Method of detecting obstructions in fluid analyzer

Abstract

Methods and systems for detecting obstructions on a sensor of a fluid analyzer, including a method including contacting a first calibration fluid with the sensor to generate a signal indicative of a first potential of the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal indicative of a second potential of the second calibration fluid; storing the first response slope; contacting the first calibration fluid with the sensor to generate a signal indicative of a third potential of the first calibration fluid; contacting a second calibration fluid with the sensor to generate a signal indicative of a fourth potential of the second calibration fluid; 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

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

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

[0003] In various situations, it is desirable to measure components of body fluids, including, for example, blood gas partial pressure in a whole blood sample, electrolyte concentration in a blood sample, and hematocrit of a blood sample. For example, measuring pCO2, pO2, pH, Na + , K + , Ca 2+ The hematocrit and hematocrit are the main clinical indications in assessing the condition of a medical patient. In addition, in order to try to use as little patient blood as possible in each analysis performed, the device used to analyze the blood sample is preferably relatively small. For example, it is important to perform blood analysis using a small amount of blood sample when a relatively large number of samples must be collected in a relatively small amount of time, or in situations where the amount of blood is limited (such as in a newborn).

[0004] 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, resulting in possible significant blood loss during patient evaluation. In addition, by reducing the size of the analyzer sufficiently to make the unit portable, the analysis can be performed at the point of care. Moreover, a reduction in size also generally means a reduction in turnaround time. Furthermore, in order to limit the number of tests that must be performed, it is desirable to collect as much information as possible when each test is completed. However, size limitations are imposed on sensors used to measure blood chemistry. These size limitations are largely due to the physical geometry of the sensor and the connections to the sensor.

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

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

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

[0008] Electrolytes are determined by potentiometric measurements, a form of electrochemical analysis. In potentiometry, the potential or voltage is measured between two electrodes in a solution. These potentials can also be generated when a metal and ions of the metal are present in solution. By using a membrane that is semipermeable to the ions, ions of different concentrations can be separated. 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 ions in the solution.

[0009] Ion selective electrodes are a modification of the potentiometric principle. A potential difference or electron flow is generated by selectively transferring the ions to be measured from the sample solution to the membrane phase. Ion selective electrodes measure the concentration of free ions of the desired analyte on the membrane where the selectivity is generated. The membrane has a complex composition and contains organic solvents, inert polymers, plasticizers and ionophores, where ionophores are molecules that increase the permeability selectivity of the membrane to specific ions.

[0010] The amperometric method measures the current produced by a redox reaction. Types of amperometric methods include enzyme electrodes such as the glucose oxidase method and the Clark-type pO2 electrode. These types of designs are known as biosensors and are suitable for testing in clinical laboratories as well as point-of-care testing. Enzyme-based biosensor technology was originally developed for measuring blood glucose. A solution of glucose oxidase is placed between the gas permeable membrane and the semipermeable outer membrane of the pO2 electrode. Glucose in the blood diffuses through the semipermeable membrane and reacts with the glucose oxidase. The glucose is converted to hydrogen peroxide and gluconic acid by the glucose oxidase.

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

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

[0013] One of the major challenges of existing fluid analyzers is the detection and removal of obstructions, such as blood clots. The presence of an obstruction may obstruct the path of the fluid analyzer, create an occupation time for the fluid analyzer, and affect the individual sensor responses, leading to, for example, the appearance of biased results regarding key blood gas parameters (e.g., pH and / or pCO2). Obstructions are often formed during the preparation of the sample for analysis. However, even with the utmost care in performing pre-analytical procedures, small obstructions may still occur in the fluid (or measurement) path.

[0014] 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 via fluid aspiration and discharge, and / or alerting a user to the presence (or absence) of the obstruction and the questionable nature of the result. Summary of the invention

[0015] The methods and systems disclosed herein are utilized to solve the following problems: detecting the presence (or absence) of an obstruction on a fluid analyzer without the need for additional sensors, removing the obstruction via fluid aspiration and discharge, and / or alerting a user to the presence (or absence) of the obstruction and the questionable nature of the results.

[0016] According to one aspect of the present disclosure, an exemplary fluid analyzer may include: a fluid channel operable to transport 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 a potential of the fluid; a first calibration fluid having a first analyte concentration; a second calibration fluid having a second analyte concentration different from the first analyte concentration; one or more calibration fluid injection ports in fluid communication with the fluid channel, the one or more calibration fluid injection ports operable to receive the first calibration fluid and the second calibration fluid; one or more valves located between the one or more calibration fluid injection ports and the sensor, the one or more valves being operable to open and close to provide one or more samples of each of the first calibration fluid and the second calibration fluid to the fluid channel; and a control system having a processor operable to execute processor executable code, which, when executed by the processor, causes the processor to run an obstruction detection algorithm, including: controlling the one or more valves to inject the first calibration fluid into the fluid channel during a first time period; The fluid and the second calibration fluid are successively delivered to the sensor through the fluid channel, and first data indicating a first response slope is stored, the first response slope being based at least in part on a first difference between first information generated by the meter and second information, the first information indicating a first potential generated by the sensor contacting the first calibration fluid, the second information indicating a second potential generated by the sensor contacting the second calibration fluid; in a second time period after the first time period, the one or more valves are controlled to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and second data indicating a second response slope is stored, the second response slope being based at least in part on a second difference between third information and fourth information generated by the meter, the third information indicating a third potential generated by the sensor contacting the first calibration fluid, the fourth information indicating a fourth potential generated by the sensor contacting the second calibration fluid; and in response to the difference between the first response slope and the second response slope exceeding (i.e., being above or below) a threshold, third data indicating an obstruction on the sensor is stored. In some embodiments, the third data is stored when the difference is above a threshold. In other embodiments, the difference and threshold may be opposite. In this embodiment, when the difference is lower than a threshold value, third data is stored.

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

[0018] According to 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 store a first calibration fluid and a second calibration fluid having a known analyte concentration; one or more channels configured to provide fluid communication between the sensor and the one or more containers; and a processor configured to determine the presence of an obstruction that obstructs the sensor, wherein the processor is configured to: in a first time period, successively flow the first calibration fluid and the second calibration fluid to the sensor, and determine a first response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; in a second time period, successively flow the first calibration fluid and the second calibration fluid to the sensor, and determine a second response sensitivity of the sensor based at least in part on the known analyte concentration and the sensor response of the sensor to the first calibration fluid and the second calibration fluid; and determine the presence of the obstruction based at least in part on a difference between the first response sensitivity and the second response sensitivity.

[0019] According to another aspect of the present disclosure, an exemplary non-transitory computer-readable medium may store an exemplary obstruction detection algorithm, the obstruction detection algorithm comprising processor executable code, which, when executed by a processor, causes the processor to: control one or more valves to successively deliver a first calibration fluid and a second calibration fluid to a sensor through a fluid channel during a first time period, and store first data indicating a first response slope, the first response slope being based at least in part on a first difference between first information generated by a meter and second information generated by the meter, the first information indicating a first potential generated by the sensor contacting the first calibration fluid, the second information indicating a second potential generated by the sensor contacting the second calibration fluid; the first calibration fluid and the second calibration fluid are successively delivered to the sensor through the fluid channel in a second time period after the first time period, and second data indicating a second response slope is stored, the second response slope being based at least in part on a second difference between third information generated by the meter and fourth information generated by the meter, the third information indicating a third potential generated by the sensor contacting the first calibration fluid, the fourth information indicating a fourth potential generated by the sensor contacting the second calibration fluid; and in response to the difference between the first response slope and the second response slope exceeding (i.e., being above or below) a threshold, third data indicating an obstruction on the sensor is stored. In some embodiments, the third data is stored when the difference is above the threshold. In other embodiments, the difference and the threshold may be opposite. In this embodiment, the third data is stored when the difference is below the threshold. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] To assist those skilled in the relevant art in making and using the subject matter of this document, 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 consistency. For clarity, not every component in every drawing may be labeled.

[0021] Figure 1 is a schematic diagram of an exemplary embodiment of a fluid analyzer constructed in accordance with the present disclosure.

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

[0023] Figure 3 It can be Figure 1 Exploded view of another embodiment of a prior art current sensor for reading a fluid analyzer.

[0024] Figure 4It can be Figure 1 A cross-sectional view of an exemplary embodiment of a prior art potentiometric sensor read by a fluid analyzer.

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

[0026] Figure 6 It is waiting for Figure 1 A top view of the sensor array being read by a fluid analyzer is depicted.

[0027] Figure 7 is a process flow diagram of an exemplary obstruction detection algorithm according to the present disclosure.

[0028] Figure 8 yes Figure 6 A time-lapse image of the sensor array of the fluid analyzer depicted in FIG.

[0029] Figures 9A-9G is with Figure 8 The time-lapse graph depicted in the figure corresponds to a graph of the sensor response of the electrochemical sensors of the sensor array. DETAILED DESCRIPTION

[0030] Before explaining 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 indicated.

[0031] The disclosure is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

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

[0033] All patents, published patent applications, and non-patent publications mentioned in the specification are indicative of the level of skill of those skilled in the art to which the presently disclosed and / or claimed inventive concepts pertain. All patents, published patent applications, and non-patent publications cited in any part of this application are expressly incorporated herein by reference in their entirety, to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

[0034] In view of the present disclosure, all non-transitory computer-readable media, control systems, fluid analyzers, and / or methods disclosed and / or claimed herein may be made and executed without undue experimentation. Although the fluid analyzers and methods of the presently disclosed and / or claimed inventive concepts have been described according to preferred embodiments, it will be apparent to those skilled in the art that changes may be applied to the fluid analyzers and / or methods and to the steps or sequence of steps of the methods described herein without departing from the concept, spirit, and scope of the presently disclosed and / or claimed inventive concepts. All such similar substitutions 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.

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

[0036] When used in conjunction with the term "comprising" in the claims and / or the specification, the use of the terms "a", "an" or "a" may mean "one", but it is also consistent with the meaning of "one or more", "at least one" and "one or more than one". The singular forms "a", "one(kind)", and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" may refer to 1 or more, 2 or more, 3 or more, 4 or more, or a greater number of compounds. The term "plurality" means "two or more". The use of the term "or" in the claims is used to mean "and / or", unless it is clearly indicated to refer only to alternatives or the alternatives are mutually exclusive, but the present disclosure supports definitions that refer only to alternatives and "and / or". Throughout this application, the term "approximately" is used to indicate that a value includes the inherent variation of error of the device, the method used to determine the value, or the variation that exists between the subjects of study. For example, but not by way of limitation, when the term "about" is used, the specified value may vary from the specified value by ±20% or ±10% or ±5% or ±1% or ±0.1%, as such variations are appropriate for performing the disclosed methods and are understood by those of ordinary skill in the art. The use of the term "at least one" will be understood to include any amount of one as well as more than one, including but not limited to 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" may extend to as many as 100 or 1000 or more, depending on the term with which it is associated; in addition, an amount of 100 / 1000 should not be considered limiting, as higher limits may also produce satisfactory results. In addition, the 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. For example, the use of ordinal terms (i.e., "first," "second," "third," "fourth," etc.) is solely for the purpose of distinguishing between two or more items and is not intended to imply any order or sequence or importance of one item relative to another, or any order of addition.

[0037] As used in the description herein, the terms "comprises," "includes," "has," "possessing," 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 but may also include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0038] In addition, unless explicitly stated to the contrary, "or" means an inclusive "or" rather than an exclusive "or". For example, one of the following satisfies condition A or B: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0039] In addition, "a" or "an" is used to describe elements and components of the embodiments herein. This is done only for convenience and to give a general sense of the inventive concept. The description should be read to include one or more, and the singular also includes the plural, unless it is obvious that it is meant otherwise. In addition, unless otherwise expressly stated, the use of the term "plurality" is intended to express "more than one".

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

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

[0042] As used herein, the term "substantially" means that the subsequent described event or condition occurs completely, or the subsequent described event or condition occurs to a great extent or degree. For example, the term "substantially" means that the subsequent described event or condition occurs at least 90% of the time, at least 95% of the time, or at least 98% of the time.

[0043] As used herein, the term "sample" will be understood to include any type of biological sample or non-biological sample that can be utilized according to the inventive concept of the current disclosure and / or claim. That is, the sample can be any fluid sample and / or a sample that can have fluidity (e.g., a biological sample mixed with a fluid matrix). Examples of available biological samples include, but are not limited to, whole blood or any part thereof (i.e., plasma or serum), saliva, sputum, cerebrospinal fluid (CSF), surgical drainage 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 although the present disclosure describes the use of a fluid analyzer to analyze biological samples, it will be appreciated by those skilled in the art that the concepts disclosed herein can be applied to any sample in which the concentration of an analyte can be determined, and therefore, the present 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, lactic acid, creatinine, etc.

[0044] As used herein, the term "fluid" refers to a liquid or gas that can pass through at least a portion of a fluid analyzer and be analyzed by components of the fluid analyzer. The fluid can be a sample, a calibration reagent (eg, a fluid or a gas), a wash fluid, or a quality control fluid.

[0045] As used herein, a circuit can be an analog and / or digital component, or one or more appropriately programmed processors (e.g., microprocessors) and associated hardware and software, or hardwired logic. In addition, a "component" may also 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), a combination of hardware and software, and / or the like.

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

[0047] When a numerical range is recorded or determined herein, the range includes its endpoints and all single integers and fractions within the range, and also includes each narrower range formed by all various possible combinations of these endpoints and internal integers and fractions to form a subset of the larger value group within the range, to the extent that each of those narrower ranges is clearly recorded. When a numerical range is stated herein as being greater than the stated value, the range is still limited and is bounded at its upper end by values ​​that can operate within the context of the present invention as described herein. When a numerical range is stated herein as being less than the stated value, the range is still bounded at its lower end by a non-zero value.

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

[0049] As used herein, the term "calibration parameters" refers to a set of data points that relate a signal from a sensor to a known analyte concentration, or one or more functions used to derive such a set of data points. The calibration parameters may 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, etc., configured to fit a function to at least two calibration points.

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

[0051] Electrochemical sensors are widely used in in vitro diagnostic instruments. These electrochemical sensors include electrodes made of metal, made of metal ink by screen printing (thick film method) or made of chemical vapor deposition of metal film (thin film method), which usually require calibration. The calibration corrects for sensor-to-sensor changes in electrode size and surface area, changes in chemical and biochemical activity during service life, electrical signal drift, etc. 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.

[0052] Reference is now made to the drawings, and in particular to the Figure 1, which shows an exemplary embodiment of a combination of a fluid analyzer 10 with a calibration cartridge 14 and one or more electrochemical sensors 18 (hereinafter referred to as "electrochemical sensors 18"). The electrochemical sensor 18 can be implemented in the form of a cartridge that is connected to the fluid analyzer 10, for example, according to Figure 1 The fluid analyzer 10 may include a housing 26 that supports and / or surrounds at least a portion of each electrochemical sensor 18 .

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

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

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

[0056]

[0057] Where m is the response slope, V high is the signal response of the electrochemical sensor 18 to the high concentration calibration reagent, V low is the signal response of the electrochemical sensor 18 to the low concentration calibration reagent, C high is the concentration of the high concentration calibration reagent, and Clow is the concentration of the low concentration calibration reagent. Signal response V high and V low is an electrical signal response, which may be a voltage signal response or a current signal response. The signal response and the corresponding concentration of the calibration reagent may be referred to as calibration parameters for determining a response slope m, which indicates the response sensitivity of a single sensor to respond to or measure the analyte concentration. Each electrochemical sensor 18 has its own slope specification over its respective service life.

[0058] When properly manufactured, each electrochemical sensor 18 has a stable near-Nernstian slope, thereby ensuring adequate accuracy and consistency in response performance (ie, response accuracy and precision). However, in an integrated sensor module of a fluid analyzer 10, each individual electrochemical sensor 18 may exhibit evidence of failure in a variety of modes.

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

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

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

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

[0063] Δm=m n -m n-1 (2)

[0064] In the absence of obstruction, Δm may be close to zero.Through experimentation, empirical data may be used to develop a threshold range to include any microclots that may not drastically affect the sensor response.

[0065] After Δm exceeds (i.e., exceeds) the threshold range, m n-1 will be stored as the “normal” response slope, and for x=1, 2, etc., the next adjacent time point (m n+1 ) is compared with the response slope (i.e., Δm * =m n+x -m n-1 ). Δm * Continued exceeding of the threshold range is evidence of continued interference with electrochemical sensor 18. In some embodiments, Δm and threshold range m n-1 In this case, when Δm is less than the threshold range, m n-1 is evidence that the obstruction continues to interfere with the electrochemical sensor 18. Thus, a change in the response slope outside of a threshold range (ie, above and / or below a predetermined value) is evidence of an obstruction.

[0066] When the foreign matter is removed from the electrochemical sensor 18 , the response slope of the electrochemical sensor 18 may return to normal (ie, close to zero or within a threshold range, meaning that the sensor signal difference in response to high and low concentrations of the calibration reagent is relatively consistent).

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

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

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

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

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

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

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

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

[0075] Figure 3, another embodiment of a current sensor 22 that can be used according to the present disclosure is shown in FIG. In this embodiment, the current sensor 22 is provided with electrodes 30 on a substrate 84, including but not limited to a reference electrode 34, a counter electrode 36, and a working electrode 38. The substrate 84 can extend outward from the electrode 30. The current sensor 22 can also be provided with a gasket 86 having an opening 90, which is sized and dimensioned to be larger than the area of ​​the substrate 84 surrounded by the electrode 30. The gasket 86 can be positioned on the substrate 84 so that the gasket 86 does not overlap with the electrode 30. Instead, the gasket 86 can engage the substrate 84 around the electrode 38. The current sensor 22 can also include a cover 94 located on the gasket 86 so that the gasket 86 is between the substrate 84 and the cover 94. The opening 90 in the gasket 86 combines with the cover 94 and the substrate 84 to form a chamber (not shown) through which a fluid can pass and interact with the electrode 30. An entry port 98 and an exit port 102 can be formed in the cover 94 to allow fluid to enter and leave the chamber (not shown).

[0076] Return to Figure 1 , the fluid can flow through the fluid channel 42 by the driving force provided by the driving device 106. The driving force may include, but is not limited to, capillary force, pressure, gravity, vacuum, electrokinetic effect, and / or the like. For example, the driving device 106 may be a pump, but is not limited thereto. The sample may be introduced into the fluid channel 42 via the sample injection port 110. The sample injection port 110 may be connected to a valve 114, which may be opened and / or closed manually or by machine to allow and / or prevent the sample from damaging the fluid channel 42. The sample may be injected manually or by machine into the sample injection port 110.

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

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

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

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

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

[0082] In embodiments where the current sensor 22 includes a counter electrode 36, the meter 126 can measure the current flow 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 reversible set of reactions and may not require a consumable electrode 30. When a voltage is applied across the working electrode 38 and the reference electrode 34, the current measured by the meter 126 is correlated to the target analyte content of the fluid.

[0083] In some embodiments, the fluid analyzer 10 may further include one or more calibration reagent injection ports 130-1, 130-2, and 130-3 (hereinafter referred to as "calibration reagent injection ports 130"), which may be in fluid communication with the fluid channel 42. The calibration reagent injection port 130 may also be in fluid communication with valves 134-1, 134-2, and 134-3 (hereinafter referred to as "valves 134"), which may be opened and / or closed manually or by machine to allow and / or prevent one or more calibration reagents and / or washing fluids from entering the fluid channel 42. Valve 134 may be an automatic valve that may be opened or closed upon receipt of an appropriate control signal. In some embodiments, the calibration reagent injection port 130-3 is a washing fluid injection port.

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

[0085] Reference again Figure 1 , the instrument 126, the drive device 106, and the valves 114, 134-1, and 134-2 can communicate with the control system 138 via a signal path 142. For example, but not limitation, Figure 1 As shown in , signal path 142 may be one or more cables that transmit data generated by instrument 126 to control system 138 and / or transmit information, signals and / or commands from control system 138 to valves 114 and 134 in electronic form and / or via a network, as described in detail herein. Figure 5138. The control system 138 may be one or more systems capable of implementing and / or executing the logic of the processes described herein. The logic implemented in the form of software instructions and / or firmware may be executed on any suitable hardware. For example, the logic implemented in the form of software instructions and / or firmware may be executed on one or more dedicated systems, on a personal computer system, on a distributed processing computer system, and / or the like. In some embodiments, the logic may be implemented in a stand-alone environment operating on a single computer system, and / or the logic may be implemented in a networked environment, such as in a distributed system using multiple computers and / or processors.

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

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

[0088] Reference now Figure 4 , the potentiometric sensor 46 generally includes two or more electrodes 30, which are shown as reference electrode 34 and working electrode 38 as examples. The working electrode 38 can be an ion selective electrode that includes a cover membrane 188, an internal electrolyte layer 192, and an internal reference electrode 196. For example, but not by way of limitation, the cover membrane can include a plasticized PVC film doped with an analyte sensing ion carrier, and can include other additives.

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

[0090] In a specific (but non-limiting) embodiment, the cover film 188 can be selected from the group including chloride sensing film, magnesium sensing film, potassium sensing film, sodium sensing film, pH sensing film, bicarbonate sensing film, calcium sensing film and blood urea nitrogen sensing film; and / or the metal salt dispersed in the carbon paste, hydrogel or hydrophilic polymer can be selected from the group including MgCl2, HCl, NaCl, KCl, KNO3 and NaClO4. In an illustrative embodiment, when dispersed in a carbon paste, a hydrogel or a hydrophilic polymer, the metal salt can be any solution. Examples of such solutions include water-based solutions. For example, but not by way of limitation, the internal reference electrode 196 can be composed of silver, silver chloride and / or the like.

[0091] Figure 5 A block diagram of the control system 138 is shown in FIG. 1 , which may include: one or more processors 146 (hereinafter referred to as “processor 146”), which work together or independently to execute processor executable code; one or more memories 150 (hereinafter referred to as “memory 150”), which are capable of storing processor executable code; one or more input devices 154 (hereinafter referred to as “input device 154”); and one or more output devices 158 (hereinafter referred to as “output device 158”).

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

[0093] In some embodiments, when executed, the processor executable code further causes the processor 146 to: control the automatic valve 134-1 to deliver the first calibration reagent through the fluid channel 42 to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 (and the counter electrode 36 when included in the current sensor 22); control the meter 126 (when the meter 126 is a potentiostat) to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the first calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18, and receive a third reading of each electrochemical sensor 18 from the meter 126; control the automatic valve 134-2 to deliver the second calibration reagent through the fluid channel 42 to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18. The fluid channel 42 is transmitted to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 (as well as the counter electrode 36 when included in the current sensor 22); the control meter 126 (when the meter 126 is a constant potential meter) applies a voltage potential sufficient to induce an electrochemical reaction in the sample of the second calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18, and receives a fourth reading of each electrochemical sensor 18 from the meter 126; the third reading, the fourth reading and the multi-point calibration algorithm (as described above) are used to calculate the second calibration parameters; and the second calibration parameters are used to measure the target analyte content in the fluid sample to calculate the second response slope m2 according to formula (4) described below.

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

[0095] In some embodiments, the step of controlling the meter 126 to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the first calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 and receiving a first reading of each electrochemical sensor 18 from the meter 126 is replaced by a step in which the processor 146 receives a first reading from the meter 126, the first reading indicating a first potential generated by the reference electrode 34 and the working electrode 38 contacting the first calibration reagent. In some embodiments, the step of controlling the meter 126 to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the second calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 and receiving a second reading from the meter 126 for each electrochemical sensor 18 is replaced by a step in which the processor 146 receives a second reading from the meter 126, the second reading indicating a second potential generated by the reference electrode 34 and the working electrode 38 contacting the second calibration reagent.

[0096] In some embodiments, the step of controlling the meter 126 to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the first calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 and receiving a third reading of each electrochemical sensor 18 from the meter 126 is replaced by a step in which the processor 146 receives a third reading from the meter 126, the third reading indicating a third potential generated by the reference electrode 34 and the working electrode 38 contacting the first calibration reagent. In some embodiments, the step of controlling the meter 126 to apply a voltage potential sufficient to induce an electrochemical reaction in the sample of the second calibration reagent to the reference electrode 34 and the working electrode 38 of each electrochemical sensor 18 and receiving a fourth reading from the meter 126 for each electrochemical sensor 18 is replaced by a step in which the processor 146 receives a fourth reading from the meter 126, the fourth reading indicating a fourth potential generated by the reference electrode 34 and the working electrode 38 contacting the second calibration reagent.

[0097] Each element of the control system 138 may be partially or completely network-based or cloud-based, and may or may not be located in a single physical location. In some embodiments, the processor 146 may communicate with the instrument 126, the drive 106, and / or the valves 114 and 134 via a network. As used herein, the terms "network-based", "cloud-based", and any variations thereof are intended to include providing configurable computing resources on demand via an interface with a computer and / or a computer network, wherein the software and / or data are at least partially located on the computer and / or computer network. The network may allow bidirectional communication of information and / or data between each element of the control system 138. The network may interface with the processor 146 and the instrument 126, the drive 106, and / or the valves 114 and 134 in a variety of ways. For example, but not limited to, the network may interface via an optical and / or electronic interface, and / or may use a variety of network topologies and / or protocols, including but not limited to Ethernet, TCP / IP, circuit switching paths, combinations thereof, and / or the like. 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 area network, a wireless network, a cellular network, a GSM network, a CDMA network, a 3G network, a 4G network, a satellite network, a radio network, a fiber optic network, a cable network, a public switched telephone network, an Ethernet, a combination thereof, and / or the like. In addition, the network may use a variety of protocols to allow a bidirectional interface and / or communication of data and / or information between the processor 146 and the instrument 126, the drive 106, and / or the valves 114 and 134.

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

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

[0100] Exemplary embodiments of processor 146 may include, but are not limited to, a digital signal processor (DSP), a central processing unit (CPU), a field programmable gate array (FPGA), a microprocessor, a multi-core processor, combinations thereof, and / or the like. In some embodiments, for example, additional processor 146 may include, but is not limited to, implementations as a personal computer, a cellular phone, a smart phone, a web-enabled television, a television set-top box, a tablet computer, an e-book reader, a laptop computer, a desktop computer, a web-enabled handheld device, a video game console, a server, a digital video recorder, a DVD player, a Blu-ray player, and / or combinations thereof.

[0101] The processor 146 can communicate with the memory 150 via a path (eg, a data bus). The processor 146 can also communicate with an input device 154 and / or an output device 158.

[0102] Processor 146 can interface and / or communicate with meter 126, drive 106, and / or valves 114 and 134. For example, processor 146 can communicate by exchanging signals (eg, analog, digital, optical, and / or the like) using a network protocol.

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

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

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

[0106] The output device 158 is capable of outputting information in a form perceptible to a user and / or processor 146. For example, the output device 158 may include, but is not limited to, implementation as a computer display, screen, touch screen, speaker, website, television, smart phone, PDA, cell phone, fax machine, printer, laptop computer, combinations thereof, and / or the like. It is to be understood that in some exemplary embodiments, the input device 154 and the output device 158 may be implemented as a single device, such as a touch screen or tablet computer. It is also to be understood that, as used herein, the term "user" is not limited to a human being, and 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, and / or the like.

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

[0108] In some embodiments, for example, outputs of meter 126 that each correspond 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 a separate data structure, such as data store 162, provided with a unique identifier, each unique identifier identifying the electrochemical sensor 18 to which a particular output of meter 126 corresponds.

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

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

[0111] During the first time period, at step 178, the processor 146 may contact the first calibration reagent having the 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) within the sensor array. This may be accomplished, for example, by the processor 146 of the control system 138 generating and sending a signal that opens the automatic valve 134-1 and actuates the drive device 106 to transfer the first calibration reagent from the fluid reservoir 132-1 through the fluid channel 42 to the chamber 54 of at least one of the electrochemical sensors 18. When a sufficient amount of the first calibration reagent is within the chamber 54, the processor 146 of the control system 138 may close the automatic valve 134-1 and deactivate the drive device 106.

[0112] Once 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), the particular electrochemical sensor 18 may generate a first reading at step 182, indicating 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 within the first calibration reagent. The meter 126 may then receive the first reading and transmit the first reading to the processor 146 of the control system 138.

[0113] In some embodiments, at least two of the electrochemical sensors 18 may generate a corresponding first reading indicating at least one of a potential and a current (i.e., a Faradaic current and / or a 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. The corresponding meter 126 may then receive the corresponding first reading from the at least two of the electrochemical sensors 18 and transmit the corresponding first reading to the processor 146 of the control system 138.

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

[0115] In some embodiments where the electrochemical sensor 18 is a potentiometric sensor 46, the meter 126 may receive a first reading from the potentiometric sensor 46 simply 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 the potential generated by the electrochemical reaction (e.g., ion movement) occurring between the potentiometric sensor 46 (i.e., the reference electrode 34 and / or the working electrode 38) and the target analyte (e.g., oxygen) within the first calibration reagent.

[0116] At 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 transmitting a signal that opens the automatic valve 134-2 and actuates the drive device 106 to transfer the second calibration reagent from the fluid reservoir 132-2 through the fluid channel 42 to 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 transmit a signal to close the automatic valve 134-2 and deactivate the drive device 106. The second predetermined target analyte level may be different from the first predetermined target analyte level.

[0117] Once 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), at step 190, each electrochemical sensor 18 may generate a second reading indicating 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 within the second calibration reagent.

[0118] In some embodiments where the electrochemical sensor 18 is a current sensor 22, the processor 146 of the control system 138 provides a control signal to the meter 126 so that the meter 126 applies a second potential sufficient to induce an electrochemical reaction in a sample of the second calibration reagent to the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38). The second potential can be determined and / or applied using a voltage potential stepping technique, in which a series of sequentially larger or smaller voltage potentials are applied. When the current from the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) tends to be stable, 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 current sensor 22. In such an embodiment, the second reading may indicate a non-Faraday current generated by an electrochemical reaction (e.g., a redox reaction) occurring between the current sensor 22 (i.e., the reference electrode 34, the counter electrode 36, and / or the working electrode 38) and the target analyte (e.g., oxygen) in the second calibration reagent. The meter 126 may then communicate the second reading to the processor 146 of the control system 138 .

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

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

[0121]

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

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

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

[0125] Once the first calibration reagent contacts the electrochemical sensor 18 (i.e., the reference electrode 34, the counter electrode 36 and / or the working electrode 38) again, at step 202, the electrochemical sensor 18 may generate a third reading indicating 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 within the first calibration reagent.

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

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

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

[0129] Once 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) again, at step 210, the electrochemical sensor 18 may generate a fourth reading, which indicates 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 within the second calibration reagent.

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

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

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

[0133]

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

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

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

[0137] In some embodiments, when the calculated difference is less than a predetermined threshold, the control system 138 uses the processor 146 to store fourth data indicating that no obstruction is detected on the electrochemical sensor 18. In some embodiments, when the calculated difference is less than the predetermined threshold, the data is not stored and normal operation of the fluid analyzer 10 continues. In some embodiments, in response to detecting that there is no obstruction, the processor 146 of the control system 138 uses the output device 158 to output an alarm or indication (e.g., an audible or visual alarm or indication) indicating that there is no obstruction in a form perceptible to the user.

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

[0139] Reference now Figure 8 , which shows Figure 6 A time lapse of the sensor array 170 is shown in FIG. Figure 8The diagram shows an obstacle 180 formed on the potassium sensor 18-3 at time 15:07 on the second day; from time 18:07 on the second day to time 12:30 on the third day, the obstacle 180 migrates from the potassium sensor 18-3 to the downstream location (i.e., the sodium sensor 18-4, the pH sensor 18-5, and the bicarbonate sensor 18-6); at time 10:17 on the fourth day, the obstacle 180 separates itself into a first obstacle 180-1 on the potassium sensor 18-3 and a second obstacle 180-2 on the pH sensor 18-5 and the bicarbonate sensor 18-6; at time 10:43 on the fifth day, the obstacle 180 further separates itself into the first obstacle 180-1 on the potassium sensor 18-3, the second obstacle 180-2 on the pH sensor 18-5 and the bicarbonate sensor 18-6. a second obstruction 180-2 on the salt sensor 18-6 and a third obstruction 180-3 on the calcium sensor 18-7; at time 10:44 on the 6th day, a fourth obstruction 180-4 appears on the sodium sensor 18-4; and at time 10:44 on the 6th day, the obstruction 180 is partially removed (i.e., the second obstruction 180-2 and the third obstruction 180-3 are removed); then, at time 10:47 on the 7th day, the obstruction 180 is further removed (i.e., the first obstruction 180-1 is removed); and at time 10:47 on the 7th day, the fourth obstruction 180-4 remains on the sodium sensor 18-4, so that the obstruction 180 is finally removed through an obstruction removal process performed by the fluid analyzer or its user.

[0140] Reference now Figures 9A-9G , which shows a depiction Figure 6 Each electrochemical sensor 18 shown in FIG. Figure 8 A graph of the slope increment 183 (ie, Δm) over a period of time corresponding to the time range shown in FIG. Fig. 9A In FIG. 1 , it can be seen that the slope increment 183 of the chloride sensor 18-1 is not outside the predetermined threshold 184 (e.g., ±3 mV / D) (millivolts per decade) of the chloride sensor 18-1. Therefore, within this time frame, the slope increment 183 of the chloride sensor 18-1 does not indicate the presence of an obstruction 180. Similarly, in Fig. 9B , it can be seen that the slope increment 183 of the magnesium sensor 18-2 is not outside the predetermined threshold 184 (eg, ±1.5 mV / D) of the magnesium sensor 18-2. Therefore, within this time frame, the slope increment 183 of the magnesium sensor 18-2 does not indicate the presence of an obstruction 180.

[0141] However, in Fig. 9C , it can be seen that during the time period from about day 2 to about day 6, the slope increment 183 of the potassium sensor 18-3 is outside of a predetermined threshold 184 (e.g., ±3 mV / D) for the potassium sensor 18-3, indicating that an obstruction 180 exists during this time period.

[0142] exist Fig.9D , it can be seen that the slope increment 183 of the sodium sensor 18-4 is outside of a predetermined threshold 184 (e.g., ±3 mV / D) during a first time period from about day 2 to about day 3 and a second time period from about day 6 to about day 8 (i.e., for most of day 7), thereby indicating that there are two obstructions 180: a first obstruction during the first time period (at Figure 8 180) and a second obstacle during the second time period (in Figure 8 It is represented as 180-4).

[0143] exist Fig.9E , it can be seen that the slope increment 183 of the pH sensor 18-5 is outside of a predetermined threshold 184 (eg, ±3 mV / D) during the time period from about day 2 to about day 4, indicating that an obstruction 180 was present during this period.

[0144] exist Fig.9F , it can be seen that the slope increment 183 of the bicarbonate sensor 18-6 is outside of a predetermined threshold 184 (e.g., ±3 mV / D) during a first time period occurring at approximately day 0 and during a second time period occurring at approximately day 4, thereby indicating that there are two obstructions 180: a first obstruction 180 ( Figure 8 ), and a second obstacle during the second time period (in Figure 8 It is represented as 180-2).

[0145] Finally, in Figure 9G In, with Figures 9A-9B Similarly, the slope increment 183 of the calcium sensor 18-7 is not outside of a predetermined threshold 184 (eg, ±1.5 mV / D) of the calcium sensor 18-7. Thus, the slope increment 183 of the calcium sensor 18-7 does not indicate the presence of an obstruction 180 during this time frame.

[0146] Although not shown depicted Figure 6 , but in some embodiments, the predetermined threshold 184 of the blood urea nitrogen sensor 18 - 8 may be, for example, ±3 mV / D.

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

[0148] In some embodiments, the magnesium-specific calibration reagent injection port is in fluid communication with a calibration cartridge 14 containing a magnesium-specific calibration reagent, which may be a calibration reagent in addition to one or more of the above-described calibration reagents. In some embodiments, the calibration cartridge 14 further comprises a magnesium-specific reservoir (not shown). The magnesium-specific reservoir may contain a magnesium-specific calibration reagent having a known target analyte level.

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

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

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

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

[0153] Non-limiting illustrative embodiments

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

[0155] 1. A fluid analyzer, comprising:

[0156] a fluid channel operable to transport a fluid;

[0157] a sensor in fluid communication with the fluid passage;

[0158] a meter operable to receive the signal generated by the sensor and convert the signal into information indicative of the electrical potential of the fluid;

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

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

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

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

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

[0164] controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid passage during a first time period, and storing first data indicating a first response slope, the first response slope being based at least in part on a first difference between first information generated by the meter and second information indicating a first potential generated by the sensor contacting the first calibration fluid, the second information indicating a second potential generated by the sensor contacting the second calibration fluid;

[0165] at a second time period after the first time period, controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid passage, and storing second data indicating a second response slope, the second response slope being based at least in part on a second difference between third information indicating a third potential generated by the sensor contacting the first calibration fluid and fourth information generated by the meter, the third information indicating a fourth potential generated by the sensor contacting the second calibration fluid; and

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

[0167] 2. The fluid analyzer of illustrative embodiment 1, wherein the sensor comprises a working electrode and a reference electrode.

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

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

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

[0171] 6. The fluid analyzer as described in any one of the illustrative embodiments 1-5 further includes a washing fluid injection port connected to the fluid of the fluid channel and a washing fluid valve located between the washing fluid injection port and the sensor, the washing fluid injection port is capable of being operated to receive a washing fluid, and the washing fluid valve is capable of being opened and closed to provide the washing fluid to the fluid channel.

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

[0173] 8. The fluid analyzer of any of Illustrative Examples 1-7, wherein the obstruction is a blood clot.

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

[0175] successively flowing a first calibration fluid and a second calibration fluid 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 known analyte concentrations and a sensor response of the sensor to the first calibration fluid and the second calibration fluid;

[0176] successively flowing 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 known analyte concentration and the sensor response of the sensor to the first and second calibration fluids; and

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

[0178] 10. The method of any one of the preceding illustrative embodiments, wherein the step of determining that the obstruction exists determines that the obstruction exists when the difference is outside a predetermined threshold range.

[0179] 11. The method as in any one of the preceding illustrative embodiments, wherein the step of determining that the obstruction exists determines that the obstruction does not exist when the difference is within a predetermined threshold range.

[0180] 12. The method of any one of the preceding illustrative embodiments, wherein the known analyte concentration of the first calibration fluid is different than the known analyte concentration of the second calibration fluid.

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

[0182] 14. The method of any one of the preceding illustrative embodiments, wherein:

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

[0184] contacting the first calibration fluid to the sensor to generate a signal that can be received by a meter and converted into first information indicative of a first one of the sensor responses, wherein the first sensor response is a potential generated by the sensor in response to contact with the first calibration fluid;

[0185] contacting the second calibration fluid to the sensor to generate a signal that can be received by the meter and converted into second information indicative of a second one of the sensor responses, wherein the second sensor response is a potential generated by the sensor in response to contact with the second calibration fluid; and

[0186] storing first data indicative of the first response slope, the first response slope being based at least in part on a difference between the first information and the second information; and

[0187] Wherein, in the second time period after the first time period, the step of successively flowing the first calibration fluid and the second calibration fluid comprises:

[0188] contacting the first calibration fluid to the sensor to generate a signal that can be received by the meter and converted into third information indicative of a third one of the sensor responses, wherein the third sensor response is a third electrical potential generated by the sensor in response to contact with the first calibration fluid;

[0189] contacting the second calibration fluid to the sensor to generate a signal that can be received by the meter and converted into fourth information indicative of a fourth one of the sensor responses, wherein the fourth sensor response is a fourth electrical potential generated by the sensor in response to contact with the second calibration fluid;

[0190] storing second data indicative of the second response slope, the second response slope being based at least in part on a difference between the third information and the fourth information; and

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

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

[0193] 16. The method of any of the preceding illustrative embodiments, further comprising the step of contacting the sensor with a washing fluid based at least in part on the step of determining that the obstruction exists.

[0194] 17. The method of any one of the preceding illustrative embodiments, further comprising the step of storing third data indicative of a blood clot on the sensor in response to a difference between the first response slope and the second response slope exceeding the threshold.

[0195] 18. A fluid analyzer, comprising:

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

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

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

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

[0200] successively flowing the first calibration fluid and the second calibration 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 known analyte concentration and a sensor response of the sensor to the first calibration fluid and the second calibration fluid;

[0201] successively flowing 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 known analyte concentration and a sensor response of the sensor to the first and second calibration fluids; and

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

[0203] 19. The fluid analyzer of any of the preceding illustrative embodiments, wherein the processor is configured to determine that the obstruction exists when a difference between the first response sensitivity and the second response sensitivity is outside a predetermined threshold range.

[0204] 20. A fluid analyzer as described in any of the preceding illustrative 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.

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

[0206] 22. The fluid analyzer as described in any of the aforementioned illustrative embodiments further includes a washing fluid injection port connected to the one or more channel fluids and a washing fluid valve located between the washing fluid injection port and the sensor, wherein the washing fluid injection port is capable of operating to receive a washing fluid, and the washing fluid valve is capable of opening and closing to provide the washing fluid to the one or more channels.

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

[0208] 24. The fluid analyzer of any one of the preceding illustrative embodiments, wherein the obstruction is a blood clot.

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

[0210] During a first time period, controlling one or more valves to successively deliver a first calibration fluid and a second calibration fluid to a sensor through a fluid channel, and storing first data indicating a first response slope, the first response slope being based at least in part on a first difference between first information generated by a meter indicating a first potential generated by the sensor contacting the first calibration fluid and second information generated by the meter indicating a second potential generated by the sensor contacting the second calibration fluid;

[0211] at a second time period after the first time period, controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and storing second data indicating a second response slope, the second response slope being based at least in part on a second difference between third information generated by the meter indicating a third potential generated by the sensor contacting the first calibration fluid and fourth information generated by the meter indicating a fourth potential generated by the sensor contacting the second calibration fluid; and

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

[0213] in conclusion

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

Claims

1. A fluid analyzer, comprising: a fluid channel operable to transport a fluid; a sensor in fluid communication with the fluid passage; a meter operable to receive the signal generated by the sensor and convert the signal into information indicative of the electrical potential of the fluid; a first calibration fluid having a first analyte concentration; a second calibration fluid having a second analyte concentration different from the first analyte concentration; one or more calibration fluid injection ports in fluid communication with the fluid channel, the one or more calibration fluid injection ports being operable to receive a first calibration fluid and a second calibration fluid; one or more valves located between the one or more calibration fluid injection ports and the sensor, the one or more valves being capable of opening and closing to provide one or more samples of each of the first calibration fluid and the second calibration fluid to the fluid channel; as well as A control system having a processor operable to execute processor executable code which, when executed by the processor, causes the processor to run an obstruction detection algorithm, comprising: controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid passage during a first time period, and storing first data indicating a first response slope, the first response slope being based at least in part on a first difference between first information generated by the meter and second information indicating a first potential generated by the sensor contacting the first calibration fluid, the second information indicating a second potential generated by the sensor contacting the second calibration fluid; at a second time period after the first time period, controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid passage, and storing second data indicating a second response slope, the second response slope being based at least in part on a second difference between third information indicating a third potential generated by the sensor contacting the first calibration fluid and fourth information generated by the meter, the third information indicating a fourth potential generated by the sensor contacting the second calibration fluid; and In response to a difference between the first response slope and the second response slope exceeding a threshold, third data indicative of an obstruction on the sensor is stored.

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

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

5. The fluid analyzer according to claim 1, wherein: The one or more valves include a first calibration valve that can be opened and closed to provide one or more samples of the first calibration fluid to the fluid channel and a second calibration valve that can be opened and closed to provide one or more samples of the second calibration fluid to the fluid channel.

6. The fluid analyzer according to claim 5 further includes a washing fluid injection port connected to the fluid of the fluid channel and a washing fluid valve located between the washing fluid injection port and the sensor, the washing fluid injection port is operable to receive a washing fluid, and the washing fluid valve is openable and closed to provide the washing fluid to the fluid channel.

7. The fluid analyzer according to claim 6, wherein: The processor executable code, when executed by the processor, further causes the processor to control the washing fluid valve based at least in part on the third data to communicate the washing fluid through the fluid passage to the sensor.

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

9. A method for detecting an obstruction on a sensor of a fluid analyzer, comprising: successively flowing a first calibration fluid and a second calibration fluid 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 known analyte concentrations and a sensor response of the sensor to the first calibration fluid and the second calibration fluid; successively flowing 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 known analyte concentration and the sensor response of the sensor to the first and second calibration fluids; as well as The presence of the obstruction on the sensor is determined, by a processor, based at least in part on a difference between the first response sensitivity and the second response sensitivity.

10. The method according to claim 9, wherein: The step of determining that the obstruction exists determines that the obstruction exists when the difference is outside a predetermined threshold range.

11. The method according to claim 9, wherein: The step of determining that the obstruction exists determines that the obstruction does not exist when the difference is within a predetermined threshold range.

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

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

14. The method according to claim 13, wherein: During the first time period, the step of successively flowing the first calibration fluid and the second calibration fluid comprises: contacting the first calibration fluid to the sensor to generate a signal that can be received by a meter and converted into first information indicative of a first one of the sensor responses, wherein the first sensor response is a potential generated by the sensor in response to contact with the first calibration fluid; contacting the second calibration fluid to the sensor to generate a signal that can be received by the meter and converted into second information indicative of a second one of the sensor responses, wherein the second sensor response is a potential generated by the sensor in response to contact with the second calibration fluid; and storing first data indicative of the first response slope, the first response slope being based at least in part on a difference between the first information and the second information; and Wherein, in the second time period after the first time period, the step of successively flowing the first calibration fluid and the second calibration fluid comprises: contacting the first calibration fluid to the sensor to generate a signal that can be received by the meter and converted into third information indicative of a third one of the sensor responses, wherein the third sensor response is a third electrical potential generated by the sensor in response to contact with the first calibration fluid; contacting the second calibration fluid to the sensor to generate a signal that can be received by the meter and converted into fourth information indicative of a fourth one of the sensor responses, wherein the fourth sensor response is a fourth electrical potential generated by the sensor in response to contact with the second calibration fluid; storing second data indicative of the second response slope, the second response slope being based at least in part on a difference between the third information and the fourth information; and In response to a difference between the first response slope and the second response slope exceeding a threshold, third data indicating the presence of the obstruction on the sensor is stored.

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

16. The method according to claim 14, wherein: The method also includes the step of contacting the sensor with a washing fluid based at least in part on the step of determining that the obstruction exists.

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

18. A fluid analyzer, comprising: a sensor configured to measure at least one parameter associated with the fluid; one or more containers configured to store a first calibration fluid and a second calibration fluid having a known analyte concentration; one or more channels configured to provide fluid communication between the sensor and the one or more containers; as well as a processor configured to determine the presence of an obstruction obstructing the sensor, wherein the processor is configured to: successively flowing the first calibration fluid and the second calibration 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 known analyte concentration and a sensor response of the sensor to the first calibration fluid and the second calibration fluid; successively flowing 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 known analyte concentration and a sensor response of the sensor to the first and second calibration fluids; and The presence of the obstruction is determined based at least in part on a difference between the first response sensitivity and the second response sensitivity.

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

20. The fluid analyzer according to claim 18, wherein: The sensor comprises a working electrode and a reference electrode, 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.

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

22. The fluid analyzer according to claim 18 further includes a washing fluid injection port connected to the one or more channel fluids and a washing fluid valve located between the washing fluid injection port and the sensor, the washing fluid injection port is operable to receive a washing fluid, and the washing fluid valve is capable of opening and closing to provide the washing fluid to the one or more channels.

23. The fluid analyzer according to claim 22, wherein: The processor is further configured to control the washing fluid valve to communicate the washing fluid through the one or more passages to the sensor in response to determining that the obstruction exists.

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

25. A non-transitory computer readable medium storing an obstruction detection algorithm, the obstruction detection algorithm comprising processor executable code which, when executed by a processor, causes the processor to: During a first time period, controlling one or more valves to successively deliver a first calibration fluid and a second calibration fluid to a sensor through a fluid channel, and storing first data indicating a first response slope, the first response slope being based at least in part on a first difference between first information generated by a meter indicating a first potential generated by the sensor contacting the first calibration fluid and second information generated by the meter indicating a second potential generated by the sensor contacting the second calibration fluid; at a second time period after the first time period, controlling the one or more valves to successively deliver the first calibration fluid and the second calibration fluid to the sensor through the fluid channel, and storing second data indicating a second response slope, the second response slope being based at least in part on a second difference between third information generated by the meter indicating a third potential generated by the sensor contacting the first calibration fluid and fourth information generated by the meter indicating a fourth potential generated by the sensor contacting the second calibration fluid; as well as In response to a difference between the first response slope and the second response slope exceeding a threshold, third data indicative of an obstruction on the sensor is stored.

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