Method for detecting obstructions in a fluid analyzer - Patent Application 20070122997

Abstract

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

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 63 / 371,943, filed August 19, 2022. The entire contents of the above-referenced patent application are expressly incorporated herein by reference. [Background technology]

[0002] In various instances, it is desirable to measure constituents in bodily fluids, including, for example, the partial pressure of blood gases in a whole blood sample, the concentration of electrolytes in a blood sample, and the hematocrit of a blood sample. + , K. + , Ca 2+ Measuring hematocrit and hemocrit values ​​are key clinical indications in assessing the condition of a medical patient. Additionally, devices used to analyze blood samples are preferably relatively small when attempting to use as little patient blood as possible for each analysis performed. Performing blood analyses using small blood samples is important, for example, when a relatively large number of samples must be drawn in a relatively short amount of time, or when blood volume is limited, such as in newborns.

[0003] For example, a patient in intensive care may require a sampling frequency of 15–20 times per day for blood gas and clinical chemistry measurements, potentially resulting in significant blood loss during patient evaluation. Additionally, reducing the size of the analyzer sufficiently to make the unit portable allows the analysis to be performed at the point of care. This reduction in size also typically means a reduction in test turnaround time. Furthermore, it is desirable to gather as much information as possible upon completion of each test to limit the number of tests that must be performed. 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 sensor and its connections.

[0004] Point-of-care blood gas analyzers allow for in vitro analysis at the patient's bedside, in the emergency room, or intensive care unit. These units use solid-state sensors with thin-film electrodes. The microchip, reagents, calibrator, and sample collection device are all contained within a disposable cartridge system. Healthcare facilities can select cartridges with additional test options, including potassium, glucose, BUN, and lactate. Because whole blood can be tested, minimal specimen processing is required; there is no need to centrifuge the sample to separate the plasma from the red blood cells before testing.

[0005] In settings involving medium- to large-volume sample testing, multi-use cartridge systems are used. These cartridges can be customized for specific analyte menus and test volumes. The number of samples measured on a single cartridge can vary from 25 to 750, and typically, once loaded into the analyzer, the cartridge has a useful life of 14 to 30 days.

[0006] The basic operating principles of blood gas analyzers have not changed significantly from previous units. Around 2005, stand-alone cartridges were introduced into some systems, paving the way for point-of-care testing and smaller units. Whole blood can be analyzed for many analytes, including electrolytes such as potassium (K+), sodium (Na+), and calcium (Ca2+), and metabolites such as glucose, lactate, blood urea nitrogen (BUN), and creatine. The sensors used for these measurements are ion electrodes or ion-selective electrodes (ISEs). These sensors are membrane-based electrochemical transducers that respond to specific ions. Biosensors are used in point-of-care testing devices as well as traditional clinical laboratory analyzers. Biosensors convert biochemical signals into electrical signals.

[0007] Electrolytes are determined by potentiometry, a form of electrochemical analysis. In potentiometry, the potential, or voltage, is measured between two electrodes in a solution. These potentials can also result when a metal and its ions are present in the solution. Different concentrations of the ions can be separated by using a membrane that is semipermeable to the ions. These systems use a reference electrode and a measuring electrode. A constant voltage is applied to the reference electrode; the difference in voltage between the reference and measuring electrodes is used to calculate the concentration of the ion in the solution.

[0008] Ion-selective electrodes are based on a modification of the potentiometry principle. A potential difference or electron flow is generated by selectively transferring the ions to be measured from the sample solution to a membrane phase. Ion-selective electrodes measure the free ion concentration of the desired analyte on a selectively engineered membrane. The membrane has a complex composition, including organic solvents, inert polymers, plasticizers, and ionophores, which are molecules that increase the selective permeability of the membrane to specific ions.

[0009] Amperometry measures the electrical current resulting from an oxidation-reduction reaction. Several types of amperometric techniques include enzyme electrodes, such as glucose oxidase, and Clark pO2 electrodes. These types of designs are commonly known as biosensors and are adaptable for clinical laboratory testing as well as point-of-care testing. Enzyme-based biosensor technology was first developed to measure blood glucose levels. A solution of glucose oxidase is placed between the gas-permeable membrane of the pO2 electrode and a semi-permeable outer membrane. Glucose in the blood diffuses through the semi-permeable membrane and reacts with the glucose oxidase. The glucose is converted by glucose oxidase to hydrogen peroxide and gluconic acid.

[0010] When a polarization voltage is applied to this electrode, it oxidizes hydrogen peroxide, contributing to the loss of electrons. Oxygen is consumed near the surface of the pO2 electrode, and the rate of consumption is measured. The rate of electron loss and pO2 decrease is directly proportional to the glucose concentration in the sample. Enzyme-based biosensors are also used to measure cholesterol, creatine, and pyruvate.

[0011] The basic operating principle of a laboratory blood gas analyzer is the same as that of the previously mentioned electrodes for pH, pCO2, and pO2; and ion electrodes for electrolyte measurements. Typically, approximately 50–120 μl of well-mixed arterial blood sample is injected into the measuring chamber through the inlet and sample probe. The sample then contacts the surface of each electrode for several seconds.

[0012] One of the major challenges with existing fluid analyzers is detecting and removing obstructions, including, for example, blood clots. The presence of obstructions can block the fluid analyzer's pathway, affect the fluid analyzer's uptime, and affect individual sensor responses, potentially resulting in biased results for, for example, important blood gas parameters (e.g., pH and / or pCO2). Obstructions typically form during the process of preparing the sample for analysis. However, even when meticulous pre-analysis procedures are performed, small obstructions can appear within the fluid (or measurement) channel. Summary of the Invention [Problem to be solved by the invention]

[0013] It would therefore be desirable to provide a fluid analyzer that is capable of detecting the presence (or absence) of an obstruction without the need for additional sensors, removing the obstruction through suction and discharge of fluid, and / or alerting the user to the presence (or absence) of an obstruction and questionable results. [Means for solving the problem]

[0014] The problem of detecting the presence (or absence) of an obstruction on a fluid analyzer without requiring additional sensors, removing the obstruction via aspiration and evacuation of fluid, and / or alerting a user to the presence (or absence) of an obstruction and questionable results is solved by the methods and systems disclosed herein.

[0015] Consistent with one aspect of the present disclosure, an exemplary fluid analyzer can include: a fluid channel operable to carry a fluid; a sensor in fluid communication with the fluid channel; a meter operable to receive a signal generated by the sensor and convert the signal into information indicative of the electrical potential of the fluid; a first calibrant fluid having a first analyte concentration; a second calibrant fluid having a second analyte concentration different from the first analyte concentration; one or more calibrant fluid injection ports in fluid communication with the fluid channel and operable to receive the first calibrant fluid and the second calibrant fluid; one or more valves located between the one or more calibrant fluid injection ports and the sensor and openable and closeable to provide one or more samples of each of the first calibrant fluid and the second calibrant fluid to the fluid channel; and a control system having a processor, the processor operable to execute processor-executable code that, when executed by the processor, causes the processor to perform an obstruction detection algorithm, the processor-executable code including: and controlling one or more valves to sequentially deliver the first and second calibrant solutions to the sensor, and storing first data indicative of a first response slope based at least in part on a first difference between first information generated by the meter indicative of a first potential produced by contacting the sensor with the first calibrant solution and second information indicative of a second potential produced by contacting the sensor with the second calibrant solution; and controlling one or more valves to sequentially deliver the first and second calibrant solutions to the sensor through the fluid channel for a second time period after the first time period. and storing second data indicative of a second response slope based at least in part on a second difference between third information indicative of a third potential produced by contacting the sensor with the first calibration liquid and fourth information produced by the meter indicative of a fourth potential produced by contacting the sensor with the second calibration liquid; and storing third data indicative of an obstruction on the sensor 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 exceeds the threshold.In other embodiments, the difference and threshold may be reversed, in which case the third data is stored when the difference is below the threshold.

[0016] Consistent with another aspect of the present disclosure, an exemplary method for detecting an obstruction on a sensor of a fluid analyzer may include: sequentially causing a flow of first and second calibration fluids having known analyte concentrations to the sensor during a first time period, and determining a first response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentrations and the first and second calibration fluids; sequentially causing a flow of the first and second calibration fluids to the sensor during a second time period, and determining a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentrations and the first and second calibration fluids; and determining, by a processor, the presence of an obstruction on the sensor based at least in part on a difference between the first and second response sensitivity.

[0017] Consistent with another aspect of the present 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 contain a first calibration fluid and a second calibration fluid having known analyte concentrations; 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 obstructing the sensor, wherein the processor: controls the flow of the first calibration fluid and the second calibration fluid to the sensor for a first time period. The method is configured to continuously induce flow and determine a first response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first and second calibration fluids; continuously induce flow of the first and second calibration fluids to the sensor during a second time period and determine a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first and second calibration fluids; and determine the presence of an obstruction based at least in part on a difference between the first and second response sensitivity.

[0018] Consistent with another aspect of the present 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 calibrant liquid and a second calibrant liquid through the fluid channel to the sensor during a first time period; and calculate a first response slope based at least in part on a first difference between first information generated by a meter indicating a first potential generated by contacting the sensor with the first calibrant liquid and second information generated by the meter indicating a second potential generated by contacting the sensor with the second calibrant liquid. and storing first data indicative of an obstruction on the sensor; controlling one or more valves to sequentially deliver the first and second calibrant solutions through the fluid channel to the sensor during a second time period after the first time period, and storing second data indicative of a second response slope based at least in part on a second difference between third information generated by the meter indicative of a third potential generated by the sensor contacting the first calibrant solution and fourth information generated by the meter indicative of a fourth potential generated by the sensor contacting the second calibrant solution; and storing third data indicative of an obstruction on the sensor in response to the difference between the first and second response slopes exceeding (i.e., exceeding or falling below) a threshold value. In some embodiments, the third data is stored when the difference exceeds the threshold value. In other embodiments, the difference and threshold value can be reversed. In this embodiment, the third data is stored when the difference falls below the threshold value.

[0019] To assist those skilled in the art in making and using the present subject matter, reference is made to the accompanying drawings, which are not intended to be drawn to scale and in which like reference numerals are intended to refer to similar elements for purposes of consistency. For purposes of clarity, not every component in every drawing may be labeled. [Brief explanation of the drawings]

[0020] [Figure 1] 1 is a schematic diagram of an exemplary embodiment of a fluid analyzer constructed in accordance with the present disclosure. [Figure 2] 2 is a cross-sectional view of an exemplary embodiment of a prior art amperometric sensor that can be read by the fluid analyzer of FIG. 1; [Figure 3] 2 is an exploded view of another embodiment of a prior art amperometric sensor that can be read by the fluid analyzer of FIG. 1. [Figure 4] 2 is a cross-sectional view of an exemplary embodiment of a prior art potentiometric sensor that can be read by the fluid analyzer of FIG. 1; [Figure 5] FIG. 2 is a block diagram of a control system for the fluid analyzer shown in FIG. [Figure 6] FIG. 2 is a top view of a sensor array read by the fluid analyzer shown in FIG. 1. [Figure 7] 1 is a process flow diagram of an exemplary obstacle detection algorithm according to the present disclosure. [Figure 8] FIG. 7 is a time course diagram of the sensor array of the fluid analyzer shown in FIG. 6. [Figure 9-1] 9A-9G are graphs of the sensor responses of the electrochemical sensors of the sensor array corresponding to the time course diagram shown in FIG. [Figure 9-2] Continued from Figure 9-1. [Figure 9-3] Continued from Figure 9-2. [Figure 9-4] Continued from Figure 9-3. DETAILED DESCRIPTION OF THE INVENTION

[0021] Before describing at least one embodiment of the present disclosure in detail, it is to be understood that the present disclosure is not limited in its application to the details of construction, experiments, exemplary data, and / or the arrangement of components set forth in the following description or illustrated in the drawings, unless otherwise stated.

[0022] The disclosure is capable of other embodiments or of being practiced or carried out in various ways, and it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.

[0023] The following detailed description refers to the accompanying drawings. The same reference numbers in different drawings may identify the same or similar elements. Unless otherwise defined herein, scientific and technical terms used in connection with the inventive concepts disclosed and / or claimed herein shall have the meanings commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. The nomenclature utilized in connection with, and laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal chemistry described herein are those well known and commonly used in the art.

[0024] All patents, published patent applications, and non-patent literature cited herein are indicative of the level of skill of those skilled in the art to which the inventive concepts disclosed and / or claimed herein pertain. All patents, published patent applications, and non-patent literature referenced in any part of this application are expressly incorporated herein by reference in their entirety to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

[0025] All of the non-transitory computer-readable medium, control system, fluid analyzer, and / or methods disclosed and / or claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the fluid analyzer and methods of the inventive concepts disclosed and / or claimed herein have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that changes can be made in the fluid analyzer and / or methods, and in the steps or sequence of steps of the methods described herein, without departing from the concept, spirit, and scope of the inventive concepts disclosed and / or claimed herein. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope, and concept of the inventive concepts as defined by the appended claims.

[0026] As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0027] In the claims and / or this specification, the use of the word "a" or "an," when used in conjunction with the word "comprising," can mean "one," but is also consistent with the meanings of "one or more," "at least one," and "one or more." The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to "a compound" can refer to one or more, two or more, three or more, four or more, or a greater number of compounds. The term "plurality" refers to "two or more." In the claims, use of the term "or" is used to mean "and / or" unless expressly indicated to refer to alternatives only or that the alternatives are mutually exclusive; however, the present disclosure accommodates definitions that refer to alternatives only and to "and / or." Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for a device, the variation of the method used to determine the value, or the variation that exists among subjects studied. For example, but not as a limitation, when the term "about" is used, the specified value may vary by ±20%, or ±10%, or ±5%, or ±1%, or ±0.1% from the specified value, as would be understood by one of ordinary skill in the art, with such variations being appropriate for practicing the disclosed methods. Use of the term "at least one" will be understood to include 1 as well as any quantity greater than 1, including, but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" can extend up to 100 or 1000 or more, depending on the accompanying term; additionally, the quantity 100 / 1000 should not be considered limiting, as higher limits may also provide satisfactory results.Additionally, use of the term "at least one of X, Y and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal numbers (i.e., "first," "second," "third," "fourth," etc.) is intended only to distinguish between two or more items and is not meant to imply, for example, any sequence or order or importance of one item relative to another, or any additional order.

[0028] As used in this description, the terms "comprises," "comprising," "includes," "including," "has," "having," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, unless otherwise stated, a process, method, article, or apparatus that includes a list of elements is not necessarily limited to only those elements and may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0029] Furthermore, unless expressly stated to the contrary, "or" refers to an inclusive "or" rather than an exclusive "or." For example, condition A or B is satisfied by one of the following: when A is true (or exists) and B is false (or does not exist), when A is false (or does not exist) and B is true (or exists), and when both A and B are true (or exist).

[0030] Additionally, the use of "a" or "an" is used to describe elements and components of the embodiments herein. This is done for convenience only and to give a general sense of the inventive concepts. This description should be read as including one or more, and the singular also includes the plural unless it is clear that this is meant to be different. Furthermore, the use of the term "plurality" is meant to indicate "more than one" unless expressly stated to the contrary.

[0031] Any reference herein to "one embodiment," "an embodiment," "some embodiments," "one example," "for example," or "an 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, appearances of the phrases "in some embodiments" or "one example" in various places in this specification do not necessarily all refer to the same embodiment.

[0032] 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" includes at least one of: A, B, C, AB, AC, BC, or ABC, and is intended to also include BA, CA, CB, CBA, BCA, ACB, BAC, or CAB if order is important in the particular context. Continuing with this example, combinations involving repeats of one or more items or terms are expressly included, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, etc. Those of skill in the art will understand that typically, no limitation exists regarding the number of items or terms in any combination, unless otherwise apparent from the context.

[0033] As used herein, the term "substantially" means that the described event or circumstance occurs entirely, or that the described event or circumstance occurs to a significant extent or degree. For example, the term "substantially" means that the described event or circumstance occurs at least 90% of the time, or at least 95% of the time, or at least 98% of the time.

[0034] As used herein, the term "sample" is understood to include any type of biological or non-biological sample that can be utilized with the inventive concepts disclosed and / or claimed herein. That is, a sample can be any fluid sample and / or a sample capable of becoming fluid (e.g., a biological sample mixed with a fluid matrix). Examples of biological samples that can be utilized include, but are not limited to, whole blood or any fraction thereof (i.e., plasma or serum), saliva, sputum, cerebrospinal fluid (CSF), surgical drain fluid, skin, interstitial fluid, tears, mucus, urine, swabs, combinations, etc. Examples of non-biological samples include wastewater, industrial fluids, etc. It should be noted that while this disclosure describes the use of a fluid analyzer to analyze biological samples, those skilled in the art will understand that the concepts disclosed herein can be applied to any sample in which the concentration of an analyte can be determined, and thus, 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, and the like.

[0035] As used herein, the term "fluid" refers to a liquid or gas that can be passed through at least a portion of a fluid analyzer and analyzed by components of the fluid analyzer. The fluid can be a sample, a calibration reagent (e.g., a fluid or gas), a cleaning solution, or a quality control fluid.

[0036] As used herein, a circuit may be analog and / or digital components, or one or more suitably programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. Also, a "component" may perform one or more functions. The term "component" may include hardware such as a processor (e.g., microprocessor), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or a combination of hardware and software.

[0037] Software may include one or more computer-readable instructions that, when executed by one or more components, cause the components to perform a specified function. It should be understood that the algorithms described herein may be stored in one or more non-transitory memories. Exemplary non-transitory memories may include random access memory, read-only memory, flash memory, etc. Such non-transitory memories may be electrical, optical, etc.

[0038] When a broad range of numerical values ​​is recited or set forth herein, the range includes its endpoints and all individual integers and fractions within the range, and also includes each of the narrower ranges formed by all the various possible combinations of those endpoints and internal integers and fractions to the same extent as if each of those narrower ranges were explicitly recited and form a subgroup within the larger group of values ​​within the recited range. Although a broad range of numerical values ​​is recited herein as being greater than the recited value, the range is nevertheless finite and bounded at its upper end by values ​​operable within the context of the invention described herein. Although a broad range of numerical values ​​is recited herein as being less than the recited value, the range is nevertheless bounded at its lower end by a value other than 0.

[0039] It should be further understood that, as used herein, the term "user" is not limited to a human being, but can include, for example, a computer, a server, a website, a processor, a network interface, a person, a user terminal, a virtual computer, combinations thereof, and the like.

[0040] As used herein, the term "calibration parameter" refers to a set of data points that correlates the signal from a sensor to a known analyte concentration, or one or more functions used to derive the set of data points. A calibration parameter can be derived by a calibration algorithm, such as a linear algorithm, a spline-based algorithm, an exponential algorithm, a least-squares algorithm, a logarithmic algorithm, or the like, configured to fit a function to at least two calibration points.

[0041] As used herein, the term "calibration logic" refers to program logic used by a processor in a control system to interpret data measured by one or more electrodes. In particular, the term "calibration logic" refers to 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.

[0042] Electrochemical sensors are widely used in in vitro diagnostic instruments. These electrochemical sensors contain electrodes fabricated from metal, from metallic inks by screen printing (thick film method), or from chemical vapor deposition of metal films (thin film method), and generally require calibration. Calibration compensates for sensor-to-sensor variations in electrode size and surface area, changes in chemical and biochemical activity over service life, and drift in the electrical signal. For example, the oxygen sensor used in the Siemens Healthcare Point of Care (POC) RAPIDPoint 500 Blood Gas Analyzer has a screen-printed platinum working electrode, a silver / silver chloride reference electrode, and a gold counter electrode.

[0043] Referring now to the figures, and particularly to FIG. 1 , a diagram of an exemplary embodiment of a fluid analyzer 10 is shown in combination with a calibration cartridge 14 and one or more electrochemical sensors 18 (hereinafter “electrochemical sensors 18”). The electrochemical sensors 18 may be implemented, for example, in the form of a cartridge connected to the fluid analyzer 10, as shown in FIG. 1. The fluid analyzer 10 may include a housing 26 that supports and / or contains at least a portion of each of the electrochemical sensors 18.

[0044] This disclosure describes an obstruction detection algorithm for determining whether any of the electrochemical sensors 18 are affected by an obstruction. In one embodiment, the method disclosed herein is a novel method for detecting the absence or presence of an obstruction at or near at least one of the electrochemical sensors 18 without the use of additional sensors. The presence of a blood clot or another obstruction on or near an individual sensor of the electrochemical sensors 18 can alter the local electrolyte environment (i.e., electrolyte diffusion kinetics, buffer volume, carryover contamination, and / or sample dilution) or the local analyte concentration around each sensor of the electrochemical sensors 18, which can significantly affect the response sensitivity (i.e., slope), kinetics, and accuracy of the results.

[0045] The methods disclosed herein use the relative slope variation at each sensor (i.e., comparing the current response slope with the response slope at an adjacent previous time point) to determine whether an individual sensor of electrochemical sensor 18 has been affected by an obstruction. When the relative slope variation exhibits a steep drop above a predetermined threshold (i.e., a threshold determined based on empirical data), the drop is an indication that an obstruction has likely formed on or near the individual sensor of electrochemical sensor 18. In response to detecting the presence of an obstruction, fluid analyzer 10 can alert a user to the presence of the obstruction and the questionable results, and / or perform an obstruction removal process (e.g., aspirating and draining fluid and / or manual obstruction removal). Alternatively, or in addition to detecting the presence of an obstruction, the methods disclosed herein can detect the absence of an obstruction when the relative slope variation does not drop below a predetermined threshold, and in response, fluid analyzer 10 can alert a user to the absence of the obstruction.

[0046] The response sensitivity of the electrochemical sensor 18 can be calculated based on the response of the electrochemical sensor 18 to the calibrator for at least two concentrations (i.e., two-point calibration). The response slope can be given by the following equation (1):

number

[0047] When properly manufactured, each of the electrochemical sensors 18 has a stable near-Nernstian slope, thereby ensuring sufficient accuracy and consistency of response performance (i.e., precision and accuracy of response). However, in the integrated sensor module of the fluid analyzer 10, each individual electrochemical sensor 18 may exhibit evidence of failure in multiple modes.

[0048] First, if the response slope of the electrochemical sensor 18 slowly decreases and eventually falls outside the specification range of the electrochemical sensor 18, this slow decrease may be evidence of an irregularity with the sensing components of the electrochemical sensor 18 (e.g., leaching of ionophores or plasticizers, migration of external sensing components, and / or dilution or hydration of components).

[0049] Second, if the response slopes of each of the electrochemical sensors 18 "move" higher or lower simultaneously, this simultaneous movement is evidence of the presence of an obstruction on or near the reference electrode, causing the reference electrode to lose its stable liquid junction potential, causing the electrochemical sensor 18 to revert to an unstable signal in response to both the high and low concentration calibration reagents.

[0050] Third, when the response slope of a particular electrochemical sensor 18 exhibits a steep gradient shift, e.g., a significant drop, this steep gradient shift can be evidence that a foreign object (i.e., an obstruction) is covering or partially covering the sensing component of the electrochemical sensor 18 (e.g., the cover membrane of an ion-selective electrode). Once a foreign object is present in a portion (e.g., most) of the sensing membrane of the electrochemical sensor 18, the local diffusion and concentration environment temporarily changes, with the foreign object acting as a layer of “contaminant,” “buffer,” or “diffusion inhibitor.” During a two-point calibration, the high-concentration calibration reagent is “diluted” by the foreign object, and the low-concentration calibration reagent is also “contaminated” by the foreign object. As a result, the response slope of the electrochemical sensor 18 suddenly drops in response to the presence of the foreign object. If the foreign object is relatively small (e.g., a microthrombus), its presence may not affect the local concentration environment, and its effect on the gradient may be negligible, allowing these electrochemical sensors 18 to operate relatively normally.

[0051] The obstruction detection algorithm described herein relates to the third failure mode described above. To detect obstructions on or near the electrochemical sensor 18 of the fluid analyzer 10, the method disclosed herein uses the current response sensitivity (m n ) was compared with the previous "normal" response sensitivity (m n-1 ) and the difference between the two response sensitivities is given by equation (2): Δm=m n -m n-1 (2) where no obstructions are present and Δm is close to 0. Through experimentation, a threshold range can be developed with experimental data to include microthrombi that do not dramatically affect the sensor response.

[0052] After Δm is exceeded (i.e., exceeded), the threshold range m n-1 is stored as the "normal" response slope, and for x=1, 2, etc., the response slopes of this and the next adjacent time points (m n+1 ) are compared (i.e., Δm * =m n+x -mn-1 ). Δm * , continues to exceed the threshold range is evidence that an obstruction continues to interfere with the electrochemical sensor 18. In some embodiments, Δm and the threshold range m n-1 can be inverted. In this case, Δm is the threshold range m n-1 A smaller value is evidence that an obstruction continues to interfere with the electrochemical sensor 18. Correspondingly, a change in the response slope outside the threshold range (i.e., above and / or below a predetermined value) is evidence of an obstruction.

[0053] When the foreign matter is removed from the electrochemical sensor 18, the response slope of the electrochemical sensor 18 can return to normal (i.e., near zero, or within a threshold range, which means that the sensor signal difference in response to the high and low concentration calibration reagents is relatively consistent).

[0054] In some embodiments, an obstruction detection algorithm can be applied to determine whether an obstruction is present for each individual electrochemical sensor 18 of the fluid analyzer 10. If the obstruction moves from an upstream position on the fluid analyzer 10 to a downstream position on the fluid analyzer 10, it can be observed by tracking the corresponding sequential drop in the gradient of the electrochemical sensor 18. If the obstruction moves from its initial position on a particular electrochemical sensor 18 without intervention, the particular electrochemical sensor 18 can return to a normal response state.

[0055] In some embodiments, each of the electrochemical sensors 18 is an amperometric sensor 22 (hereinafter, "amperometric sensor 22"). An exemplary amperometric sensor is shown in FIG. 2. The amperometric sensor 22 generally includes two or more electrodes 30, which are shown, by way of example, as a reference electrode 34, a counter electrode 36, and a working electrode 38. While FIG. 1 shows the reference electrode 34 located upstream of the counter electrode 36 and the working electrode 38, in one embodiment, the reference electrode 34 is located downstream of the counter electrode 36 and the working electrode 38 (not shown). It should be noted that other sensor configurations may be used, such as opposing sensor arrays having different electrode configurations, including, for example, coplanar and / or opposing electrode configurations.

[0056] In some embodiments, the reference electrode 34, counter electrode 36, and working electrode 38 of the amperometric sensor 22 are selected to be capable of effecting an electrochemical reaction, i.e., reduction-oxidation (hereinafter "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 effecting an electrochemical reaction with a target analyte or a reaction by-product of the target analyte in a sample. In one embodiment, the reference electrode 34 can be constructed from silver / silver chloride, the counter electrode 36 can be constructed from gold, and the working electrode 38 can be constructed from platinum. However, it should be understood that the reference electrode 34, counter electrode 36, and working electrode 38 can also be constructed from other materials, including gold, platinum, silver, and combinations thereof.

[0057] In another embodiment, each of the electrochemical sensors 18 is a potentiometric sensor 46 (hereinafter "potentiometric sensor 46") (shown in FIG. 4). The potentiometric sensor 46 generally includes two or more electrodes 30, shown by way of example as a reference electrode 34 and a working electrode 38.

[0058] In some embodiments, the reference electrode 34 and working electrode 38 of the potentiometric sensor 46 are selected to be capable of producing an electrochemical reaction, i.e., ionic activity, in the presence of chemical species in a fluid, such as a simple solution, a quality control reagent, and / or a calibration reagent. In some embodiments, the working electrode 38 detects, but is not limited to, chloride ions (Cl - ), magnesium ions (Mg 2+ ), potassium ions (K + ), sodium ions (Na + ), hydrogen ions (H + ), bicarbonate ion (HCO3 - ), calcium ions (Ca 2+ ), and / or urea molecules (CO(NH2)2), and other chemical species, including ion electrodes or ion-selective electrodes (hereinafter "ISE").

[0059] The fluid analyzer 10 may include a fluid channel 42 through which fluids, such as samples, quality control fluids, wash solutions, and / or calibration reagents, may pass to contact at least one of the electrochemical sensors 18, including, but not limited to, an amperometric sensor 22 and / or a potentiometric sensor 46.

[0060] 1 and 2, in one embodiment, each of the amperometric sensors 22 is assembled on a substrate 50 within a housing 26 that defines a chamber 54. In this embodiment, the working electrode 38 is positioned between the reference electrode 34 and the counter electrode 36. The amperometric sensors 22 may include a dielectric layer 58. The substrate 50 may be constructed from a dielectric material, such as plastic, ceramic, or silicon. The dielectric layer 58 may include openings for one or more electrodes 30 of the amperometric sensors 22, including, but not limited to, the reference electrode 34, the counter electrode 36, and the working electrode 38. The electrodes 30 of the amperometric sensors 22 may be covered by an electrolyte layer 62 (e.g., Nafion®) and / or a permeable membrane 66 (e.g., a copolymer). Fluids, such as calibration reagents or samples, enter the chambers 54 through an inlet port 70 and exit the chambers 54 through an outlet port 74. The housing 26 may include a cover 78 that encloses the amperometric sensor 22 and a gasket 82 that engages the permeable membrane 66 and the cover 78 to seal the chamber 54 , the inlet port 70 , and the exit port 74 .

[0061] The fluid can pass through the fluid channel 42 and enter the chamber 54 defined by the housing 26 that supports and / or contains the amperometric sensor 22, and thus the fluid can assist in creating an electrochemical reaction between the target analyte or a reaction by-product of the target analyte and the amperometric sensor 22.

[0062] FIG. 3 illustrates another embodiment of an amperometric sensor 22 that can be used in accordance with the present disclosure. In this embodiment, the amperometric sensor 22 includes electrodes 30, including, but not limited to, a reference electrode 34, a counter electrode 36, and a working electrode 38, on a substrate 84. The substrate 84 can extend outward from the electrodes 30. The amperometric sensor 22 can also include a gasket 86 having an opening 90 sized and dimensioned to be larger than the area of ​​the substrate 84 encompassed by the electrodes 30. The gasket 86 can be positioned on the substrate 84 such that the gasket 86 does not overlap the electrodes 30. Rather, the gasket 86 can engage the substrate 84 around the electrodes 38. The amperometric sensor 22 can also include a cover 94 positioned on the gasket 86, such that the gasket 86 is positioned between the substrate 84 and the cover 94. The opening 90 in the gasket 86, along 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 in the cover 94 (not shown) to allow fluid to enter and exit the chamber.

[0063] Referring again to FIG. 1 , the fluid can flow through the fluidic channel 42 due to a driving force provided by the driving device 106. The driving force can include, but is not limited to, capillary force, pressure, gravity, vacuum, electrokinesis, etc. The driving device 106 can be, for example, but is not limited to, a pump. A sample can be introduced into the fluidic channel 42 via a sample injection port 110. The sample injection port 110 can be in communication with a valve 114, which can be opened and / or closed manually or mechanically to allow and / or prevent the sample from damaging the fluidic channel 42. The sample can be injected into the sample injection port 110 manually or mechanically.

[0064] In some embodiments, the fluid channel 42 can be a hollow channel. The fluid channel 42 can also include a waste outlet 116, whereby the fluid exits the fluid channel 42 after contacting at least one, and preferably all, of the amperometric sensors 22.

[0065] For example, with reference to FIG. 2 , fluidic channel 42 can deliver sample to chamber 54. Chamber 54 can indirectly intersect with amperometric sensor 22, including, for example, but not limited to, reference electrode 34, counter electrode 36, and working electrode 38, via electrolyte layer 62 and permeable membrane 66. In some embodiments, chamber 54 can be a hollow channel. Substrates 50 and 84 can be formed from materials including, but not limited to, plastic, ceramic, glass, and / or any material capable of housing electrode 30. For example, in some embodiments, substrates 50 and 84 can be formed from polyethylene terephthalate (hereinafter, “PET”).

[0066] 2 , the electrodes 30 of the amperometric sensor 22, including, for example, the reference electrode 34, the counter electrode 36, and the working electrode 38, can include one or more conductive layers 118 (hereinafter, “conductive layer 118”). The conductive layer 118 can be formed from any suitable conductive material, including, but not limited to, carbon, silver, silver chloride, gold, platinum, palladium, etc. The conductive layer 118 can be applied using sputtering, electroplating, screen printing, inkjet printing, bonding, and / or any other technique capable of applying a conductive material to the housing 26 in conjunction with the fabrication of the amperometric sensor 22.

[0067] In some embodiments, the conductive layer 118 is formed by laser ablation of a metal film in which gold is sputtered onto a backing. Alternatively, in some embodiments, the conductive layer 118 is formed from localized positioning of carbon within the housing 26. As shown in FIGS. 1 and 2 , the electrodes 30, including but not limited to the reference electrode 34, counter electrode 36, and working electrode 38, can also include leads 122 for connection to a meter 126.

[0068] In some embodiments, the meter 126 is a potentiostat. In such embodiments, the meter 126 can receive signals generated by the reference electrode 34, the counter electrode 36, and the working electrode 38, which are in contact with a fluid containing a target analyte, such as oxygen in a sample, a quality control reagent, and / or a calibration reagent, and convert the signals into information correlating the potential to the amount of the target analyte in the fluid. The meter 126 can measure the current between two of the electrodes 30 and control the voltage difference between the two of the electrodes 30. For example, when the amperometric sensor 22 includes the reference electrode 34 and the working electrode 38, the meter 126 can 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.

[0069] In embodiments in which the amperometric sensor 22 includes a counter electrode 36, the meter 126 can measure the current between the working electrode 38 and the counter electrode 36 and control 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 that do not require the consumption of electrodes 30. The current measured by the meter 126 when a voltage is applied to the working electrode 38 and the reference electrode 34 is correlated to the target analyte content of the fluid.

[0070] 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, "calibration reagent injection ports 130") that may be in fluid communication with the fluid channel 42. The calibration reagent injection ports 130 may also be in communication with valves 134-1, 134-2, and 134-3 (hereinafter, "valves 134") that may be manually or mechanically opened and / or closed to allow and / or prevent one or more calibration reagents and / or cleaning fluids from entering the fluid channel 42. The valves 134 may be automatic valves that may be opened or closed upon receiving a suitable control signal. In some embodiments, the calibration reagent injection port 130-3 is a cleaning fluid injection port.

[0071] 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, "reservoirs 132"). Reservoir 132-1 can 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 having 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 wash fluid. The wash fluid may be an aqueous wash reagent, typically containing a surfactant, for example, to remove the calibration reagent and / or sample from the interior of housing 26 abutting chamber 54.

[0072] Referring again to FIG. 1 , the instrument 126, the actuation device 106, and the valves 114, 134-1, and 134-2 can communicate with the control system 138 via signal paths 142. As shown in FIG. 1 , the signal paths 142 can be, for example, but not limited to, one or more cables that carry data generated by the instrument 126 to the control system 138 and / or information, signals, and / or commands from the control system 138 to the valves 114 and 134 in electronic form and / or via a network as described in more detail herein. The control system 138 is shown in more detail in FIG. 5 . The control system 138 can be one or more systems capable of implementing and / or executing the logic of the processes described herein. Logic embodied in the form of software instructions and / or firmware can be executed on any suitable hardware. For example, the logic embodied in the form of software instructions and / or firmware can be executed on one or more dedicated systems, personal computer systems, distributed processing computer systems, etc. In some embodiments, the logic may be implemented in a stand-alone environment operating on a single computer system and / or may be implemented in a networked environment, such as a distributed system using multiple computers and / or processors.

[0073] 1 , in some embodiments, the calibration cartridge 14 containing the calibration reagent is in fluid communication with one or more quality control fluid injection ports (hereinafter “quality control fluid injection ports”) (not shown) that are in fluid communication with the fluidic channel 42. In one embodiment, the quality control injection ports (not shown) are in fluid communication with one or more quality control fluid valves (hereinafter “quality control fluid valves”) (not shown), whereby the quality control fluid valves (not shown) can be manually or mechanically opened and / or closed to allow and / or prevent the quality control fluid from entering the fluidic channel 42. The quality control fluid valves (not shown) can be automatic valves that can open or close upon receiving a suitable control signal.

[0074] In some embodiments, the fluid analyzer 10 includes multiple electrochemical sensors 18 and multiple corresponding meters 126 .

[0075] 4, potentiometric sensor 46 generally includes two or more electrodes 30, shown by way of example as a reference electrode 34 and a working electrode 38. Working electrode 38 may be an ion-selective electrode including a cover membrane 188, an internal electrolyte layer 192, and an internal reference electrode 196. The cover membrane may include, for example, but not limited to, a plasticized PVC membrane doped with an analyte-sensing ionophore, and may also include other additives.

[0076] The internal electrolyte layer 192 can include, for example, without limitation, 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 can be screen printed onto at least a portion of the internal reference electrode 196. At least a portion of the cover membrane 188 can be disposed on at least a portion of the internal electrolyte layer 192. Any internal reference electrode 196 and cover membrane 188 known in the art or otherwise contemplated herein can be utilized with the methods described herein, so long as the potentiometric sensor 46 is capable of functioning with the methods described herein.

[0077] In certain (non-limiting) embodiments, the cover membrane 188 can be selected from the group including a chloride-sensing membrane, a magnesium-sensing membrane, a potassium-sensing membrane, a sodium-sensing membrane, a pH-sensing membrane, a bicarbonate-sensing membrane, a calcium-sensing membrane, and a blood urea nitrogen-sensing membrane; and / or the metal salt dispersed in carbon paste, hydrogel, or hydrophilic polymer can be selected from the group including MgCl, HCl, NaCl, KCl, KNO, and NaClO. In the illustrated embodiment, the metal salt can be any solution dispersed in carbon paste, hydrogel, or hydrophilic polymer. Examples of such solutions include aqueous solutions. The internal reference electrode 196 can be constructed from, for example, but not limited to, silver, silver chloride, etc.

[0078] FIG. 5 shows a block diagram of control system 138, which may include one or more processors 146 (hereinafter “processors 146”) that function together or independently to execute processor-executable code, one or more memories 150 (hereinafter “memories 150”) capable of storing processor-executable code, one or more input devices 154 (hereinafter “input devices 154”), and one or more output devices 158 (hereinafter “output devices 158”).

[0079] In some embodiments, when executed, the processor-executable code causes the processor 146 to, during a first time period: control the automated valve 134-1 to route a first calibration reagent through the fluid channel 42 to the reference electrode 34 and working electrode 38 (and counter electrode 36, if included in the amperometric sensor 22) of each electrochemical sensor 18; control the meter 126 (when the meter 126 is a potentiostat) to apply a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in a sample of the first calibration reagent and receive a first reading for each electrochemical sensor 18 from the meter 126; and route a second calibration reagent through the fluid channel 42 to the reference electrode 34 and working electrode 38 (and counter electrode 36, if included in the amperometric sensor 22). 6); controlling the meter 126 (when the meter 126 is a potentiostat) to apply a voltage potential to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in the sample of the second calibration reagent and to receive from the meter 126 a second reading for each electrochemical sensor 18; calculating first calibration parameters for each electrochemical sensor 18 using the first readings, the second readings, and a multi-point calibration algorithm such as that described in U.S. Pat. No. 11,293,889 to Li (incorporated herein by reference); measuring the target analyte content in the fluid sample using the first calibration parameters and calculating a first response slope m1 according to equation (3) described below.

[0080] In some embodiments, when executed, the processor-executable code further causes the processor 146 to, during a second time period after the first time period: control the automated valve 134-1 to route the first calibration reagent through the fluid channel 42 to the reference electrode 34 and the working electrode 38 (and the counter electrode 36, if included in the amperometric sensor 22) of each electrochemical sensor 18; control the meter 126 (when the meter 126 is a potentiostat) to apply a voltage potential to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in the sample of the first calibration reagent and receive a third reading for each electrochemical sensor 18 from the meter 126; controlling automatic valve 134-2 to send a second calibration reagent to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 (and counter electrode 36 if included in amperometric sensor 22); applying a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in the sample of second calibration reagent, and controlling meter 126 (when meter 126 is a potentiostat) to receive a fourth reading for each electrochemical sensor 18 from meter 126; calculating a second calibration parameter using the third reading, the fourth reading, and a multi-point calibration algorithm (described above); measuring the target analyte content in the fluid sample using the second calibration parameter and calculating a second response slope m2 according to equation (4) described below.

[0081] In some embodiments, when executed, the processor-executable code further causes the processor 146 to: determine whether the difference between the first response slope m1 and the second response slope m2 for each electrochemical sensor 18 is above or below a predetermined threshold (i.e., outside a predetermined threshold range) according to equation (2) above; and store data indicative of an obstruction on the electrochemical sensor 18 in response to a determination that the difference between the first response slope m1 and the second response slope m2 (i.e., Δm) is outside the predetermined threshold range.

[0082] In some embodiments, the step of controlling the meter 126 to apply a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in a sample of the first calibration reagent and to receive a first reading for each electrochemical sensor 18 from the meter 126 is replaced by the step of the processor 146 receiving a first reading from the meter 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 controlling the meter 126 to apply a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in a sample of the second calibration reagent and to receive a second reading from the meter 126 for each electrochemical sensor 18 is replaced by the step of the processor 146 receiving a second reading from the meter 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.

[0083] In some embodiments, the step of controlling the meter 126 to apply a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in the sample of the first calibration reagent and to receive a third reading from the meter 126 for each electrochemical sensor 18 is replaced by the step of the processor 146 receiving a third reading from the meter 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 controlling the meter 126 to apply a voltage potential to the reference electrode 34 and working electrode 38 of each electrochemical sensor 18 sufficient to induce an electrochemical reaction in a sample of the second calibration reagent and to receive a fourth reading from the meter 126 for each electrochemical sensor 18 is replaced by the step of the processor 146 receiving a fourth reading from the meter 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.

[0084] Each element of the control system 138 can be partially or completely network-based or cloud-based and may or may not be located at a single physical location. In some embodiments, the processor 146 can communicate with the instruments 126, the actuation device 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 computational resources on demand via interfacing with a computer and / or computer network, software and / or data located at least partially on the computer and / or computer network. The network can enable bidirectional communication of information and / or data between each element of the control system 138. The network can interface with the processor 146 and the instruments 126, the actuation device 106, and / or the valves 114 and 134 in various ways. For example, without limitation, the network can interface via optical and / or electronic interfaces and / or can use multiple network topographies and / or protocols, including, but not limited to, Ethernet, TCP / IP, circuit-switched paths, combinations thereof, etc. For example, in some embodiments, the network may be implemented as the World Wide Web (or Internet), a local area network (LAN), a wide area network (WAN), a metropolitan 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, an optical network, a cable network, a public switched telephone network, an Ethernet network, combinations thereof, and the like.Additionally, the network may enable bidirectional interfacing and / or communication of data and / or information between the processor 146 and the instruments 126, the actuation devices 106, and / or the valves 114 and 134 using various protocols.

[0085] In some embodiments, the network can be the Internet and / or other networks. For example, if the network is the Internet, the primary user interface of the control system 138 can be delivered via a series of web pages (e.g., target analyte concentration determination web pages). Note that the primary user interface of the control system 138 can also be another type of interface, including, but not limited to, a Windows-based application.

[0086] Processor 146 may be implemented as a single processor or multiple processors acting together or independently to execute the logic described herein. In particular embodiments, when more than one processor 146 is used, it should be understood that the processors 146 may be remotely located, co-located, or may comprise a single multi-core processor. Processor 146 may read and / or execute processor-executable code and / or may create, manipulate, retrieve, modify, and / or store data structures in memory 150.

[0087] Exemplary embodiments of processor 146 may include, but are not limited to, for example, a digital signal processor (DSP), a central processing unit (CPU), a field programmable gate array (FPGA), a microprocessor, a multi-core processor, combinations thereof, etc. In some embodiments, additional processor 146 may include, but is not limited to, an implementation as, for example, a personal computer, a cellular phone, a smartphone, a network-enabled television set, a television set-top box, a tablet, an e-reader, a laptop computer, a desktop computer, a network-enabled handheld device, a video game console, a server, a digital video recorder, a DVD player, a Blu-Ray player, and / or combinations thereof.

[0088] The processor 146 may be in communication with a memory 150 via a path (e.g., a data bus). The processor 146 may also be in communication with an input device 154 and / or an output device 158.

[0089] The processor 146 may interface with and / or communicate with the instrument 126, the actuation device 106, and / or the valves 114 and 134. For example, the processor 146 may communicate by exchanging signals (e.g., analog, digital, optical, etc.) using a network protocol.

[0090] The memory 150 is capable of storing processor-executable code. Additionally, the memory 150 may be implemented as conventional non-transitory memory such as, for example, random access memory (RAM), a CD-ROM, a hard drive, a solid-state drive, a flash drive, a memory card, a DVD-ROM, a floppy disk, an optical drive, or a combination thereof.

[0091] In some embodiments, memory 150 can be located in the same physical location as processor 146, and / or memory 150 can be located remotely from processor 146. For example, memory 150 can be located remotely from processor 146 and can communicate with other processors via a network. Additionally, when more than one memory 150 is used, a first memory can be located in the same physical location as processor 146, and additional memories 150 can be located in physical locations remote from processor 146. Additionally, memory 150 can be implemented as "cloud memory" (i.e., one or more memories 150 can be partially or fully network-based or accessible using a network).

[0092] The input devices 154 may receive information entered from a user and / or the processor 146 and may transmit such information to the processor 146, the network, and / or the gauges 126, the actuation device 106, and / or the valves 114 and 134. The input devices 154 may include, but are not limited to, implementations as, for example, a keyboard, a touch screen, a mouse, a trackball, a microphone, a fingerprint reader, an infrared port, a slide-out keyboard, a flip-out keyboard, a cell phone, a PDA, a video game controller, a remote control, a fax machine, a network interface, combinations thereof, and the like.

[0093] Output device(s) 158 may output information in a form perceivable by a user and / or processor 146. For example, output device(s) 158 may include, but are not limited to, implementations as, for example, a computer monitor, a screen, a touchscreen, a speaker, a website, a television set, a smartphone, a PDA, a mobile phone, a fax machine, a printer, a laptop computer, combinations thereof, etc. It should be understood that in some exemplary embodiments, input device(s) 154 and output device(s) 158 may be implemented as a single device, such as, for example, a touchscreen or a tablet. It should be further understood that, as used herein, the term user is not limited to a human being, but may include, for example, a computer, a server, a website, a processor, a network interface, a person, a user terminal, a virtual computer, combinations thereof, etc.

[0094] Memory 150 may store processor-executable code and / or information, including one or more databases and / or data tables 162 (hereinafter “data store 162”) and program logic 166 (also referred to herein as “calibration logic”). In some embodiments, the processor-executable code may be stored as a data structure, such as, for example, data store 162. In some embodiments, outputs of instrument 126, actuation device 106, and / or valves 114 and 134 may be stored in data store 162 in memory 150.

[0095] In some embodiments, the outputs of meter 126, each corresponding to a particular one of electrochemical sensors 18, may be stored in memory 150 as a data structure, such as data store 162. In some embodiments, each output of meter 126 may be stored as an individual data structure (e.g., data store 162) that includes a unique identifier, each unique identifier identifying the electrochemical sensor 18 to which a particular output of meter 126 corresponds.

[0096] Referring now to FIG. 6, another exemplary embodiment of a sensor array 170 of the fluid analyzer 10 is shown. The sensor array 170 can include multiple electrochemical sensors 18. In the embodiment shown in FIG. 6, 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 can 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 can be arranged in any order.

[0097] 7 illustrates one embodiment of an obstruction detection algorithm 174 for detecting the presence (or absence) of an obstruction in at least one of the electrochemical sensors 18 of the fluid analyzer 10. The algorithm 174 includes computer-executable instructions that can be periodically executed by the processor 146 to ensure that the electrochemical sensors 18 are providing accurate results.

[0098] During a first time period, in step 178, the processor 146 may contact a first calibration reagent having a first predetermined target analyte level (or concentration) 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) in the sensor array. This may be accomplished, for example, by the processor 146 of the control system 138 generating and sending a signal to open the automatic valve 134-1 and actuate the actuation device 106 to direct the first calibration reagent from the fluid reservoir 132-1 through the fluid channel 42 to the chamber 54 of at least one of the electrochemical sensors 18. When a sufficient amount of the first calibration reagent is in the chamber 54, the processor 146 of the control system 138 may close the automatic valve 134-1 and stop the actuation device 106.

[0099] After the first calibration reagent contacts at least one of the electrochemical sensors 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), in step 182, the particular electrochemical sensor 18 may generate a first reading indicative of at least one of the potential and current (i.e., faradaic and / or non-faradaic current) generated by the electrochemical reaction occurring 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. The meter 126 may then receive the first reading and pass the first reading to the processor 146 of the control system 138.

[0100] In some embodiments, at least two of the electrochemical sensors 18 can generate respective first readings indicative of at least one of the potential and current (i.e., faradaic and / or non-faradaic current) generated by an 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 in the first calibration reagent. A corresponding meter 126 can then receive the respective first readings from the at least two of the electrochemical sensors 18 and pass the respective first readings to a processor 146 of the control system 138.

[0101] In some embodiments in which the electrochemical sensor 18 is an amperometric sensor 22, the processor 146 of the control system 138 again provides a control signal to the meter 126 causing the meter 126 to apply a first potential to the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to induce an electrochemical reaction in the sample of the first calibration reagent. The meter 126 then receives a first reading from the amperometric sensor 22. In such embodiments, the first reading may indicate a faradaic current produced by an electrochemical reaction (e.g., a redox reaction) occurring between the amperometric 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) in the first calibration reagent.

[0102] In some embodiments in which the electrochemical sensor 18 is a potentiometric sensor 46, the meter 126 may simply receive a first reading from the potentiometric sensor 46 in response to the first calibration reagent contacting the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, the first reading may indicate a potential produced by an electrochemical reaction (e.g., ionic activity) occurring between the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) in the first calibration reagent.

[0103] In step 186, the processor 146 may contact a second calibration reagent having a second predetermined target analyte level (or concentration) with at least one, some, or all of the electrochemical sensors 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) in the sensor array 170. This may be accomplished, for example, by the processor 146 of the control system 138 generating and passing a signal to open the automatic valve 134-2 and actuate the actuation device 106 to direct the second calibration reagent from the fluid reservoir 132-2 through the fluid channel 42 and into the chamber 54. When a sufficient amount of the second calibration reagent is in the chamber 54, the processor 146 of the control system 138 may generate and pass a signal to close the automatic valve 134-2 and deactivate the actuation device 106. The second predetermined target analyte level may be different from the first predetermined target analyte level.

[0104] After the second calibration reagent contacts the electrochemical sensors 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), in step 190, each of the electrochemical sensors 18 can generate a second reading indicative of at least one of the potential and current (i.e., faradaic current and / or non-faradaic current) generated by the electrochemical reaction occurring 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.

[0105] In some embodiments in which the electrochemical sensor 18 is an amperometric sensor 22, the processor 146 of the control system 138 provides a control signal to the meter 126 to cause the meter 126 to apply a second potential to the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) that is insufficient to induce an electrochemical reaction in the sample of the second calibration reagent. The second potential can be determined and / or applied using a voltage potential stepping technique in which a series of successively greater or lesser voltage potentials are applied. When the current from the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) levels off, it is determined that the second potential is insufficient to induce an electrochemical reaction in the calibration reagent. The meter 126 then receives a second reading from the amperometric sensor 22. In such embodiments, the second reading may indicate a non-faradaic current produced by an electrochemical reaction (e.g., a redox reaction) occurring between the amperometric 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) in the second calibration reagent. The meter 126 may then pass the second reading to the processor 146 of the control system 138.

[0106] In some embodiments in which the electrochemical sensor 18 is a potentiometric sensor 46, the meter 126 receives a second reading from the potentiometric sensor 46 in response to contacting the second calibration reagent with the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, the second reading may indicate a potential produced by an electrochemical reaction (e.g., ionic activity) occurring between the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) in the second calibration reagent.

[0107] The meter 126 can transmit data indicative of the first reading and / or the second reading to a processor 146 of the control system 138, and the control system 138 can use the processor 146 to calculate a first response slope using the first reading and / or the second reading for each of the electrochemical sensors 18. The first response slope of an individual sensor can be calculated by the processor 146 based at least in part on the difference between the first reading and the second reading produced by the same individual sensor. In some embodiments, the first response slope m1 is calculated by the processor 146 using equation (3):

number

[0108] In some embodiments, in response to receiving data indicative of the first reading and / or the second reading from the meter 126, the processor 146 of the control system 138 calculates first calibration parameters using the first reading, the second reading, and the multi-point calibration algorithm (described above). The first calibration parameters may be stored in a data table 162 in the memory 150 and may be used to measure the target analyte content of the fluid.

[0109] In a second time period after the first time period, in step 198, the processor 146 may again contact the first calibration reagent, having the first predetermined target analyte level, with the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38). This may be accomplished, for example, by the processor 146 of the control system 138 generating and passing a signal to open the automatic valve 134-1 and actuate the actuation device 106 to direct the first calibration reagent from the fluid reservoir 132-1 through the fluid channel 42 and into the chamber 54. When a sufficient amount of the first calibration reagent is in the chamber 54, the control system 138 may close the automatic valve 134-1 and stop the actuation device 106.

[0110] Again, after the first calibration reagent contacts the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), in step 202, the electrochemical sensor 18 can generate a third reading indicative of at least one of the potential and current (i.e., faradaic current and / or non-faradaic current) generated by the occurrence of an 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.

[0111] In some embodiments in which the electrochemical sensor 18 is an amperometric sensor 22, the processor 146 of the control system 138 again provides a control signal to the meter 126 causing the meter 126 to apply a first potential to the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) sufficient to induce an electrochemical reaction in the sample of the first calibration reagent. The meter 126 then receives a third reading from the amperometric sensor 22. In such embodiments, the third reading may indicate a faradaic current produced by an electrochemical reaction (e.g., a redox reaction) occurring between the amperometric 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) in the first calibration reagent.

[0112] In some embodiments in which the electrochemical sensor 18 is a potentiometric sensor 46, the meter 126 again receives a third reading from the potentiometric sensor 46 in response to the first calibration reagent contacting the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, the third reading may indicate a potential produced by an electrochemical reaction (e.g., ionic activity) occurring between the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) in the first calibration reagent.

[0113] At step 206, the processor 146 may again contact the second calibration reagent, having a second predetermined target analyte level, with the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38). This may be accomplished, for example, by the control system 138 opening the automated valve 134-2 and actuating the actuation device 106 to direct the second calibration reagent from the fluid reservoir 132-2 through the fluid channel 42 and into the chamber 54. When a sufficient amount of the second calibration reagent is in the chamber 54, the control system 138 may close the automated valve 134-2 and stop the actuation device 106. The second predetermined target analyte level may be different from the first predetermined target analyte level.

[0114] Again, after the second calibration reagent contacts the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38), in step 210, the electrochemical sensor 18 can generate a fourth reading indicative of at least one of the potential and current (i.e., faradaic current and / or non-faradaic current) generated by the electrochemical reaction occurring 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.

[0115] In some embodiments in which the electrochemical sensor 18 is an amperometric sensor 22, the processor 146 of the control system 138 again provides a control signal to the meter 126 causing the meter 126 to apply a second potential to the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) that is insufficient to induce an electrochemical reaction in the sample of the second calibration reagent. The second potential can be determined and / or applied using a voltage potential stepping technique in which a series of successively greater or lesser voltage potentials are applied. When the current from the amperometric sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) levels off, it is determined that the second potential is insufficient to induce an electrochemical reaction in the calibration reagent. The meter 126 then receives a fourth reading from the amperometric sensor 22. In such an embodiment, the fourth reading may indicate a non-faradaic current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the amperometric 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) in the second calibration reagent.

[0116] In some embodiments in which the electrochemical sensor 18 is a potentiometric sensor 46, the meter 126 receives a fourth reading from the potentiometric sensor 46 in response to the second calibration reagent contacting the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38). In such embodiments, the fourth reading may indicate a potential produced by an electrochemical reaction (e.g., ionic activity) occurring between the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and a target analyte (e.g., oxygen) in the second calibration reagent.

[0117] The meter 126 can transmit data indicative of the third reading and / or the fourth reading to a processor 146 of the control system 138, which can use the third reading and / or the fourth reading generated from the same individual sensor to calculate a second response slope for the individual one of the sensors 18. The second response slope can be based at least in part on the difference between the third reading and the fourth reading. If the first reading, the second reading, the third reading, and the fourth reading are generated from the same individual sensor, then the first response slope m1 and the second response slope m2 can be calculated from the same individual sensor. In some embodiments, the second response slope m2 is calculated by the processor 146 using equation (4):

number

[0118] In some embodiments, in response to receiving data indicative of the third and / or fourth readings from meter 126, processor 146 of control system 138 calculates second calibration parameters using the third and fourth readings and the multi-point calibration algorithm (described above). The second calibration parameters may be stored in data table 162 in memory 150 and may be used to measure the target analyte content of the fluid.

[0119] In step 218, the processor 146 of the control system 138 calculates the difference (also referred to herein as the “delta slope”) between the first and second response slopes (i.e., Δm = |m1 − m2|) and compares the calculated difference to a predetermined threshold. This difference may be calculated based on the same individual sensor (i.e., based on the first and second response slopes calculated from the same individual sensor). If 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 at 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 to correlate to the particular electrochemical sensor 18. In some embodiments, in response to detecting an obstruction, the processor 146 of the control system 138 opens / closes the automatic valve 134-3 (also referred to herein as the "cleaning solution valve 134-3") and activates / deactivates the actuation device 106 to pass a cleaning solution through the fluid channel 42 and the chamber 54 to clean the electrochemical sensor 18 for removal of the obstruction. In some embodiments, in response to detecting an obstruction, the processor 146 of the control system 138 uses the output device 158 to output third data in a form perceptible by a user, such as an audio or visual alert, to alert or indicate to the user of the presence of the obstruction.

[0120] In some embodiments, if 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 is detected by the electrochemical sensor 18. In some embodiments, if the calculated difference is less than a predetermined threshold, no data is stored and normal operation of the fluid analyzer 10 continues. In some embodiments, in response to detecting the absence of an obstruction, the processor 146 of the control system 138 uses the output device 158 to output a warning or indication (e.g., an audio or visual warning or indication) that indicates the absence of an obstruction in a form perceptible by a user.

[0121] Thereafter, using the fluid analyzer 10, a fluid sample having an unknown target analyte content can be applied 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.

[0122] Referring now to Figure 8, a time course of the sensor array 170 shown in Figure 6 is shown. Figure 8 shows that at 15:07 on day 2, an obstacle 180 formed on potassium sensor 18-3; that from 18:07 on day 2 to 12:30 on day 3, the obstacle 180 moved from potassium sensor 18-3 to a downstream position (i.e., sodium sensor 18-4, pH sensor 18-5, and bicarbonate sensor 18-6); that at 10:17 on day 4, the obstacle 180 separated into a first obstacle 180-1 on potassium sensor 18-3 and a second obstacle 180-2 on pH sensor 18-5 and bicarbonate sensor 18-6; and that at 10:43 on day 5, the obstacle 180 separated into a first obstacle 180-1 on potassium sensor 18-3, a second obstacle 180-2 on bicarbonate sensor 18-6, and a calcium sensor 18-6. at 10:44 on the sixth day, a fourth obstacle 180-4 is present on the sodium sensor 18-4; at 10:44 on the sixth day, the obstacle 180 is partially removed (i.e., the second obstacle 180-2 and the third obstacle 180-3 are removed); then, at 10:47 on the seventh day, the obstacle 180 is further removed (i.e., the first obstacle 180-1 is removed); and at 10:47 on the seventh day, the fourth obstacle 180-4 remains on the sodium sensor 18-4, indicating that the obstacle 180 is finally removed by an obstruction removal process performed by the fluid analyzer or its user.

[0123] 9A-9G, graphs are shown illustrating the delta slope 183 (i.e., Δm) for each of the electrochemical sensors 18 shown in FIG. 6 over a period corresponding to the time frame shown in FIG. 8. In FIG. 9A, it can be seen that nowhere within this time frame does the delta slope 183 for the chloride sensor 18-1 fall outside a predetermined threshold 184 (e.g., ±3 mV / D) (millivolts per decade) for the chloride sensor 18-1. Thus, nowhere within this time frame does the delta slope 183 for the chloride sensor 18-1 indicate the presence of an obstruction 180. Similarly, in FIG. 9B, it can be seen that nowhere within this time frame does the delta slope 183 for the magnesium sensor 18-2 fall outside a predetermined threshold 184 (e.g., ±1.5 mV / D) for the magnesium sensor 18-2. Thus, nowhere within this time frame does the delta slope 183 for the magnesium sensor 18-2 indicate the presence of an obstruction 180.

[0124] However, in FIG. 9C it can be seen that during the period from about day 2 to about day 6, the delta slope 183 for potassium sensor 18-3 is outside of a predetermined threshold 184 (e.g., ±3 mV / D) for potassium sensor 18-3, thus indicating the presence of an obstruction 180 during that period.

[0125] In FIG. 9D, it can be seen that during a first period from about day 2 to about day 3 and a second period from about day 6 to about day 8 (i.e., mostly day 7), the delta slope 183 for sodium sensor 18-4 is outside a predetermined threshold 184 (e.g., ±3 mV / D), thus indicating the presence of two obstructions 180: during that first period, a first obstruction (shown as 180 in FIG. 8) is present, and during that second period, a second obstruction (shown as 180-4 in FIG. 8) is present.

[0126] In FIG. 9E, it can be seen that during the period from about day 2 to about day 4, the delta slope 183 for pH sensor 18-5 is outside a predetermined threshold 184 (e.g., ±3 mV / D), thus indicating the presence of an obstruction 180 during that period.

[0127] In FIG. 9F, it can be seen that during a first period occurring on approximately day 0 and a second period occurring on approximately day 4, the delta slope 183 for bicarbonate sensor 18-6 is outside a predetermined threshold 184 (e.g., ±3 mV / D), thus indicating the presence of two obstructions 180: during that first period, a first obstruction 180 (not shown in FIG. 8) is present, and during that second period, a second obstruction (shown as 180-2 in FIG. 8) is present.

[0128] 9A-9B, the delta slope 183 for calcium sensor 18-7 is nowhere outside of a predetermined threshold 184 (e.g., ±1.5 mV / D) for calcium sensor 18-7. Thus, nowhere during this time frame does the delta slope 183 for calcium sensor 18-7 indicate the presence of an obstruction 180.

[0129] Although a graph showing the delta slope 183 of the blood urea nitrogen sensor 18-8 shown in FIG. 6 is not shown, in some embodiments, the predetermined threshold 184 for the blood urea nitrogen sensor 18-8 may be, for example, ±3 mV / D.

[0130] In some embodiments, the fluid analyzer 10 can further include a magnesium-only calibration reagent injection port (not shown), which can be in fluid communication with the fluid channel 42. The magnesium-only calibration reagent injection port can also be in communication with a magnesium-only valve (not shown), which can be manually or mechanically opened and / or closed to allow and / or prevent the magnesium-only calibration reagent from entering the fluid channel 42. The magnesium-only valve can be an automatic valve that can open or close upon receiving a suitable control signal.

[0131] In some embodiments, the magnesium-specific calibration reagent injection port is in fluid communication with a calibration cartridge 14 that includes a magnesium-specific calibration reagent, which may be included in addition to one or more calibration reagents described above. In some embodiments, the calibration cartridge 14 further includes a magnesium-specific reservoir (not shown). The magnesium-specific reservoir may contain a magnesium-specific calibration reagent having a known target analyte level.

[0132] In some embodiments, magnesium sensor 18-2 may be subject to interference caused by calcium ions present in the fluid sample. To correct for such interference, in some embodiments, when executed, the processor-executable code further causes processor 146 to, during a first time period: control an automated magnesium-specific valve to route magnesium-specific calibration reagent through fluid channel 42 to reference electrode 34 and working electrode 38 of magnesium sensor 18-2 (and counter electrode 36, if included in amperometric sensor 22); apply a voltage potential to reference electrode 34 and working electrode 38 of magnesium sensor 18-2 sufficient to induce an electrochemical reaction in the sample of magnesium-specific calibration reagent; and control meter 126 (when meter 126 is a potentiostat) to receive a fifth reading for magnesium sensor 18-2 from meter 126.

[0133] In some embodiments, the process of calculating the first calibration parameter for each electrochemical sensor 18 using the first reading, the second reading, and the multi-point calibration algorithm (described above) can be further described as calculating the first calibration parameter for 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 parameters for the other electrochemical sensors 18 using the first reading, the second reading, and the multi-point calibration algorithm.

[0134] Further, in some embodiments, when executed, the processor-executable code further causes the processor 146 to, during a second time period after the first time period: control the automatic magnesium-specific valve to send magnesium-specific calibration reagent through the fluid channel 42 to the reference electrode 34 and working electrode 38 of the magnesium sensor 18-2 (and the counter electrode 36 if included in the amperometric sensor 22); and control the meter 126 (when the meter 126 is a potentiostat) to apply a voltage potential to the reference electrode 34 and working electrode 38 of the magnesium sensor 18-2 sufficient to induce an electrochemical reaction in the sample of magnesium-specific calibration reagent, and receive a sixth reading for the magnesium sensor 18-2 from the meter 126.

[0135] In some embodiments, the process of calculating the second calibration parameter for each electrochemical sensor 18 using the third reading, the fourth reading, and the multi-point calibration algorithm (described above) can be further described as calculating the second calibration parameter for magnesium sensor 18-2 using the third reading, the fourth reading, the sixth reading, and the multi-point calibration algorithm, and calculating the second calibration parameters for the other electrochemical sensors 18 using the first reading, the second reading, and the multi-point calibration algorithm.

[0136] Non-limiting exemplary embodiments The following is a numbered list of non-limiting exemplary embodiments of the inventive concepts disclosed herein:

[0137] 1. A fluid analyzer comprising: a fluid channel operable to carry a fluid; a sensor in fluid communication with the fluid channel; a meter operable to receive the signal produced by the sensor and convert the signal into information indicative of the electrical potential of the fluid; a first calibrator solution having a first analyte concentration; a second calibrator solution having a second analyte concentration different from the first analyte concentration; one or more calibration fluid injection ports in fluid communication with the fluid channel and operable to receive a first calibration fluid and a second calibration fluid; one or more valves positioned between the one or more calibrant liquid injection ports and the sensor, the valves being openable and closeable to provide one or more samples of each of the first calibrant liquid and the second calibrant liquid to the fluid channel; a control system having a processor, the processor operable to execute processor-executable code that, when executed by the processor, causes the processor to perform an obstacle detection algorithm, the processor-executable code comprising: controlling one or more valves to sequentially deliver a first calibrant solution and a second calibrant solution through the fluid channel to the sensor during a first time period, and storing first data indicative of a first response slope based at least in part on a first difference between first information generated by the meter indicative of a first potential produced by contacting the sensor with the first calibrant solution and second information indicative of a second potential produced by contacting the sensor with the second calibrant solution; controlling the one or more valves to sequentially deliver the first calibrant solution and the second calibrant solution through the fluid channel to the sensor during a second time period after the first time period, and storing second data indicative of a second response slope based at least in part on a second difference between third information indicative of a third potential produced by contacting the sensor with the first calibrant solution and fourth information produced by the meter indicative of a fourth potential produced by contacting the sensor with the second calibrant solution; and storing third data indicative of an obstruction on the sensor in response to the difference between the first response slope and the second response slope exceeding a threshold.

[0138] 2. The fluid analyzer of exemplary embodiment 1, wherein the sensor includes a working electrode and a reference electrode.

[0139] 3. The fluid analyzer of any one of exemplary 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.

[0140] 4. A fluid analyzer as described in any one of exemplary embodiments 1-3, wherein the first response slope is based at least in part on a quotient having 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 based at least in part on a quotient having 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.

[0141] 5. A fluid analyzer as described in any one of exemplary embodiments 1 to 4, wherein the one or more valves include a first calibration valve and a second calibration valve, the first calibration valve being openable and closeable to provide one or more samples of a first calibration liquid to the fluid channel, and the second calibration valve being openable and closeable to provide one or more samples of a second calibration liquid to the fluid channel.

[0142] 6. A fluid analyzer as described in one of exemplary embodiments 1 to 5, further comprising a cleaning fluid injection port in fluid communication with the fluid channel and a cleaning fluid valve positioned between the cleaning fluid injection port and the sensor, wherein the cleaning fluid injection port is operable to receive cleaning fluid and the cleaning fluid valve is openable and closeable to provide cleaning fluid to the fluid channel.

[0143] 7. A fluid analyzer as described in any one of exemplary embodiments 1 to 6, wherein the processor executable code, when executed by the processor, further causes the processor to control a wash fluid valve to send wash fluid through the fluid channel to the sensor based at least in part on the third data.

[0144] 8. The fluid analyzer of any one of exemplary embodiments 1-7, wherein the obstruction is a thrombus.

[0145] 9. A method for detecting an obstruction on a sensor of a fluid analyzer, comprising: sequentially causing a flow of a first calibrant fluid and a second calibrant fluid having a known analyte concentration to the sensor for a first time period, and determining a first response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; sequentially causing a flow of the first calibrant fluid and the second calibrant fluid to the sensor for a second time period and determining a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; and determining, by the processor, a presence of an obstacle on the sensor based at least in part on a difference between the first response sensitivity and the second response sensitivity.

[0146] 10. The method according to any one of the preceding exemplary embodiments, wherein the step of determining the presence of an obstacle determines the presence of an obstacle when the difference is outside a predetermined threshold range.

[0147] 11. The method according to any one of the preceding exemplary embodiments, wherein the step of determining the presence of an obstacle determines the absence of an obstacle when the difference is within a predetermined threshold range.

[0148] 12. The method of any one of the preceding exemplary embodiments, wherein the known analyte concentration of the first calibrator fluid and the known analyte concentration of the second calibrator fluid are different.

[0149] 13. The method of any one of the preceding exemplary embodiments, wherein the first response sensitivity is a first response slope of the sensor, and the second response sensitivity is a second response slope of the sensor, and the method further includes 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 solution and the second calibration solution, respectively, by the difference between the logarithms of the known concentrations.

[0150] 14. The step of sequentially causing a flow of a first calibration liquid and a second calibration liquid during a first time period comprises: contacting a first calibration fluid with the sensor to generate a signal receivable by the meter and convertible to first information indicative of a first one of the sensor responses, the first sensor response being an electrical potential generated by the sensor in response to contacting the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal receivable by the meter and convertible to second information indicative of a second one of the sensor responses, the second sensor response being an electrical potential generated by the sensor in response to contacting the second calibration fluid; storing first data indicative of a first response slope based at least in part on a difference between the first information and the second information; The step of sequentially causing the flow of the first calibration liquid and the second calibration liquid in a second time period after the first time period includes: contacting a first calibration fluid with the sensor to generate a signal receivable by the meter and convertible to third information indicative of a third one of the sensor responses, the third sensor response being a third electrical potential generated by the sensor in response to contacting the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal receivable by the meter and convertible to fourth information indicative of a fourth one of the sensor responses, the fourth sensor response being a fourth electrical potential generated by the sensor in response to contacting the second calibration fluid; storing second data indicative of a second response slope based at least in part on a difference between the third information and the fourth information; and storing third data indicative of a presence of an obstacle on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold.

[0151] 15. The method of any one of the preceding exemplary embodiments, wherein the first response slope has the difference between the first information and the second information as the dividend and is based at least in part on a quotient having the difference between the logarithms of the known analyte concentrations as the divisor, and the second response slope has the difference between the third information and the fourth information as the dividend and is based at least in part on a quotient having the difference between the logarithms of the known analyte concentrations as the divisor.

[0152] 16. The method of any one of the preceding exemplary embodiments, wherein the method further comprises contacting a cleaning fluid with the sensor based at least in part on determining the presence of an obstruction.

[0153] 17. The method of any one of the preceding exemplary embodiments, wherein the method further includes storing third data indicative of a thrombus on the sensor in response to the difference between the first response slope and the second response slope exceeding a threshold value.

[0154] 18. A fluid analyzer comprising: a sensor configured to measure at least one parameter associated with the fluid; one or more containers configured to contain a first calibrant liquid and a second calibrant liquid having known analyte concentrations; 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 obstacle obstructing the sensor, the processor comprising: sequentially causing a flow of a first calibrant fluid and a second calibrant fluid to the sensor for a first time period, and determining a first response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; sequentially causing a flow of the first calibrant fluid and the second calibrant fluid to the sensor for a second time period, and determining a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; The fluid analyzer is configured to determine the presence of an obstruction based at least in part on a difference between the first response sensitivity and the second response sensitivity.

[0155] 19. The fluid analyzer of any one of the preceding exemplary embodiments, wherein the processor is configured to determine the presence of an obstruction when a difference between the first response sensitivity and the second response sensitivity is outside a predetermined threshold range.

[0156] 20. The fluid analyzer of any one of the preceding exemplary embodiments, wherein the sensor includes a working electrode and a reference electrode, and 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.

[0157] 21. The fluid analyzer of any one of the preceding exemplary 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 the processor is configured to determine 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 liquid and the second calibration liquid by the difference between the logarithms of the known concentrations, respectively.

[0158] 22. A fluid analyzer as described in any one of the preceding exemplary embodiments, further comprising a wash fluid injection port in fluid communication with one or more channels, and a wash fluid valve located between the wash fluid injection port and the sensor, wherein the wash fluid injection port is operable to receive wash fluid, and the wash fluid valve is openable and closeable to provide wash fluid to the one or more channels.

[0159] 23. The fluid analyzer of any one of the preceding exemplary embodiments, wherein the processor is further configured to control a wash fluid valve to direct wash fluid through one or more channels to the sensor in response to determining the presence of an obstruction.

[0160] 24. The fluid analyzer of any one of the preceding exemplary embodiments, wherein the obstruction is a thrombus.

[0161] 25. A non-transitory computer-readable medium storing an obstacle detection algorithm including processor-executable code, the processor-executable code, when executed by a processor, causing the processor to: controlling one or more valves to sequentially deliver a first calibrant solution and a second calibrant solution through the fluid channel to the sensor during a first time period, and storing first data indicative of a first response slope based at least in part on a first difference between first information generated by the meter indicative of a first potential generated by contacting the sensor with the first calibrant solution and second information generated by the meter indicative of a second potential generated by contacting the sensor with the second calibrant solution; controlling the one or more valves to sequentially deliver the first calibrant solution and the second calibrant solution through the fluid channel to the sensor during a second time period after the first time period, and storing second data indicative of a second response slope based at least in part on a second difference between third information generated by the meter indicative of a third potential generated by contacting the sensor with the first calibrant solution and fourth information generated by the meter indicative of a fourth potential generated by contacting the sensor with the second calibrant solution; a non-transitory computer-readable medium that stores third data indicative of an obstruction on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold;

[0162] conclusion Thus, in accordance with the inventive concepts disclosed herein, there are provided compositions and devices, and methods of making and using the same, that fully satisfy the objects and advantages set forth hereinabove. While the inventive concepts disclosed herein have been described in conjunction with the specific figures, experiments, results, and language set forth hereinabove, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the inventive concepts disclosed herein.

Claims

1. 1. A fluid analyzer comprising: a fluid channel operable to carry a fluid; a sensor in fluid communication with the fluid channel; a meter operable to receive the signal produced by the sensor and convert the signal into information indicative of the electrical potential of the fluid; a first calibrator solution having a first analyte concentration; a second calibrator solution having a second analyte concentration different from the first analyte concentration; one or more calibration fluid injection ports in fluid communication with the fluid channel and operable to receive a first calibration fluid and a second calibration fluid; one or more valves positioned between the one or more calibrant liquid injection ports and the sensor, the valves being openable and closeable to provide one or more samples of each of the first calibrant liquid and the second calibrant liquid to the fluid channel; a control system having a processor executing processor-executable code for executing an obstacle detection algorithm, the processor-executable code comprising: controlling one or more valves to sequentially deliver a first calibrant solution and a second calibrant solution through the fluid channel to the sensor during a first time interval, and storing first data indicative of a first response slope based at least in part on a first difference between first information generated by the meter indicative of a first potential generated by contacting the sensor with the first calibrant solution and second information indicative of a second potential generated by contacting the sensor with the second calibrant solution; controlling the one or more valves to sequentially deliver the first calibrant solution and the second calibrant solution through the fluid channel to the sensor during a second time interval after the first time interval, and storing second data indicative of a second response slope based at least in part on a second difference between third information indicative of a third potential produced by contacting the sensor with the first calibrant solution and fourth information produced by the meter indicative of a fourth potential produced by contacting the sensor with the second calibrant solution; storing third data indicative of an obstacle on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold; and a wash fluid inlet port in fluid communication with the fluid channel, and a wash fluid valve located between the wash fluid inlet port and the sensor, the wash fluid inlet port operable to receive wash fluid, and the wash fluid valve openable and closeable to provide wash fluid to the fluid channel. The fluid analyzer.

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

3. 3. The fluid analyzer of claim 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.

4. 2. The fluid analyzer of claim 1, wherein the first response slope has a difference between the first information and the second information as a dividend and is based at least in part on a quotient having a difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as a divisor, and the second response slope has a difference between the third information and the fourth information as a dividend and is based at least in part on a quotient having a difference between the logarithm of the first analyte concentration and the logarithm of the second analyte concentration as a divisor.

5. 2. The fluid analyzer of claim 1, wherein the one or more valves include a first calibration valve and a second calibration valve, the first calibration valve being openable and closeable to provide one or more samples of a first calibration liquid to the fluid channel, and the second calibration valve being openable and closeable to provide one or more samples of a second calibration liquid to the fluid channel.

6. The fluid analyzer of claim 1 , wherein the processor executable code, when executed by the processor, further causes the processor to control a wash fluid valve to send wash fluid through the fluid channel to the sensor based at least in part on the third data.

7. 10. The fluid analyzer of claim 1, wherein the obstruction is a thrombus.

8. 1. A method for detecting an obstruction on a sensor of a fluid analyzer, comprising: sequentially causing a flow of first and second calibrant fluids having known analyte concentrations to the sensor during a first time interval, and determining a first response sensitivity of the sensor based at least in part on the sensor responses of the sensor to the known analyte concentrations and the first and second calibrant fluids; sequentially causing a flow of the first calibrant fluid and the second calibrant fluid to the sensor during a second time interval and determining a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; determining, by the processor, a presence of an obstacle on the sensor based at least in part on a difference between the first response sensitivity and the second response sensitivity; the known analyte concentration of the first calibrator fluid is different from the known analyte concentration of the second calibrator fluid; The method.

9. The method of claim 8 , wherein the step of determining the presence of an obstacle determines the presence of an obstacle when the difference is outside a predetermined threshold range.

10. The method of claim 8 , wherein the step of determining the presence of an obstacle determines the absence of an obstacle when the difference is within a predetermined threshold range.

11. 9. The method of claim 8, wherein the first response sensitivity is a first response slope of the sensor and the second response sensitivity is a second response slope of the sensor, and the method further comprises 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 solution and the second calibration solution, respectively, by the difference between the logarithms of the known analyte concentrations.

12. The step of sequentially causing a flow of the first calibration liquid and the second calibration liquid during the first time interval includes: contacting a first calibration fluid with the sensor to generate a signal receivable by the meter and convertible to first information indicative of a first one of the sensor responses, the first sensor response being an electrical potential generated by the sensor in response to contacting the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal receivable by the meter and convertible to second information indicative of a second one of the sensor responses, the second sensor response being an electrical potential generated by the sensor in response to contacting the second calibration fluid; storing first data indicative of a first response slope based at least in part on a difference between the first information and the second information; The step of sequentially causing the flow of the first calibration liquid and the second calibration liquid at a second time interval after the first time interval includes: contacting a first calibration fluid with the sensor to generate a signal receivable by the meter and convertible to third information indicative of a third one of the sensor responses, the third sensor response being a third electrical potential generated by the sensor in response to contacting the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal receivable by the meter and convertible to fourth information indicative of a fourth one of the sensor responses, the fourth sensor response being a fourth electrical potential generated by the sensor in response to contacting the second calibration fluid; storing second data indicative of a second response slope based at least in part on a difference between the third information and the fourth information; and storing third data indicative of the presence of an obstacle on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold.

13. 13. The method of claim 12, wherein the first response slope has the difference between the first information and the second information as the dividend and is based at least in part on a quotient having the difference between the logarithms of the known analyte concentrations as the divisor, and the second response slope has the difference between the third information and the fourth information as the dividend and is based at least in part on a quotient having the difference between the logarithms of the known analyte concentrations as the divisor.

14. The method of claim 12 , further comprising contacting a cleaning fluid with the sensor based at least in part on determining the presence of an obstruction.

15. 13. The method of claim 12, further comprising storing third data indicative of a thrombus on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold.

16. 1. A fluid analyzer comprising: a sensor configured to measure at least one parameter associated with the fluid; one or more containers configured to contain a first calibrator solution and a second calibrator solution having known analyte concentrations; one or more channels configured to provide fluid communication between the sensor and the one or more containers; Ru and; and a processor configured to determine the presence of an obstacle obstructing the sensor, the processor comprising: sequentially causing a flow of a first calibrant fluid and a second calibrant fluid to the sensor during a first time interval, and determining a first response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; sequentially causing a flow of the first calibrant fluid and the second calibrant fluid to the sensor during a second time interval, and determining a second response sensitivity of the sensor based at least in part on the sensor response of the sensor to the known analyte concentration and the first calibrant fluid and the second calibrant fluid; configured to determine the presence of an obstacle based at least in part on a difference between the first response sensitivity and the second response sensitivity; the known analyte concentration of the first calibrator fluid is different from the known analyte concentration of the second calibrator fluid; The fluid analyzer.

17. 17. The fluid analyzer of claim 16, wherein the processor is configured to determine the presence of an obstruction when a difference between the first response sensitivity and the second response sensitivity is outside a predetermined threshold range.

18. 17. The fluid analyzer of claim 16, wherein the sensor includes a working electrode and a reference electrode, and 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.

19. 17. The fluid analyzer of claim 16, wherein the first response sensitivity is a first response slope of the sensor and the second response sensitivity is a second response slope of the sensor, and the processor is configured to determine 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 liquid and the second calibration liquid, respectively, by the difference between the logarithms of the known analyte concentrations.

20. 17. The fluid analyzer of claim 16, further comprising a wash fluid injection port in fluid communication with one or more channels and a wash fluid valve positioned between the wash fluid injection port and the sensor, the wash fluid injection port operable to receive wash fluid and the wash fluid valve openable and closeable to provide wash fluid to the one or more channels.

21. 21. The fluid analyzer of claim 20, wherein the processor is further configured to control a wash fluid valve to direct wash fluid through one or more channels to the sensor in response to determining the presence of an obstruction.

22. 17. The fluid analyzer of claim 16, wherein the obstruction is a thrombus.

23. 1. A non-transitory computer readable medium storing an obstacle detection algorithm including processor executable code that, when executed by a processor, causes the processor to: controlling one or more valves to sequentially deliver a first calibrant solution and a second calibrant solution through the fluid channel to the sensor during a first time interval; and storing first data indicative of a first response slope based at least in part on a first difference between first information generated by the meter indicative of a first potential generated by contacting the sensor with the first calibrant solution and second information generated by the meter indicative of a second potential generated by contacting the sensor with the second calibrant solution; During a second time interval after the first time interval, the one or more valves are controlled to sequentially deliver the first calibration liquid and the second calibration liquid through the fluid channel to the sensor, and the sensor detects the first calibration liquid and the second calibration liquid. storing second data indicative of a second response slope based at least in part on a second difference between third information generated by the meter indicative of a third potential produced by contacting the sensor with the first calibration liquid and fourth information generated by the meter indicative of a fourth potential produced by contacting the sensor with a second calibration liquid; storing third data indicative of an obstacle on the sensor in response to a difference between the first response slope and the second response slope exceeding a threshold; the known analyte concentration of the first calibrator fluid is different from the known analyte concentration of the second calibrator fluid; a meter operable to receive a signal generated by the sensor and convert the signal into information indicative of the electrical potential of the fluid; the one or more valves are positioned between the one or more calibrant liquid injection ports and the sensor and are openable and closeable to provide one or more samples of each of the first calibrant liquid and the second calibrant liquid to the fluid channel; The non-transitory computer-readable medium.

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