Interference correction of clinical assays

Abstract

Improved methods of analyzing a biological sample to determine a target analyte concentration that is corrected for interference are provided. Methods provided herein comprise analyzing a biological sample with one or more assays and applying the data to determine a corrected concentration of a target analyte. Also provided herein are clinical chemistry instruments comprising one or more assay systems, a processor configured to receive data from the one or more assay systems and determine a final concentration of a target analyte that is corrected for interference.

Description

INTERFERENCE CORRECTION OF CLINICAL ASSAYSBACKGROUND

[0001] Assays for determining the concentration of a particular target molecule are important tools in many areas of research and medicine. For example, clinical chemistry assays for determining the concentration of a target molecule(s) e.g., electrolytes) can be important to making a proper diagnosis of a patient and / or determining the appropriate treatment plan for the patient.

[0002] Interference is a common problem in a variety of assays, including clinical chemistry assays. More specifically, interference in an assay for determining the concentration of a particular target analyte can cause either an artificially high or an artificially low reported result of the target analyte concentration, depending on the nature of the interference. In the clinical chemistry setting, such a false result can lead to a poor patient outcome by causing an incorrect diagnosis or an inappropriate treatment plan. At the very least, it can cause the patient to undergo unnecessary additional testing (including, for example, additional unnecessary blood draws) in order to arrive at the appropriate diagnosis or treatment plan.

[0003] Interference can come from various sources. One example of assay interference is hemolysis interference. Hemolysis interference in electrolyte assays, such as potassium assays, is a major issue in determining electrolyte levels in a patient to evaluate whether the patient has an electrolyte imbalance (e.g., hyperkalemia or hypokalemia). This is particularly an issue in the emergency room, where blood draws can be more difficult and more likely to induce hemolysis. An electrolyte imbalance can be a medical emergency, and hemolytic interference leads to uncertainty as to whether a high or normal result of an electrolyte assay is real or not.

[0004] Thus, there is a need for improved assays that are able to correct for interference.SUMMARY

[0005] In at least one aspect, the disclosure provides a method of analyzing a blood sample to determine a potassium concentration that is corrected for interference comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration that is corrected for interference.

[0006] In another aspect, the disclosure provides a method of analyzing a blood sample to determine a potassium concentration that is corrected for interference comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; and applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference.

[0007] In a further aspect, the disclosure provides a method of determining a potassium imbalance comprising at least the steps of: analyzing a blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration that is corrected for interference.

[0008] In a still further aspect, the disclosure provides a method of determining a potassium imbalance comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the bloodsample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference.

[0009] In another aspect, the disclosure provides a method of analyzing a blood sample including an interference indicator to determine a potassium concentration that is corrected for interference comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration in the blood sample that is not corrected for interference; receiving, at a processor, data corresponding to the uncorrected potassium concentration; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and receiving, at the processor, data corresponding to the concentration of the interference indicator; determining, by the processor, a corrected potassium concentration that is corrected for interference, wherein the corrected potassium concentration is determined by applying the data from the second assay to the data from the first assay.

[0010] In a further aspect, the disclosure provides a method of analyzing a blood sample including an interference indicator to determine a potassium concentration that is corrected for interference comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; receiving, at a processor, data corresponding to the preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; receiving, at the processor, data corresponding to the concentration of the interference indicator; determining, by the processor, a final potassium concentration that is corrected for interference, wherein the final potassium concentration is determined by applying the data from the second assay to the data from the first assay.

[0011] In a still further aspect, the disclosure provides a method for improving the determination of potassium concentration in a biological sample comprising at least the steps of: analyzing the biological sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the biological sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference.

[0012] In an additional aspect, the disclosure provides a method for improving the determination of potassium concentration in a biological sample comprising at least the steps of: analyzing the biological sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the biological sample; analyzing the biological sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference.

[0013] In another aspect, the disclosure provides a method of indicating whether a patient has an electrolyte imbalance, comprising at least the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; and reporting the corrected electrolyte concentration.

[0014] In a further aspect, the disclosure provides a method of indicating whether a patient has an electrolyte imbalance, comprising at least the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary electrolyte concentration in the biological sample; analyzing the biological sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample; applying the data from the second assay to the data from the first assay to determine a final electrolyte concentration that is corrected for interference; and reporting the final electrolyte concentration.

[0015] It should be appreciated by those skilled in the relevant art that in some embodiments related to the above aspects, the first assay is an ion selective electrode (ISE) assay.

[0016] It should be appreciated by those skilled in the relevant art that in some embodiments relating to the above aspects, the interference indicator is hemoglobin. Additionally, in some embodiments relating to the above aspects, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. Moreover, in some embodiments of the presently described technology, the method(s) further comprise quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some further embodiments, the quantitative determination further comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychromeOD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In someembodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix (known by those skilled in the relevant art as “regularization”). Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0017] In some embodiments relating to the above aspects, the method further comprises the step of quantitatively determining the uncorrected potassium concentration using the ISE assay.

[0018] In some embodiments relating to the above aspects, the applying the data step comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data step further comprises the steps of multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subsequently subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0019] In some further embodiments relating to the above aspects, the method(s) further comprises, after reporting the corrected electrolyte concentration, the step of indicating whether the corrected electrolyte concentration is above or below an electrolyte imbalance threshold.

[0020] In some embodiments relating to the above aspects, the reporting further comprises reporting the uncorrected electrolyte concentration.

[0021] In some embodiments relating to the above aspects, the reporting comprises reporting the comparative values between the uncorrected electrolyte concentration and the corrected electrolyte concentration.

[0022] In some embodiments relating to the above aspects, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold,reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration.

[0023] In another aspect, the disclosure of the presently described technology provides at least one method for determining potassium concentration in a blood sample, the improvement comprising the step of determining a corrected potassium concentration by attenuating interference. In some embodiments of at least this aspect, the improvement further comprises the step of applying a concentration of an interference indicator to an uncorrected potassium concentration that is not corrected for interference to remove interference. In some further embodiments, the interference indicator is hemoglobin. In some embodiments, the improvement further comprises determining the uncorrected potassium concentration using an ion selective electrode (ISE) assay. In some additional embodiments, the improvement further comprises the step of determining the hemoglobin concentration using a lipemia, icterus, and hemolysis (LIH) assay. Moreover, in some embodiments, the method further comprises the step of quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In still further embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the biological sample at the two or more wavelengths. Still further, in some embodiments, the quantitative determination further comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, andwherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix (known by those skilled in the relevant art as “regularization”). Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0024] In some embodiments, the applying step further comprises the step of applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying step further comprises the steps of multiplying the concentration of the interference indicator by the correction factor to determine an interference magnitude; and subsequently subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration.

[0025] In another aspect, the disclosure of the present technology provides at least one method of correcting for interference in an assay comprising the steps of: analyzing a sample with a first assay, wherein the first assay determines an uncorrected target analyte concentration that is not corrected for interference; analyzing the sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected target analyte concentration that is corrected for interference.

[0026] In a further aspect, the disclosure provides at least one method for correcting for interference in an assay comprising the steps of: analyzing a sample with a first assay, wherein the first assay is performed to determine a preliminary target analyte concentration in the sample; analyzing the sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the sample; and applying the data from the second assay to the data from the first assay to determine a final target analyte concentration that is corrected for interference.

[0027] In some embodiments relating to the above aspects, the target analyte is one or more electrolytes. In some embodiments, the target analyte is potassium. In some embodiments, the target analyte is an enzyme. In some embodiments, the target analyte is lactate dehydrogenase(LDH).

[0028] In some embodiments relating to the above aspects, the interference indicator is hemoglobin. In some embodiments, the concentration of hemoglobin is determined using a lipemia, icterus, and hemolysis (LIH) assay.

[0029] In a still further aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having an electrolyte imbalance, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; and reporting the corrected concentration of the one or more electrolytes.

[0030] In another aspect, the disclosure provides a method of treating a patient suspected of having an electrolyte imbalance, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes that is corrected for interference; and reporting the final concentration of the one or more electrolytes.

[0031] In some embodiments relating to the above aspects, the method further comprises, after reporting corrected concentration of the one or more electrolytes, the step of determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining the treatment plan for the patient, the step of treating the patient for the electrolyte imbalance with the treatment plan.

[0032] In some embodiments relating to the above aspects, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises the step of measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the blood sample at the two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to the provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelatedvariation to the covariance matrix. Moreover, in some further embodiments, the non-hemoglobin sources of variation include variation caused by instrumentation.

[0033] In some embodiments relating to the above aspects, the applying the data step further comprises the step of applying a correction factor to determine the corrected electrolyte concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration.

[0034] In some embodiments relating to the above aspects, the reporting step further comprises reporting the uncorrected electrolyte concentration. In some embodiments, the reporting step comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration.

[0035] In some embodiments relating to the above aspects, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof. In some embodiments, the treatment plan of the presently described technology is used to treat hyperkalemia. In some embodiments, the treatment plan of the presently described technology is used to treat hypokalemia that is masked by interference.

[0036] In a further aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having an electrolyte imbalance, wherein the patient issuspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration.

[0037] In a still further aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having an electrolyte imbalance, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than thereporting threshold, reporting both the final electrolyte concentration and the preliminary electrolyte concentration.

[0038] In some embodiments relating to the above aspects, the method(s) further comprises, after reporting the concentration of the one or more electrolytes, the step of determining whether the patient has a hemolytic disorder and determining a treatment plan for that patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, the step of treating the patient for the electrolyte imbalance with the treatment plan.

[0039] In some embodiments relating to the above aspects, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises the step of quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the blood sample at the two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to the provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. . In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In someadditional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0040] In some embodiments relating to the above aspects, the applying the data step further comprises the step of applying a correction factor to determine the corrected electrolyte concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subsequently subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration.

[0041] In some embodiments relating to the above aspects, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0042] In an aspect, the disclosure of the present technology also provides at least one method of treating a patient suspected of having hyperkalemia, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the first assay to the data from the second assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference; and reporting the corrected potassium concentration.

[0043] In another aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having hyperkalemia, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood samplewith a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; and applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference; reporting the final potassium concentration.

[0044] In a further aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference; and reporting the corrected potassium concentration.

[0045] In a still further aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference; and reporting the final potassium concentration.

[0046] In some embodiments relating to the above aspects, the method further comprises, after reporting the corrected potassium concentration, the step of determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining atreatment plan for the patient, the step of treating the patient for hyperkalemia with the treatment plan.

[0047] In some embodiments relating to the above aspects, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises the step of quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the blood sample at the two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0048] In some embodiments relating to the above aspects, the applying the data step further comprises the step of applying a correction factor to determine a correction potassiumconcentration. In some embodiments, the applying the data step further comprises the steps of multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration.

[0049] In some embodiments relating to the above aspects, the reporting further comprises the step of reporting the uncorrected potassium concentration. In some embodiments, the reporting further comprises the step of reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments relating to the above aspects, the method(s) of the present technology further comprise the steps of establishing a reporting threshold; comparing the difference of the corrected potassium concentration and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0050] In another aspect, the disclosure provides at least one method of treating a patient suspected of having hyperkalemia, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of potassium that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the potassium, wherein the corrected potassium concentration is corrected for interference; reporting an electrolyte data set, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium and the uncorrected potassium concentration against the reporting threshold; and if the differenceof the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0051] In a further aspect, the disclosure provides at least one method of treating a patient suspected of having hyperkalemia, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration, wherein the final potassium concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the preliminary electrolyte concentration.

[0052] In a still further aspect, the disclosure provides at least one method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of potassium that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the potassium, wherein the corrected potassium concentration is corrected for interference; reporting an electrolyte data set, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of thecorrected potassium and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0053] In an additional aspect, the disclosure of the present technology provides at least one method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration, wherein the final potassium concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the preliminary electrolyte concentration.

[0054] In some embodiments relating to the above aspects, the method further comprises, after reporting an electrolyte concentration, the step of determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, the step of treating the patient for the hypokalemia masked by interference with the treatment plan.

[0055] In some embodiments relating to the above aspects, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In someembodiments, the method further comprises the step of quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the blood sample at the two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0056] In some embodiments relating to the above aspects, the applying the data step further comprises the step of applying a correction factor to determine a correction potassium concentration. In some embodiments, the applying the data step comprises the steps of multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration.

[0057] In some embodiments relating to the above aspects, the reporting further comprises the step of reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises the step of reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration.

[0058] In some embodiments relating to the above aspects, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0059] In another aspect, the disclosure of the present technology provides at least one method for determining the necessity of a secondary blood draw, wherein the method comprises the steps of collecting a first blood sample with a first blood draw; analyzing the first blood sample with an assay to determine the concentration of hemoglobin; establishing a re-draw threshold; comparing the concentration of hemoglobin to the re-draw threshold; and if the concentration of hemoglobin is greater than the re-draw threshold, collecting a second blood sample with a secondary blood draw.

[0060] In some embodiments relating to the above aspect, the establishing the re-draw threshold further comprises the steps of: (i) establishing a correction factor uncertainty; (ii) establishing an assay target error threshold; and (iii) calculating the re-draw threshold based on the correction factor uncertainty and the assay target error threshold.

[0061] In some embodiments relating to the above aspect, the assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises the step of quantitatively determining the concentration of hemoglobin using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination step further comprises the step of determining a linear combination of the optical densities (OD) of the blood sample at the at least two or more wavelengths. In some embodiments, the quantitative determination step further comprises thestep of producing one or more covariance matrices associated with substances that may interfere with the hemoglobin quantitation.

[0062] In a further aspect, the disclosure of the present technology provides a clinical chemistry instrument comprising at least the steps of: a first assay system configured to determine an uncorrected potassium concentration that is not corrected for interference, the first assay system comprising a first sensor; and a second assay system for determining the concentration of an interference indicator, the second assay system comprising a second sensor; and a processor configured to receive data from the first and second sensors to determine a corrected potassium concentration that is corrected for the interference.

[0063] In a still further aspect, the disclosure of the present technology provides a clinical chemistry instrument comprising at least the steps of: a first assay system configured to determine a preliminary potassium concentration, the first assay system comprising a first sensor; and a second assay system for determining the concentration of an interference indicator, the second assay system comprising a second sensor; and a processor configured to receive data from the first and second sensors to determine a final potassium concentration that is corrected for the interference.

[0064] In some embodiments relating to the above aspects, the corrected potassium concentration is corrected for interference without the need for further assay processing beyond the clinical chemistry instrument, itself.

[0065] In some embodiments relating to the above aspects, the interference indicator is hemoglobin. In some embodiments, the first assay system is configured to run an ion selective electrode (ISE) assay. In some embodiments, the second assay system is configured to run a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the second assay system is configured to quantitatively determine the interference indicator concentration, wherein the quantitative determination comprises the step of measuring, using the first instrument, optical densities at two or more wavelengths. In some embodiments, the processor is configured to applythe data received from the second sensor to the data received from the first sensor to determine the corrected potassium concentration. In some embodiments, the processor is configured to apply the data received from the second sensor to the data received from the first sensor to determine the final potassium concentration. In still further embodiments, the quantitative determination further comprises the step of determining a linear combination of the optical densities (OD) of the biological sample at the two or more wavelengths. Still further, in some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, non-hemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data step comprises applying a correction factor. In some embodiments, the applying the data step further comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subsequently subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration. In some embodiments, the applying the data step comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interferencemagnitude; and subsequently subtracting the interference magnitude from the preliminary potassium concentration to determine the final potassium concentration. The various aspects and embodiments of the present disclosure include, without limitation systems, methods, devices, components, and / or software for implementing the various functions and processes described herein.DESCRIPTION OF DRAWINGS

[0067] Various aspects and embodiments of the present disclosure are shown in the drawings and described therein and elsewhere throughout the disclosure. In the drawings, like references indicate like parts.

[0068] FIG. 1 provides a flowchart of an example method in accordance with the disclosure.

[0069] FIG. 1 B provides a flowchart of an example method in accordance with the disclosure.

[0070] FIG. 2 illustrates the spectral components of lipemia.

[0071] FIG. 3 illustrates the spectral components of bilirubin.

[0072] FIG. 4 illustrates the spectral components of hemoglobin.

[0073] FIG. 5 illustrates hemoglobin quantitation in the presence of lipemia in the absence of bilirubin and hemoglobin.

[0074] FIG. 6 illustrates hemoglobin quantitation in the presence of bilirubin in the absence of lipemia and hemoglobin.

[0075] FIG. 7 illustrates hemoglobin quantitation in the presence of hemoglobin in the absence of lipemia and bilirubin.

[0076] FIG. 8 illustrates correction factors for 20 donor samples.

[0077] FIG. 9 illustrates uncorrected, corrected, and unhemolyzed potassium results.

[0078] FIG. 10 illustrates an example visual representation for the determination of a re-draw threshold.DETAILED DESCRIPTION

[0079] Clinical assays are subject to interference from many sources. Interference may cause the reported result to be higher or lower than in the absence of the interference. Spectrometric assays are one example of a clinical assay. Spectrometric assays typically involve a chemical reaction to form a chromophore, the optical density (OD) of which is measured at selected wavelengths. A person of ordinary skill in the art would understand that optical density is synonymous with absorbance for purposes of this disclosure. Interference in these types of assays can come from several sources. For example, interference may be caused by substances other than the chromophore, which absorb light at the wavelengths being monitored. Interference may also be caused by an interferent that disrupts the chemical reaction leading to the chromophore. The interferent may react directly with an analyte measured by the assay, with an intermediate product leading to the chromophore, or with the chromophore itself.

[0080] In some examples, there may be a measurable or quantifiable indicator of the interference. Some examples of this can include interference caused by the physical environment and / or specimen handling. Aspects of this disclosure include methods and systems for correcting for this type of interference. For example, some clinical assays measure the level of an analyte in serum or plasma. However, the same analyte may be present at a different level inside the blood cells. Some of these cells may be lysed by the physical environment, such as the process of the blood draw or post-draw specimen handling. The lysed cells release their contents into the extracellular fluid, thereby changing the analyte level.

[0081] Red blood cells (erythrocytes or RBCs) are particularly prone to lysis. RBC lysing is known as hemolysis, and is often caused by the phlebotomy procedure. Blood typically travels at a high speed through the small diameter needle. For instance, a 22 gauge needle has an inside diameter of 0.413 mm. If 5 mL of blood were to be drawn into a tube in 5 seconds, the blood would travel through the needle at 4.8 meters / second. This causes considerable turbulence and shear forces, which stress the RBCs and may cause hemolysis. While much has been written aboutphlebotomy procedures and other specimen handling procedures to minimize hemolysis, it continues to be common. Difficult blood draws, especially when requiring smaller-diameter needles, increase the risk of hemolysis. This is especially prevalent in emergency departments, where patients may be dehydrated and significantly ill.

[0082] Potassium, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and magnesium are examples of commonly measured analytes that are present at higher levels in RBCs than in serum or plasma. Thus, hemolysis increases the analyte levels subsequently measured.

[0083] Hemolysis interference can be particularly significant in assays for measuring potassium. Potassium levels are about 30 times higher in RBCs than in serum or plasma, causing hemolysis to have a potentially large impact on the reported potassium concentration. Furthermore, high or low potassium can be a medical emergency involving dangerous heart arrhythmias and even cardiac arrest. If hemolysis is present, it is difficult for the clinician to distinguish between a high potassium concentration that is due to hemolysis (pseudohyperkalemia) and a high potassium concentration in the absence of hemolysis (hyperkalemia). While an EKG is a quick test that can sometimes help clarify the diagnosis, waiting for a re-draw can take a long time and time can often be an important factor in these situations. As such, there is not always sufficient time for the blood to be redrawn and reanalyzed, and the clinician must make a treatment decision based on the data at hand, which can potentially be impacted by hemolysis interference. Thus, aspects of the present disclosure include one or more methods for correcting potassium results for interference from hemolysis. A person of ordinary skill in the art would appreciate that the disclosed methods and systems can be applied to other analytes subject to interference, whether from hemolysis or other sources of interference.

[0084] Hemolysis interference can occur irrespective of the analytical technique employed to measure the analyte. This is because hemolysis may release the analyte into the surrounding fluid, making it impossible to distinguish the portion of the analyte present in the fluid prior tohemolysis from the portion released by hemolysis. However, for some analytes, the amount of hemoglobin in the fluid may be a suitable indicator of the amount of excess analyte due to hemolysis. Hence, a mathematical correction for hemolysis may be made to the analyte level based on a measurement of the hemoglobin level. Though hemoglobin is described as an indicator for hemolysis, it must be appreciated that other analytes released from RBC by hemolysis may also be used as hemolysis indicators (e.g., LDH and AST).

[0085] Example methods in accordance with the disclosure of the present technology comprise a mathematical correction that relies on three factors: 1 ) hemoglobin in the serum or plasma is due to in vitro hemolysis, rather than in vivo hemolysis; 2) accurate hemoglobin quantitation; and 3) the analyte:hemoglobin ratio within RBCs is consistent between patients.

[0086] Various assays may be employed to measure analytes, such as potassium. For example, the analyte may be measured using an ion selective electrode (ISE) assay. In other examples, an analyte (e.g., potassium, LDH, or AST) may be measured spectrometrically. Various assays may be employed to measure an interference indicator. For example, hemoglobin may be measured using a serum indices (LIH) assay. LIH assays are routinely run, especially when samples are suspected of having interferents. Thus, a hemoglobin measurement is generally available without requiring additional assays. A person of ordinary skill in the art would appreciate that different assays may be conducted at different times and / or take different lengths of time to complete.

[0087] LIH assays are commonly viewed as being only semiquantitative, thereby being insufficiently accurate to be reliably used in a process for correcting for interference. Aspects in accordance with this disclosure include methods and systems for quantitatively measuring an interference indicator, such as hemoglobin, with an LIH assay. This quantitation that comprises using raw optical density data at several wavelengths can be used to accurately quantitate hemoglobin. Furthermore, the quantitative determination of hemoglobin can be designed to be minimally affected by other common interferents, such as bilirubin and lipemia. Thus, aspects ofthis disclosure include methods for the quantitative determination of hemoglobin, among other analytes, using LIH data in a manner that minimizes interference from interferents such as bilirubin and lipemia. This is particularly important in neonates, who often have icterus.

[0088] A person of ordinary skill in the art would further appreciate that clinical expertise (including, for example, a review of the patient history) must be employed to distinguish between in vivo hemolysis resulting from a patient having a hemolytic disorder and the much more common in vitro hemolysis. Thus, aspects of the presently described technology include reporting a corrected analyte (e.g., potassium) concentration, an uncorrected analyte concentration, or both the corrected and uncorrected analyte concentration, depending on various clinical factors. While, as noted above, different assays may be completed at different times, an advantage of methods in accordance with the disclosure of the present technology includes reporting a corrected result, such as a calculated result, to a clinician at the same time as an uncorrected result.Methods of Analyzing a Biological Sample

[0089] In an aspect, the disclosure of the present technology provides methods of analyzing biological samples, such as blood samples, urine samples, tissue samples, saliva samples. Methods in accordance with the disclosure include methods of analyzing biological samples, such as blood samples, to determine a concentration of a target analyte. Target analytes may include, for example, electrolytes, proteins, enzymes, small molecules, among other biologically relevant molecules. To illustrate, target analytes may include, for example, potassium, sodium, or chloride. In other examples, the target analyte may be lactate dehydrogenase (LDH). In further examples, the target analyte may be aspartate aminotransferase (AST).

[0090] In some embodiments, the method(s) of the present technology may be a method(s) of analyzing a blood sample to determine a concentration of one or more electrolytes that is corrected for interference. For example, methods in accordance with the disclosure of the present technology include methods for analyzing a blood sample to determine a potassium concentrationthat is corrected for interference. In other examples, the disclosure provides methods of determining a potassium imbalance. In further examples, the disclosure provides methods for improving the determination of potassium concentration in a biological sample, methods for indicating whether a patient has an electrolyte imbalance, or methods of correcting for interference in an assay.

[0091] As described above, methods in accordance with the disclosure include methods of determining a potassium concentration that is corrected for interference along with methods for improving the determination of a potassium concentration in a biological sample. The method may comprise analyzing a blood sample with one or more assays. For example, the biological sample may be analyzed with a first assay and a second assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample and wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample. The method may further comprise applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference. Thus, the final potassium concentration may be a corrected potassium concentration.

[0092] As described above, methods in accordance with the disclosure include methods of indicating whether a patient has an electrolyte imbalance e.g., a potassium imbalance), comprising the step of collecting at least one biological sample, such as a blood sample, from the patient. The method may further comprise analyzing the blood sample with one or more assays. For example, the biological sample may be analyzed with a first assay and a second assay, wherein the first assay is performed to determine a preliminary target analyte concentration in the biological sample and wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample. The target analyte may comprise various molecules, such as electrolytes proteins, enzymes, small molecules, or other biologically relevant molecules. In some examples, the target analyte comprises one or more electrolytes, such as potassium, sodium, or chloride. The method may further comprise the step of applying the datafrom the second assay to the data from the first assay to determine a target analyte concentration that is corrected for interference. In some embodiments, the method further comprises reporting the final target analyte concentration. Thus, in some embodiments, methods in accordance with the disclosure may comprise, for example, the steps of collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; and reporting the corrected electrolyte concentration.

[0093] In some embodiments, methods for indicating whether a patient has an electrolyte imbalance may further comprise, after reporting the corrected electrolyte concentration, the step of indicating whether the corrected electrolyte concentration is above or below an electrolyte imbalance threshold. The electrolyte imbalance threshold may be determined based on the clinical significance of a measured electrolyte concentration for the patient (e.g., medical history, medications, hydration status, and other clinical observations and factors). In some embodiments, the reporting step may further comprise, in addition to reporting the corrected electrolyte concentration, also reporting the uncorrected electrolyte concentration. In other embodiments, the reporting may comprise reporting the comparative values between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, what is reported may depend upon the comparison between the corrected and uncorrected electrolyte concentrations and a reporting threshold. For example, in some embodiments a method of indicating whether a patient has an electrolyte imbalance may further comprise the steps of: (i) establishing a reporting threshold; (ii) comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and(iii) if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration. In some embodiments, the reporting threshold may be based on a clinically significant difference or a total allowable error. It should be appreciated by one of ordinary skill in the art that various total allowable errors may be utilized. For example, the total allowable error for potassium may be 0.2 mmol / L (Royal College of Pathologists of Australasia (RCPA)), 0.5 mmol / L (CLIA ’88, Clinical Laboratory Improvement Amendments (CLIA), College of American Pathologists (CAP)), 5.8% (2004 update of the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC) table of Desirable Quality Specifications based on Biological Variation), 6% (Canadian Fixed limits from the College of Physicians and Surgeons of Saskatchewan (CFX)), 5.0% (EFLM European Federation of Clinical Chemistry and Laboratory Medicine), or 4.1% (EFLM median CV estimate). The total allowable error may be determined using methods appreciated by one of ordinary skill in the art. See, e.g., CLSI EP21 ED2:2016. In some embodiments, the reporting may comprise the step of reporting the uncorrected electrolyte and a comment. The content of the comment may depend on various factors, such as the policies or preferences of the clinician or laboratory. For example, the comment may report the difference between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the comment may report the uncorrected electrolyte concentration and a comment that hemolysis is present. In some embodiments, the comment may report the uncorrected electrolyte concentration and a comment that hemolysis is present along with the corrected electrolyte concentration. In some embodiments, the amount of hemolysis-induced excess potassium may be reported as a range based on the uncertainty of the correction factor, which may be determined as described herein.

[0094] In some embodiments, data from the one or more assays may be received at and applied by a processor. For example, methods for analyzing a biological sample can comprise analyzing the blood sample with a first assay, wherein the first assay is performed to determine apreliminary potassium concentration in the blood sample and receiving, at a processor, data corresponding to the preliminary potassium concentration. The method may further comprise analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of the interference indicator in the blood sample; receiving, at the processor, data corresponding to the concentration of the interference indicator. After the processor receives the data from each assay, the method may further comprise determining, by the processor, a final potassium concentration that is corrected for interference, wherein the final potassium concentration is determined by applying the data from the second assay to the data from the first assay. Thus, in some embodiments, methods in accordance with the disclosure may comprise, for example, the steps of analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; receiving, at a processor, data corresponding to the preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; receiving, at the processor, data corresponding to the concentration of the interference indicator; and determining, by the processor, a final potassium concentration that is corrected for interference, wherein the final potassium concentration is determined by applying the data from the second assay to the data from the first assay.

[0095] Various types of assays may be incorporated into methods in accordance with the disclosure of the presently described technology. For example, as described above, in some embodiments methods for analyzing a biological sample may comprise analyzing the biological sample with a first assay, wherein the first assay is performed to determine an uncorrected (or preliminary) concentration or one or more target analytes. For example, the first assay may be performed to determine an uncorrected concentration of one or more electrolytes, such as potassium, sodium, or chloride. In some embodiments, the first assay may be an ion selective electrode (ISE) assay. In some embodiments, the first assay may be an assay for determiningthe concentration of other target analytes subject to interference, such as aspartate aminotransferase (AST) or lactate dehydrogenase (LDH). In some embodiments, the methods may comprise analyzing the biological sample with an ISE assay, wherein the ISE assay is performed to determine a preliminary concentration of one or more electrolytes, such as a preliminary potassium concentration. In some embodiments, the preliminary potassium concentration is an uncorrected potassium concentration that is not corrected for interference.

[0096] As described above, methods in accordance with the disclosure may comprise methods for correcting for interference. In some embodiments, interference indicators may comprise small molecules, proteins, enzymes, or other entities that may cause interference with a determination of a target analyte. For example, in some embodiments, the interference may be hemoglobin.

[0097] Various types of assays may be employed to measure the concentration of the interference indicator, depending on the nature of the interference indicator. As described above, in some embodiments of the present technology, methods of analyzing a biological sample may comprise, for example, analyzing the biological sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In further embodiments, the interference indicator may be hemoglobin and an LIH assay is performed to determine the concentration of hemoglobin in the biological sample. In some embodiments, the assay may be a serum hemoglobin assay.

[0098] In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using an LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. For example, in some embodiments the quantitative determination comprises measuring optical densities at up to 2, up to 5, up to 8, up to 10, up to 20, up to 50, up to 100, up to 200, or up to 500 wavelengths. In some embodiments, the quantitative determination comprises measuring optical densities at 2, 3, 4, 5, 6, 7, 8, 9, 10,11 , 12, or 13 wavelengths. In some embodiments, the quantitative determination comprises measuring optical densities at 7 wavelengths, ranging from 340 nm to 540 nm (e.g., 340, 380, 410, 450, 480, 520, and 540 nm)

[0099] The quantitative determination step may further comprise applying a linear combination of the optical densities (OD) of the sample at the two or more wavelengths. In further examples, the quantitative determination step may further comprise producing one or more covariance matrices associated with substances that may interfere with the interference indicator quantitation. For example, the quantitative determination may further comprise producing one or more covariance matrices associated with sources of variation in hemoglobin optical density measurements that are not caused by changes in the hemoglobin concentration.

[0100] Thus, in some embodiments, the quantitative determination comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation. The determination of the polychrome OD may comprise the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix. The polychrome vector may then be applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, nonhemoglobin sources of variation comprise lipemia and bilirubin. In some additional embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix (known by those skilled in the relevant art as “regularization”). Moreover, in some further embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. Example 1 describes an example process in accordance with the disclosure ofthe present technology for the quantitative determination of hemoglobin in a biological sample from optical density (OD) data.

[0101] As discussed above, one or more methods in accordance with the disclosure of the present technology may comprise applying the data from the second assay to the data from the first assay to determine a final target analyte (e.g., one or more electrolytes, such as potassium) concentration. The final electrolyte concentration may be a corrected electrolyte concentration that is corrected for interference. Thus, in some examples, the method(s) comprises applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference. The applying the data may comprise applying a correction factor to determine the corrected potassium concentration. In some embodiments, the applying the data may comprise the steps of: (i) multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and (ii) subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration. The correction factor may be determined based on various factors, including clinical data, among other factors. This may be expressed mathematically in the form of an equation as Kcorr= K0— c H, where Kcorrand Koare the corrected and uncorrected potassium concentrations, respectively, H is the concentration of the interference indicator, and c is a correction factor.

[0102] In some embodiments, the correction may depend on whether positive or negative interference is involved. For example, positive interference may be caused by an electrolyte concentration inside erythrocytes that is greater than in serum, thus leading hemolysis to cause excess electrolytes to be present in the serum. Patient-to-patient variability can be expressed as an excess electrolyte range, which may be calculated as a correction factor range multiplied by the hemoglobin concentration. The uncertainty of the estimated excess electrolyte concentration (which may equal the uncertainty of the corrected target analyte concentration) may be calculated as the larger of the differences between the estimated excess concentration and the excesselectrolyte range limits. In some examples, the correction factor range may represent 2.5% to 97.5% of patient samples. In some examples, the correction factor may be the midpoint of the correction factor range, or the 50th percentile of patient samples. In some embodiments, the excess electrolyte range may provide a range of corrections that may be subtracted from the uncorrected electrolyte concentration. Example 2 describes an example process in accordance with the disclosure of the present technology for the determination of a correction factor. As illustrated in Example 2, aspects of the disclosure include determination of a correction factor that has low patient-to-patient variability. An additional exemplary process is described in van Rossum, 2021 , Clinica Chimica Acta 522:83-87.

[0103] FIG. 1 illustrates a flow chart of an example method in accordance with the disclosure. FIG. 1 illustrates an online process 170 and off-line processes 175 and 190. As shown in FIG. 1 , biological sample 105 may be analyzed with a first assay 1 10 and a second assay 115. An interference correction 130 may be determined by applying data from the first assay 110 to data from the second assay 115. To that end, second assay 115 may be configured, for example, to quantitatively determine the concentration of an interference indicator as described herein. The quantitative determination may comprise a wavelength selection 125 and measurement of a single absorbance spectrum or two or more absorbance spectra, including, for example, a hemoglobin absorbance spectrum 140, a lipemia absorbance spectrum 145, a bilirubin absorbance spectrum 150, and optionally other sources of variation 155. In some examples, the quantitative determination may comprise a wavelength selection and measurement of a single absorbance spectrum (e.g., a hemoglobin spectrum). In some examples, the quantitative determination may comprise a wavelength selection 125 and measurement of two or more absorbance spectra. In some examples, a covariance matrix 160 may be created from the lipemia absorbance spectrum 145, bilirubin absorbance spectrum 150, and optionally other sources of variation 155. A polychrome OD 165 may be determined from the covariance matrix 160 and the hemoglobin absorbance spectrum 140 and applied to quantitatively determine an interferenceindicator concentration e.g., a hemoglobin concentration). The quantitative interference indicator concentration may then be applied to the data from first assay 1 10 to determine a corrected target analyte (e.g., potassium) concentration through interference correction 130 as described herein. Interference correction 130 further comprises applying a correction factor as described herein. To this end, clinical data 180 may be analyzed to determine a correction factor 185 at process 190. Data from this process may then be reported at report 135. As illustrated in FIG. 1 B, the hemoglobin absorbance spectrum 140 can be characterized at 195 with an extinction coefficient vector (a) 215 that characterizes the hemoglobin spectrum. Further, the lipemia absorbance spectrum 145, the bilirubin absorbance spectrum 150, and other sources of variation 155 (collectively referred to as non-hemoglobin sources of variation), can be characterized at 200 with a covariance matrix ( V) 160 associated with non-hemoglobin sources of variation. A polychrome vector (k) 205 that is a function of the extinction coefficient vector 215 and the covariance matrix 160 can then be determined. The Polychrome OD 165 is then determined from the polychrome vector (k) 205 and measured optical densities 210. Example 1 describes an example process in accordance with the disclosure of the present technology for the quantitative determination of hemoglobin in a biological sample from optical density (OD) data.Methods of Treatment

[0104] In an aspect, the disclosure of the present technology provides one or more methods of treating a patient comprising the methods of analyzing biological samples described above. For example, methods in accordance with the disclosure of the present technology include, for example, one or more methods of treating a patient suspected of having an electrolyte imbalance. In some embodiments, the method of treatment may be a method of treating a patient suspected of having hyperkalemia or a method of treating a patient suspected of having hypokalemia. In some embodiments, the method of treatment may be a method of treating a patient suspected of having hyperkalemia or hypokalemia that is masked by interference (e.g., interference fromhemolysis). In some embodiments, the patient does not have a hemolytic disorder. In some embodiments, the patient is suspected of having a hemolytic disorder. Hemolytic disorders may include inherited hemolytic anemias, such as sickle cell disease, thalassemia, red cell membrane disorders (e.g., hereditary spherocytosis, hereditary elliptocytosis, and hereditary pyropoikliocytosis, hereditary stomatocytosis, and hereditary exocytosis), pyruvate kinase deficiency (PKD), and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Hemolytic disorders may also include acquired hemolytic anemias, such as immune hemolytic anemia, autoimmunehemolytic anemia (AIHA), alloimmune hemolytic anemia, drug-induced hemolytic anemia, mechanical hemolytic anemias, paroxysmal nocturnal hemoglobinuria (PNH), malaria, babesiosis, and other infectious anemias. In vivo hemolysis may also be caused by a medical procedure (e.g., dialysis) or trauma (e.g., foot strikes during running). In such cases, the patient does not have a hemolytic disease, but the hemolysis reflects what is in the patient’s body, as contrasted with in vitro hemolysis, where the hemolysis does not correspond with the patient's body.

[0105] In some embodiments, methods in accordance with the disclosure comprise collecting at least one biological sample {e.g., a blood sample) from a patient. As discussed in detail above, the method(s) of the present technology may comprise analyzing the blood sample with one or more assays. For example, the biological sample may be analyzed with a first assay and a second assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes e.g., potassium) in the biological sample and wherein the second assay is performed to determine a concentration of an interference indicator {e.g., hemoglobin) in the biological sample. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the LIH assay may quantitatively determine a hemoglobin concentration. As discussed in detail above, such a quantitative determination may comprise, for example, measuring optical densities at two or more wavelengths.

[0106] Thus, in some embodiments, the quantitative determination comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation. The determination of the polychrome OD may comprise the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix. The polychrome vector may then be applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, wherein the polychrome OD is proportional to the hemoglobin concentration. Example 1 describes an example process in accordance with the disclosure of the present technology for the quantitative determination of hemoglobin in a biological sample from optical density (OD) data.

[0107] The method may further comprise applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes that is corrected for interference. In some embodiments, the method further comprises reporting the final concentration of the one or more electrolytes. Thus, in some embodiments, methods in accordance with the disclosure of the present technology may, for example, comprise collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; and reporting the corrected electrolyte concentration.

[0108] In some embodiments, after reporting the final or corrected concentration of the one or more electrolytes, a treatment plan for the patient is determined. Various treatmentmethodologies may be employed as part of a treatment plan. The treatment plan may include any treatment for electrolyte imbalance, hyperkalemia and / or hypokalemia identified as suitable by a clinician. Viera, A. J., et al., Potassium Disorders: Hypokalemia and Hyperkalemia, Am Fam Physician. 2015;92(6):487-495. In some embodiments, the treatment plan may include hemodialysis or administration of at least one of an oral rehydration salt (ORS) solution, oral potassium, intravenous (IV) fluids, IV electrolyte (e.g., potassium) infusion, a diuretic, a blood pressure medication (e.g., an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), a beta blocker), a potassium binder, insulin, a sympathomimetic medication, a potassium-sparing diuretic, or calcium gluconate, or combinations thereof. Additionally or alternatively, the treatment plan may include cessation or reduction in the dose of a medication including, for example, a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, calcium gluconate, an non-steroidal anti-inflammatory drug (NSAID), heparin, lithium, a calcineurin inhibitor, or combinations thereof. After determining the treatment plan for the patient, the patient may be treated for electrolyte imbalance using the treatment plan. The treatment plan may be utilized to treat disorders, conditions, or symptoms related to electrolyte imbalance. For example, in some embodiments, the treatment plan is used to treat hyperkalemia. In other embodiments, the treatment plan is used to treat hypokalemia masked by interference.

[0109] A treatment plan may be determined based on the data from the one or more assays described above. In some embodiments, the treatment plan may be determined by the final or corrected concentration of the one or more electrolytes. In some embodiments, the treatment plan may be determined based on the preliminary or uncorrected concentration of the one or more electrolytes. In some embodiments, the treatment plan may be determined based on a combination of the preliminary (or uncorrected) and the final (or corrected) concentration of the one or more electrolytes. A person of ordinary skill in the art would understand that other factors,such as a patient’s medical history, current signs and symptoms, and test and lab results, will also be taken into account in determining a treatment plan.

[0110] As described above, applying the data from a first assay to the data from a second assay may comprise applying a correction factor to determine the corrected electrolyte concentration. In some embodiments, the applying the data step may comprise the further steps of: (i) multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and (ii) subsequently subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0111] In some embodiments, methods of treating a patient in accordance with the disclosure of the present technology may further comprise, after reporting the corrected electrolyte concentration, the step of indicating whether the corrected electrolyte concentration is above or below an electrolyte imbalance threshold. The electrolyte imbalance threshold may be determined based on the clinical significance of a measured electrolyte concentration for the patient. In some embodiments, the reporting may further comprise, in addition to reporting the corrected electrolyte concentration, also reporting the uncorrected electrolyte concentration. In some embodiments, what is reported may depend upon the comparison between the corrected and uncorrected electrolyte concentrations and a reporting threshold. For example, in some embodiments a method of indicating whether a patient has an electrolyte imbalance may further comprise the steps of: (i) establishing a reporting threshold; (ii) comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and (iii) if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration. In some embodiments, the reporting threshold may be based on a clinically significant difference or a total allowable error. It should be appreciated by one of ordinary skill in the art that various total allowable errors may be utilized. For example, the total allowable error for potassium may be 0.2 mmol / L (Royal College of Pathologists of Australasia(RCPA)), 0.5 mmol / L (CLIA ’88, Clinical Laboratory Improvement Amendments (CLIA), College of American Pathologists (CAP)), 5.8% (2004 update of the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC) table of Desirable Quality Specifications based on Biological Variation), 6% (Canadian Fixed limits from the College of Physicians and Surgeons of Saskatchewan (CFX)), 5.0% (EFLM European Federation of Clinical Chemistry and Laboratory Medicine), or 4.1% (EFLM median CV estimate). The total allowable error may be determined using methods appreciated by one of ordinary skill in the art. See, e.g., CLSI EP21 ED2:2016.

[0112] In some embodiments, the reporting may comprise reporting the uncorrected electrolyte and a comment. For example, the comment may report the difference between the uncorrected electrolyte concentration and the corrected electrolyte concentration.Methods for Determining the Necessity of a Secondary Blood Draw

[0113] In an aspect, the disclosure of the present technology provides one or more methods for determining the necessity of a secondary blood draw. Interference, such as hemoglobin, can necessitate the need for one or more additional blood draws prior to analysis of the blood sample with an assay, such as the assays described herein. For example, a method for determining the necessity of a secondary blood draw may comprise the steps of collecting a first blood sample with a first blood draw; analyzing the first blood sample with an assay to determine the concentration of hemoglobin; establishing a re-draw threshold; and comparing the concentration of hemoglobin to the re-draw threshold. In some embodiments, if the concentration of hemoglobin is greater than the re-draw threshold, the method may further comprise collecting a second blood sample with a secondary blood draw.

[0114] In some embodiments, the re-draw threshold may be based on an uncertainty level of the interference. For example, the re-draw threshold may be determined based on a point at which the uncertainty of the interference becomes clinically significant. This uncertainty can be evaluated against various factors, such as total allowable error. It should be appreciated by oneof ordinary skill in the art that various total allowable errors may be utilized. For example, the total allowable error for potassium may be 0.2 mmol / L (Royal College of Pathologists of Australasia (RCPA)), 0.5 mmol / L (CLIA ’88, Clinical Laboratory Improvement Amendments (CLIA), College of American Pathologists (CAP), 5.8% (2004 update of the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC) table of Desirable Quality Specifications based on Biological Variation), 6% (Canadian Fixed limits from the College of Physicians and Surgeons of Saskatchewan (CFX), 5.0% (EFLM European Federation of Clinical Chemistry and Laboratory Medicine) 4.1% (EFLM median CV estimate). The total allowable error may be determined using methods appreciated by one of ordinary skill in the art. See, e.g., CLSI EP21 ED2:2016.

[0115] In some embodiments, establishing the re-draw threshold may comprise the steps of: (i) establishing a correction factor uncertainty; (ii) establishing an assay target error threshold; and (iii) calculating the re-draw threshold based on the correction factor uncertainty and the assay target error threshold. Example 2 describes an example process in accordance with the disclosure of the present technology for the determination of a correction factor, including a correction factor uncertainty.

[0116] FIG. 10 illustrates an example visual representation for how a re-draw threshold may be determined in accordance with the present disclosure. For purposes of the example depicted in FIG. 10, the maximum allowable error was assumed to be 0.2 mmol / L. For the uncorrected result, the difference between the corrected and uncorrected result is equal to the maximum allowable error below 100 mg / dL hemolysis. That represents a redraw threshold in the absence of correction. For the corrected result, the uncertainty of the result is equivalent to the uncertainty of the correction, which is the difference between the corrected result and the limits of the corrected result range. This equals the maximum allowable error at nearly 500 mg / dL hemolysis. This is shown in FIG. 10 as the re-draw threshold. It should be appreciated by one of ordinary skill in the art that, if the corrected result is not at the mid-point of the corrected result range, the re-draw threshold would need to be adjusted accordingly.

[0117] In some embodiments, the assay employed to analyze the blood sample is an LIH assay. In some embodiments, the method further comprises quantitatively determining the concentration of hemoglobin using the LIH assay using methods discussed in detail above. For example, in some embodiments, the quantitative determination may comprise measuring optical densities at least two or more wavelengths. In some embodiments, the quantitative determination may comprise determining a linear combination of the optical densities of a sample comprising hemoglobin at the at least two or more wavelengths. In some embodiments, the quantitative determination may comprise producing one or more covariance matrices associated with substances that may interfere with hemoglobin quantitation. Thus, in some embodiments, the quantitative determination comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation. The determination of the polychrome OD may comprise the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix. The polychrome vector may then be applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, wherein the polychrome OD is proportional to the hemoglobin concentration. Example 1 describes an example process in accordance with the disclosure of the present technology for the quantitative determination of hemoglobin in a biological sample from optical density (OD) data.

[0118] As discussed above, in some embodiments of the present technology, one or more methods may comprise determining an excess electrolyte range that may be calculated as the correction factor range (e.g., as discussed above in

[0102] ) multiplied by the hemoglobin concentration. The uncertainty of the estimated excess electrolyte concentration (which equals the uncertainty of the corrected concentration) would be calculated as the larger of the differencesbetween the estimated excess concentration and the excess electrolyte range limits. For instance, if the estimated excess concentration is 0.8 mmol / L, and the excess electrolyte range limits are 0.7 and 1.0 mmol / L, then the larger of the differences between the estimated excess concentration and the excess electrolyte range limits is 0.2 mmol / L. The excess electrolyte range may provide a range of corrections that may be subtracted from the uncorrected electrolyte concentration to yield the corrected electrolyte concentration. If the larger of the differences between the estimated excess electrolyte and the limits of the excess electrolyte range is larger than an uncertainty threshold e.g., clinically significant difference, total allowable error), the corrected result may be deemed clinically unreliable, and the sample must be redrawn. In some embodiments, the uncertainty threshold may depend on the corrected potassium concentration; e.g., a biologic variation of 4.85%. In some embodiments, the correction is proportional to the hemoglobin level, and so is the largest difference between the estimated excess electrolyte and the limits of the excess electrolyte range. Thus, for a given corrected potassium concentration, there may be a hemoglobin concentration threshold at which the largest difference equals the uncertainty threshold. If hemoglobin is above the hemoglobin concentration threshold, the uncertainty is greater than the uncertainty threshold, and the sample must be redrawn unless the patient is known to be hemolytic.Clinical Chemistry Instrument

[0119] In some aspects and in a number of embodiments, the disclosure of the present technology provides systems or apparatuses, such as clinical chemistry instruments, comprising one or more assay systems. Example clinical chemistry instruments in accordance with the disclosure of the present technology may be configured to determine a corrected concentration of one or target analytes utilizing methods for analyzing a biological sample as described above. For example, a clinical chemistry instrument in accordance with the disclosure of the present technology may comprise a first assay system configured to determine a preliminaryconcentration of one or more electrolytes, a second assay system configured to determine a concentration of an interference indicator, and a processor configured to receive data and determine a final concentration of the one or more electrolytes that is corrected for interference. In some embodiments, the clinical chemistry instrument may comprise a single assay system configured to determine a preliminary concentration of one or more electrolytes and a concentration of an interference indicator. In some embodiments, the clinical chemistry instrument may comprise a first assay system configured to determine a preliminary potassium concentration, the first assay system comprising a first sensor; and a second assay system for determining the concentration of the interference indicator, the second assay system comprising a second sensor; and a processor configured to receive data from the first and second sensors and determine a final potassium concentration that is corrected for interference. In some embodiments, the preliminary potassium concentration is an uncorrected potassium concentration that is not corrected for interference. In some embodiments, the final potassium concentration is a corrected potassium concentration that is corrected for interference. Thus, example clinical chemistry instruments may comprise a first assay system configured to determine an uncorrected potassium concentration that is not corrected for interference, the first assay system comprising a first sensor; and a second assay system for determining the concentration of the interference indicator, the second assay system comprising a second sensor; and a processor configured to receive data from the first and second sensors and determine a corrected potassium concentration that is corrected for interference.

[0120] In some embodiments, the final or corrected potassium concentration is corrected for interference without the need for further assay processing beyond the clinical chemistry instrument, itself. Such an outcome provides at least one advantage of the present technology over conventional systems and apparatuses.

[0121] Assay systems in accordance with the disclosure of the present technology may also be configured to determine an uncorrected (or preliminary) concentration or one or more targetanalytes. For example, the first assay may be performed to determine an uncorrected concentration of one or more electrolytes, such as potassium, sodium, or chloride. In some embodiments, the first assay may be an ion selective electrode (ISE) assay. In some embodiments, the first assay may be an assay for determining the concentration of other target analytes subject to interference, such as aspartate aminotransferase (AST) or lactate dehydrogenase (LDH).

[0122] Assay systems in accordance with the disclosure may be configured to determine a concentration of one or more target analytes and to correct for interference. For example, in some embodiments of the present technology, the target analyte may be one or more electrolytes (e.g., potassium) and an interference indicator may be hemoglobin. Thus, in some embodiment the second assay system may be configured to run a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the LIH assay may be configured to quantitatively determine the hemoglobin concentration using methods discussed in detail above. For example, in some embodiments, the quantitative determination may comprise measuring optical densities at least two or more wavelengths. In some embodiments, the quantitative determination may comprise determining a linear combination of the optical densities of hemoglobin at the at least two or more wavelengths. In some embodiments, the quantitative determination may comprise producing one or more covariance matrices associated with substances that may interfere with hemoglobin quantitation. Thus, in some embodiments, the quantitative determination comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of nonhemoglobin sources of variation. The determination of the polychrome OD may comprise the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix. The polychrome vector may then be applied to the measured optical densities(ODs) at the two or more wavelengths to provide the polychrome OD, wherein the polychrome OD is proportional to the hemoglobin concentration. Example 1 describes an example process in accordance with the disclosure of the present technology for the quantitative determination of hemoglobin in a biological sample from optical density (OD) data.

[0123] As discussed above, clinical chemistry instruments, in accordance with the disclosure of the present technology, may include a processor configured to receive data from the first and second sensors and determine a final or corrected concentration of one or more target analytes, such as potassium. In some embodiments, the processor may be configured to apply the data received from the first sensor to the data received from the second sensor to determine the final, or corrected, potassium concentration. Further, the application of the data may comprise methods described above. Thus, in some embodiments, the applying the data may comprise applying a correction factor. In some embodiments, the applying the data may comprise the steps of: (i) multiplying the target interference indicator concentration by the correction factor to determine an interference magnitude; and (ii) subsequently subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.EXAMPLESExample 1 - Hemoglobin Quantitation

[0124] A hemoglobin optical density (“OD”) (also referred to herein as a polychrome OD) that is unaffected by lipemia and bilirubin interference was developed. Coefficients of a linear combination of the ODs at a group of wavelengths were calculated, with the coefficients of the linear combination determined so as to minimize the effects of non-hemoglobin sources of variation without biasing the estimate of hemoglobin. The coefficients for the linear combination were determined using:

[0125] where k is the polychrome vector, that is, a vector of the linear-combination coefficients; a is the extinction coefficient vector, that is, a vector containing the relative ODs of the interference indicator (hemoglobin); V is the covariance matrix of the non-hemoglobin sources of variation, in this case, from lipemia and bilirubin interference, and T is mathematical matrix transpose operation. Methods of optimization for sources of variation using the above equation have been reported. See, e.g., Luenberger, D.G., “Optimization by Vector Space Methods (1969); U.S. Patent No. 5,014,216. To determine the effect on measured ODs of each substance / interferent ( / .e., hemoglobin, lipemia, or bilirubin), groups of samples were created. Each group of samples included 11 different amounts of a chosen substance / interferent ( / .e., hemoglobin, lipemia, or bilirubin) spiked into a common serum pool, then the OD of each sample was measured in 4 replicates using the LIH assay of an AU 480 instrument (Beckman Coulter, Inc., Brea, CA). Then the following procedure was followed.

[0126] In step (i), for each group, singular value decomposition was applied to the measured ODs from the LIH assays to determine the principal spectral component and the magnitude of the principal spectral component; the principal spectral component was then multiplied by its magnitude to represent the typical effect of the substance / interferent in that group.

[0127] In step (ii), an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths was determined as follows: A covariance matrix associated with hemoglobin sources of variation (from groups where the hemoglobin level was varied between samples) was computed from the sums of the outer products of the results of step (i). The sums of the outer products refers to there being multiple groups for hemoglobin, with each group having its own principal component and magnitude. The resulting sum represents a covariance due to variations in hemoglobin concentration. The principal eigenvector of the hemoglobin covariance matrix represents the OD spectrum of hemoglobin. The extinction coefficient vector (a) is proportional to the principal eigenvector of the hemoglobin covariance matrix.

[0128] In step (iii), a covariance matrix associated with non-hemoglobin sources of variation ( I / ) (from groups where bilirubin or lipemia levels varied between samples, but the hemoglobin level remained constant) was computed from the sums of the outer products of the results of step (i). The sums of the outer products refers to there being multiple groups for each interfered, with each group having its own principal component and magnitude. Any variability between the groups may be due to factors such as variability in the substance and the use of different analyzers. The outer product for each group will be a rank 1 covariance matrix, but when they are summed, the matrix will have a higher rank. The additional components represent the variability of the substance and measurement. For instance, lipemia does not have an exact composition, but exhibits a distribution of particle sizes that may vary from group to group. Thus, the sums of the outer products cause the linear combination to minimize the effect of all the groups as an ensemble, rather than just a single group. The use of a covariance matrix calculated from the sums of multiple groups increases the robustness of the hemoglobin quantitation against variations in the type of lipemia or variations in the configuration of bilirubin.

[0129] FIG. 2 shows the main, 2nd, and 3rdcomponents of the effects of lipemia, FIG. 3 shows the main, 2nd, and 3rdcomponents of bilirubin, and FIG. 4 shows the main, 2nd, and 3rdcomponents of hemoglobin. The main effects correspond with typical spectra of the substances. The 2ndand 3rdeffects incorporate the variability between the different data groups. The variability of hemoglobin was very low, which is expected because hemoglobin is a specific molecule that is ring-locked in a configuration that cannot undergo major changes. However, bilirubin is more variable - especially note the 2ndcomponent at 410 nm and 480 nm. Though bilirubin is a specific molecule, it is not ringlocked as hemoglobin is, so it can exist in various geometric configurations, having slightly different spectra. Finally, lipemia is not a specific molecule; rather, its spectra depends on the distribution of lipid particle sizes. This will generally cause the spectrum to slope more or less steeply, as shown by the 2ndcomponent corresponding to a slope.

[0130] It should be appreciated by one of ordinary skill in the art that other non-hemoglobin sources of variation may be accounted for in a covariance matrix V. For example, variations due to the light source may be accounted for. However, in this instance such variations were characterized by measuring the ODs of water blanks. Because the resulting covariance was so small as to be negligible for the purposes of this study, V was not adjusted to account for variations in the light source.

[0131] Empirical regularization was employed to account for remaining non-hemoglobin sources of variation. Regularization involves adding a small amount of uncorrelated variation to V, equivalent to adding a small constant to the diagonal elements of the covariance matrix, causing all the eigenvalues of Vto be increased by that constant, thereby preventing any of the components from being excessively small. Thenwill not have excessively large components, and k will have a smaller norm, corresponding with better robustness against unexpected variations.

[0132] The polychrome vector (k) was then computed using the formula above. The resulting polychrome vector was (-.2104, -.3096, 1 .4041 , -1.1509, .4806, -.0978, -.1175), and had a norm of 1 .9211 . The expected magnitude of interference was calculated by multiplying k by the principal spectrum of each data group. The RMS interference for lipemia and bilirubin was attenuated down to 0.26% and 1 .7%, respectively.

[0133] Experimentation showed that using the shortest 7 or 8 wavelengths of the wavelengths on an AU 480 (Beckman Coulter, Inc., Brea, CA) provided good performance. The seven shortest wavelengths, which ranged from 340 nm to 540 nm, were used, along with regularization of 0.0003. The wavelengths used were 340, 380, 410, 450, 480, 520, and 540 nm.

[0134] Performance was then evaluated using an AU 480 (Beckman Coulter, Inc., Brea, CA).The hemoglobin judgment value for the 66 data groups was computed using the k described above (called “polychrome OD” herein), and then compared against the LIH assay’s hemoglobinJudgement Value (“AU OD”). The polychrome OD is proportional to the hemoglobinconcentration. The Polychrome ODs were calculated from the dot product (also referred to as the inner product) of the polychrome vector and the measured ODs, as illustrated in the formula below: polychrome OD = k 0DmeasT

[0135] The polychrome ODs were calculated at measuring point 3 (MP3) (assay; roughly 40 s after addition of the sample) and measuring point 0 (MPO) (blank; the first measuring point prior to addition of sample), then the final polychrome OD was calculated using ODMPS - (90 / 91.2) ODMPO- The factor of 90 / 91 .2 comes from using 90 mL reagent and 1 .2 mL sample to correct for dilution due to the addition of the sample. The AU ODs provided by the instrument have been scaled. It was found that 0.266 ODAU - 0.002 closely matches the polychrome ODs. FIGS. 5-7 shows the polychrome and AU ODs as diamonds and open circles, respectively; FIGS. 5, 6 and 7 show the lipemia, bilirubin and hemoglobin data, respectively. FIG. 5 illustrates hemoglobin quantitation in the presence of lipemia in the absence of bilirubin and hemoglobin. FIG. 6 illustrates hemoglobin quantitation in the presence of bilirubin in the absence of lipemia and hemoglobin. FIG. 7 illustrates hemoglobin quantitation in the presence of hemoglobin in the absence of lipemia and bilirubin. Because the lipemia and bilirubin samples do not contain hemoglobin, the correct ODs are zero. The AU ODs show some lipemia interference and stronger bilirubin interference. Figure 7 shows the ODs for the hemoglobin samples. The correspondence between the two ODs is very close, with a correlation coefficient of 0.999967.Example 2 - Between-patient variation in intra-erythrocyte potassium / hemoglobin ratio

[0136] Whole blood samples were collected from a mix of 20 male and female donors. Two tubes were collected from each donor. A hemolysate was then prepared from each tube. Each tube was inverted and centrifuged at 3000 rpm for 10 minutes. The supernatant from each tube using a Pasteur pipette was discarded and replaced with 0.9% NaCI, using approximately 60 - 70% of the volume of red blood cells. Each tube was sealed and gently inverted 10 times to resuspend the cells. The tubes were centrifuged at 3000 rpm for 10 minutes and the supernatant was discarded. The cells in each tube were washed using 0.9% NaCI one more time. The tubes were resuspended using approximately half the volume of deionized water to the packed cells instead of saline solution, or less if it was suspected that the final hemoglobin concentration in the test pool may recover below the required concentration (500 mg / dL - 1000 mg / dL) after dilution. Finally, the tubes were frozen for several days.

[0137] The tubes were then thawed and brought to room temperature. The two tubes from the same donor were combined, resulting in 20 individual lysate suspensions. The lysate suspensions were centrifuged for 18 minutes at 4,200 rpm to remove the stroma. The individual supernatants (hemolysates) were collected separately using a Pasteur pipette. Each pellet was discarded for each of the individual supernatants. The individual hemolysates were re-frozen until the day of testing.

[0138] Testing was performed using a Beckman Coulter ALI480. First, the hemoglobin levels of 3 of the hemolysates (2 replicates) were measured using the HbA1 c Offline assay. The hemoglobin results were 17.75, 19.04 and 17.60 g / dL, giving an average of 18.13 g / dL Based on this, it was determined that 0.3 mL hemolysate would be spiked into 5.7 mL serum pool to give hemoglobin levels of about 900 mg / dL. The donor serum samples were thawed and pooled to create a baseline serum pool. The serum pool was divided into 21 portions - 20 portions, 5.7 mL each, for the 20 hemolysates, and one larger portion for measuring the baseline. Each of the 5.7 mL portions were spiked with 0.3 mL of one of the hemolysates. The larger baseline portion was not spiked. After running controls, potassium and LIH were measured as follows: 1 ) baseline portion, 5 reps; 2) four reps of each of the 20 spiked portions; 3) baseline portion, 5 reps.

[0139] A hemoglobin judgement value was used, which is based on the optical densities (CDs) at measuring point 3, using the following equation:H — 4.56(OD410OD480OD6Q0+ OD80Q)

[0140] where H is the hemoglobin judgement value as computed by the AU480 software, and the subscripts identify the wavelengths of the ODs used. One outlier was identified, namely, the 4threplicate of donor sample 9. The outlier result was 4.4547, compared with a mean result of the other 3 replicates of 4.3182. The outlier was deleted from the analysis.

[0141] Though the Hemoglobin judgement value is subject to interference from bilirubin, the icterus judgment values were all quite small and consistent from sample to sample. Therefore, interference from bilirubin is not expected to affect the analysis. The mean potassium and hemoglobin result was calculated for each donor sample. The baseline potassium and hemoglobin values were subtracted from the corresponding results. Finally, correction factors were computed as (K- baseline K) / (H - baseline H), where and H are the potassium results and hemoglobin judgement values, respectively. The correction factors represent the hemolysis- induced potassium I hemoglobin ratio for each donor, in units of (mM / L) / (H judgement unit). The mean correction factor was 0.769, and ranged from 0.680 to 0.821 , or 11 .5% below to 6.7% above the mean. The CV was 4.3%. FIG. 8 shows the individual correction factors.

[0142] The uncertainty of the correction factor is a key factor in applying hemolysis correction to potassium. As the following equation shows, Kcorr= Kmeas- cH, the correction is proportional to H. Likewise, the uncertainty of the correction will also be proportional to H. If H is large enough, the uncertainty of hemolysis correction may be unacceptable. For instance, suppose the maximum permissible error in the corrected potassium result were set at E. If the uncertainty of the correction factor c is de, then the uncertainty of the corrected result (ignoring the uncertaintyof the measured result) is H Ac. The requirement that H Ac < E yields H < — , giving an upper limit to the amount of hemolysis which can be acceptably corrected. The smaller Ac, the higher the upper limit of H.

[0143] When the Beckman Coulter LIH assay (OSR62166) is run on an analyzer in the AU family, the hemolysis result is reported as “N”, “+”, “++”, “+++”, “++++”, or “+++++”. Thesecategories are intended to be concordant with the traditional visual hemolysis categories, and correspond approximately with 0 - 50 mg / dL, 50 - 100 mg / dL, 100 - 200 mg / dL, 200 - 300 mg / dL, 300 - 500 mg / dL and > 500 mg / dL hemoglobin, respectively. A conservative total allowable error for potassium is 0.2 mmol / L, given by the Royal College of Pathologists of Australasia (RCPA). Using the most extreme value of c from the study, Ac = 0.0883. This gives an upper limit of H of 2.26. This corresponds approximately to 500 mg / dL hemoglobin, which is very severe hemolysis, corresponding with an AU flag on the border between ++++ and +++++. The AU currently flags potassium at + or higher. In one study, 7.41% of the samples were flagged at + or higher. By contrast, only 0.16% of the samples were ++++ or higher, and only 0.03% were +++++.

[0144] The mean correction factor can be used to estimate the level of H at which the difference between the corrected and uncorrected results exceed the allowable error. This is given by W = - = 0.26, which corresponds to about 60 mg / dL, slightly above the lower limit for flagging +. Thus, without hemolysis correction, samples flagged as + usually have clinically inaccurate results. However, with hemolysis correction, samples flagged as +, ++, +++, and most ++++ still give acceptably accurate results, but +++++ would still be flagged as inaccurate. Thus, even in the presence of correction-factor uncertainty, hemolysis causes clinically unacceptable interference much less often with hemolysis corrected results (e.g., 0.16%) than with uncorrected results (e.g., 7.41%).

[0145] It is also helpful to examine the effects of applying hemolysis correction on the data. Correction was applied using the above equation, where c is set to 0.769, the mean correction factor. FIG. 9 shows uncorrected potassium results as circles and the corrected results as “x” symbols. The goal of hemolysis correction is to estimate the pre-hemolysis potassium result. This is represented by the un-spiked serum pool, shown by the dashed line.

[0146] The level of hemolysis, approximately 900 mg / dL, is more severe than would be expected to be encountered in a clinical setting. Even so, Table 1 shows that the corrected resultsare far closer to the pre-hemolysis value than the uncorrected results. Of the 80 corrected results, the largest deviation was -0.41 mmol / L (Rep 2 of Sample 1 ), and 90% of the results were within ±0.2 mmol / L. The mean deviation was a negligible -0.02 mmol / L. This compares very favorably with the performance of the uncorrected results, which had minimum, mean and maximum deviations of 2.56, 3.09 and 3.77 mmol / L.

[0147] Table 1. Performance of Uncorrected and Corrected Potassium Results1RMS refers to “Root Mean Squared”

[0148] Finally, it must be noted that some (e.g., about 2% of) patients have hemolytic disease. See, e.g., Hemolyzed Specimens: Major Challenge for Identifying and Rejecting Specimens in Clinical Laboratories, Oman. Med. J. 2019 Mar; 34(2): 94-98. In such cases, the clinician must use their judgment on whether H is due mainly to in vitro or in vivo hemolysis, making the corrected or uncorrected results applicable, respectively. For this reason, it is advisable that both the uncorrected and corrected results be available.

[0149] When used herein, the terms “preferred” and “preferably” refer to embodiments of the disclosure that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the disclosure.

[0150] The term “comprises”, “includes”, “has” and similar variations thereof do not have a limiting meaning where these terms appear in the description and claims. Such terms will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. In contrast, the term “consisting of” means including, and limited to, whatever follows the phrase “consisting of”. Thus, the phrase “consisting of” indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of” is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements.

[0151] Unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one.

[0152] As used herein, the term “or” is generally employed in its usual sense including “and / or” unless the content clearly dictates otherwise.

[0153] The term “and / or” means one or all of the listed elements or a combination of any two or more of the listed elements.

[0154] As used herein, the recitations of numerical ranges by endpoints include all numbers subsumed within that range (for example, 1 to 5 includes 1 , 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.). Further, reference within the disclosure of the phrase, “up to” a stated number (for example, up to 50) includes the number (for example, 50).

[0155] When used herein, the terms “in the range” or “within a range” (and similar phrases) with reference to numerical values includes the endpoints of the stated numerical range.

[0156] For any method disclosed herein that includes discrete steps, the steps may be conducted in any feasible order, and if appropriate and operationally possible, any combination of two or more steps may be conducted simultaneously.

[0157] All headings are for the convenience of the reader and should not be used to limit the meaning of the text that follows the heading, unless so specified. Further, all patent and nonpatent references that are referenced herein are incorporated by reference herein in their entirety.

[0158] Reference throughout this specification to “one embodiment,” “an embodiment,” “certain embodiments,” or “some embodiments,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout this specification are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments.

[0159] Unless otherwise indicated, all numbers that reflect quantity of components, a measured value, molecular weights, and so forth as used in the specification and claims are to be understood as being inclusive of variation in the measured quantity as would be expected by the skilled artisan making the measurement and exercising a level of care commensurate with the objective of the measurement and the precision of the associated measuring equipment. Accordingly, unless otherwise indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the disclosure. At the very least each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. In some instances, the term “about” may be used before a numerical designation, e.g., pH, temperature, amount, or concentration, which indicates an approximation which may vary by amounts that do not have any significant effect on the resulting structure, stability, activity, or result-effective variable or parameter.

[0160] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. One of skill will appreciate that all numerical values inherently contain a range necessarily resulting from the standard deviation found in their respective testing measurements.

[0161] While the present disclosure has described certain embodiments, various changes may be made and equivalents may be substituted without departing from the scope of the present invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the present disclosure without departing from the scope of the appended claims. Therefore, the present disclosure is not limited to the particular embodiment disclosed, but includes all embodiments falling within the scope of the appended claims.

[0162] In at least one aspect, the disclosure provides a method of analyzing a blood sample to determine a potassium concentration that is corrected for interference comprising at least the steps of: analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration that is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of nonhemoglobin sources of variation, wherein determining the polychrome OD comprises the stepsof: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with nonhemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0163] In at least one aspect, the disclosure provides a method of analyzing a blood sample to determine a potassium concentration that is corrected for interference comprising: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; and applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assayis a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of nonhemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with nonhemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0164] In at least one aspect, the disclosure provides a method of determining a potassium imbalance comprising: analyzing a blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference;analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; andapplying the data from the second assay to the data from the first assay to determine a corrected potassium concentration that is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interferencemagnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0165] In at least one aspect, the disclosure provides a method of determining a potassium imbalance comprising: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix.In some embodiments, the non-hemoglobin sources of variation includes variation caused byinstrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0166] In at least one aspect, the disclosure provides a method of analyzing a blood sample including an interference indicator to determine a potassium concentration that is corrected for interference comprising: analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration in the blood sample that is not corrected for interference; receiving, at a processor, data corresponding to the uncorrected potassium concentration; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of the interference indicator; and receiving, at the processor, data corresponding to the concentration of the interference indicator; determining, by the processor, a corrected potassium concentration that is corrected for interference, wherein the corrected potassium concentration is determined by applying the data from the second assay to the data from the first assay. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficientvector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0167] In at least one aspect, the disclosure provides a method of analyzing a blood sample including an interference indicator to determine a potassium concentration that is corrected for interference comprising: analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; receiving, at a processor, data corresponding to the preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of the interference indicator in the blood sample; receiving, at the processor, data corresponding to the concentration of the interference indicator; determining, by the processor, a final potassium concentration that is corrected for interference, wherein the final potassium concentration is determined by applying the data from the second assay to the data from the first assay. In someembodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of nonhemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with nonhemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0168] In at least one aspect, the disclosure provides a method for improving the determination of potassium concentration in a biological sample comprising: analyzing the biological sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the biological sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determiningthe uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0169] In at least one aspect, the disclosure provides a method for improving the determination of potassium concentration in a biological sample comprising: analyzing the biological sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the biological sample; analyzing the biological sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of nonhemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with nonhemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities(ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

[0170] In at least one aspect, the disclosure provides a method of indicating whether a patient has an electrolyte imbalance, comprising: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; and reporting the corrected electrolyte concentration. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises thedetermination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprises quantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration. In some embodiments, the method further comprises, after reporting the corrected electrolyte concentration, indicating whether the corrected electrolyte concentration is above or below an electrolyte imbalance threshold. In some embodiments, the reporting further comprises reporting the uncorrected electrolyte concentration. In some embodiments, the reporting comprises reporting the comparative values between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyteconcentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration.

[0171] In at least one aspect, the disclosure provides a method of indicating whether a patient has an electrolyte imbalance, comprising: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary electrolyte concentration in the biological sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the biological sample; applying the data from the second assay to the data from the first assay to determine a final electrolyte concentration that is corrected for interference; and reporting the final electrolyte concentration. In some embodiments, wherein the first assay is an ion selective electrode (ISE) assay. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to thehemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the nonhemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprisesquantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration. In some embodiments, the method further comprises, after reporting the corrected electrolyte concentration, indicating whether the corrected electrolyte concentration is above or below an electrolyte imbalance threshold. In some embodiments, the reporting further comprises reporting the uncorrected electrolyte concentration. In some embodiments, the reporting comprises reporting the comparative values between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration.

[0172] In at least one aspect, the disclosure provides a method for determining potassium concentration in a blood sample, the improvement comprising determining a corrected potassium concentration by attenuating interference. In some embodiments, the improvement further comprises applying a concentration of an interference indicator to an uncorrected potassium concentration that is not corrected for interference to remove interference. In some embodiments,the interference indicator is hemoglobin. In some embodiments, the improvement further comprises determining the uncorrected potassium concentration using an ion selective electrode(ISE) assay. In some embodiments, the improvement further comprises determining the hemoglobin concentration using a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying comprising the steps of: multiplying the concentration of the interference indicator by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration.

[0173] In at least one aspect, the disclosure provides a method of correcting for interference in an assay comprising: analyzing a sample with a first assay, wherein the first assay determines an uncorrected target analyte concentration that is not corrected for interference; analyzing the sample with a second assay, wherein the second assay determines the concentration of an interference indicator; and applying the data from the second assay to the data from the first assay to determine a corrected target analyte concentration that is corrected for interference. In some embodiments, the target analyte is one or more electrolytes. In some embodiments, the target analyte is potassium. In some embodiments, the target analyte is an enzyme. In some embodiments, the target analyte is lactate dehydrogenase (LDH). In some embodiments, the interference indicator is hemoglobin. In some embodiments, the concentration of hemoglobin is determined using a lipemia, icterus, and hemolysis (LIH) assay.

[0174] In at least one aspect, the disclosure provides a method for correcting for interference in an assay comprising : analyzing a sample with a first assay, wherein the first assay is performed to determine a preliminary target analyte concentration in the sample; analyzing the sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the sample; and applying the data from the second assay to the data from the first assay to determine a final target analyte concentration that is corrected for interference. In some embodiments, the target analyte is one or more electrolytes. In some embodiments, the target analyte is potassium. In some embodiments, the target analyte is an enzyme. In some embodiments, the target analyte is lactate dehydrogenase (LDH). In some embodiments, the interference indicator is hemoglobin. In some embodiments, the concentration of hemoglobin is determined using a lipemia, icterus, and hemolysis (LIH) assay.

[0175] In at least one aspect, the disclosure provides a method of treating a patient suspected of having an electrolyte imbalance, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of oneor more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes. In some embodiments, the method further comprises, wherein the method further comprises, after reporting corrected concentration of the one or more electrolytes, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining the treatment plan for the patient, treating the patient for the electrolyte imbalance with the treatment plan. In some embodiments, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, theproducing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine the corrected electrolyte concentration. In some embodiments, the reporting further comprises reporting the uncorrected electrolyte concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof. In some embodiments, the treatment plan utilized is used to treat hyperkalemia. In some embodiments, the treatment plan utilized is used to treat hypokalemia that is masked by interference.

[0176] In at least one aspect, the disclosure provides a method of treating a patient suspected of having an electrolyte imbalance, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes; analyzing the blood sample with a second assay,wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes that is corrected for interference; reporting the final concentration of the one or more electrolytes. In some embodiments, the method further comprises, wherein the method further comprises, after reporting corrected concentration of the one or more electrolytes, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining the treatment plan for the patient, treating the patient for the electrolyte imbalance with the treatment plan. In some embodiments, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine the corrected electrolyte concentration. In some embodiments, the reporting further comprises reporting the uncorrected electrolyte concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected electrolyte concentration and the corrected electrolyte concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof. In some embodiments, the treatment plan utilized is used to treat hyperkalemia. In some embodiments, the treatment plan utilized is used to treat hypokalemia that is masked by interference.

[0177] In at least one aspect, the disclosure provides a method of treating a patient suspected of having an electrolyte imbalance, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of one or more electrolytes that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of aninterference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the corrected electrolyte concentration is greater than the reporting threshold, reporting both the corrected electrolyte concentration and the uncorrected electrolyte concentration. In some embodiments, the method further comprises, after reporting the concentration of the one or more electrolytes, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the electrolyte imbalance with the treatment plan. In some embodiments, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator ishemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or morewavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the nonhemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprisesquantitatively determining the uncorrected potassium concentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0178] In at least one aspect, the disclosure provides a method of treating a patient suspected of having an electrolyte imbalance, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes, wherein the corrected electrolyte concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the differenceof the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the preliminary electrolyte concentration. In some embodiments, the method further comprises, after reporting the concentration of the one or more electrolytes, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the electrolyte imbalance with the treatment plan. In some embodiments, the one or more electrolytes comprises potassium. In some embodiments, the interference indicator ishemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the nonhemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the method further comprisesquantitatively determining the uncorrected potassiumconcentration using the ISE assay. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected electrolyte concentration to determine a corrected electrolyte concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0179] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hyperkalemia, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; appyling the data from the first assay to the data from the second assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected for interference; reporting the corrected potassium concentration. In some embodiments, the method further comprises, after reporting the corrected potassium concentration, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for hyperkalemia with the treatmentplan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (OD) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychromeoptical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the nonhemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium concentration and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0180] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hyperkalemia, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference; reporting the final potassium concentration. In some embodiments, the method further comprises, after reporting the corrected potassium concentration, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for hyperkalemia with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (OD) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobinconcentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium concentration and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0181] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected potassium concentration that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected potassium concentration, wherein the corrected potassium concentration is corrected forinterference; reporting the corrected potassium concentration. In some embodiments, the method further comprises, after reporting the corrected potassium concentration, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for hyperkalemia with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (OD) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, whereinthe comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium concentration and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0182] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration in the blood sample; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration that is corrected for interference; reporting the final potassium concentration. In some embodiments, the method further comprises, after reporting the corrected potassium concentration, determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for hyperkalemia with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitativedetermination comprises measuring optical densities (OD) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the nonhemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a corrected potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by a correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium concentration and the uncorrected potassium concentration against the reporting threshold; and if the difference of the correctedpotassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration.

[0183] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hyperkalemia, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of potassium that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the potassium, wherein the corrected potassium concentration is corrected for interference; reporting an electrolyte data set, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration. In some embodiments, the method further comprises, after reporting an electrolyte concentration, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the hypokalemia masked by interference with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes theeffects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a correction potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0184] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hyperkalemia, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the bloodsample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration, wherein the final potassium concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the preliminary electrolyte concentration. In some embodiments, the method further comprises, after reporting an electrolyte concentration, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the hypokalemia masked by interference with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is afunction of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a correction potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0185] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay determines an uncorrected concentration of potassium that is not corrected for interference; analyzing the blood sample with a second assay, wherein the second assay determines the concentration of an interference indicator; applying the data from the second assay to the data from the first assay to determine a corrected concentration of the potassium, wherein the corrected potassium concentration iscorrected for interference; reporting an electrolyte data set, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected potassium and the uncorrected potassium concentration against the reporting threshold; and if the difference of the corrected potassium concentration is greater than the reporting threshold, reporting both the corrected potassium concentration and the uncorrected potassium concentration. In some embodiments, the method further comprises, after reporting an electrolyte concentration, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the hypokalemia masked by interference with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix.In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a correction potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting the uncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0186] In at least one aspect, the disclosure provides a method of treating a patient suspected of having hypokalemia masked by interference, wherein the patient is suspected of having a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary potassium concentration; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample; applying the data from the second assay to the data from the first assay to determine a final potassium concentration, wherein the final potassium concentration is corrected for interference; reporting the corrected concentration of the one or more electrolytes, wherein the reporting comprises the steps of: establishing a reporting threshold; comparing the difference of the final electrolyte concentration and the preliminary electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the preliminaryelectrolyte concentration. In some embodiments, the method further comprises, after reporting an electrolyte concentration, determining whether the patient has a hemolytic disorder and determining a treatment plan for the patient. In some embodiments, the method further comprises, after determining a treatment plan for the patient, treating the patient for the hypokalemia masked by interference with the treatment plan. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay is an ion selective electrode (ISE) assay. In some embodiments, the second assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities (ODs) at two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor to determine a correction potassium concentration. In some embodiments, the reporting further comprises reporting the uncorrected potassium concentration. In some embodiments, the reporting comprises reporting theuncorrected electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected potassium concentration and the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine a corrected potassium concentration. In some embodiments, the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.

[0187] In at least one aspect, the disclosure provides a method for determining the necessity of a secondary blood draw, wherein the method comprises: collecting a first blood sample with a first blood draw; analyzing the first blood sample with an assay to determine the concentration of hemoglobin; establishing a re-draw threshold; comparing the concentration of hemoglobin to the re-draw threshold; and if the concentration of hemoglobin is greater than the re-draw threshold, collecting a second blood sample with a secondary blood draw. In some embodiments, establishing the re-draw threshold further comprises the steps of: (i) establishing a correction factor uncertainty; (ii) establishing an assay target error threshold; and (iii) calculating the re-draw threshold based on the correction factor uncertainty and the assay target error threshold. In some embodiments, the assay is a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the method further comprises quantitatively determining the concentration of hemoglobin using the LIH assay, wherein the quantitative determination comprises measuring optical densities at at least two or more wavelengths. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs atthe two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation.

[0188] In at least one aspect, the disclosure provides a clinical chemistry instrument comprising: a first assay system configured to determine an uncorrected potassium concentration that is not corrected for interference, the first assay system comprising a first sensor; and a second assay system for determining the concentration of an interference indicator, the second assay system comprising a second sensor; and a processor configured to receive data from the first and second sensors and determine a corrected potassium concentration that is corrected for interference. In some embodiments, the corrected potassium concentration is corrected for interference without the need for further assay processing beyond the clinical chemistry instrument, itself. In some embodiments, the interference indicator is hemoglobin. In some embodiments, the first assay system is configured to run an ion selective electrode (ISE) assay. In some embodiments, the second assay system is configured to run a lipemia, icterus, and hemolysis (LIH) assay. In some embodiments, the second assay system is configured to quantitatively determine the interference indicator concentration, wherein the quantitative determination comprises measuring, using the first instrument, optical densities at two or more wavelengths. In some embodiments, the processor is configured to apply the data received from the second sensor to the data received from the first sensor to determine the corrected potassium concentration. In some embodiments, the processor is configured to apply the data received from the second sensor to the data received from the first sensor to determine the final potassiumconcentration. In some embodiments, the quantitative determination further comprises the determination of polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of: (i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths; (ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and (iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration. In some embodiments, the non-hemoglobin sources of variation comprise lipemia and bilirubin. In some embodiments, the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix. In some embodiments, the non-hemoglobin sources of variation includes variation caused by instrumentation. In some embodiments, the applying the data comprises applying a correction factor. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration. In some embodiments, the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the preliminary potassium concentration to determine the final potassium concentration.

Claims

WHAT IS CLAIMED IS:1 . A method for determining potassium concentration in a blood sample, the improvement comprising determining a corrected potassium concentration by attenuating interference.

2. The method of claim 1 , wherein the improvement further comprises applying a concentration of an interference indicator to an uncorrected potassium concentration that is not corrected for interference to remove interference.

3. The method of claim 2, wherein the interference indicator is hemoglobin.

4. The method of any of claims 2-3, wherein the improvement further comprises determining the uncorrected potassium concentration using an ion selective electrode (ISE) assay.

5. The method of any of claims 3-4, wherein the improvement further comprises determining the hemoglobin concentration using a lipemia, icterus, and hemolysis (LIH) assay.

6. The method of claim 5, wherein the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths.

7. The method of claim 6, wherein the quantitative determination further comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of:(i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths;(ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and(iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix,wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration.

8. The method of claim 7, wherein the non-hemoglobin sources of variation comprise lipemia and bilirubin.

9. The method of any of claims 7-8, wherein the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix.

10. The method of any of claims 7-9, wherein the non-hemoglobin sources of variation include variation caused by instrumentation.11 . The method of any of claims 2-10, wherein the applying comprises applying a correction factor to determine a corrected potassium concentration.

12. The method of claim 1 1 , wherein the applying comprising the steps of: multiplying the concentration of the interference indicator by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

13. A method of treating a patient suspected of having an electrolyte imbalance, wherein the patient does not have a hemolytic disorder, comprising the steps of: collecting at least one blood sample from the patient; analyzing the blood sample with a first assay, wherein the first assay is performed to determine a preliminary concentration of one or more electrolytes; analyzing the blood sample with a second assay, wherein the second assay is performed to determine a concentration of an interference indicator in the blood sample;applying the data from the second assay to the data from the first assay to determine a final concentration of the one or more electrolytes that is corrected for interference; reporting the final concentration of the one or more electrolytes.

14. The method of claim 13, wherein the method further comprises, after reporting corrected concentration of the one or more electrolytes, determining a treatment plan for the patient.

15. The method of claim 14, wherein the method further comprises, after determining the treatment plan for the patient, treating the patient for the electrolyte imbalance with the treatment plan.

16. The method of any of claims 13-15, wherein the one or more electrolytes comprises potassium.

17. The method of any of claims 13-16, wherein the interference indicator is hemoglobin.

18. The method of claim 13-17, wherein the first assay is an ion selective electrode (ISE) assay.

19. The method of any of claims 13-18, wherein the second assay is a lipemia, icterus, and hemolysis (LIH) assay.

20. The method of claim 19, wherein the method further comprises quantitatively determining the hemoglobin concentration using the LIH assay, wherein the quantitative determination comprises measuring optical densities at two or more wavelengths.21 . The method of claim 20, wherein the quantitative determination further comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of:(i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths;(ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and(iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration.

22. The method of claim 21 , wherein the non-hemoglobin sources of variation comprise lipemia and bilirubin.

23. The method of any of claims 21 -22, wherein the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix.

24. The method of any of claims 21 -23, wherein the non-hemoglobin sources of variation include variation caused by instrumentation.

25. The method of any of claims 13-24, wherein the applying the data comprises applying a correction factor to determine the final concentration of the one or more electrolytes.

26. The method of claim 13-25, wherein the reporting further comprises reporting the preliminary concentration of the one or more electrolytes.

27. The method of claim 26, wherein the reporting comprises reporting the preliminary electrolyte concentration and a comment, wherein the comment reports the difference between the uncorrected electrolyte concentration and the final concentration of the one or more electrolytes.

28. The method of claim 25, wherein the applying the data comprises the steps of:multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the preliminary concentration of the one or more electrolytes to determine the final concentration of one or more electrolytes.

29. The method of any of claims 13-28, wherein the method further comprises the steps of: establishing a reporting threshold; comparing the difference of the corrected electrolyte concentration and the uncorrected electrolyte concentration against the reporting threshold; and if the difference of the final electrolyte concentration is greater than the reporting threshold, reporting both the final electrolyte concentration and the uncorrected electrolyte concentration.

30. The method of any of claims 14-29, wherein the treatment plan utilizes at least one or more of a diuretic, a blood pressure medication, a potassium binder, insulin, a sympathomimetic medication, or calcium gluconate, or combinations thereof.31 . The method of any of claims 15-30, wherein the treatment plan utilized is used to treat hyperkalemia.

32. The method of any of claims 15-31 , wherein the treatment plan utilized is used to treat hypokalemia that is masked by interference.

33. A clinical chemistry instrument comprising: a first assay system configured to determine a preliminary potassium concentration, the first assay system comprising a first sensor; and a second assay system for determining the concentration of an interference indicator, the second assay system comprising a second sensor; anda processor configured to receive data from the first and second sensors and determine a final potassium concentration that is corrected for interference.

34. The clinical chemistry instrument of claim 33, wherein the final potassium concentration is corrected for interference without the need for further assay processing beyond the clinical chemistry instrument, itself.

35. The clinical chemistry instrument of any of claims 33-34, wherein the interference indicator is hemoglobin.

36. The clinical chemistry instrument of any of claims 33-35, wherein the first assay system is configured to run an ion selective electrode (ISE) assay.

37. The clinical chemistry instrument of any of claims 33-35, wherein the second assay system is configured to run a lipemia, icterus, and hemolysis (LIH) assay.

38. The clinical chemistry instrument of claim 37, wherein the second assay system is configured to quantitatively determine the interference indicator concentration, wherein the quantitative determination comprises measuring, using the first assay system, optical densities at two or more wavelengths.

39. The clinical chemistry instrument of any of claims 33-38, wherein the processor is configured to apply the data received from the second sensor to the data received from the first sensor to determine the final potassium concentration.

40. The clinical chemistry instrument of any of claims 33-39, wherein the quantitative determination further comprises the determination of a polychrome optical density (OD) of the biological sample that minimizes the effects of non-hemoglobin sources of variation, wherein determining the polychrome OD comprises the steps of:(i) producing an extinction coefficient vector that characterizes the OD spectrum of hemoglobin at the two or more wavelengths;(ii) producing a covariance matrix associated with non-hemoglobin sources of variation in the measured ODs at the two or more wavelengths; and(iii) producing a polychrome vector that is a function of the extinction coefficient vector and the covariance matrix, wherein the polychrome vector is applied to the measured optical densities (ODs) at the two or more wavelengths to provide the polychrome OD, and wherein the polychrome OD is proportional to the hemoglobin concentration.41 . The clinical chemistry instrument of claim 40, wherein the non-hemoglobin sources of variation comprise lipemia and bilirubin.

42. The clinical chemistry instrument of any of claims 40-41 , wherein the producing a covariance matrix comprises adding uncorrelated variation to the covariance matrix.

43. The clinical chemistry instrument of any of claims 40-42, wherein the non-hemoglobin sources of variation include variation caused by instrumentation.

44. The clinical chemistry instrument of any of claims 38-44, wherein the applying the data comprises applying a correction factor.

45. The clinical chemistry instrument of claim 44, wherein the applying the data comprises the steps of: multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the uncorrected potassium concentration to determine the corrected potassium concentration.

46. The clinical chemistry instrument of claim 39, wherein the applying the data comprises the steps of:multiplying the interference indicator concentration by the correction factor to determine an interference magnitude; and subtracting the interference magnitude from the preliminary potassium concentration to determine the final potassium concentration.

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