Methods for detecting obstructions in fluid analyzers

Abstract

A method and system for detecting obstruction on a sensor of a fluid analyzer, comprising: contacting a first calibration fluid with a sensor to generate a signal indicating a first potential of the first calibration fluid; contacting a second calibration fluid with a sensor to generate a signal indicating a second potential of the second calibration fluid; storing a first response slope; contacting the first calibration fluid with a sensor to generate a signal indicating a third potential of the first calibration fluid; contacting the second calibration fluid with a sensor to generate a signal indicating a fourth potential of the second calibration fluid; storing a second response slope; and storing data indicating obstruction on the sensor in response to the difference between the first response slope and the second response slope exceeding a threshold.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 371,943, filed August 19, 2022, pursuant to 35 USC §119(e). The entire contents of the aforementioned patent application are hereby expressly incorporated herein by reference. Background Technology

[0003] In various situations, it is desirable to measure components in body fluids, such as partial pressures of blood gases in whole blood samples, electrolyte concentrations in blood samples, and hematocrit in blood samples. Examples include measuring pCO2, pO2, pH, and Na+. + K + Ca 2+ Hematocrit is a key clinical indicator in assessing a patient's condition. Additionally, to attempt to use as little patient blood as possible in each analysis performed, the apparatus used to analyze blood samples is preferably relatively small. It is important to perform blood analyses using small blood samples, for example, when a relatively large number of samples must be collected in a relatively short time, or in situations where blood volume is limited (such as in newborns).

[0004] For example, patients in intensive care may require 15-20 samplings per day for blood gas and clinical chemistry measurements, potentially leading to significant blood loss during patient assessment. Additionally, by significantly reducing the size of the analyzer to make the unit portable, analyses can be performed at the point of care. Moreover, smaller size generally also means less turnaround time. Furthermore, to limit the number of tests that must be performed, it is desirable to collect as much information as possible upon completion of each test. However, size limitations are imposed on the sensors used to measure blood chemistry. These size limitations are largely due to the physical geometry of the sensors and the connections to them.

[0005] Point-of-care blood gas analyzers allow for in vitro analysis at the patient's bedside, in the emergency room, or in the intensive care unit. These units use solid-state sensors with thin-film electrodes. The microchip, reagents, calibrator, and sampling device are all contained within a single-use cartridge system. Healthcare facilities can opt for cartridges with additional testing options, including potassium, glucose, blood urea nitrogen (BUN), and lactate. Because whole blood can be tested, minimal sample handling is required; there is no need to centrifuge the sample and separate plasma from red blood cells before testing.

[0006] In environments requiring medium to high volume sample testing, multipurpose cartridge systems are used. These cartridges can be customized for specific analyte menus and testing volumes. The number of samples that can be measured on a cartridge can vary from 25 to 750, and once loaded into the analyzer, the cartridge typically has a lifespan between 14 and 30 days.

[0007] The basic operating principle of blood gas analyzers has not changed significantly compared to earlier units. Around 2005, freestanding cartridges were introduced into several analytical systems, paving the way for point-of-care testing and compact units. Whole blood can be analyzed for many analytes, including electrolytes potassium (K+), sodium (Na+), and calcium (Ca2+), as well as metabolites such as glucose, lactate, blood urea nitrogen (BUN), and creatine. The sensors used for these measurements are ion-specific or ion-selective electrodes (ISEs). These sensors are membrane-based electrochemical sensors that respond to specific ions. Biosensors are used in analyzers in traditional clinical laboratories and also in point-of-care testing devices. Biosensors convert biochemical signals into electrical signals.

[0008] Electrolytes are determined by potentiometry, a form of electrochemical analysis. In potentiometry, a potential or voltage is measured between two electrodes in a solution. These potentials can also be generated when a metal and its ions are present in the solution. Different concentrations of ions can be separated by using a membrane that is semi-permeable to ions. These systems use a reference electrode and a measuring electrode. A constant voltage is applied to the reference electrode; the voltage difference between the reference and measuring electrodes is used to calculate the concentration of ions in the solution.

[0009] Ion-selective electrodes are an improvement on the principle of potentiometric measurement. They generate a potential difference or electron flow by selectively transferring the analyte ions from the sample solution to the membrane phase. Ion-selective electrodes measure the concentration of free ions of the desired analyte on the selectively generated membrane. The membrane has a complex composition, containing organic solvents, inert polymers, plasticizers, and ion carriers, where the ion carriers are molecules that increase the membrane's permeation selectivity for specific ions.

[0010] Amperometric methods measure the current generated by redox reactions. Types of current analysis include enzyme electrodes, such as glucose oxidase electrodes and Clark-type pO2 electrodes. These types are designed as biosensors and are suitable for testing in clinical laboratories as well as at the point of care. Enzyme-based biosensor technology was initially developed for measuring blood glucose. A solution of glucose oxidase is placed between a gas-permeable membrane and a semi-permeable outer membrane of the pO2 electrode. Glucose in the blood diffuses through the semi-permeable membrane and reacts with glucose oxidase. Glucose is converted into hydrogen peroxide and gluconic acid by glucose oxidase.

[0011] A polarization voltage is applied to the electrode, which oxidizes hydrogen peroxide and causes electron loss. Oxygen is consumed near the surface of the pO2 electrode, and its consumption rate is measured. The rate of electron loss and the rate of decrease in pO2 are proportional to the glucose concentration in the sample. Enzyme-based biosensors are also used to measure cholesterol, creatine, and pyruvate.

[0012] The basic operating principle of a laboratory blood gas analyzer is the same as that described earlier for the electrodes used for pH, pCO2, and pO2, as well as the ion-specific electrodes used for measuring electrolytes. Typically, approximately 50–120 μl of a well-mixed arterial blood sample is injected into the measurement chamber through the inlet and sample probe. The sample then contacts the surface of each electrode for a few seconds.

[0013] One of the main challenges of existing fluid analyzers is detecting and removing obstructions, such as blood clots. The presence of obstructions can hinder the flow path of the fluid analyzer, increase its occupancy time, and affect the response of individual sensors, thus leading to biased results, for example, regarding key blood gas parameters (e.g., pH and / or pCO2). Obstructions typically form during the preparation of the sample for analysis. However, even with extremely careful pre-analytical procedures, small obstructions can still occur in the fluid (or measurement) channels.

[0014] Therefore, it is desirable to provide a fluid analyzer that can detect the presence (or absence) of an obstruction without the need for additional sensors, remove the obstruction by fluid suction and discharge, and / or alert the user to the presence (or absence) of the obstruction and the questionability of the result. Summary of the Invention

[0015] The methods and systems disclosed herein are used to address the following problems: detecting the presence (or absence) of obstructions on a fluid analyzer without the need for additional sensors, removing such obstructions via fluid suction and discharge, and / or alerting the user to the presence (or absence) of obstructions and the questionability of the results.

[0016] According to one aspect of this disclosure, an exemplary fluid analyzer may include: a fluid channel operable to deliver a fluid; a sensor in fluid communication with the fluid channel; an instrument operable to receive a signal generated by the sensor and convert the signal into information indicating the potential of the fluid; a first calibration fluid having a first analyte concentration; a second calibration fluid having a second analyte concentration different from the first analyte concentration; one or more calibration fluid inlet ports in fluid communication with the fluid channel, the one or more calibration fluid inlet ports operable to receive the first calibration fluid and the second calibration fluid; one or more valves located between the one or more calibration fluid inlet ports and the sensor, the one or more valves being operable to provide one or more samples of each of the first calibration fluid and the second calibration fluid to the fluid channel; and a control system having a processor operable to execute processor-executable code, the processor-executable code, when executed by the processor, causing the processor to run an obstruction detection algorithm, including: controlling the one or more valves to deliver the first calibration fluid to the sensor during a first time period. The fluid and the second calibration fluid are sequentially delivered to the sensor through the fluid channel, and first data indicating a first response slope is stored, the first response slope being at least partially based on a first difference between first information and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid; in a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; and third data indicating a blockage on the sensor is stored in response to the difference between the first response slope and the second response slope exceeding (i.e., above or below) a threshold. In some embodiments, the third data is stored when the difference is above the threshold. In other embodiments, the difference and the threshold may be opposite. In this embodiment, when the difference is below a threshold, third data is stored.

[0017] According to another aspect of this disclosure, an exemplary method for detecting obstruction on a sensor of a fluid analyzer may include: in a first time period, successively flowing a first calibration fluid and a second calibration fluid having a known analyte concentration to the sensor, and determining a first response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; in a second time period, successively flowing the first calibration fluid and the second calibration fluid to the sensor, and determining a second response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; and determining the presence of obstruction on the sensor by a processor based at least in part on the difference between the first response sensitivity and the second response sensitivity.

[0018] According to another aspect of this disclosure, an exemplary fluid analyzer may include: a sensor configured to measure at least one parameter associated with a fluid; one or more containers configured to store a first calibration fluid and a second calibration fluid having a known analyte concentration; one or more channels configured to provide fluid communication between the sensor and the one or more containers; and a processor configured to determine the presence of an obstruction to the sensor, wherein the processor is configured to: in a first time period, sequentially flow the first calibration fluid and the second calibration fluid to the sensor and determine a first response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; in a second time period, sequentially flow the first calibration fluid and the second calibration fluid to the sensor and determine a second response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; and determine the presence of the obstruction based at least in part on the difference between the first response sensitivity and the second response sensitivity.

[0019] According to another aspect of this disclosure, an exemplary non-transitory computer-readable medium may store an exemplary obstruction detection algorithm including processor-executable code that, when executed by a processor, causes the processor to: control one or more valves to sequentially deliver a first calibration fluid and a second calibration fluid through a fluid channel to a sensor during a first time period; and store first data indicating a first response slope, the first response slope being at least partially based on a first difference between first information generated by an instrument and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid. In a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid through the fluid channel to the sensor, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information generated by the instrument and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; and third data indicating a blockage on the sensor is stored in response to the difference between the first response slope and the second response slope exceeding (i.e., above or below) a threshold. In some embodiments, the third data is stored when the difference is above the threshold. In other embodiments, the difference and the threshold may be opposite. In this embodiment, the third data is stored when the difference is below the threshold. Attached Figure Description

[0020] To assist those skilled in the art in making and using the subject matter of this document, reference has been made to the accompanying drawings, which are not intended to be drawn to scale, and in the drawings, for consistency, the same reference numerals are intended to refer to similar elements. For clarity, not every part in every drawing may be labeled.

[0021] Figure 1 This is a schematic diagram of an exemplary embodiment of a fluid analyzer constructed according to the present disclosure.

[0022] Figure 2 It is possible to be Figure 1 A cross-sectional view of an exemplary embodiment of a current sensor of the prior art read by a fluid analyzer.

[0023] Figure 3 It is possible to be Figure 1 An exploded view of another embodiment of a current sensor in the prior art, read by a fluid analyzer.

[0024] Figure 4It is possible to be Figure 1 A cross-sectional view of an exemplary embodiment of a potential sensor of the prior art read by a fluid analyzer.

[0025] Figure 5 yes Figure 1 The block diagram of the control system of the fluid analyzer is depicted in the figure.

[0026] Figure 6 It is pending. Figure 1 A top view of the sensor array read by the fluid analyzer depicted in the image.

[0027] Figure 7 This is a flowchart illustrating an exemplary obstacle detection algorithm based on this disclosure.

[0028] Figure 8 yes Figure 6 The time-lapse diagram depicts the sensor array of the fluid analyzer.

[0029] Figure 9A-9G Is with Figure 8 The time-lapse graph depicted in the figure corresponds to a graph of the sensor response of the electrochemical sensor array. Detailed Implementation

[0030] Before explaining at least one embodiment of this disclosure in detail, it is to be understood that, unless otherwise stated, this disclosure is not limited in its application to the details of construction, experiment, exemplary data and / or component arrangement set forth in the following description or illustrated in the accompanying drawings.

[0031] This disclosure can have other embodiments or can be practiced or performed in various ways. Furthermore, it should be understood that the wording and terminology used herein are for descriptive purposes and should not be considered limiting.

[0032] The following detailed description refers to the accompanying drawings. Identical reference numerals in different drawings may designate the same or similar elements. Unless otherwise defined herein, scientific and technical terms used in connection with the currently disclosed and claimed inventive concepts shall have the meanings commonly understood by one of ordinary skill in the art. Furthermore, unless the context requires otherwise, singular terms shall include plural and plural terms shall include singular. The nomenclature used in connection with analytical chemistry, synthetic organic chemistry, and medical and medicinal chemistry described herein, as well as their laboratory procedures and techniques, are those well-known and commonly used in the art.

[0033] All patents, published patent applications, and non-patent publications mentioned in this specification demonstrate the skill of a person skilled in the art to which the currently disclosed and / or claimed inventive concepts pertain. All patents, published patent applications, and non-patent publications cited in any part of this application are expressly incorporated herein by reference in their entirety, as if each individual patent or publication were specifically and individually identified as incorporated by reference.

[0034] In view of this disclosure, all non-transitory computer-readable media, control systems, fluid analyzers, and / or methods disclosed and / or claimed herein can be manufactured and performed without excessive experimentation. While fluid analyzers and methods of the currently disclosed and / or claimed inventive concepts have been described according to preferred embodiments, it will be apparent to those skilled in the art that variations can be applied to the fluid analyzers and / or methods, as well as to the steps or sequences of steps of the methods described herein, without departing from the concept, spirit, and scope of the currently disclosed and / or claimed inventive concepts. All such similar alternatives and modifications that will be apparent to those skilled in the art are considered to be within the spirit, scope, and concept of the inventive concepts as defined by the appended claims.

[0035] As used in accordance with this disclosure, unless otherwise stated, the following terms shall be understood to have the following meanings:

[0036] When used in conjunction with the term "comprising" in the claims and / or description, the use of the terms "a," "an," or "a kind" may mean "one," but it is also consistent with the meaning of "one or more," "at least one," and "one or more." The singular forms "a," "an (kind)," and "the" include a plurality of referents unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" may refer to one or more, two or more, three or more, four or more, or more compounds. The term "a plurality" means "two or more." The use of the term "or" in the claims is intended to mean "and / or," unless it is clearly indicated that only alternatives are referred to or that the alternatives are mutually exclusive; however, this disclosure supports the definition of referring only to alternatives and "and / or." Throughout this application, the term "about" is used to indicate that a value includes the means, the inherent variation in the error of the method used to determine the value, or the variation that exists between the objects of study. For example, but not as a limitation, when using the term "about," the specified value may vary from the prescribed value by ±20%, ±10%, ±5%, ±1%, or ±0.1%, as such variation is appropriate for performing the disclosed method and is understood by one of ordinary skill in the art. The use of the term "at least one" will be understood to include any quantity of one or more, including but not limited to 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" can be extended to up to 100 or 1000 or more, depending on the term it is associated with; additionally, quantities of 100 / 1000 should not be considered limiting, as higher limits may also produce satisfactory results. Furthermore, the use of the term "at least one of X, Y, and Z" will be understood to include individual X, individual Y, and individual Z, as well as any combination of X, Y, and Z. For example, the use of ordinal terms (i.e., “first,” “second,” “third,” “fourth,” etc.) is solely for the purpose of distinguishing two or more items and is not intended to imply any order or sequence or importance of one item relative to another, or any order of addition.

[0037] As used in the description herein, the terms “comprising,” “including,” “having,” “owning,” or any other variation thereof are intended to cover non-exclusive inclusion. For example, unless otherwise stated, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may also include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0038] Furthermore, unless explicitly stated otherwise, "or" implies both "or" and "or" rather than mutually exclusive "or". For example, one of the following conditions A or B is satisfied: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0039] Furthermore, the terms "a" or "an" are used to describe the elements and components of the embodiments herein. This is done merely for convenience and to give a general meaning to the inventive concepts. The description should be interpreted as including one or more, and the singular includes the plural, unless it is obvious otherwise. Additionally, unless explicitly stated otherwise, the term "a plurality of" is used to mean "more than one".

[0040] As used herein, any reference to “an embodiment,” “an embodiment,” “some embodiments,” “an example,” “for example,” or “example” means that a particular element, feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. For example, the terms “in some embodiments” or “an example” appearing throughout the specification do not necessarily refer to the same embodiment.

[0041] As used herein, the term "or combinations thereof" refers to all permutations and combinations of the items listed preceding the term. For example, "A, B, C, or combinations thereof" is intended to include at least one of the following: A, B, C, AB, AC, BC, or ABC, and also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB if the order is significant in the particular context. Continuing with this example, what is explicitly included are combinations that contain repetitions of one or more items or terms, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, etc. Those skilled in the art will understand that there is generally no limit to the number of items or terms in any combination unless otherwise apparent from the context.

[0042] As used herein, the term “substantially” means that the events or conditions described below occur completely, or that the events or conditions described below occur to a great extent or degree. For example, the term “substantially” means that the events or conditions described below occur at least 90% of the time, at least 95% of the time, or at least 98% of the time.

[0043] As used herein, the term "sample" will be understood to include any type of biological or non-biological sample that can be utilized according to the inventive concepts currently disclosed and / or claimed. That is, a sample can be any fluid sample and / or a sample capable of being fluid (e.g., a biological sample that mixes with a fluid matrix). Examples of usable biological samples include, but are not limited to, whole blood or any portion thereof (i.e., plasma or serum), saliva, sputum, cerebrospinal fluid (CSF), surgical drainage, skin, interstitial fluid, tears, mucus, urine, swabs, combinations thereof, etc. Examples of non-biological samples include wastewater, industrial fluids, etc. It should be noted that although this disclosure describes the use of a fluid analyzer to analyze biological samples, those skilled in the art will appreciate that the concepts disclosed herein can be applied to any sample in which the concentration of an analyte can be determined, and therefore, this disclosure is not limited to biological samples. Exemplary target analytes include, but are not limited to, oxygen, or metabolites, including but not limited to, glucose, lactate, creatinine, etc.

[0044] As used herein, the term "fluid" refers to a liquid or gas that can pass through at least a portion of a fluid analyzer and be analyzed by components of the fluid analyzer. Fluids can be samples, calibration reagents (e.g., fluids or gases), wash fluids, or quality control fluids.

[0045] As used herein, a circuit can be an analog and / or digital component, or one or more appropriately programmed processors (e.g., microprocessors) and associated hardware and software, or hard-wired logic. Furthermore, a “component” can also perform one or more functions. The term “component” can include hardware such as processors (e.g., microprocessors), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), combinations of hardware and software, and / or the like.

[0046] Software may include one or more computer-readable instructions that, when executed by one or more components, cause those components to perform a specified function. It should be understood that the algorithms described herein may be stored on one or more non-transitory memories. Exemplary non-transitory memories may include random access memory, read-only memory, flash memory, and / or the like. Such non-transitory memories may be electrical, optical, and / or similar.

[0047] When a numerical range is described or defined herein, the range includes its endpoints and all individual integers and fractions within that range, and also includes each of the narrower ranges formed by all the various possible combinations of these endpoints and the internal integers and fractions, to form a subgroup of the larger value group within the range, to the extent that each of those narrower ranges is explicitly described. When a numerical range is stated herein as being greater than the stated value, the range remains finite and is defined at its upper end by values ​​operable within the context of the invention as described herein. When a numerical range is stated herein as being less than the stated value, the range remains defined at its lower end by non-zero values.

[0048] It should also be understood that, as used herein, the term “user” is not limited to humans and may include, for example, computers, servers, websites, processors, network interfaces, people, user terminals, virtual computers, combinations thereof, etc.

[0049] As used herein, "calibration parameters" refers to a set of data points that correlates a signal from a sensor with a known analyte concentration, or one or more functions used to obtain such a set of data points. Calibration parameters can be derived from calibration algorithms, such as linear algorithms configured to fit a function to at least two calibration points, spline-based algorithms, exponential algorithms, least squares algorithms, logarithmic algorithms, etc.

[0050] As used herein, the term "calibration logic" refers to the program logic within a controlled system used by a processor to interpret data measured by one or more electrodes. Specifically, the term "calibration logic" is the program logic of a control system used by a processor to interpret data from an electrochemical sensor having at least a working electrode and a reference electrode.

[0051] Electrochemical sensors are widely used in in vitro diagnostic instruments. These sensors include electrodes made of metal, fabricated by screen printing with metallic ink (thick film method), or by chemical vapor deposition of metal films (thin film method), and typically require calibration. This calibration corrects for changes in the sensor's electrode size and surface area, variations in chemical and biochemical activity over its lifespan, electrical signal drift, etc. For example, the oxygen sensor used in the Siemens Healthcare Point of Care (POC) RAPIDPoint 500 blood gas analyzer features a screen-printed platinum working electrode, a silver / silver chloride reference electrode, and a gold counter electrode.

[0052] Now refer to the attached diagram, and especially to... Figure 1The illustration shows an exemplary embodiment of a combination of a fluid analyzer 10, a calibration cartridge 14, and one or more electrochemical sensors 18 (hereinafter referred to as "electrochemical sensors 18"). The electrochemical sensors 18 can be implemented in the form of a cartridge connected to the fluid analyzer 10, for example, according to... Figure 1 As shown in the diagram. The fluid analyzer 10 may include a housing 26 that supports and / or surrounds at least a portion of each electrochemical sensor 18.

[0053] This disclosure describes an obstacle detection algorithm for determining whether any electrochemical sensor 18 is affected by an obstacle. In one embodiment, the currently disclosed method is a novel way to detect the presence or absence of an obstacle on or near at least one of the electrochemical sensors 18 without using additional sensors. The presence of a blood clot or other obstacle on or near a single electrochemical sensor 18 can alter the local electrolyte environment (i.e., electrolyte diffusion kinetics, buffer capacity, residual contamination, and / or sample dilution) or the local analyte concentration around a corresponding one of the electrochemical sensors 18, which can significantly affect response sensitivity (i.e., slope), kinetics, and result accuracy.

[0054] The currently disclosed method uses the relative slope change at each sensor (i.e., comparing the current response slope with the response slope at an adjacent previous time point) to determine whether each sensor of the electrochemical sensor 18 is affected by obstruction. A sudden drop in the relative slope change exceeding a predetermined threshold (i.e., a threshold determined based on empirical data) is an indication that obstruction may be forming at or near each sensor of the electrochemical sensor 18. In response to detecting the presence of obstruction, the fluid analyzer 10 may alert the user to the presence of obstruction and the suspicion of the result and / or perform an obstruction removal procedure (e.g., fluid aspiration and effusion and / or manual obstruction removal). Alternatively, or in addition to detecting the presence of obstruction, the currently disclosed method may detect the absence of obstruction when the relative slope change does not drop below the predetermined threshold, and in response, the fluid analyzer 10 may alert the user to the absence of obstruction.

[0055] The response sensitivity of the electrochemical sensor 18 can be calculated based on its response to at least two concentrations of calibrators (i.e., two-point calibration). The response slope can be given by the following equation (1):

[0056]

[0057] Where m is the response slope, V high It is the signal response of electrochemical sensor 18 to high concentrations of calibration reagent, V low It is the signal response of electrochemical sensor 18 to low concentrations of calibration reagent, C high It is the concentration of the high-concentration calibration reagent, and Clow This refers to the concentration of a low-concentration calibration reagent. Signal response V high and V low This is the electrical signal response, which can be a voltage signal response or a current signal response. The signal response and the corresponding concentration of the calibration reagent can be referred to as the calibration parameter used to determine the response slope m, which indicates the sensitivity of a single sensor to the response to or measurement of the analyte concentration. Each electrochemical sensor 18 has its own slope specification within its respective lifetime.

[0058] When properly manufactured, each electrochemical sensor 18 has a stable near-Nernstian slope, thus ensuring sufficient accuracy and consistency in response performance (i.e., response accuracy and precision). However, in the integrated sensor module of the fluid analyzer 10, each individual electrochemical sensor 18 may exhibit evidence of failure in multiple modes.

[0059] First, when the response slope of the electrochemical sensor 18 slowly decreases and eventually falls out of the specification range of the electrochemical sensor 18, this slow decrease may be evidence of irregularities in the sensing element of the electrochemical sensor 18 (e.g., leaching of ion carriers or plasticizers, migration of foreign sensing elements and / or dilution or hydration of elements).

[0060] Second, when the response slope of each electrochemical sensor 18 simultaneously "shifts" to higher or lower, this simultaneous shift may be evidence of obstruction on or near the reference electrode, causing the reference electrode to lose its stable liquid junction potential. This could cause the electrochemical sensor 18 to return unstable signals in response to both high and low concentrations of calibration reagents.

[0061] Third, when the response slope of a particular electrochemical sensor 18 exhibits a sudden shift, such as a sharp drop, this sudden shift may be evidence of foreign matter (i.e., obstruction) coating or partially coating the sensing element of the electrochemical sensor 18 (e.g., the covering film of an ion-selective electrode). Once a foreign matter appears on a portion (e.g., a large portion) of the sensing film of the electrochemical sensor 18, the local diffusion and concentration environment is temporarily altered, and the foreign matter acts as a “contamination” layer, a “buffer” layer, or a “diffusion slowing” layer. During two-point calibration, the high-concentration calibration reagent is “diluted” by the foreign matter, while the low-concentration calibration reagent is also “contaminated” by the foreign matter. As a result, the response slope of the electrochemical sensor 18 drops abruptly in response to the presence of the foreign matter. If the foreign matter is relatively small (i.e., microclumps), its presence may not affect the local concentration environment, and its effect on the slope may be negligible, thus allowing these electrochemical sensors 18 to operate relatively normally.

[0062] The obstacle detection algorithm described herein relates to the third fault mode described above. To detect obstacles on or near the electrochemical sensor 18 of the fluid analyzer 10, the currently disclosed method uses the current response sensitivity (m...) of the electrochemical sensor 18... n ) and the previous "normal" response sensitivity (m) of the same electrochemical sensor 18 n-1 The difference between the two response sensitivities is given by equation (2):

[0063] Δm=m n -m n-1 (2)

[0064] In the absence of obstructions, Δm may approach zero. Through experimentation, empirical data can be used to establish a threshold range to include any microclusters that may not drastically affect the sensor response.

[0065] After Δm exceeds (i.e., exceeds) the threshold range, m n-1 The slope of the "normal" response will be stored for x = 1, 2, etc., and the next adjacent time point (m) will be stored. n+1 The response slope of ) is compared with that of (i.e., Δm) * =m n+x -m n-1 ). Δm * Continuing to exceed the threshold range is evidence that further interference with the electrochemical sensor 18 is impeded. In some embodiments, Δm and the threshold range m n-1 Conversely, in this case, when Δm is less than the threshold range, m n-1 This is evidence that the electrochemical sensor 18 is being further interfered with. Therefore, changes in the response slope exceeding the threshold range (i.e., above and / or below a predetermined value) are evidence of this interference.

[0066] When the foreign object is removed from the electrochemical sensor 18, the response slope of the electrochemical sensor 18 can be restored to normal (i.e., close to zero or within the threshold range, which means that the sensor signal difference in response to high concentration and low concentration calibration reagents is relatively consistent).

[0067] In some embodiments, the obstruction detection algorithm is applied to determine the presence of an obstruction for each individual electrochemical sensor 18 of the fluid analyzer 10. This can be observed by tracking a corresponding, continuous decrease in the slope of the electrochemical sensor 18 as the obstruction migrates from an upstream position to a downstream position on the fluid analyzer 10. When the obstruction migrates from its initial position on a particular electrochemical sensor 18 without any intervention, that particular electrochemical sensor 18 can return to a normal response state.

[0068] In some embodiments, each electrochemical sensor 18 is a current sensor 22 (hereinafter referred to as "current sensor 22"). Figure 2 An exemplary current sensor is shown. The current sensor 22 typically includes two or more electrodes 30, which are shown as a reference electrode 34, a counter electrode 36, and a working electrode 38, as an example. Although... Figure 1 The reference electrode 34 is shown upstream of the counter electrode 36 and the working electrode 38, but in one embodiment, the reference electrode 34 is downstream of the counter electrode 36 and the working electrode 38 (not shown). It should be noted that other sensor arrangements, such as opposing sensor arrays with different electrode arrangements, may be used, for example, including coplanar electrode arrangements and / or opposing electrode arrangements.

[0069] In some embodiments, the reference electrode 34, counter electrode 36, and working electrode 38 of the current sensor 22 are selected to be capable of generating an electrochemical reaction, i.e., reduction-oxidation (hereinafter referred to as "redox"), in the presence of oxygen at a suitable voltage potential. In one embodiment, the reference electrode 34, counter electrode 36, and working electrode 38 are selected to be capable of generating an electrochemical reaction with a target analyte or a reaction byproduct of the target analyte in the sample. In one embodiment, the reference electrode 34 may be made of silver / silver chloride, the counter electrode 36 may be made of gold, and the working electrode 38 may be made of platinum. However, it should be understood that the reference electrode 34, counter electrode 36, and working electrode 38 may be made of other materials, including gold, platinum, silver, and combinations thereof.

[0070] In other embodiments, each electrochemical sensor 18 is a potential sensor 46 (hereinafter referred to as "potential sensor 46"). Figure 4 (as shown in the diagram). The potential sensor 46 typically includes two or more electrodes 30, which are shown as a reference electrode 34 and a working electrode 38, for example.

[0071] In some embodiments, the reference electrode 34 and the working electrode 38 of the potential sensor 46 are selected to generate an electrochemical reaction, i.e., ionic activity, in the presence of substances such as simple solutions, quality control reagents, and / or calibration reagents in the fluid. In some embodiments, the working electrode 38 is an ion-specific or ion-selective electrode (hereinafter referred to as "ISE") for sensing other substances, including but not limited to chloride ions (Cl... - ), magnesium ions (Mg 2+ ), potassium ions (K) + Sodium ions (Na) + ), hydrogen ions (H) + ), bicarbonate ions (HCO3) - ), calcium ions (Ca 2+) and / or urea molecules (CO(NH2)2).

[0072] The fluid analyzer 10 may include a fluid channel 42 through which fluids such as samples, quality control fluids, washing fluids and / or calibration reagents can be passed to contact at least one of the electrochemical sensors 18, including but not limited to current sensor 22 and / or potential sensor 46.

[0073] Now for reference Figure 1 and Figure 2 In one embodiment, each current sensor 22 is assembled on a substrate 50 within a housing 26 defining a chamber 54. In this embodiment, a working electrode 38 is located between a reference electrode 34 and a counter electrode 36. The current sensor 22 may be provided with a dielectric layer 58. The substrate 50 may be made of a dielectric material such as plastic, ceramic, or silicon. The dielectric layer 58 may include openings for one or more electrodes 30 of the current sensor 22, including but not limited to the reference electrode 34, the counter electrode 36, and the working electrode 38. The electrodes 30 of the current sensor 22 may be provided with an electrolyte layer 62 (e.g., The housing 26 may be covered with a permeation membrane 66 (e.g., a copolymer). Fluids such as calibration reagents or samples enter the chamber 54 through the inlet port 70 and exit the chamber 54 through the exit port 74. The housing 26 may be provided with a cover 78 that encloses the current sensor 22; and a gasket 82 that engages the permeation membrane 66 and the cover 78 to seal the chamber 54, the inlet port 70, and the exit port 74.

[0074] Fluid can pass through fluid channel 42 and enter a chamber 54 defined by housing 26 that supports and / or surrounds current sensor 22, such that the fluid can help generate an electrochemical reaction between the target analyte or its reaction byproduct and current sensor 22.

[0075] Figure 3Another embodiment of a current sensor 22 that can be used according to this disclosure is shown. In this embodiment, the current sensor 22 has electrodes 30 disposed on a substrate 84, including but not limited to a reference electrode 34, a counter electrode 36, and a working electrode 38. The substrate 84 may extend outward from the electrodes 30. The current sensor 22 may also have a pad 86 having an opening 90, the size and dimensions of which are configured to be larger than the area of ​​the substrate 84 surrounded by the electrodes 30. The pad 86 may be positioned on the substrate 84 such that the pad 86 does not overlap with the electrodes 30. Instead, the pad 86 may engage the substrate 84 around the electrodes 38. The current sensor 22 may also include a cover 94 located on the pad 86 such that the pad 86 is positioned between the substrate 84 and the cover 94. The opening 90 in the pad 86, together with the cover 94 and the substrate 84, forms a chamber (not shown) through which fluid can pass and interact with the electrodes 30. An inlet port 98 and an outlet port 102 may be formed within the cover 94 to allow fluid to enter and exit the chamber (not shown).

[0076] Return to Figure 1 Fluid can flow through fluid channel 42 by a driving force provided by drive device 106. This driving force may include, but is not limited to, capillary force, pressure, gravity, vacuum, electrodynamic effects, and / or the like. For example, drive device 106 may be a pump, but is not limited thereto. A sample can be introduced into fluid channel 42 via sample injection port 110. Sample injection port 110 may be in communication with valve 114, which can be opened and / or closed manually or mechanically to allow and / or prevent sample damage to fluid channel 42. The sample can be injected manually or mechanically into sample injection port 110.

[0077] In some embodiments, the fluid channel 42 may be a hollow channel. The fluid channel 42 may also include a waste outlet 116, whereby fluid exits the fluid channel 42 after contacting at least one, and preferably all, of the current sensors 22.

[0078] refer to Figure 2 For example, fluid channel 42 can deliver a sample to chamber 54. Chamber 54 may indirectly intersect current sensor 22 via electrolyte layer 62 and permeation membrane 66, including but not limited to, reference electrode 34, counter electrode 36, and working electrode 38. In some embodiments, chamber 54 may be a hollow channel. Substrates 50 and 84 may be formed of materials including but not limited to plastics, ceramics, glass, and / or any material capable of containing electrode 30. For example, in some embodiments, substrates 50 and 84 may be formed of polyethylene terephthalate (hereinafter referred to as "PET").

[0079] like Figure 2As shown, the electrodes 30 for the current sensor 22, including, for example, a reference electrode 34, a counter electrode 36, and a working electrode 38, may include one or more conductive layers 118 (hereinafter referred to as "conductive layer 118"). The conductive layer 118 may be formed of any suitable conductive material, including but not limited to carbon, silver, silver chloride, gold, platinum, palladium, and / or the like. The conductive layer 118 may be applied by sputtering, electroplating, screen printing, inkjet printing, bonding, and / or using any other technique capable of applying conductive material to the housing 26 associated with the manufacture of the current sensor 22.

[0080] In some embodiments, the conductive layer 118 is formed by laser ablation of a gold sputtered metal film on a backing. Alternatively, in some embodiments, the conductive layer 118 is formed by locally positioning carbon within the housing 26. Figure 1 and Figure 2 As shown, the electrode 30, including but not limited to the reference electrode 34, the counter electrode 36, and the working electrode 38, may also include a lead 122 for connection to the instrument 126.

[0081] In some embodiments, instrument 126 is a potentiostat. In such embodiments, instrument 126 may receive signals generated by a reference electrode 34, a counter electrode 36, and a working electrode 38 in contact with a fluid containing a target analyte (e.g., oxygen, quality control reagents, and / or calibration reagents in a sample), and convert the signals into information to correlate the potential with the amount of the target analyte in the fluid. Instrument 126 may measure the current between two of the plurality of electrodes 30 and control the voltage difference between the two electrodes of the plurality of electrodes 30. For example, when current sensor 22 includes a reference electrode 34 and a working electrode 38, instrument 126 may measure the current between the reference electrode 34 and the working electrode 38 and control the voltage difference between the reference electrode 34 and the working electrode 38.

[0082] In embodiments where the current sensor 22 includes a counter electrode 36, the instrument 126 measures the current flow between the working electrode 38 and the counter electrode 36 and controls the voltage difference between the working electrode 38 and the reference electrode 34. The reference electrode 34, the counter electrode 36, and the working electrode 38 can provide a reversible reaction or a set of reversible reactions, and may not require the consumption of electrode 30. When a voltage is applied across the working electrode 38 and the reference electrode 34, the current measured by the instrument 126 is correlated with the content of the target analyte in the fluid.

[0083] In some embodiments, the fluid analyzer 10 may further include one or more calibration reagent injection ports 130-1, 130-2, and 130-3 (hereinafter referred to as "calibration reagent injection ports 130") that are in fluid communication with the fluid channel 42. Calibration reagent injection ports 130 may also be in communication with valves 134-1, 134-2, and 134-3 (hereinafter referred to as "valve 134") that can be manually or mechanically opened and / or closed to allow and / or prevent one or more calibration reagents and / or wash fluids from entering the fluid channel 42. Valve 134 may be an automatic valve that opens or closes upon receiving a suitable control signal. In some embodiments, calibration reagent injection port 130-3 is a wash fluid injection port.

[0084] In some embodiments, the calibration reagent injection port 130 is in fluid communication with a calibration cartridge 14 containing one or more calibration reagents. In some embodiments, the calibration cartridge 14 includes at least three reservoirs 132-1, 132-2, and 132-3 (hereinafter referred to as "reservoir 132"). Reservoir 132-1 may contain a first calibration reagent having a first known target analyte level (e.g., 105 mM chloride, 0.3 mM magnesium, 4 mM potassium, 160 mM sodium, 7.4 pH, 30 mmHg bicarbonate, 1.2 mM calcium, and / or 10 mg / dL blood urea nitrogen). Reservoir 132-2 may contain a second calibration reagent with a second known target analyte level (e.g., 100 mM chloride, 0.6 mM magnesium, 8 mM potassium, 115 mM sodium, 6.8 pH, 70 mmHg bicarbonate, 0.6 mM calcium, and / or 70 mg / dL blood urea nitrogen), and reservoir 132-3 may contain a washing fluid. For example, the washing fluid may be an aqueous washing agent, typically containing a surfactant, to remove the calibration reagent and / or sample from the interior of housing 26 adjacent to chamber 54.

[0085] Refer again Figure 1 Instrument 126, drive 106, and valves 114, 134-1, and 134-2 can communicate with control system 138 via signal path 142. For example, but without limitation, such as... Figure 1 As shown, signal path 142 may be one or more cables that electronically and / or via a network transmit data generated by instrument 126 to control system 138 and / or transmit information, signals and / or commands from control system 138 to valves 114 and 134, as detailed herein. Figure 5The control system 138 is shown in more detail below. The control system 138 can be one or more systems capable of implementing and / or performing the processes described herein. The logic, implemented in the form of software instructions and / or firmware, can be executed on any suitable hardware. For example, the logic implemented in the form of software instructions and / or firmware can be executed on one or more dedicated systems, on a personal computer system, on a distributed processing computer system, and / or the like. In some embodiments, the logic can be implemented in an independent environment operating on a single computer system, and / or the logic can be implemented in a networked environment, such as in a distributed system using multiple computers and / or processors.

[0086] Refer again Figure 1 In some embodiments, the calibration cartridge 14 containing the calibration reagent is in fluid communication with one or more quality control fluid inlet ports (hereinafter referred to as "quality control fluid inlet ports") (not shown), which are in fluid communication with the fluid channel 42. In one embodiment, the quality control inlet port (not shown) is in fluid communication with one or more quality control fluid valves (hereinafter referred to as "quality control fluid valves") (not shown), whereby the quality control fluid valves (not shown) can be opened and / or closed manually or mechanically to allow and / or prevent quality control fluid from entering the fluid channel 42. The quality control fluid valves (not shown) may be automatic valves that open or close upon receiving a suitable control signal.

[0087] In some embodiments, the fluid analyzer 10 includes a plurality of electrochemical sensors 18 and a plurality of corresponding instruments 126.

[0088] Now for reference Figure 4 The potential sensor 46 typically includes two or more electrodes 30, shown by way of example as a reference electrode 34 and a working electrode 38. The working electrode 38 may be an ion-selective electrode, which includes a cover film 188, an internal electrolyte layer 192, and an internal reference electrode 196. For example, but not by way of limitation, the cover film may include a plasticized PVC film doped with an analyte sensing ion carrier, and may include other additives.

[0089] For example, but not as a limitation, the internal electrolyte layer 192 may comprise an aqueous solution and / or a hydrogel / hydrophilic polymer as the internal electrolyte. In one embodiment, a metal salt in solution is dispersed in a carbon paste, hydrogel, or hydrophilic polymer to form the internal electrolyte layer 192. At least a portion of the internal electrolyte layer 192 may be screen-printed onto at least a portion of the internal reference electrode 196. At least a portion of the cover film 188 may be disposed on at least a portion of the internal electrolyte layer 192. Any internal reference electrode 196 known in the art or otherwise contemplated herein may be used according to the methods described herein, provided that the potential sensor 46 functions according to the methods described herein.

[0090] In certain (but not limiting) embodiments, the cover membrane 188 may be selected from the group consisting of chloride sensing membranes, magnesium sensing membranes, potassium sensing membranes, sodium sensing membranes, pH sensing membranes, bicarbonate sensing membranes, calcium sensing membranes, and blood urea nitrogen sensing membranes; and / or the metal salt dispersed in a carbon paste, hydrogel, or hydrophilic polymer may be selected from the group consisting of MgCl2, HCl, NaCl, KCl, KNO3, and NaClO4. In illustrative embodiments, when dispersed in a carbon paste, hydrogel, or hydrophilic polymer, the metal salt may be any solution. Examples of such solutions include aqueous solutions. For example, but not by limitation, the internal reference electrode 196 may be made of silver, silver chloride, and / or the like.

[0091] Figure 5 The diagram shows a block diagram of a control system 138, which may include: one or more processors 146 (hereinafter referred to as "processor 146"), which operate together or independently to execute processor executable code; one or more memories 150 (hereinafter referred to as "memory 150") capable of storing processor executable code; one or more input devices 154 (hereinafter referred to as "input devices 154"); and one or more output devices 158 (hereinafter referred to as "output devices 158").

[0092] In some embodiments, when executed, processor-executable code causes processor 146 to: control automatic valve 134-1 to deliver a first calibration reagent through fluid channel 42 to the reference electrode 34 and working electrode 38 (and, when included in current sensor 22) of each electrochemical sensor 18; control instrument 126 (when instrument 126 is a potentiostat) to apply a voltage potential sufficient to induce an electrochemical reaction in a sample of the first calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18, and receive a first reading from instrument 126 for each electrochemical sensor 18; control automatic valve 134-2 to deliver a second calibration reagent through fluid channel 42 to the reference electrode 34 and working electrode 38 (and, when included in current sensor 22) during a first time period. And when included in current sensor 22, counter electrode 36); control instrument 126 (when instrument 126 is a potentiostat) applies a voltage potential sufficient to initiate an electrochemical reaction in the sample of the second calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18, and receives a second reading of each electrochemical sensor 18 from instrument 126; calculates a first calibration parameter for each electrochemical sensor 18 using the first reading, the second reading, and a multi-point calibration algorithm (e.g., the multi-point calibration algorithm described by Li in U.S. Patent No. 11,293,889) (which is incorporated herein by reference); and uses the first calibration parameter to measure the content of the target analyte in the fluid sample to calculate a first response slope m1 according to equation (3) described below.

[0093] In some embodiments, when executed, the processor-executable code further causes the processor 146, in a second time period following the first time period, to: control the automatic valve 134-1 to deliver the first calibration reagent through the fluid channel 42 to the reference electrode 34 and working electrode 38 (and the counter electrode 36 when included in the current sensor 22) of each electrochemical sensor 18; control the instrument 126 (when the instrument 126 is a potentiostat) to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the first calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18, and receive a third reading from the instrument 126 for each electrochemical sensor 18; control the automatic valve 134-2 to deliver the second calibration reagent through the fluid channel 42. Fluid channel 42 delivers to the reference electrode 34 and working electrode 38 (and counter electrode 36 when included in current sensor 22) of each electrochemical sensor 18; control instrument 126 (when instrument 126 is a potentiostat) applies a voltage potential sufficient to initiate an electrochemical reaction in the sample of the second calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18, and receives a fourth reading from each electrochemical sensor 18 from instrument 126; a second calibration parameter is calculated using the third reading, the fourth reading, and a multi-point calibration algorithm (as described above); and the content of the target analyte in the fluid sample is measured using the second calibration parameter to calculate the second response slope m2 according to equation (4) described below.

[0094] In some embodiments, when executed, the processor executable code further causes the processor 146 to: determine, according to the above equation (2), whether the difference between the first response slope m1 and the second response slope m2 of each electrochemical sensor 18 is higher or lower than a predetermined threshold (i.e., outside the predetermined threshold range); and in response to determining that the difference (i.e., Δm) between the first response slope m1 and the second response slope m2 is outside the predetermined threshold range, store data indicating a blockage on the electrochemical sensor 18.

[0095] In some embodiments, the step of the control instrument 126 applying a voltage potential sufficient to initiate an electrochemical reaction in a sample of the first calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 and receiving a first reading of each electrochemical sensor 18 from the instrument 126 is replaced by the step of the processor 146 receiving a first reading from the instrument 126, the first reading indicating a first potential generated by the reference electrode 34 and working electrode 38 in contact with the first calibration reagent. In some embodiments, the step of the control instrument 126 applying a voltage potential sufficient to initiate an electrochemical reaction in a sample of the second calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 and receiving a second reading of each electrochemical sensor 18 from the instrument 126 is replaced by the step of the processor 146 receiving a second reading from the instrument 126, the second reading indicating a second potential generated by the reference electrode 34 and working electrode 38 in contact with the second calibration reagent.

[0096] In some embodiments, the step of the control instrument 126 applying a voltage potential sufficient to initiate an electrochemical reaction in a sample of the first calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 and receiving a third reading of each electrochemical sensor 18 from the instrument 126 is replaced by the step of the processor 146 receiving a third reading from the instrument 126, the third reading indicating a third potential generated by the reference electrode 34 and working electrode 38 in contact with the first calibration reagent. In some embodiments, the step of the control instrument 126 applying a voltage potential sufficient to initiate an electrochemical reaction in a sample of the second calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 and receiving a fourth reading of each electrochemical sensor 18 from the instrument 126 is replaced by the step of the processor 146 receiving a fourth reading from the instrument 126, the fourth reading indicating a fourth potential generated by the reference electrode 34 and working electrode 38 in contact with the second calibration reagent.

[0097] Each element of the control system 138 may be partially or entirely network-based or cloud-based, and may or may not be located in a single physical location. In some embodiments, the processor 146 may communicate with the instrument 126, the drive 106, and / or the valves 114 and 134 via a network. As used herein, the terms “network-based,” “cloud-based,” and any variations thereof are intended to include providing configurable computing resources on demand via an interface with a computer and / or computer network, wherein the software and / or data reside at least partially on the computer and / or computer network. The network may allow bidirectional communication of information and / or data between each element of the control system 138. The network may interface with the processor 146 and the instrument 126, the drive 106, and / or the valves 114 and 134 in various ways. For example, but without limitation, the network may interface via optical and / or electronic interfaces, and / or may use a variety of network topologies and / or protocols, including but not limited to Ethernet, TCP / IP, circuit-switched paths, combinations thereof, and / or the like. For example, in some embodiments, the network may be implemented as the World Wide Web (or the Internet), a Local Area Network (LAN), a Wide Area Network (WAN), a Metropolitan Area Network, a wireless network, a cellular network, a GSM network, a CDMA network, a 3G network, a 4G network, a satellite network, a radio network, a fiber optic network, a cable network, a public switched telephone network, Ethernet, combinations thereof, and / or the like. Additionally, the network may use various protocols to allow bidirectional interface and / or data and / or information communication between the processor 146 and the instrument 126, the drive device 106, and / or the valves 114 and 134.

[0098] In some embodiments, the network may be the Internet and / or other networks. For example, if the network is the Internet, the main user interface of the control system 138 may be delivered via a series of web pages (e.g., a target analyte concentration determination web page). It should be noted that the main user interface 38 of the control system may also be another type of interface, including but not limited to Windows-based applications.

[0099] Processor 146 may be implemented as a single processor or multiple processors, which operate together or independently to perform the logic as described herein. It is to be understood that, in some embodiments, when more than one processor 146 is used, the processors 146 may be located remotely from each other, in the same location, or comprise a single multi-core processor. Processor 146 is capable of reading and / or executing processor-executable code and / or creating, manipulating, retrieving, modifying data structures and / or storing data structures in memory 150.

[0100] Exemplary embodiments of processor 146 may include, but are not limited to, digital signal processors (DSPs), central processing units (CPUs), field-programmable gate arrays (FPGAs), microprocessors, multi-core processors, combinations thereof, and / or the like. In some embodiments, for example, additional processor 146 may include, but is not limited to, implementations of personal computers, cellular phones, smartphones, network-enabled televisions, set-top boxes, tablet computers, e-book readers, laptops, desktop computers, network-enabled handheld devices, video game consoles, servers, digital video recorders, DVD players, Blu-ray players, and / or combinations thereof.

[0101] Processor 146 can communicate with memory 150 via a path (e.g., a data bus). Processor 146 can also communicate with input device 154 and / or output device 158.

[0102] Processor 146 is capable of interfaceing and / or communicating with instrument 126, drive 106 and / or valves 114 and 134. For example, processor 146 is capable of communicating by exchanging signals (e.g., analog, digital, optical and / or similar signals) using network protocols.

[0103] The memory 150 is capable of storing processor-executable code. Alternatively, the memory 150 can be implemented as a conventional non-transient memory, such as random access memory (RAM), CD-ROM, hard disk drive, solid-state drive, flash drive, memory card, DVD-ROM, floppy disk, optical disk drive, combinations thereof, and / or the like.

[0104] In some embodiments, memory 150 may be located in the same physical location as processor 146, and / or memory 150 may be located remotely from processor 146. For example, memory 150 may be located remotely from processor 146 and communicate with other processors via a network. Additionally, when more than one memory 150 is used, the first memory may be located in the same physical location as processor 146, and the additional memory 150 may be located physically remotely from processor 146. Furthermore, memory 150 may be implemented as "cloud storage" (i.e., one or more memories 150 may be partially or entirely network-based or accessed using a network).

[0105] Input device 154 is capable of receiving information input from a user and / or processor 146, and of transmitting such information to processor 146, network and / or instrument 126, drive device 106 and / or valves 114 and 134. For example, input device 154 may include, but is not limited to, implementations of keyboard, touch screen, mouse, trackball, microphone, fingerprint reader, infrared port, slide-out keyboard, flip keyboard, mobile phone, PDA, video game controller, remote control, fax machine, network interface, and combinations thereof.

[0106] Output device 158 is capable of outputting information in a form perceptible to the user and / or processor 146. For example, output device 158 may include, but is not limited to, implementations of a computer monitor, screen, touchscreen, speaker, website, television, smartphone, PDA, mobile phone, fax machine, printer, laptop, combinations thereof, and / or the like. It is to be understood that in some exemplary embodiments, input device 154 and output device 158 may be implemented as a single device, such as a touchscreen or tablet computer. It is also to be understood that, as used herein, the term "user" is not limited to humans and may, for example, include computers, servers, websites, processors, network interfaces, people, user terminals, virtual computers, combinations thereof, and / or the like.

[0107] Memory 150 may store processor-executable code and / or information, including one or more databases and / or data tables 162 (hereinafter referred to as "data storage 162") and program logic 166 (also referred to herein as "calibration logic"). For example, in some embodiments, the processor-executable code may be stored as a data structure such as data storage 162. In some embodiments, the outputs of instrument 126, drive 106, and / or valves 114 and 134 may be stored in data storage 162 within memory 150.

[0108] In some embodiments, for example, the outputs of instruments 126, each corresponding to a specific one of the electrochemical sensors 18, may be stored in memory 150 as data structures (such as data storage 162). In some embodiments, each output of instrument 126 may be stored as a separate data structure (e.g., data storage 162) with a unique identifier, each unique identifier identifying the electrochemical sensor 18 corresponding to a specific output of instrument 126.

[0109] Now for reference Figure 6 The image shows another exemplary embodiment of the sensor array 170 of the fluid analyzer 10. The sensor array 170 may include a plurality of electrochemical sensors 18. Figure 6In the illustrated embodiment, the sensor array 170 includes a chloride sensor 18-1, a magnesium sensor 18-2, a potassium sensor 18-3, a sodium sensor 18-4, a pH sensor 18-5, a bicarbonate sensor 18-6, a calcium sensor 18-7, and a blood urea nitrogen sensor 18-8. However, in other embodiments, the sensor array 170 may include any combination of electrochemical sensors 18 capable of determining at least one analyte in a sample. It should be understood that the electrochemical sensors 18 may be arranged in any order.

[0110] Figure 7 An embodiment of an obstacle detection algorithm 174 is illustrated for detecting the presence (or absence) of an obstacle on at least one of the electrochemical sensors 18 of a fluid analyzer 10. Algorithm 174 includes computer-executable instructions that can be periodically executed by processor 146 to ensure that the electrochemical sensors 18 provide accurate results.

[0111] During the first time period, at step 178, processor 146 may contact at least one of the electrochemical sensors 18 (i.e., reference electrode 34, counter electrode 36, and / or working electrode 38) within the sensor array with a first calibration reagent having a first predetermined target analyte level (or concentration). This can be achieved, for example, by processor 146 of control system 138 generating and sending a signal that opens automatic valve 134-1 and actuates drive 106 to transfer the first calibration reagent from fluid reservoir 132-1 through fluid channel 42 to chamber 54 of at least one of the electrochemical sensors 18. When a sufficient amount of the first calibration reagent is present in chamber 54, processor 146 of control system 138 may close automatic valve 134-1 and deactivate drive 106.

[0112] Once the first calibration reagent comes into contact with at least one of the electrochemical sensors 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), at step 182, the specific electrochemical sensor 18 generates a first reading indicating at least one of the potential and current (i.e., a Faraday current and / or a non-Faraday current) generated by the electrochemical reaction between the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte within the first calibration reagent. The instrument 126 can then receive the first reading and transmit it to the processor 146 of the control system 138.

[0113] In some embodiments, at least two of the electrochemical sensors 18 may generate a corresponding first reading indicating at least one of a potential and a current (i.e., a Faraday current and / or a non-Faraday current) generated by the electrochemical reaction occurring between each of the at least two of the electrochemical sensors 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte within the first calibration reagent. The corresponding instrument 126 may then receive the corresponding first reading from the at least two of the electrochemical sensors 18 and transmit the corresponding first reading to the processor 146 of the control system 138.

[0114] In some embodiments where the electrochemical sensor 18 is a current sensor 22, the processor 146 of the control system 138 again provides a control signal to the instrument 126 to cause the instrument 126 to apply a first potential to the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to initiate an electrochemical reaction in the sample of the first calibration reagent. The instrument 126 then receives a first reading from the current sensor 22. In such embodiments, this first reading may indicate a Faraday current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte (e.g., oxygen) within the first calibration reagent.

[0115] In some embodiments where the electrochemical sensor 18 is a potential sensor 46, the instrument 126 may receive a first reading from the potential sensor 46 only in response to a first calibration reagent contacting the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, the first reading may indicate the potential generated by an electrochemical reaction (e.g., ionic activity) occurring between the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) within the first calibration reagent.

[0116] At step 186, processor 146 may cause a second calibration reagent having a second predetermined target analyte level (or concentration) to contact at least one, some, or all of the electrochemical sensors 18 in the sensor array 170 (i.e., reference electrode 34, counter electrode 36, and / or working electrode 38). This can be achieved, for example, by processor 146 of control system 138 generating and transmitting a signal that opens automatic valve 134-2 and actuates drive 106 to transfer the second calibration reagent from fluid reservoir 132-2 through fluid channel 42 to chamber 54. When a sufficient amount of the second calibration reagent is present in chamber 54, processor 146 of control system 138 may generate and transmit a signal to close automatic valve 134-2 and deactivate drive 106. The second predetermined target analyte level may differ from the first predetermined target analyte level.

[0117] Once the second calibration reagent comes into contact with the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), at step 190, each electrochemical sensor 18 can generate a second reading indicating at least one of the potential and current (i.e., Faraday current and / or non-Faraday current) generated by the electrochemical reaction between the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte within the second calibration reagent.

[0118] In some embodiments where the electrochemical sensor 18 is a current sensor 22, the processor 146 of the control system 138 provides a control signal to the instrument 126 to cause the instrument 126 to apply a second potential to the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to initiate an electrochemical reaction in the sample of the second calibration reagent. This second potential can be determined and / or applied using a voltage-potential stepping technique, in which a series of voltage potentials, larger or smaller in sequence, are applied. When the current from the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) tends to stabilize, it is determined that the second potential is insufficient to induce an electrochemical reaction in the calibration reagent. The instrument 126 then receives a second reading from the current sensor 22. In such embodiments, this second reading may indicate a non-Radaic current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and a target analyte (e.g., oxygen) within the second calibration reagent. Then, instrument 126 can transmit the second reading to processor 146 of control system 138.

[0119] In some embodiments where the electrochemical sensor 18 is a potential sensor 46, the instrument 126 receives a second reading from the potential sensor 46 in response to a second calibration reagent contacting the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, this second reading may indicate the potential generated by an electrochemical reaction (e.g., ionic activity) occurring between the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) within the second calibration reagent.

[0120] Instrument 126 can transmit data indicating a first reading and / or a second reading to processor 146 of control system 138, which can use processor 146 to calculate a first response slope using the first reading and / or the second reading for each electrochemical sensor 18. The first response slope of a single sensor can be calculated by processor 146 based at least in part on the difference between the first and second readings generated by the same single sensor. In some embodiments, the first response slope m1 is calculated by processor 146 using equation (3):

[0121]

[0122] Wherein, V1 is the first reading of the sensor, V2 is the second reading of the same sensor, C1 is the concentration of the first calibration reagent, and C2 is the concentration of the second calibration reagent. At step 194, the processor 146 of the control system 138 may store first data indicating the first response slope. This first data may be stored in a data table 162 within the memory 150 and may be used, as described below, to determine whether (or not) an obstruction exists at a particular electrochemical sensor in the electrochemical sensor 18.

[0123] In some embodiments, in response to receiving data indicating a first reading and / or a second reading from instrument 126, processor 146 of control system 138 uses the first reading, the second reading, and a multi-point calibration algorithm to calculate a first calibration parameter (as described above). The first calibration parameter may be stored in data table 162 within memory 150 and used to measure the content of a target analyte in the fluid.

[0124] In a second time period following the first time period, at step 198, the processor 146 may re-expose the first calibration reagent, having a first predetermined target analyte level, to the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38). This can be achieved, for example, by the processor 146 of the control system 138 generating and transmitting a signal that opens the automatic valve 134-1 and actuates the drive device 106 to transfer the first calibration reagent from the fluid reservoir 132-1 through the fluid channel 42 to the chamber 54. When a sufficient amount of the first calibration reagent is present in the chamber 54, the control system 138 may close the automatic valve 134-1 and deactivate the drive device 106.

[0125] Once the first calibration reagent comes into contact with the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) again, at step 202, the electrochemical sensor 18 can generate a third reading indicating at least one of the potential and current (i.e., Faraday current and / or non-Faraday current) generated by the electrochemical reaction between the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte in the first calibration reagent.

[0126] In some embodiments where the electrochemical sensor 18 is a current sensor 22, the processor 146 of the control system 138 again provides a control signal to the instrument 126 to cause the instrument 126 to apply a first potential to the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to initiate an electrochemical reaction in the sample of the first calibration reagent. The instrument 126 then receives a third reading from the current sensor 22. In such embodiments, this third reading may indicate a Faraday current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte (e.g., oxygen) within the first calibration reagent.

[0127] In some embodiments where the electrochemical sensor 18 is a potential sensor 46, in response to the first calibration reagent re-contacting the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38), the instrument 126 receives a third reading from the potential sensor 46. In such embodiments, this third reading may indicate the potential generated by an electrochemical reaction (e.g., ionic activity) occurring between the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and the target analyte (e.g., oxygen) within the first calibration reagent.

[0128] At step 206, processor 146 may re-expose the second calibration reagent, having a second predetermined target analyte level, to the electrochemical sensor 18 (i.e., the reference electrode 34, counter electrode 36, and / or working electrode 38). This can be achieved, for example, by control system 138 opening automatic valve 134-2 and actuating drive 106 to transfer the second calibration reagent from fluid reservoir 132-2 fluid channel 42 to chamber 54. When a sufficient amount of the second calibration reagent is present in chamber 54, control system 138 may close automatic valve 134-2 and deactivate drive 106. The second predetermined target analyte level may differ from the first predetermined target analyte level.

[0129] Once the second calibration reagent comes into contact with the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) again, at step 210, the electrochemical sensor 18 can generate a fourth reading indicating at least one of the potential and current (i.e., Faraday current and / or non-Faraday current) generated by the electrochemical reaction between the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte in the second calibration reagent.

[0130] In some embodiments where the electrochemical sensor 18 is a current sensor 22, the processor 146 of the control system 138 again provides a control signal to the instrument 126 to cause the instrument 126 to apply a second potential to the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to initiate an electrochemical reaction in the sample of the second calibration reagent. This second potential can be determined and / or applied using a voltage-potential stepping technique, in which a series of voltage potentials, larger or smaller in sequence, are applied. When the current from the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) tends to stabilize, it is determined that the second potential is insufficient to induce an electrochemical reaction in the calibration reagent. The instrument 126 then receives a fourth reading from the current sensor 22. In such embodiments, this fourth reading may indicate a non-Radaic current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte (e.g., oxygen) within the second calibration reagent.

[0131] In some embodiments where the electrochemical sensor 18 is a potential sensor 46, in response to a second calibration reagent contacting the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38), the instrument 126 receives a fourth reading from the potential sensor 46. In such embodiments, this fourth reading may indicate the potential generated by an electrochemical reaction (e.g., ionic activity) occurring between the potential sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) within the second calibration reagent.

[0132] Instrument 126 can transmit data indicating a third and / or fourth reading to processor 146 of control system 138, which uses the third and / or fourth readings generated by a single sensor to calculate a second response slope of the same single sensor among sensors 18. This second response slope may be based at least in part on the difference between the third and fourth readings. A first response slope m1 and a second response slope m2 may be calculated by the same single sensor, wherein the first, second, third, and fourth readings are generated by the same single sensor. In some embodiments, the second response slope m2 is calculated by processor 146 using equation (4):

[0133]

[0134] Wherein, V3 is the third reading of the sensor, V4 is the fourth reading of the same sensor, C1 is the concentration of the first calibration reagent, and C2 is the concentration of the second calibration reagent. At step 214, the processor 146 of the control system 138 stores second data indicating the second response slope. This second data may be stored in a data table 162 within the memory 150 and may be used, as described below, to determine whether (or not) an obstruction exists at a particular electrochemical sensor in the electrochemical sensor 18.

[0135] In some embodiments, in response to receiving data indicating a third and / or fourth reading from instrument 126, processor 146 of control system 138 uses the third and fourth readings and a multi-point calibration algorithm to calculate a second calibration parameter (as described above). The second calibration parameter may be stored in data table 162 within memory 150 and used to measure the content of the target analyte in the fluid.

[0136] At step 218, the processor 146 of the control system 138 calculates the difference between the first response slope and the second response slope (also referred to herein as the “slope increment”) (i.e., Δm = |m1 - m2|) and compares the calculated difference with a predetermined threshold. This difference may be calculated based on the same single sensor (i.e., based on the first and second response slopes calculated by the same single sensor). When the calculated difference is greater than the predetermined threshold, the processor 146 of the control system 138 stores third data indicating that an obstruction has been detected on the electrochemical sensor 18. When the sensor array 170 includes multiple electrochemical sensors 18, the processor 146 may store the third data for each electrochemical sensor 18 in a manner associated with a specific electrochemical sensor 18. In some embodiments, in response to the detection of an obstruction, the processor 146 of the control system 138 opens / closes the automatic valve 134-3 (also referred to herein as the “wash fluid valve 134-3”) and actuates / deactivates the drive device 106 to deliver wash fluid through the fluid channel 42 and the chamber 54 to wash the electrochemical sensor 18, thereby removing the obstruction. In some embodiments, in response to the detection of an obstruction, the processor 146 of the control system 138 uses the output device 158 to output third data in a user-perceptible form to alert or indicate the presence of the obstruction to the user, such as an auditory or visual alarm.

[0137] In some embodiments, when the calculated difference is less than a predetermined threshold, the control system 138 uses the processor 146 to store fourth data indicating that no obstruction was detected on the electrochemical sensor 18. In some embodiments, when the calculated difference is less than the predetermined threshold, no data is stored and normal operation of the fluid analyzer 10 continues. In some embodiments, in response to the detection of no obstruction, the processor 146 of the control system 138 uses the output device 158 to output an alarm or indication (e.g., an audible or visual alarm or indication) indicating the absence of obstruction in a user-perceptible form.

[0138] Subsequently, the fluid analyzer 10 can be used to apply a fluid sample with an unknown target analyte content to the electrochemical sensor 18 (i.e., the working electrode 34, the counter electrode 36, and / or the reference electrode 38), and the target analyte content of the fluid sample can then be measured using the first calibration parameter and / or the second calibration parameter.

[0139] Now for reference Figure 8 , which shows Figure 6 The sensor array 170 shown is viewed over time. Figure 8The diagram illustrates the barrier 180 formed on potassium sensor 18-3 at 15:07 on day 2; from 18:07 on day 2 to 12:30 on day 3, barrier 180 migrates from potassium sensor 18-3 to downstream locations (i.e., sodium sensor 18-4, pH sensor 18-5, and bicarbonate sensor 18-6); at 10:17 on day 4, barrier 180 separates into a first barrier 180-1 on potassium sensor 18-3 and a second barrier 180-2 on pH sensor 18-5 and bicarbonate sensor 18-6; at 10:43 on day 5, barrier 180 further separates into the first barrier 180-1 on potassium sensor 18-3, bicarbonate... A second barrier 180-2 appears on the salt sensor 18-6 and a third barrier 180-3 appears on the calcium sensor 18-7; at 10:44 on the 6th day, a fourth barrier 180-4 appears on the sodium sensor 18-4; and at 10:44 on the 6th day, barrier 180 is partially removed (i.e., the second barrier 180-2 and the third barrier 180-3 are removed); then at 10:47 on the 7th day, barrier 180 is further removed (i.e., the first barrier 180-1 is removed); and at 10:47 on the 7th day, the fourth barrier 180-4 remains on the sodium sensor 18-4 so that barrier 180 can be finally removed by a barrier removal process performed by the fluid analyzer or its user.

[0140] Now for reference Figure 9A-9G The depiction is shown Figure 6 Each electrochemical sensor 18 shown is in relation to Figure 8 The graph shows the slope increment of 183 (i.e., Δm) within the corresponding time period for the time range shown. Figure 9A As can be seen, the slope increment 183 of the chloride sensor 18-1 is not outside the predetermined threshold 184 (e.g., ±3 mV / D) (mV per decade) of the chloride sensor 18-1. Therefore, within this time frame, the slope increment 183 of the chloride sensor 18-1 does not indicate the presence of a blockage 180. Similarly, in Figure 9B As can be seen, the slope increment 183 of the magnesium sensor 18-2 is not outside the predetermined threshold 184 (e.g., ±1.5 mV / D) of the magnesium sensor 18-2. Therefore, within this time range, the slope increment 183 of the magnesium sensor 18-2 does not indicate the presence of an obstruction 180.

[0141] However, in Figure 9C As can be seen, during the period from approximately day 2 to approximately day 6, the slope increment 183 of potassium sensor 18-3 is outside the predetermined threshold 184 of potassium sensor 18-3 (e.g., ±3mV / D), thus indicating the presence of a barrier 180 during this period.

[0142] exist Figure 9D In the diagram, it can be seen that the slope increment 183 of the sodium sensor 18-4 is outside the predetermined threshold 184 (e.g., ±3 mV / D) during the first time period from approximately day 2 to approximately day 3 and the second time period from approximately day 6 to approximately day 8 (i.e., for most of day 7), thus indicating the presence of two barriers 180: a first barrier during the first time period (in Figure 8 (represented as 180) and the second obstacle during that second time period (in Figure 8 (represented as 180-4 in Chinese).

[0143] exist Figure 9E In the data, it can be seen that the slope increment 183 of the pH sensor 18-5 is outside the predetermined threshold 184 (e.g., ±3 mV / D) during the time period from approximately day 2 to approximately day 4, thus indicating the presence of a barrier 180 during this period.

[0144] exist Figure 9F In the diagram, it can be seen that the slope increment 183 of the bicarbonate sensor 18-6 is outside the predetermined threshold 184 (e.g., ±3 mV / D) during the first time period occurring approximately on day 0 and the second time period occurring approximately on day 4, thus indicating the presence of two barriers 180: a first barrier 180 during the first time period (…). Figure 8 (not shown in the image), and a second obstruction during that second time period (in the image). Figure 8 (represented as 180-2).

[0145] Finally, Figure 9G In, with Figures 9A-9B Similarly, the slope increment 183 of the calcium sensor 18-7 is not outside the predetermined threshold 184 (e.g., ±1.5 mV / D) of the calcium sensor 18-7. Therefore, within this time range, the slope increment 183 of the calcium sensor 18-7 does not indicate the presence of a blockage 180.

[0146] Although no depiction is shown Figure 6 The graph shows the slope increment 183 of the blood urea nitrogen sensor 18-8, but in some embodiments, the predetermined threshold 184 of the blood urea nitrogen sensor 18-8 may be, for example, ±3mV / D.

[0147] In some embodiments, the fluid analyzer 10 may further include a magnesium-specific calibration reagent injection port (not shown) that is in fluid communication with the fluid channel 42. This magnesium-specific calibration reagent injection port may also be in communication with a magnesium-specific valve (not shown) that can be manually or mechanically opened and / or closed to allow and / or prevent magnesium-specific calibration reagent from entering the fluid channel 42. The magnesium-specific valve may be an automatic valve that opens or closes upon receiving a suitable control signal.

[0148] In some embodiments, the magnesium-specific calibration reagent inlet port is in fluid communication with a calibration cartridge 14 containing a magnesium-specific calibration reagent, which may be a calibration reagent other than one or more of the calibration reagents described above. In some embodiments, the calibration cartridge 14 also includes a magnesium-specific reservoir (not shown). This magnesium-specific reservoir may contain a magnesium-specific calibration reagent with a known target analyte level.

[0149] In some embodiments, the magnesium sensor 18-2 may experience interference caused by calcium ions present in the fluid sample. To correct for this interference, in some embodiments, when executed, the processor-executable code also causes the processor 146 to: control an automatic magnesium-specific valve to deliver a magnesium-specific calibration reagent through the fluid channel 42 to the reference electrode 34 and working electrode 38 (and the counter electrode 36 when included in the current sensor 22) of the magnesium sensor 18-2; control the instrument 126 (when the instrument 126 is a potentiostat) to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the magnesium-specific calibration reagent to the reference electrode 34 and working electrode 38 of the magnesium sensor 18-2; and receive a fifth reading of the magnesium sensor 18-2 from the instrument 126.

[0150] In some embodiments, the step of calculating the first calibration parameter of each electrochemical sensor 18 using the first reading, the second reading, and the multi-point calibration algorithm (as described above) can be further described as calculating the first calibration parameter of the magnesium sensor 18-2 using the first reading, the second reading, the fifth reading, and the multi-point calibration algorithm, and calculating the first calibration parameter of the other electrochemical sensors 18 using the first reading, the second reading, and the multi-point calibration algorithm.

[0151] Furthermore, in some embodiments, when executed, the processor-executable code also causes the processor 146, after the first time period, to: control an automatic magnesium-specific valve to deliver a magnesium-specific calibration reagent through fluid channel 42 to the reference electrode 34 and working electrode 38 (and the counter electrode 36 when included in the current sensor 22) of the magnesium sensor 18-2; control an instrument 126 (when the instrument 126 is a potentiostat) to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the magnesium-specific calibration reagent to the reference electrode 34 and working electrode 38 of the magnesium sensor 18-2; and receive a sixth reading of the magnesium sensor 18-2 from the instrument 126.

[0152] In some embodiments, the step of calculating the second calibration parameter of each electrochemical sensor 18 using a third reading, a fourth reading, and a multi-point calibration algorithm (as described above) can be further described as calculating the second calibration parameter of magnesium sensor 18-2 using a third reading, a fourth reading, a sixth reading, and a multi-point calibration algorithm, and calculating the second calibration parameter of other electrochemical sensors 18 using a first reading, a second reading, and a multi-point calibration algorithm.

[0153] Non-limiting illustrative examples

[0154] The following is a list of numbered non-limiting illustrative embodiments of the inventive concept disclosed herein:

[0155] 1. A fluid analyzer, comprising:

[0156] A fluid channel that is operable to transport fluid;

[0157] A sensor in fluid communication with the fluid channel;

[0158] An instrument that is operable to receive signals generated by the sensor and convert the signals into information indicating the potential of the fluid;

[0159] A first calibration fluid having a first analyte concentration;

[0160] A second calibration fluid having a second analyte concentration different from that of the first analyte;

[0161] One or more calibration fluid injection ports are in fluid communication with the fluid channel, and the one or more calibration fluid injection ports are operable to receive a first calibration fluid and a second calibration fluid;

[0162] One or more valves located between the one or more calibration fluid injection ports and the sensor, the one or more valves being capable of opening and closing to provide one or more samples of each of the first calibration fluid and the second calibration fluid to the fluid channel; and

[0163] A control system having a processor operable to execute processor-executable code, which, when executed by the processor, causes the processor to run an obstruction detection algorithm, including:

[0164] During a first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and first data indicating a first response slope is stored, the first response slope being at least partially based on a first difference between first information and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid;

[0165] In a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; and

[0166] In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating an obstruction on the sensor is stored.

[0167] 2. The fluid analyzer as described in illustrative embodiment 1, wherein the sensor includes a working electrode and a reference electrode.

[0168] 3. The fluid analyzer as described in any of the illustrative embodiments 1-2, wherein the working electrode is one of a chloride ion selective electrode, a magnesium ion selective electrode, a potassium ion selective electrode, a sodium ion selective electrode, a hydrogen ion selective electrode, a bicarbonate ion selective electrode, a calcium ion selective electrode, and a blood urea nitrogen ion selective electrode.

[0169] 4. The fluid analyzer as described in any of the illustrative embodiments 1-3, wherein the first response slope is at least partially based on the quotient of the difference between the first information and the second information as the dividend and the difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as the divisor, and the second response slope is at least partially based on the quotient of the difference between the third information and the fourth information as the dividend and the difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as the divisor.

[0170] 5. The fluid analyzer as described in any of the illustrative embodiments 1-4, wherein the one or more valves include a first calibration valve and a second calibration valve, the first calibration valve being capable of opening and closing to provide one or more samples of the first calibration fluid to the fluid channel, and the second calibration valve being capable of opening and closing to provide one or more samples of the second calibration fluid to the fluid channel.

[0171] 6. The fluid analyzer as described in any of the illustrative embodiments 1-5 further includes a wash fluid injection port in fluid communication with the fluid channel and a wash fluid valve located between the wash fluid injection port and the sensor, the wash fluid injection port being operable to receive wash fluid, and the wash fluid valve being operable to open and close to provide the wash fluid to the fluid channel.

[0172] 7. The fluid analyzer as described in any of the illustrative embodiments 1-6, wherein the processor-executable code, when executed by the processor, further causes the processor to control the washing fluid valve at least in part based on the third data, so as to deliver the washing fluid through the fluid channel to the sensor.

[0173] 8. The fluid analyzer as described in any of the illustrative embodiments 1-7, wherein the obstruction is a blood clot.

[0174] 9. A method for detecting obstructions on a sensor of a fluid analyzer, comprising:

[0175] In a first time period, a first calibration fluid and a second calibration fluid having a known analyte concentration are successively flowed to the sensor, and a first response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid;

[0176] In a second time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and a second response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response to the first calibration fluid and the second calibration fluid; and

[0177] The presence of the obstruction on the sensor is determined by the processor based at least in part on the difference between the first response sensitivity and the second response sensitivity.

[0178] 10. The method as described in any of the foregoing illustrative embodiments, wherein the step of determining the presence of the barrier determines the presence of the barrier when the difference is outside a predetermined threshold range.

[0179] 11. The method as described in any of the foregoing illustrative embodiments, wherein the step of determining the presence of the obstacle determines that the obstacle does not exist when the difference is within a predetermined threshold range.

[0180] 12. The method as described in any of the foregoing illustrative embodiments, wherein the known analyte concentration of the first calibration fluid is different from the known analyte concentration of the second calibration fluid.

[0181] 13. The method as described in any of the foregoing illustrative embodiments, wherein the first response sensitivity is a first response slope of the sensor, the second response sensitivity is a second response slope of the sensor, and wherein the method further comprises the step of determining each of the first response slope and the second response slope by correspondingly dividing the difference between the sensor responses of the sensor to the first calibration fluid and the second calibration fluid by the difference between the logarithms of the known concentrations.

[0182] 14. The method as described in any of the foregoing illustrative embodiments, wherein:

[0183] During the first time period, the step of successively flowing the first calibration fluid and the second calibration fluid includes:

[0184] The first calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into first information indicating a first sensor response in the sensor response, wherein the first sensor response is a potential generated by the sensor in response to contact with the first calibration fluid;

[0185] The second calibration fluid is brought into contact with the sensor to generate a signal capable of being received by the instrument and converted into second information indicating a second sensor response in the sensor response, wherein the second sensor response is a potential generated by the sensor in response to contact with the second calibration fluid; and

[0186] Store first data indicating the slope of the first response, the first response slope being at least partially based on the difference between the first information and the second information; and

[0187] The step of successively flowing the first calibration fluid and the second calibration fluid during the second time period following the first time period includes:

[0188] The first calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into third information indicating a third sensor response in the sensor response, wherein the third sensor response is a third potential generated by the sensor in response to contact with the first calibration fluid;

[0189] The second calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into fourth information indicating a fourth sensor response in the sensor response, wherein the fourth sensor response is a fourth potential generated by the sensor in response to contact with the second calibration fluid;

[0190] Store second data indicating the second response slope, the second response slope being at least partially based on the difference between the third information and the fourth information; and

[0191] In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating the presence of the obstruction on the sensor is stored.

[0192] 15. The method as described in any of the foregoing illustrative embodiments, wherein the first response slope is based at least in part on a quotient with the difference between the first information and the second information as the dividend and the difference between the logarithms of the known analyte concentrations as the divisor, and the second response slope is based at least in part on a quotient with the difference between the third information and the fourth information as the dividend and the difference between the logarithms of the known analyte concentrations as the divisor.

[0193] 16. The method as described in any of the foregoing illustrative embodiments, wherein the method further comprises the step of: contacting the sensor with the washing fluid at least in part based on the step of determining the presence of the obstruction.

[0194] 17. The method as described in any of the foregoing illustrative embodiments, wherein the method further comprises the step of: storing third data indicating a blood clot on the sensor in response to the difference between the first response slope and the second response slope exceeding the threshold.

[0195] 18. A fluid analyzer, comprising:

[0196] A sensor configured to measure at least one parameter associated with a fluid;

[0197] One or more containers configured to store a first calibration fluid and a second calibration fluid having known analyte concentrations;

[0198] One or more channels configured to provide fluid communication between the sensor and the one or more containers; and

[0199] A processor configured to determine the presence of an obstruction to the sensor, wherein the processor is configured to:

[0200] In a first time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and the first response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid;

[0201] In a second time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and a second response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; and

[0202] The presence of the barrier is determined at least in part based on the difference between the first response sensitivity and the second response sensitivity.

[0203] 19. A fluid analyzer as described in any of the foregoing illustrative embodiments, wherein the processor is configured to determine the presence of the obstruction when the difference between the first response sensitivity and the second response sensitivity is outside a predetermined threshold range.

[0204] 20. The fluid analyzer as described in any of the foregoing illustrative embodiments, wherein the sensor includes a working electrode and a reference electrode, the working electrode being one of a chloride ion selective electrode, a magnesium ion selective electrode, a potassium ion selective electrode, a sodium ion selective electrode, a hydrogen ion selective electrode, a bicarbonate ion selective electrode, a calcium ion selective electrode, and a blood urea nitrogen ion selective electrode.

[0205] 21. A fluid analyzer as described in any of the foregoing illustrative embodiments, wherein the first response sensitivity is a first response slope of the sensor, the second response sensitivity is a second response slope of the sensor, and wherein the processor is configured to determine each of the first response slope and the second response slope by correspondingly dividing the difference between the sensor responses of the sensor to the first calibration fluid and the second calibration fluid by the difference between the logarithms of the known concentrations.

[0206] 22. The fluid analyzer as described in any of the foregoing illustrative embodiments further includes a wash fluid injection port in fluid communication with the one or more channels and a wash fluid valve located between the wash fluid injection port and the sensor, the wash fluid injection port being operable to receive wash fluid, and the wash fluid valve being operable to open and close to provide the wash fluid to the one or more channels.

[0207] 23. The fluid analyzer as described in any of the foregoing illustrative embodiments, wherein the processor is further configured to control the wash fluid valve to deliver the wash fluid through the one or more channels to the sensor in response to determining that the obstruction is present.

[0208] 24. The fluid analyzer as described in any of the foregoing illustrative embodiments, wherein the obstruction is a blood clot.

[0209] 25. A non-transitory computer-readable medium storing an obstruction detection algorithm, the obstruction detection algorithm comprising processor-executable code, the processor-executable code, when executed by a processor, causing the processor to:

[0210] In a first time period, one or more valves are controlled to sequentially deliver a first calibration fluid and a second calibration fluid to a sensor through a fluid channel, and first data indicating a first response slope is stored, the first response slope being at least partially based on a first difference between first information generated by an instrument and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid;

[0211] In a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information generated by the instrument and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; and

[0212] In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating an obstruction on the sensor is stored.

[0213] in conclusion

[0214] Therefore, compositions and apparatus, as well as methods of producing and using them, are provided based on the currently disclosed inventive concept, which fully satisfy the purposes and advantages set forth above. Although the currently disclosed inventive concept has been described in conjunction with the specific figures, experiments, results, and language set forth above, it will be apparent to those skilled in the art that many alternatives, modifications, and variations will be readily apparent. Therefore, it is intended to cover all such alternatives, modifications, and variations that fall within the spirit and broad scope of the currently disclosed inventive concept.

Claims

1. A fluid analyzer, comprising: A fluid channel that is operable to transport fluid; A sensor in fluid communication with the fluid channel; An instrument that is operable to receive signals generated by the sensor and convert the signals into information indicating the potential of the fluid; A first calibration fluid having a first analyte concentration; A second calibration fluid having a second analyte concentration different from that of the first analyte; One or more calibration fluid injection ports are in fluid communication with the fluid channel, and the one or more calibration fluid injection ports are operable to receive a first calibration fluid and a second calibration fluid; One or more valves located between the one or more calibration fluid injection ports and the sensor, the one or more valves being able to open and close to provide one or more samples of each of the first calibration fluid and the second calibration fluid to the fluid channel; as well as A control system having a processor operable to execute processor-executable code, which, when executed by the processor, causes the processor to run an obstruction detection algorithm, including: During a first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and first data indicating a first response slope is stored, the first response slope being at least partially based on a first difference between first information and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid; In a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; and In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating the presence of an obstruction on the sensor is stored.

2. The fluid analyzer according to claim 1, wherein, The sensor includes a working electrode and a reference electrode.

3. The fluid analyzer according to claim 2, wherein, The working electrode is one of the following: chloride ion selective electrode, magnesium ion selective electrode, potassium ion selective electrode, sodium ion selective electrode, hydrogen ion selective electrode, bicarbonate ion selective electrode, calcium ion selective electrode, and blood urea nitrogen ion selective electrode.

4. The fluid analyzer according to claim 1, wherein, The first response slope is at least partially based on the quotient of the difference between the first information and the second information as the dividend and the difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as the divisor, and the second response slope is at least partially based on the quotient of the difference between the third information and the fourth information as the dividend and the difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as the divisor.

5. The fluid analyzer according to claim 1, wherein, The one or more valves include a first calibration valve and a second calibration valve, the first calibration valve being capable of opening and closing to provide one or more samples of the first calibration fluid to the fluid channel, and the second calibration valve being capable of opening and closing to provide one or more samples of the second calibration fluid to the fluid channel.

6. The fluid analyzer of claim 5 further includes a wash fluid injection port in fluid communication with the fluid channel and a wash fluid valve located between the wash fluid injection port and the sensor, the wash fluid injection port being operable to receive wash fluid, and the wash fluid valve being operable to open and close to provide the wash fluid to the fluid channel.

7. The fluid analyzer according to claim 6, wherein, When executed by the processor, the processor-executable code also causes the processor to control the washing fluid valve, at least in part, based on the third data, to deliver the washing fluid through the fluid channel to the sensor.

8. The fluid analyzer according to claim 1, wherein, The obstruction is a blood clot.

9. A method for detecting obstruction on a sensor of a fluid analyzer according to any one of claims 1 to 8, comprising: In a first time period, a first calibration fluid and a second calibration fluid having a known analyte concentration are successively flowed to the sensor, and a first response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; In a second time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and a second response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; as well as The presence of the obstruction on the sensor is determined by the processor based at least in part on the difference between the first response sensitivity and the second response sensitivity; Wherein, the first response sensitivity is the first response slope of the sensor, and the second response sensitivity is the second response slope of the sensor.

10. The method according to claim 9, wherein, The step of determining the existence of the obstacle is to determine the existence of the obstacle when the difference is outside a predetermined threshold range.

11. The method according to claim 9, wherein, The step of determining the existence of the obstacle is to determine that the obstacle does not exist when the difference is within a predetermined threshold range.

12. The method according to claim 9, wherein, The known analyte concentration of the first calibration fluid is different from the known analyte concentration of the second calibration fluid.

13. The method according to claim 9, wherein, The method further includes the step of determining each of the first response slope and the second response slope by dividing the difference between the sensor responses of the sensor to the first calibration fluid and the second calibration fluid by the difference between the logarithms of the known analyte concentrations.

14. The method of claim 13, wherein: During the first time period, the step of successively flowing the first calibration fluid and the second calibration fluid includes: The first calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into first information indicating a first sensor response in the sensor response, wherein the first sensor response is a potential generated by the sensor in response to contact with the first calibration fluid; The second calibration fluid is brought into contact with the sensor to generate a signal capable of being received by the instrument and converted into second information indicating a second sensor response in the sensor response, wherein the second sensor response is a potential generated by the sensor in response to contact with the second calibration fluid; and Store first data indicating the slope of the first response, the first response slope being at least partially based on the difference between the first information and the second information; and The step of successively flowing the first calibration fluid and the second calibration fluid during the second time period following the first time period includes: The first calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into third information indicating a third sensor response in the sensor response, wherein the third sensor response is a third potential generated by the sensor in response to contact with the first calibration fluid; The second calibration fluid is brought into contact with the sensor to generate a signal that can be received by the instrument and converted into fourth information indicating a fourth sensor response in the sensor response, wherein the fourth sensor response is a fourth potential generated by the sensor in response to contact with the second calibration fluid; Store second data indicating the second response slope, the second response slope being at least partially based on the difference between the third information and the fourth information; and In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating the presence of the obstruction on the sensor is stored.

15. The method according to claim 14, wherein, The first response slope is based at least in part on the quotient of the difference between the first information and the second information as the dividend and the difference between the logarithms of the known analyte concentrations as the divisor, and the second response slope is based at least in part on the quotient of the difference between the third information and the fourth information as the dividend and the difference between the logarithms of the known analyte concentrations as the divisor.

16. The method of claim 14, wherein, The method further includes the step of bringing the washing fluid into contact with the sensor, at least in part based on the step of determining the presence of the obstruction.

17. The method of claim 14, wherein, The method further includes the step of: in response to the difference between the first response slope and the second response slope exceeding the threshold, storing third data indicating a blood clot on the sensor.

18. A fluid analyzer, comprising: A sensor configured to measure at least one parameter associated with a fluid; One or more containers configured to store a first calibration fluid and a second calibration fluid having known analyte concentrations, wherein the first calibration fluid and the second calibration fluid have different analyte concentrations; One or more channels configured to provide fluid communication between the sensor and the one or more containers; as well as A processor configured to determine the presence of an obstruction to the sensor, wherein the processor is configured to: In a first time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and the first response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; In a second time period following the first time period, the first calibration fluid and the second calibration fluid are successively flowed to the sensor, and a second response sensitivity of the sensor is determined based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; and The presence of the barrier is determined at least in part based on the difference between the first response sensitivity and the second response sensitivity; Wherein, the first response sensitivity is the first response slope of the sensor, and the second response sensitivity is the second response slope of the sensor. Wherein, the first response slope is at least partially based on a first difference between first information and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid. The second response slope is at least partially based on a second difference between third information and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid.

19. The fluid analyzer according to claim 18, wherein, The processor is configured to determine that the barrier exists when the difference between the first response sensitivity and the second response sensitivity is outside a predetermined threshold range.

20. The fluid analyzer according to claim 18, wherein, The sensor includes a working electrode and a reference electrode. The working electrode is one of the following: a chloride ion selective electrode, a magnesium ion selective electrode, a potassium ion selective electrode, a sodium ion selective electrode, a hydrogen ion selective electrode, a bicarbonate ion selective electrode, a calcium ion selective electrode, and a blood urea nitrogen ion selective electrode.

21. The fluid analyzer according to claim 18, wherein, The processor is configured to determine each of the first response slope and the second response slope by correspondingly dividing the difference between the sensor responses of the sensor to the first calibration fluid and the second calibration fluid by the difference between the logarithms of the known analyte concentrations.

22. The fluid analyzer of claim 18, further comprising a wash fluid injection port in fluid communication with the one or more channels and a wash fluid valve located between the wash fluid injection port and the sensor, the wash fluid injection port being operable to receive wash fluid, and the wash fluid valve being operable to open and close to provide the wash fluid to the one or more channels.

23. The fluid analyzer according to claim 22, wherein, The processor is also configured to control the wash fluid valve to deliver the wash fluid to the sensor through the one or more channels in response to determining that the obstruction is present.

24. The fluid analyzer according to claim 18, wherein, The obstruction is a blood clot.

25. A non-transitory computer-readable medium storing an obstruction detection algorithm, the obstruction detection algorithm comprising processor-executable code, the processor-executable code, when executed by a processor applied to a fluid analyzer according to any one of claims 1 to 8 and 18 to 24, causing the processor to: In a first time period, one or more valves are controlled to sequentially deliver a first calibration fluid and a second calibration fluid to a sensor through a fluid channel, and first data indicating a first response slope is stored, the first response slope being at least partially based on a first difference between first information generated by an instrument and second information generated by the instrument, the first information indicating a first potential generated by the sensor in contact with the first calibration fluid, and the second information indicating a second potential generated by the sensor in contact with the second calibration fluid; In a second time period following the first time period, the one or more valves are controlled to sequentially deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being at least partially based on a second difference between third information generated by the instrument and fourth information generated by the instrument, the third information indicating a third potential generated by the sensor in contact with the first calibration fluid, and the fourth information indicating a fourth potential generated by the sensor in contact with the second calibration fluid; as well as In response to the difference between the first response slope and the second response slope exceeding a threshold, third data indicating the presence of an obstruction on the sensor is stored.

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