboratory instruments 10PRE, 10POST, 10AI to output the sample container 30 to the wrong orientation; and/or

Marking the analysis result(s) obtained by processing the biological sample(s) held in the sample container(s) 30 with the respective identifier tag(s) 32; and/or

Create a log entry in the database 22 indicating the tag quality, the sample identifier ID, and any data read from the identifier tag(s) 32.

Furthermore, depending on the tag quality signal(s) from the laboratory instruments 10PRE, 10POST, 10AI, the control unit 20 may determine the degradation of the identifier tag reader 12 based on a sequence of two or more signals indicative of degraded tag quality, which sequence corresponds to readings of multiple identifier tags 32 by the same identifier tag reader 12. Furthermore, the control unit 20 is further configured to: the degradation of identifier tag writer 60 is determined based on a sequence of two or more signals indicative of degraded tag quality corresponding to readings of identifier tag 32 originating from one particular supplier and/or written by one particular identifier tag writer 60. Alternatively or additionally, based on a sequence of two or more signals indicative of degraded label quality, the control unit 20 is configured to issue an alert: a certain supplier/source/provider or identifier tag 32 is a sample container 30 provided with a low quality tag. This is advantageous in case of disputes about the reason for failure of the sample container identification allowing a so-called root cause analysis, so that the provider/operator of the laboratory instrument 10PRE, 10POST, 10AI can identify whether the failure is in the identifier tag 32 or the identifier tag reader(s) 12. Additionally, the control unit 20 is configured to: it is determined whether the tag quality corresponding to the identifier tag(s) 32 is below a critical tag quality threshold, and the analysis result(s) obtained by processing the biological sample(s) held in the sample container(s) 30 with the corresponding identifier tag(s) 32 is/are flagged.

Turning now to fig. 5-8, particular embodiments of the laboratory instruments 10PRE, 10POST, 10AI are depicted.

Fig. 5 shows a PRE-analysis laboratory instrument 10PRE, which comprises: a sample container sorting unit 14, the sample container sorting unit 14 being configured to sort the sample containers 30 holding biological samples into sample carriers 40, each sample Carrier 40 being identified by means of a Carrier identifier (Carrier-ID) of a Carrier label 42 attached to the sample Carrier 40, the PRE-analysis laboratory instrument 10PRE being further configured to send a signal to the laboratory control unit to associate the sample identifier ID(s) of the sorted sample containers 30 with the sample Carrier identifier(s) of the corresponding sample Carrier(s) 40.

For embodiments in which PRE-analysis laboratory instrument 10PRE sorts sample containers 30 into sample carriers 40, one or more analysis laboratory instruments 10AI are further configured to: the Carrier identifier Carrier-ID is read from the Carrier tag 42 and transmitted to the laboratory control unit 20 along with the test inquiry. Correspondingly, the laboratory control unit 20 is configured to: if the Carrier identifier Carrier-ID and the sample identifier ID of the test query do not match the association made by the PRE-analysis laboratory instrument 10PRE at the time of sorting, a warning/error signal is generated. In this way, classification and/or processing errors of the sample carrier 40 may be identified.

For PRE-analysis laboratory instruments 10PRE, the query for processing commands by PRE-analysis laboratory instrument(s) 10PRE to laboratory control unit 20 includes: the next target query. Correspondingly, when queried by the PRE-analysis laboratory instrument 10PRE, the control unit 20 is configured to send data indicating the next target instrument for the biological sample based on the sample identifier ID of the biological sample and the list of test commands.

Fig. 6 shows a further embodiment of a PRE-analysis laboratory instrument 10PRE, comprising an aliquoting unit 16, which aliquoting unit 16 is configured to prepare aliquots of biological sample(s) from the sample container(s) 30 and to provide each of said aliquots with a sample identifier ID on an identifier tag 32 by means of an identifier tag writer 60. Correspondingly, the control unit is configured to determine the degradation of the identifier tag writer 60 of the PRE-analysis laboratory instrument 10PRE based on a sequence of two or more signals indicative of degraded tag quality, which sequence corresponds to the reading of the identifier tag 32 originating from an aliquot of that particular PRE-analysis laboratory instrument 10 PRE.

Fig. 7 shows an embodiment of analytical laboratory instrument 10AI, which analytical laboratory instrument 10AI comprises an analysis unit 18, which analysis unit 18 is configured to carry out an analytical test for measuring the presence and/or concentration of at least one analyte in a biological sample, wherein the query for a processing command by analytical laboratory instrument 10AI to laboratory control unit 20 comprises the following test queries: the test query pertains to the analytical test(s) performed on the biological sample based on the sample identifier ID of the biological sample. Correspondingly, the laboratory control unit 20 is configured to retrieve a list of test commands from the database based on the sample identifier ID, the list of test commands comprising one or more test commands, each test command indicating one or more process steps to be performed on the biological sample. When queried by the analysis instrument 10AI and the test command list has been retrieved, the control unit 20 transmits a test command to the querying analysis instrument 10AI based on the sample identifier ID. Then, in response to the test command, the analytical laboratory instrument 10AI carries out an analytical test on the biological sample.

FIG. 8 illustrates an embodiment of POST-analysis laboratory instrument 10POST including memory unit 19. Post-analysis laboratory instrument 10AI is configured to store sample container 30 into storage unit 19 or retrieve sample container 30 from storage unit 19. The query by POST-analysis laboratory instrument(s) 10POST to the laboratory control unit for the process command includes: containers to be stored in the storage unit 19 or retrieved from the storage unit 19. Correspondingly, when queried by POST-analysis laboratory instrument 10POST, control unit 20 sends data indicative of sample container 30 to be retrieved from storage unit 19. POST-analysis laboratory instrument 10POST stores sample container 30 or retrieves sample container 30 from storage unit 19 in response to data indicating sample container 30 to be stored or retrieved.

For POST-analysis laboratory instruments 10POST, the valid query sequence patterns include the following validity conditions: that is, the query of the container to be retrieved must be followed by a test query, wherein no test query after the query of the container to be retrieved indicates that the sample identifier ID cannot be read from the identifier tag 32 by one of the laboratory instruments 10PRE, 10POST, 10 AI. In other words, knowing that sample container 30 is retrieved from POST-analysis laboratory instrument 10POST for an analytical test to be conducted, if no test query is received, the control unit may conclude that analytical instrument 10AI cannot identify the sample.

Further disclosed and proposed is a computer program product comprising computer executable instructions for carrying out the disclosed method in one or more embodiments contained herein, when the program is executed on a computer or a computer network. In particular, the computer program may be stored on a computer readable data carrier or on a server computer. Thus, in particular, one, more than one or even all of the method steps as indicated above may be carried out by using a computer or a network of computers, preferably by using a computer program.

As used herein, a computer program product refers to a program as a tradable product. The product may generally be presented in any format, such as in a paper format, or on a computer-readable data carrier, either internal or at a remote location. In particular, the computer program product may be distributed over a data network (such as a cloud environment). Furthermore, not only is the computer program product, but the execution hardware may also be located internally or in a cloud environment.

Further disclosed and proposed is a computer readable medium comprising instructions which, when executed by a computer system, cause the laboratory system to carry out a method according to one or more embodiments disclosed herein.

Further disclosed and proposed is a modulated data signal comprising instructions that, when executed by a computer system, cause a laboratory system to carry out a method according to one or more embodiments disclosed herein.

With reference to the computer-implemented aspects of the disclosed methods, one or more, or even all, of the method steps of a method according to one or more embodiments disclosed herein may be carried out by using a computer or a network of computers. Thus, in general, any method step comprising the provision and/or manipulation of data may be carried out by using a computer or a network of computers. Generally, these method steps may generally include any method steps in addition to those that require manual work, such as providing a sample and/or performing some aspect of an actual measurement.

List of reference numerals

Laboratory system 1

Laboratory instruments 10PRE, 10POST, 10AI

Pre-analysis laboratory instrument 10PRE

Analytical laboratory instrument 10AI

POST-analysis laboratory instrument 10POST

Identifier tag reader 12

Sample container sorting unit 14

Aliquoting unit 16

Analysis unit 18

Memory cell 19

Control unit 20

Database 22

Sample container 30

Identifier tag 32

Sample carrier 40

Carrier label 42

Sample transport system 50

Identifier tag writer 60

Receiving and identifying samples step 102

Query processing commands (including: next target, test commands) step 104

Transmitting tag quality signal step 105

Send process command step 106

Sending stop processing command/marking the result step 107

Transporting the sample to the next target step 108

Sample processing step 110

Verify query sequence step 120

An alarm/warning step 122 is generated.