US-12625131-B2 - Method of detecting presence or absence of a clot in a liquid sample analyzer

US12625131B2US 12625131 B2US12625131 B2US 12625131B2US-12625131-B2

Abstract

The disclosure relates to a method of detecting a clot in a measurement chamber of a liquid sample analyzer, wherein the liquid sample analyzer comprises at least two analyte sensors, a first analyte sensor, for measuring a first analyte in a liquid sample, and one or more second analyte sensors, for measuring one or more second analytes in the liquid sample in the measurement chamber, the method comprising the steps of, (a) at least partly filling the measurement chamber with a known solution having a composition comprising the first analyte at a pre-determined level, and the second one or more analytes at pre-determined levels, (b) obtaining a first sequence of measurement results by the first analyte sensor, and simultaneously obtaining a second sequence of measurement results by the second, one or more analyte sensors, (c) determining a change of the first sequence of measurement results, (d) determining a change of the second or more sequence of measurement results, and (e) comparing the change of the first sequence of measurement results with the second sequence of measurement results.

Inventors

Michael Taagaard
Peter Aage Frischauf
Flemming Aas

Assignees

RADIOMETER MEDICAL APS

Dates

Publication Date: 20260512
Application Date: 20211013
Priority Date: 20151222

Claims (20)

1 . A method of detecting a clot in a measurement chamber of a liquid sample analyzer, wherein the liquid sample analyzer comprises a first analyte sensor, for measuring a first analyte in a liquid sample, and a second analyte sensor, for measuring a second analyte in the liquid sample in the measurement chamber, the method comprising the steps of: (a) at least partly filling the measurement chamber with a known solution having a composition comprising the first analyte at a first pre-determined level, and the second analyte at a second pre-determined level, (b) obtaining a first sequence of measurement results by the first analyte sensor, the first sequence of measurement results including at least a first measurement value and a second measurement value of the first analyte, and simultaneously obtaining a second sequence of measurement results by the second analyte sensor, the second sequence of measurement results including at least a first measurement value and a second measurement value of the second analyte; (c) determining a first mathematical resultant based on a change of the first sequence of measurement results based on the first and second measurement values of the first sequence of measurement results; (d) determining a second mathematical resultant based on a change of the second sequence of measurement results based on the first and second measurement values of the second sequence of measurement results; (e) obtaining a difference between the change of the first sequence of measurement results and the change of the second sequence of measurement results, such that the first mathematical resultant being based on the first and second measurement values of the first sequence of measurement results is mathematically analyzed with the second mathematical resultant being based on the first and second measurement values of the second sequence of measurement results; and (f) as a result of the difference obtained, performing either: (1) a clot removal procedure, or (2) flowing the known solution and/or liquid sample through the measurement chamber.
2 . The method according to claim 1 , wherein determining each of the changes based on respective first and second measurement values includes determining a respective rate of change, wherein presence of the clot is determined if the difference between the rate of change of the first sequence of measurement results and the change of the second sequence of measurement results is above a threshold.
3 . The method according to claim 1 , wherein presence of a clot is determined if the difference between the change based on the first and second measurement values of the first sequence of measurement results and the change based on the first and second measurement values of the second sequence of measurement results is above a threshold.
4 . The method according to claim 1 , wherein absence of a clot is determined if the difference between the change of the first sequence of measurement results and the change of the second sequence of measurement results is below a threshold.
5 . The method according to claim 1 , wherein the first and second analyte sensors are located at different locations along the measurement chamber.
6 . The method according to claim 1 , wherein the first and/or second sequence of measurement results are used for maintaining a calibration of the first and/or second analyte sensors for subsequent measurements.
7 . The method according claim 1 , wherein the first and second analyte sensors are configured to measure one or more physical parameters of the first and second analytes to thereby obtain the respective first measurement values and the second measurement values, wherein the one or more physical parameters includes at least one of: an analyte concentration, a partial pressure of a gas in liquid, or a pH-value.
8 . The method according to claim 1 , wherein the first and second analyte sensors are adapted for measuring the same type of physical parameters, wherein the first and second analytes are the same.
9 . The method according to claim 1 , wherein the first and second analyte sensors are adapted for measuring the same type of physical parameters for different analytes, wherein the first and second analytes are different.
10 . The method according to claim 1 , wherein the first and second analyte sensors are electrochemical sensors, each sensor comprising an ion selective electrode.
11 . The method according to claim 1 , wherein the first analyte sensor includes an electrochemical sensor, wherein the electrochemical sensor includes an electrode device with a solid state inner reference system.
12 . The method according to claim 1 , wherein the first and second analyte sensors are optical sensors.
13 . The method according to claim 1 , wherein the liquid sample analyzer comprises a third analyte sensor, for further determining which of the first and second analyte sensors are affected by a clot in the measurement chamber, to thereby be an affected analyte sensor, by cross comparing a change in measurement results of the affected analyte sensor against a respective change in measurement results of the other analyte sensors, wherein the clot is affecting the affected analyte sensor where the change in measurement results is deviating from a respective change in measurement results of the other analyte sensors.
14 . The method of claim 1 , the method further including triggering an alarm to indicate a presence of the clot.
15 . A liquid sample analyzer adapted for performing a method of clot detection, the liquid sample analyzer comprising: (a) a measurement chamber with an inlet for feeding a liquid sample to the measurement chamber, and an outlet for discharging the liquid sample from the measurement chamber; (b) a first analyte sensor; (c) a second analyte sensor; (d) a third analyte sensor; each of the second analyte sensor and the third analyte sensor facing the measurement chamber, the first, second, and third analyte sensors each being arranged for measuring an analyte in the liquid sample in the measurement chamber; and (e) a signal processor configured for: (i) obtaining a first sequence of measurement results by the first analyte sensor, the first sequence of measurement results including at least a first measurement value and a second measurement value, obtaining a second sequence of measurement results by the second analyte sensor, the second sequence of measurement results respectively including at least a first measurement value and a second measurement value, and obtaining a third sequence of measurement results by the third analyte sensor, the third sequence of measurement results respectively including at least a first measurement value and a second measurement value, (ii) determining a change based on respective first and second measurement values of each of the first, second, and third sequence of measurement results, (iii) calculating a first average change using the first and second measurement values of each of the second and third sequence of measurement results, (iv) calculating a difference between the change based on the first and second measurement values of the first sequence of measurement results and the calculated first average change, and (v) as a result of the calculated difference, performing either: (A) a clot removal procedure, or (B) further feeding the liquid sample to the measurement chamber.
16 . The liquid sample analyzer according to claim 15 , wherein the liquid sample analyzer is adapted for measurement of blood parameters in a whole blood sample.
17 . The liquid sample analyzer according to claim 15 , wherein the first and second analyte sensors are located at different locations along the measurement chamber.
18 . A method of detecting a clot in a measurement chamber of a liquid sample analyzer, wherein the liquid sample analyzer comprises a first analyte sensor, a second analyte sensor, and a third analyte sensor, each of the first, second, and third analyte sensors being for measuring an analyte in a liquid sample in the measurement chamber, the method comprising the steps of: (a) at least partly filling the measurement chamber with a known solution having a composition comprising the analyte at a first pre-determined level; (b) obtaining a first sequence of measurement results by the first analyte sensor, the first sequence of measurement results including at least a first measurement value and a second measurement value, obtaining a second sequence of measurement results by the second analyte sensor, the second sequence of measurement results respectively including at least a first measurement value and a second measurement value, and obtaining a third sequence of measurement results by the third analyte sensor, the third sequence of measurement results respectively including at least a first measurement value and a second measurement value; (c) determining a change based on respective first and second measurement values of each of the first, second, and third sequence of measurement results; (d) calculating a first average change using the first and second measurement values of each of the second and third sequence of measurement results; (e) calculating a difference between the change based on the first and second measurement values of the first sequence of measurement results and the calculated first average change; and (f) as a result of the calculated difference, performing either: (1) a clot removal procedure, or (2) flowing the known solution and/or liquid sample through the measurement chamber.
19 . The method of claim 18 , wherein the analyte is selected from calcium, potassium, and sodium.
20 . The method of claim 18 , the method further comprising: (a) calculating a second average change using the first and second measurement values of each of the first and third sequence of measurement results; and (b) comparing the change based on the first and second measurement values of the second sequence of measurement results with the calculated second average change to thereby determine if a clot is present.

Description

This application is a continuation of U.S. patent application Ser. No. 16/064,742, filed Jun. 21, 2018, which is a national stage filing under 35 U.S.C. § 371 of International Application No. PCT/EP2016/081643, filed on Dec. 19, 2016, which claims priority of Danish Patent Application No. PA 2015 00831, filed Dec. 22, 2015. The contents of these applications are each incorporated herein by reference. The present invention relates in one aspect to a method of detecting a clot in a liquid sample analyzer comprising one or more analyte sensors for measuring a physical parameter for respective analytes, and to a liquid sample analyzer comprising a measuring chamber with one or more such analyte sensors, and a signal processor configured for detecting a clot in the measuring chamber. In a particular aspect, the present invention relates to a method of detecting a clot in a blood analyzer comprising one or more analyte sensors for measuring blood parameters, and to a blood analyzer comprising a measuring chamber with one or more such analyte sensors, and a signal processor configured for detecting a clot in the measuring chamber. According to a yet further aspect, a computer-implemented method of detecting a clot in a liquid sample analyzer, and a corresponding software product that can be loaded into a signal processor of a liquid sample analyzer are provided. Also in this aspect, the liquid sample analyzer may be a blood analyzer for analyzing e.g. a whole blood sample. BACKGROUND OF THE INVENTION Analyzers for measuring physical parameters of analytes in a liquid sample by means of respective analyte sensors are widely used in various industries, such as food industry, environmental industry, as well as medical and clinical industry. To ensure both accurate and precise results, the performance of such analyzers and the associated sensors is continuously scrutinized. This typically includes both detailed calibration and quality control procedures using standardized reference liquids including the respective analytes in well-defined compositions. The accurate and precise operation of analyzer systems is of particular importance in clinical analysis applications for analyzing physical parameters of analytes in bodily fluids, such as whole blood. In addition to the accuracy, precision, and reliability requirements, such analyzer systems for clinical applications are also subject to further critical constraints, such as a short time to obtaining a measurement result, and the capability of providing the highly reliable results from very small sample volumes. The combination of all these constraints is particularly relevant in blood analyzers. Blood analyzers provide measurements of various parameters for analyzing the blood of a mammal subject, e.g. for establishing and/or monitoring a biological condition of the subject. Typically, the mammal subject is a human patient. In a variety of instances it is desirable to measure e.g. the partial pressure of blood gasses in a whole blood sample of the mammal subject, concentrations of electrolytes and metabolites in the blood sample, as well as the hematocrit value of the blood sample. For example, measuring pCO2, pO2, pH, Na+, K+, Ca2+, Cl−, glucose, lactate and hemoglobin values are primary clinical indications in assessing the condition of a medical patient. A number of different analyzers currently exist for making such measurements. Such analyzers are able to perform precise measurements in order to provide the most meaningful diagnostic information. In order to use as little of the patient's blood as possible in each analysis performed, the measuring chamber which is employed to analyze a blood sample is preferably relatively small. Performing blood analysis using a small blood sample is important when a relatively large number of samples must be taken in a relatively short amount of time or if the volume of blood is limited, as in neonates. For example, patients in intensive care require a sampling frequency of 15-20 per day for blood gas and clinical chemistry measurements, leading to a potentially large loss of blood during patient assessment. Furthermore, in order to limit the number of tests which must be performed it is desirable to gather as much information as possible upon completion of each test. Furthermore, for the same reasons, it is important that the measurements and corresponding analysis results obtained from these measurements are reliable. Each measurement is therefore typically subject to a calibration and/or quality control procedure using different rinsing, calibration and/or reference liquids and the measurement chamber is thoroughly rinsed after each measurement to avoid contamination of any subsequent measurements. However, a common issue in blood analyzers, in particular in systems with very small measurement chambers, is due to the presence of clots in whole blood samples. The clots may result in the formation of plugs impeding, obstructing