Enzymatic cleaning agents for automated clinical analyzers and methods of use thereof

Abstract

A method of cleaning an electrode subsystem is provided. In some embodiments, methods of cleaning an electrode subsystem involve providing a cleaning composition comprising: (i) one or more cleaning enzymes; (ii) one or more pH adjusting agents; (iii) one or more matrix components; (iv) one or more buffering components; and (v) one or more preservatives, wherein the cleaning composition has a pH range of from about 7.2 to about 7.4. The method further involves flowing a cleaning composition through an electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 486,727, filed on February 24, 2023, which is incorporated herein by reference in its entirety. Field of the Invention

[0003] The present disclosure relates to enzymatic cleaners for automated clinical analyzers and methods of cleaning components of automated clinical analyzers with enzymatic cleaning solutions. Background of the Invention

[0005] Immunoassays and chemistry analyzers are used to calculate the concentration of certain substances in samples of serum, plasma, urine, and / or other body fluids. Substances that can be analyzed by these instruments include certain metabolites, electrolytes, proteins, and / or drugs. Some immunoassays and chemistry analyzers can also be used for in vitro diagnostic testing.

[0006] Chemistry analyzers (also referred to herein as clinical analyzers or A primary goal of chemical and biological sensors (e.g., ion-selective electrodes / sensors) within a flowmeter (e.g., an analyzer) is to rapidly process large volumes of serum, plasma, and urine samples. As samples are processed over time, buildup (proteins, lipids, etc.) can form in the system, including manifolds, tubing, and subassemblies (e.g., including ion-selective sensor systems). The coating of the buildup changes the interface between the sample and the system, affecting the ability to detect air / liquids. Excessive buildup also leads to sample carryover, resulting in unstable signals, causing detection errors, and worsening calibration.

[0007] Some immunoassay and clinical chemistry analyzers currently use strong cleaning agents, such as bleach, to clean the analyzer. Some aspects of the analyzer may have performance that is negatively impacted by the use of strong cleaning agents, such as ion selective electrodes (ISEs). Therefore, the use of cleaning agents that are not detrimental to the performance and life of the electrodes is desirable.

[0008] The present disclosure is directed to overcoming these and other deficiencies in the art. SUMMARY OF THE INVENTION

[0010] One aspect of the present disclosure relates to a method for cleaning an electrode subsystem. This method involves providing a cleaning composition comprising: (i) one or more cleaning enzymes; (ii) one or more pH adjusting agents; (iii) one or more matrix components; (iv) one or more buffer components; and (v) one or more preservatives, wherein the cleaning composition has a pH range of about 7.2 to about 7.4. This method further involves flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

[0011] Another aspect of the present disclosure relates to a method for cleaning an electrode subsystem. This method involves providing a cleaning composition comprising: (i) a lipase; (ii) an amylase; (iii) one or more pH adjusters selected from hydrochloric acid and sodium hydroxide; (iv) one or more matrix components selected from bovine serum albumin, zinc chloride, and magnesium chloride hexahydrate; (v) a HEPES buffer; and (vi) one or more preservatives selected from streptomycin sulfate, gentamicin sulfate, amphotericin B, and clotrimazole; wherein the cleaning composition has a pH range of about 7.2 to about 7.4. This method further involves flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figures 1A-1D is shown using pancreatic enzymes from porcine pancreas ( Figure 1A ), trypsin and lipase ( Figure 1B ), lipase ( Figure 1C ) and amylase ( Figure 1D ) and a graph of the calibration stability of the standard A and B air readings on the sensor processed.

[0014] Figures 2A-2D is a graph showing the calibration stability of the K slope and standard A and B air readings on the following sensor: IMT Cleaner treatment once for a total of 4 treatments for the tested medium volume sensor ( Figure 2A ), start using every other week from the 28th day IMT Cleaner treats a medium volume sensor once for a total of 3 treatments ( Figure 2B ), roughly weekly IMT cleaning agent treatment once a total of 5 treatments of the test of large capacity sensor ( Figure 2C ), and every 5000 samples

[0015] IMT cleaning agent treatment once tested the largest capacity sensor ( Figure 2D ).

[0016] Figure 3 The results of 10 and 50 replicates are shown. Graph of the calibration stability of the Na, K, and Cl sensors of one sensor cartridge before and after IMT cleaner treatment.

[0017] Figure 4 The 50 replicates are shown Graph of the calibration stability of the Na, K, and Cl sensors of three sensor cartridges before and after IMT detergent treatment.

[0018] Figure 5 It is shown Graph of amylase stability in IMT detergents.

[0019] Figures 6A-6B is shown for lipase ( Figure 6A ) and amylase ( Figure 6B ) is a regression plot of the stability of .

[0020] Figure 7 is a schematic diagram showing the integrated multi-sensor technology (IMT) manifold assembly.

[0021] Figures 8A-8D is a flow chart illustrating a method of cleaning a fluid system according to the present disclosure. Figure 8A and 8C A method of cleaning a fluid system is shown that involves combining a concentrated enzymatic cleaning composition with a diluent, flowing the diluted enzymatic cleaning composition through a fluid conduit, a cartridge containing one or more ion-selective sensors, and through an outlet port. Figure 8B and 8D A method of cleaning a fluid system is shown that involves flowing an enzymatic cleaning composition through a fluid conduit, a cartridge containing one or more ion-selective sensors, and through an outlet port. Detailed Description of the Invention

[0023] definition

[0024] Unless otherwise stated, the definitions and embodiments described in this and other sections are intended to apply to all embodiments and aspects of the disclosure described herein to which they are suitable as those skilled in the art would understand.

[0025] Unless the context clearly dictates otherwise, the singular forms "a," "an," and "the" include plural referents. Thus, for example, reference to "a method" includes one or more methods and / or steps of the type described herein and / or that will become apparent to one of ordinary skill in the art upon reading this disclosure. In another example, reference to "a compound" includes both a single compound and a plurality of different compounds.

[0026] The term "about" or "approximately" includes within a statistically meaningful range of a value. Such a range can be within an order of magnitude, for example, within 50%, or within 20%, or within 10%, or within 5% (or any amount or range within 5-50%) of a given value or range. The permissible variations encompassed by the term "about" or "approximately" may depend on the context.

[0027] As used herein, the term "and / or" means that the listed features are present or used individually or in combination. In practice, the term means that "at least one" or "one or more" of the listed features are used or present.

[0028] As will be understood by one of ordinary skill in the art, for any and all purposes, such as with respect to providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof, as well as any values ​​within the range. Any listed range can be easily identified as fully describing and allowing the same range to be decomposed into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be easily decomposed into a lower third, a middle third, and an upper third, etc. As will be understood by one of ordinary skill in the art, all language such as "at most," "at least," etc. includes the numerals recited and refers to a range that can subsequently be decomposed into subranges or specific values ​​thereof as discussed above. Finally, as will be understood by one of ordinary skill in the art, and as discussed above, ranges include each individual value.

[0029] In understanding the scope of the present disclosure, as used herein, the term "comprising" and its derivatives are expected to be open terms, which specify the existence of stated features, elements, components, groups, integers and / or steps, but do not exclude the existence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words with similar meanings, such as the terms "including", "involving", "having" and their derivatives. As used herein, the term "consisting of ... " and its derivatives are expected to be closed terms, which specify the existence of stated features, elements, components, groups, integers and / or steps, but exclude the existence of other unstated features, elements, components, groups, integers and / or steps. As used herein, the term "substantially consisting of ... " is expected to specify the existence of stated features, elements, components, groups, integers and / or steps, and the existence of those features, elements, components, groups, integers and / or steps that do not substantially affect the basic and novel characteristics of features, elements, components, groups, integers and / or steps. In embodiments or claims where the term comprising (or similar terms) is used as a transitional phrase, such embodiments are also contemplated in which the term "comprising" is replaced with the term "consisting of" or "consisting essentially of. The methods, kits, systems, and / or compositions of the present disclosure may comprise, consist essentially of, or consist of the disclosed components.

[0030] In some embodiments comprising an "additional" or "second" component, as used herein, the second component is different from the other components or the first component. A "third" component is different from the other components, the first component, and the second component, and further listed or "additional" components are similarly different.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although some embodiments of methods and materials are now described, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in conjunction with which they are cited.

[0032] Before further describing the present disclosure, it should be understood that this disclosure is not limited to the particular embodiments described, as such embodiments may, of course, vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting, as the scope of the present disclosure will be limited only by the appended claims.

[0033] Methods for cleaning the electrode subsystem

[0034] One aspect of the present disclosure relates to a method for cleaning an electrode subsystem. This method involves (a) providing a cleaning composition comprising: (i) one or more cleaning enzymes; (ii) one or more pH adjusting agents; (iii) one or more matrix components; (iv) one or more buffer components; and (v) one or more preservatives, wherein the cleaning composition has a pH range of about 7.2 to about 7.4. This method further involves (b) causing the cleaning composition to flow through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

[0035] In some embodiments, the method further involves (c) flowing a rinse solution through the electrode subsystem, wherein flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.

[0036] Suitable wash solutions that may be used include water (eg, dd water), buffer solutions (eg, PBS (phosphate buffered saline), HEPES free acid (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid), HEPES

[0014] Examples of the present invention include sodium salt of 2-hydroxyethylpiperazine-N'-(2-ethanesulfonic acid) sodium salt), phosphate salts, TRIS (2-amino-2-(hydroxymethyl)-1,3-propanediol), TES (2-[(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)amino]ethanesulfonic acid), MOPS (3-(N-morpholino)propanesulfonic acid), PIPES (1,4-piperazinediethanesulfonic acid), TAPS ([tris(hydroxymethyl)methylamino]propanesulfonic acid), Bicine (N,N-bis(2-hydroxyethyl)glycine), Tricine (N-[tris(hydroxymethyl)methyl]glycine), CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid), cacodylate (dimepreserthylarsenic acid), and MES (2-(N-morpholino)ethanesulfonic acid), preservative solutions (e.g., antimicrobial or antifungal compositions), and combinations thereof.

[0037] In some embodiments, the cleaning compositions are substantially free of sodium hypochlorite.

[0038] According to the present disclosure, cleaning enzymes that can be used in cleaning compositions include, but are not limited to, amylases, lipases, trypsins, pepsins, and combinations thereof. In some embodiments, cleaning enzymes that can be used in cleaning compositions include, but are not limited to, amylases, lipases, and combinations thereof.

[0039] The term "amylase" refers to an enzyme that catalyzes the hydrolysis of starch. Suitable exemplary amylases include, but are not limited to, alpha-amylase, beta-amylase, amyloglucosidase (glucoamylase), fungal amylase, and pullulanase.

[0040] The term "lipase" refers to an enzyme that catalyzes the hydrolysis of triglycerides. Suitable exemplary lipases include, but are not limited to, pancreatic lipase, microbial lipase, and plant lipase.

[0041] The terms "inlet port" and "entry port" are used interchangeably and refer to a point of entry into a system, such as a fluid system.

[0042] According to the present disclosure, one or more pH adjusters that can be used in the cleaning composition include, but are not limited to, hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, phosphoric acid, tetramethylammonium hydroxide, CAPSO free acid (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid), citric acid, acetic acid, CHES (2-(cyclohexylamino)ethanesulfonic acid), borates, and combinations thereof.

[0043] According to the present disclosure, one or more matrix components that may be used in the cleaning composition include, but are not limited to, bovine serum albumin, human serum albumin, zinc chloride, and magnesium chloride hexahydrate.

[0044] According to the present disclosure, one or more buffer components that can be used in the cleaning composition include, but are not limited to, HEPES free acid (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid), HEPES Na salt (2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) sodium salt), phosphates, TRIS (2-amino-2-(hydroxymethyl)-1,3-propanediol), TES (2-[(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)amino]ethanesulfonic acid), MOPS (3-(N-morpholino)propanesulfonic acid), PIPES (1,4-piperazine diethanesulfonic acid), TAPS ([tris(hydroxymethyl)methylamino]propanesulfonic acid), Bicine (N,N-bis(2-hydroxyethyl)glycine), Tricine (N-[tris(hydroxymethyl)methyl]glycine), CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid), dimethylarsenic acid (dimethylarsenic acid), acid)) and MES (2-(N-morpholino)ethanesulfonic acid)).

[0045] According to the present disclosure, one or more preservatives that may be used in the cleaning composition include, but are not limited to, streptomycin sulfate, gentamicin sulfate, amphotericin B, clotrimazole, chloramphenicol, ampicillin, neomycin sulfate, isothiazolinone, and sodium gallate.

[0046] According to the present disclosure, the cleaning compositions have a pH range of about 7.2 to about 7.4, about 7.21 to about 7.39, about 7.22 to about 7.38, about 7.23 to about 7.37, about 7.24 to about 7.36, about 7.25 to about 7.35, about 7.26 to about 7.34, about 7.27 to about 7.33, about 7.28 to about 7.32, about 7.29 to about 7.4, about 7.3 to about 7.4, about 7.31 to about 7.39, about 7.32 to about 7.39, about 7.33 to about 7.39, about 7.34 to about 7.39, or about 7.35 to about 7.39.

[0047] In some embodiments, the cleaning composition further comprises a diluent. Any suitable diluent can be used. For example, the diluent can be selected from water, a buffer, a saline-based solution, a preservative, a pH adjusting agent, and albumin.

[0048] In some embodiments, the method further comprises (d) calibrating the sensor.

[0049] Another aspect of the present disclosure relates to a method for cleaning an electrode subsystem. This method involves (a) providing a cleaning composition comprising: (i) a lipase; (ii) an amylase; (iii) one or more pH adjusters selected from hydrochloric acid and sodium hydroxide; (iv) one or more matrix components selected from bovine serum albumin, zinc chloride, and magnesium chloride hexahydrate; (v) a HEPES buffer; and (vi) one or more preservatives selected from streptomycin sulfate, gentamicin sulfate, amphotericin B, and clotrimazole; wherein the cleaning composition has a pH range of about 7.2 to about 7.4. This method further involves (b) flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

[0050] In some embodiments, the method further comprises (c) flowing a rinse solution through the electrode subsystem, wherein flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.Any of the rinse solutions mentioned above can be used.

[0051] In some embodiments, the cleaning composition further comprises a diluent. Any suitable diluent can be used. For example, the diluent can be selected from water, a buffer, a saline-based solution, a preservative, a pH adjusting agent, and albumin.

[0052] In some embodiments, the method further comprises (d) calibrating the sensor.

[0053] In some embodiments, the lipase is present in the cleaning composition in an amount of at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 1100 U / L, at least about 1200 U / L, at least about 1300 U / L, at least about 1400 U / L, at least about 1500 U / L, at least about 1600 U / L, at least about 1700 U / L, at least about 1800 U / L, at least about 1900 U / L, at least about 2000 U / L, at least about 2100 U / L, at least about 2200 U / L, at least about 2300 U / L, at least about 2400 U / L, at least about 2500 U / L, at least about 2600 U / L, at least about 2700 U / L, at least about 2800 U / L, at least about 2900 U / L, at least about 0 U / L, at least about 1800 U / L, at least about 1900 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, at least about 7000 U / L, at least about 8000 U / L, at least about 9000 U / L, at least about 10000 U / L, at least about 11000 U / L, at least about 12000 U / L, at least about 13000 U / L, at least about 14000 U / L, at least about 15000 U / L, or at least about 16000 U / L.

[0054] In some embodiments, the lipase is present in an amount within a range having a lower limit selected from the group consisting of: 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L, 2500 U / L, 2600 U / L, 2700 U / L, 2800 U / L, 2900 U / L, U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700 U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L, 8000U / L, 9000U / L, 10000U / L, 11000U / L, 12000U / L, 13000U / L, 14000U / L and 15000U / L,and an upper limit selected from the group consisting of 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L, 2500 U / L, 2600 U / L, 2700 U / L, 2800 U / L, 2900 U / L, 3000 U / L, 3100 U / L, 3200 U / L 00U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L , 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700 U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L, 8000U / L, 9000U / L, 1 0000U / L, 11000U / L, 12000U / L, 13000U / L, 14000U / L, 15000U / L and 16000U / L. ,

[0055] In some embodiments, the lipase is present in the cleaning composition in an amount of: about 100 U / L to about 16,000 U / L; about 100 U / L to about 15,000 U / L; about 100 U / L to about 14,000 U / L; about 100 U / L to about 13,000 U / L; about 100 U / L to about 12,000 U / L; about 100 U / L to about 11,000 U / L; about 100 U / L to about 10,000 U / L; about 100 U / L to about 9,000 U / L; about 100 U / L to about 8,000 U / L; about 100 U / L to about 7,000 U / L; about 100 U / L to about 6,000 U / L; about 100 U / L to about 5,000 U / L; about 100 U / L to about 1 about 4000U / L; about 100U / L to about 3000U / L; about 100U / L to about 2000U / L; about 100U / L to about 1900U / L; about 100U / L to about 1800U / L; about 100U / L to about 1700U / L; about 100U / L to about 1600U / L; about 100U / L to about 1500U / L; about 100U / L to about 1400U / L; about 100U / L to about 1300U / L; about 100U / L to about 1200U / L; about 100U / L to about 1100U / L; about 100U / L to about 1000U / L; about 100U / L to about 900U / L; about 100U / L to about 800U / L; about 1 100U / L to about 700U / L; about 100U / L to about 600U / L; about 100U / L to about 500U / L; about 100U / L to about 400U / L; about 100U / L to about 300U / L; about 100U / L to about 200U / L; about 150U / L to about 2000U / L; about 150U / L to about 1800U / L; about 150U / L to about 1600U / L; about 150U / L to about 1400U / L; about 150U / L to about 1200U / L; about 150U / L to about 1000U / L; about 150U / L to about 800U / L; about 150U / L to about 600U / L; about 150U / L to about 400U / L; about 20 0 U / L to about 15000 U / L; about 300 U / L to about 14000 U / L; about 400 U / L to about 13000 U / L; about 500 U / L to about 12000 U / L; about 600 U / L to about 11000 U / L; about 700 U / L to about 10000 U / L; about 800 U / L to about 9000 U / L; about 900 U / L to about 8000 U / L; about 1000 U / L to about 7000 U / L; about 1000 U / L to about 6000 U / L; about 1000 U / L to about 5000 U / L; about 1000 U / L to about 4000 U / L; about 1000 U / L to about 3000 U / L; about 1000 U / L to about 2000 U / L;About 1000 U / L to about 1900 U / L; about 1000 U / L to about 1800 U / L; about 1000 U / L to about 1700 U / L; about 1000 U / L to about 1600 U / L; about 1000 U / L to about 1500 U / L; about 1000 U / L to about 1400 U / L; about 1000 U / L to about 1300 U / L; about 1000 U / L to about 1200 U / L; about 1000 U / L to about 1100 U / L L; about 500 U / L to about 1900 U / L; about 600 U / L to about 1800 U / L; about 700 U / L to about 1700 U / L; about 800 U / L to about 1600 U / L; about 900 U / L to about 1600 U / L; about 1000 U / L to about 1600 U / L; about 1200 U / L to about 1600 U / L; about 1300 U / L to about 1600 U / L; or about 1400 U / L to about 1600 U / L. ;

[0056] In some embodiments, the amylase is present in the cleaning composition in an amount of at least about 50 U / L, at least about 60 U / L, at least about 70 U / L, at least about 80 U / L, at least about 90 U / L, at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, at least about 7000 U / L, or at least about 8000 U / L.

[0057] In some embodiments, the amylase is present in an amount within a range having a lower limit selected from the group consisting of: 50 U / L, 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 600 0 U / L and 7000 U / L, and an upper limit selected from the group consisting of: 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L, 2500 U / L, 2600 U / L / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 40 00U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L and 8000U / L.

[0058] In some embodiments, the amylase is present in the cleaning composition in an amount of: about 50 U / L to about 8000 U / L; about 50 U / L to about 7000 U / L; about 50 U / L to about 6000 U / L; about 50 U / L to about 5000 U / L; about 50 U / L to about 4000 U / L; about 50 U / L to about 3000 U / L; about 50 U / L to about 2000 U / L; about 50 U / L to about 1000 U / L; about 50 U / L to about 900 U / L; about 50 U / L to about 800 U / L; about 50 U / L to about 700 U / L; about 50 U / L to about 600 U / L; about 50 U / L to about 500 U / L; about 50 U / L to about 400 U / L; about 50 U / L to about 300 U / L; about 50 U / L to about 200 U / L; about 50 U / L to about 100 U / L; about 70 U / L to about 800 U / L; about 100 U / L to about 8000 U / L; about 200 U / L to about 7000 U / L; about 300 U / L to about 6000 U / L; about 400 U / L to about 5000 U / L; about 500 U / L to about 4000 U / L; about 600 U / L to about 3000 U / L ; about 700 U / L to about 2000 U / L; about 800 U / L to about 1000 U / L; about 500 U / L to about 2000 U / L; about 500 U / L to about 1500 U / L; about 500 U / L to about 1000 U / L; about 600 U / L to about 1000 U / L; about 600 U / L to about 900 U / L; or about 600 U / L to about 800 U / L.

[0059] In some embodiments, the cleaning compositions include trypsin. Trypsin may be present in the cleaning compositions in an amount of at least about 50 U / L, at least about 60 U / L, at least about 70 U / L, at least about 80 U / L, at least about 90 U / L, at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, at least about 7000 U / L, or at least about 8000 U / L.

[0060] In some embodiments, trypsin is present in an amount within a range having a lower limit selected from the group consisting of: 50 U / L, 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L , 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700 U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 60 1800U / L, 1900U / L, 2000U / L, 2100U / L, 2200U / L, 2300U / L, 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 5100U / L, 5200U / L, 5300U / L, 5400U / L U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 40 00U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L and 8000U / L.

[0061] In some embodiments, trypsin is present in the cleaning composition in an amount of about 50 U / L to about 8000 U / L; about 50 U / L to about 7000 U / L; about 50 U / L to about 6000 U / L; about 50 U / L to about 5000 U / L; about 50 U / L to about 4000 U / L; about 50 U / L to about 3000 U / L; about 50 U / L to about 2000 U / L; about 50 U / L to about 1000 U / L; about 50 U / L to about 900 U / L; about 50 U / L to about 800 U / L; about 50 U / L to about 700 U / L; about 50 U / L to about 600 U / L; about 50 U / L to about 500 U / L; about 50 U / L to about 400 U / L; about 50 U / L to about 300 U / L; about 50 U / L to about 20 0U / L; about 50U / L to about 100U / L; about 70U / L to about 800U / L; about 100U / L to about 8000U / L; about 200U / L to about 7000U / L; about 300U / L to about 6000U / L; about 400U / L to about 5000U / L; about 500U / L to about 4000U / L; about 600U / L to about 3000U / L ; about 700 U / L to about 2000 U / L; about 800 U / L to about 1000 U / L; about 500 U / L to about 2000 U / L; about 500 U / L to about 1500 U / L; about 500 U / L to about 1000 U / L; about 600 U / L to about 1000 U / L; about 600 U / L to about 900 U / L; or about 600 U / L to about 800 U / L.

[0062] In some embodiments, the cleaning compositions include pepsin. Pepsin may be present in the cleaning compositions in an amount of at least about 50 U / L, at least about 60 U / L, at least about 70 U / L, at least about 80 U / L, at least about 90 U / L, at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, at least about 7000 U / L, or at least about 8000 U / L.

[0063] In some embodiments, pepsin is present in an amount within a range having a lower limit selected from the group consisting of: 50 U / L, 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L , 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700 U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 60 1800U / L, 1900U / L, 2000U / L, 2100U / L, 2200U / L, 2300U / L, 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 5100U / L, 5200U / L, 5300U / L, 5400U / L U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 40 00U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L and 8000U / L.

[0064] In some embodiments, pepsin is present in the cleaning composition in an amount of: about 50 U / L to about 8000 U / L; about 50 U / L to about 7000 U / L; about 50 U / L to about 6000 U / L; about 50 U / L to about 5000 U / L; about 50 U / L to about 4000 U / L; about 50 U / L to about 3000 U / L; about 50 U / L to about 2000 U / L; about 50 U / L to about 1000 U / L; about 50 U / L to about 900 U / L; about 50 U / L to about 800 U / L; about 50 U / L to about 700 U / L; about 50 U / L to about 600 U / L; about 50 U / L to about 500 U / L; about 50 U / L to about 400 U / L; about 50 U / L to about 300 U / L; about 50 U / L to about 20 0U / L; about 50U / L to about 100U / L; about 70U / L to about 800U / L; about 100U / L to about 8000U / L; about 200U / L to about 7000U / L; about 300U / L to about 6000U / L; about 400U / L to about 5000U / L; about 500U / L to about 4000U / L; about 600U / L to about 3000U / L ; about 700 U / L to about 2000 U / L; about 800 U / L to about 1000 U / L; about 500 U / L to about 2000 U / L; about 500 U / L to about 1500 U / L; about 500 U / L to about 1000 U / L; about 600 U / L to about 1000 U / L; about 600 U / L to about 900 U / L; or about 600 U / L to about 800 U / L.

[0065] In some embodiments, the cleaning compositions include pseudocholinesterase (PCHE). PCHE may be present in the cleaning compositions in an amount of at least about 1 U / mL, at least about 10 U / mL, at least about 20 U / mL, at least about 30 U / mL, at least about 40 U / mL, at least about 50 U / mL, at least about 60 U / mL, at least about 70 U / mL, at least about 80 U / mL, at least about 90 U / mL, at least about 100 U / mL, at least about 110 U / mL, at least about 120 U / mL, at least about 130 U / mL, at least about 140 U / mL, at least about 150 U / mL, at least about 160 U / mL, at least about 170 U / mL, at least about 180 U / mL, at least about 190 U / mL, or at least about 200 U / mL.

[0066] In some embodiments, PCHE is present in an amount within a range having a lower limit selected from the group consisting of: 1 U / mL, 10 U / mL, 20 U / mL, 30 U / mL, 40 U / mL, 50 U / mL, 60 U / mL, 70 U / mL, 80 U / mL, 90 U / mL, 100 U / mL, 110 U / mL, 120 U / mL, 130 U / mL, 140 U / mL, 150 U / mL, 160 U / mL, 170 U / mL, 180 U / mL, mL or 190 U / mL, and an upper limit selected from the group consisting of 5 U / mL, 10 U / mL, 20 U / mL, 30 U / mL, 40 U / mL, 50 U / mL, 60 U / mL, 70 U / mL, 80 U / mL, 90 U / mL, 100 U / mL, 110 U / mL, 120 U / mL, 130 U / mL, 140 U / mL, 150 U / mL, 160 U / mL, 170 U / mL, 180 U / mL, 190 U / mL, or 200 U / mL.

[0067] In some embodiments, PCHE is present in the cleaning composition in an amount of: about 1 U / mL to about 200 U / mL; about 1 U / mL to about 190 U / mL; about 1 U / mL to about 180 U / mL; about 1 U / mL to about 170 U / mL; about 1 U / mL to about 160 U / mL; about 1 U / mL to about 150 U / mL; about 1 U / mL to about 140 U / mL; about 1 U / mL to about 130 U / mL; about 1 U / mL to about 120 U / mL; about 1 U / mL to about 110 U / mL; about 1 U / mL to about 100 U / mL; about 1 U / mL to about 90 U / mL; about 1 U / mL to about 80 U / mL; about 1 U / mL to about 70 U / mL; about 1 U / mL to about 60 U / mL; about 1 U / mL to about 50 U / mL; about 1 U / mL to about 40 U / mL; about 1 U / mL to about About 30 U / mL; about 1 U / mL to about 20 U / mL; about 1 U / mL to about 10 U / mL; about 5 U / mL to about 170 U / mL; about 10 U / mL to about 160 U / mL; about 20 U / mL to about 150 U / mL; about 30 U / mL to about 140 U / mL; about 40 U / mL to about 130 U / mL; about 50 U / mL to about 120 U / mL; about 60 U / mL to about 110 U / mL; about 70 U / mL to about 100 U / mL; about 10 U / mL to about 90 U / mL; about 10 U / mL to about 80 U / mL; about 10 U / mL to about 70 U / mL; about 10 U / mL to about 60 U / mL; about 10 U / mL to about 50 U / mL; about 10 U / mL to about 40 U / mL; about 10 U / mL to about 30 U / mL; or about 10 U / mL to about 20 U / mL.

[0068] In some embodiments, the cleaning compositions include gamma-glutamyl transpeptidase (GGT). GGT may be present in the cleaning compositions in an amount of at least about 50 U / L, at least about 60 U / L, at least about 70 U / L, at least about 80 U / L, at least about 90 U / L, at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, at least about 7000 U / L, at least about 8000 U / L, or at least about 9000 U / L.

[0069] In some embodiments, GGT is present in an amount within a range having a lower limit selected from the group consisting of: 50 U / L, 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 380 0U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 700 0 U / L and 8000 U / L, and an upper limit selected from the group consisting of 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L, 2500 U / L, 2600 U / L, 2700 U / L 700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L, 7000U / L, 8000U / L and 9000U / L.

[0070] In some embodiments, GGT is present in the cleaning composition in an amount of: about 50 U / L to about 9000 U / L; 50 U / L to about 8000 U / L; about 50 U / L to about 7000 U / L; about 50 U / L to about 6000 U / L; about 50 U / L to about 5000 U / L; about 50 U / L to about 4000 U / L; about 50 U / L to about 3000 U / L; about 50 U / L to about 2000 U / L; about 5 0U / L to about 1000U / L; about 50U / L to about 900U / L; about 80U / L to about 875U / L; about 50U / L to about 800U / L; about 50U / L to about 700U / L; about 50U / L to about 600U / L; about 50U / L to about 500U / L; about 50U / L to about 400U / L; about 50U / L to about 300U / L; about 50U / L to about 200U / L; about 50U / L to about 150U / L About 100 U / L; 100 U / L to about 8000 U / L; about 200 U / L to about 7000 U / L; about 300 U / L to about 6000 U / L; about 400 U / L to about 5000 U / L; about 500 U / L to about 4000 U / L; about 600 U / L to about 3000 U / L; about 700 U / L to about 2000 U / L; about 800 U / L to about 1000 U / L; about 500 U / L to about 9000 U / L; about 500 U / L to about 8000 U / L; about 500 U / L to about 7000 U / L; about 500 U / L to about 6000 U / L; about 500 U / L to about 5000 U / L; about 500 U / L to about 4000 U / L; about 500 U / L to about 3000 U / L; about 500 U / L to about 2000 U / L; about 500 U / L to about 1000 U / L; or about 600 U / L to about 900 U / L.

[0071] In some embodiments, the cleaning compositions include lactate dehydrogenase (LDH). LDH may be present in the cleaning compositions in an amount of at least about 50 U / L, at least about 60 U / L, at least about 70 U / L, at least about 80 U / L, at least about 90 U / L, at least about 100 U / L, at least about 200 U / L, at least about 300 U / L, at least about 400 U / L, at least about 500 U / L, at least about 600 U / L, at least about 700 U / L, at least about 800 U / L, at least about 900 U / L, at least about 1000 U / L, at least about 2000 U / L, at least about 3000 U / L, at least about 4000 U / L, at least about 5000 U / L, at least about 6000 U / L, or at least about 7000 U / L.

[0072] In some embodiments, LDH is present in an amount within a range having a lower limit selected from the group consisting of: 50 U / L, 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, U / L, 2400U / L, 2500U / L, 2600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L , 3700U / L, 3800U / L, 3900U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 500 0 U / L and 6000 U / L, and an upper limit selected from the group consisting of 100 U / L, 200 U / L, 300 U / L, 400 U / L, 500 U / L, 600 U / L, 700 U / L, 800 U / L, 900 U / L, 1000 U / L, 1100 U / L, 1200 U / L, 1300 U / L, 1400 U / L, 1500 U / L, 1600 U / L, 1700 U / L, 1800 U / L, 1900 U / L, 2000 U / L, 2100 U / L, 2200 U / L, 2300 U / L, 2400 U / L, 2500 U / L, 2600 U / L, 600U / L, 2700U / L, 2800U / L, 2900U / L, 3000U / L, 3100U / L, 3200U / L, 3300U / L, 3400U / L, 3500U / L, 3600U / L, 3700U / L, 3800U / L, 3900 U / L, 4000U / L, 4100U / L, 4200U / L, 4300U / L, 4400U / L, 4500U / L, 4600U / L, 4700U / L, 4800U / L, 4900U / L, 5000U / L, 6000U / L and 7000U / L.

[0073] In some embodiments, LDH is present in the cleaning composition in an amount of: about 50 U / L to about 7000 U / L; about 50 U / L to about 6000 U / L; about 50 U / L to about 5000 U / L; about 50 U / L to about 4000 U / L; about 50 U / L to about 3000 U / L; about 50 U / L to about 2000 U / L; about 50 U / L to about 1000 U / L; about 50 U / L to about 900 U / L; about 50 U / L to about 800 U / L; about 50 U / L to about 700 U / L; about 60 U / L to about 700 U / L; about 50 U / L to about 600 U / L; about 50 U / L to about 500 U / L ; about 50 U / L to about 400 U / L; about 50 U / L to about 300 U / L; about 50 U / L to about 200 U / L; about 50 U / L to about 100 U / L; 100 U / L to about 7000 U / L; about 200 U / L to about 6000 U / L; about 300 U / L to about 5000 U / L; about 400 U / L to about 4000 U / L; about 500 U / L to about 3000 U / L; about 500 U / L to about 2000 U / L; about 500 U / L to about 1000 U / L; about 600 U / L to about 900 U / L; about 600 U / L to about 800 U / L; or about 600 U / L to about 700 U / L.

[0074] In some embodiments, the cleaning composition comprises:

[0075] Components concentration lipase About 100 to about 16,000 U / L amylase About 50 to about 8000 U / L Pseudocholinesterase (PCHE) About 1 to about 200 U / mL γ-Glutamyl transpeptidase (GGT) About 50 to about 9000 U / L Lactate dehydrogenase (LDH) About 50 to about 7000 U / L

[0076] In some embodiments, the cleaning composition includes magnesium chloride hexahydrate. Magnesium chloride hexahydrate may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.001 g / L, 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0. ... 0.03g / L, 0.04g / L, 0.05g / L, 0.06g / L, 0.07g / L, 0.08g / L, 0.09g / L, 0.1g / L, 0.2g / L ,0.3g / L, 0.4g / L, 0.5g / L, 0.6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0 g / L and 5.0 g / L, and an upper limit selected from the group consisting of 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L , 0.06g / L, 0.07g / L, 0.08g / L, 0.09g / L, 0.1g / L, 0.2g / L, 0.3g / L, 0.4g / L, 0.5g / L, 0 .6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L and 6.0g / L. For example, in some embodiments, magnesium chloride hexahydrate is present in an amount of about 0.0001 g / L to about 6.0 g / L; about 0.001 g / L to about 6.0 g / L; about 0.01 g / L to about 6.0 g / L; about 0.1 g / L to about 6.0 g / L; about 0.1 g / L to about 5.0 g / L; about 0.1 g / L to about 4.0 g / L; about 0.1 g / L to about 3.0 g / L; about 0.1 g / L to about 2.0 g / L; about 0.1 g / L to about 1.0 g / L; about 0.1 g / L L to about 0.9 g / L; about 0.2 g / L to about 0.8 g / L; about 0.3 g / L to about 0.7 g / L; about 0.4 g / L to about 0.6 g / L; about 0.4 g / L to about 0.5 g / L; about 0.04 g / L to about 0.1 g / L; about 0.04 g / L to about 0.95 g / L; about 0.04 g / L to about 0.85 g / L; about 0.04 g / L to about 0.75 g / L; about 0.04 g / L to about 0.65 g / L; or about 0.04 g / L to about 0.55 g / L.

[0077] In some embodiments, the cleaning composition includes zinc chloride. The zinc chloride may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.001 mg / L, 0.002 mg / L, 0.003 mg / L, 0.004 mg / L, 0.005 mg / L, 0.006 mg / L, 0.007 mg / L, 0.008 mg / L, 0.009 mg / L, 0.01 mg / L, 0.02 mg / L, 0.03 mg / L, 0.04 mg / L, 0.05 mg / L, 0.06 mg / L, 0.07 mg / L, 0.08 mg / L, 0.09 mg / L, 0.1 mg / L, 0.2 mg / L , 0.3mg / L, 0.4mg / L, 0.5mg / L, 0.6mg / L, 0.7mg / L, 0.8mg / L, 0.9mg / L, 1.0mg / L, 2.0mg / L, 3.0mg / L, 4.0mg / L, 5.0mg / L, 10mg / L, 20mg / L, 3 0mg / L, 40mg / L, 50mg / L, 60mg / L, 70mg / L, 80mg / L, 90mg / L, 100mg / L, 110mg / L, 120mg / L, 130mg / L, 140mg / L, 150mg / L, 160mg / L, 170mg / L,1 80mg / L and 190mg / L, and an upper limit selected from the group consisting of: 0.002mg / L, 0.003mg / L, 0.004mg / L, 0.005mg / L, 0.006mg / L, 0.007mg / L, 0.008mg / L, 0.009mg / L, 0.01mg / L, 0.02mg / L, 0.03mg / L, 0.04mg / L, 0.05mg / L, 0.06mg / L, 0.07mg / L, 0.08mg / L, 0.09mg / L, 0.1mg / L, 0.2mg / L, 0.3mg / L, 0.4mg / L, 0.5mg / L L, 0.6mg / L, 0.7mg / L, 0.8mg / L, 0.9mg / L, 1.0mg / L, 2.0mg / L, 3.0mg / L, 4.0mg / L, 5.0mg / L, 10mg / L, 20mg / L, 30mg / L, 40mg / L, 50mg / L, 60mg / L, 70mg / L, 80mg / L, 90mg / L, 100mg / L, 110mg / L, 120mg / L, 130mg / L, 140mg / L, 150mg / L, 160mg / L, 170mg / L, 180mg / L, 190mg / L and 200mg / L.For example, in some embodiments, zinc chloride may be present in an amount of about 0.001 mg / L to about 200.0 mg / L; about 0.01 mg / L to about 200.0 mg / L; about 0.1 g / L to about 200.0 mg / L; about 1.0 mg / L to about 200 mg / L; about 1.0 mg / L to about 100 mg / L; about 1.0 mg / L to about 80 mg / L; about 1.0 mg / L to about 60 mg / L; about 1.0 mg / L to about 40 mg / L; about 1.0 mg / L to about about 14.0 mg / L to about 20 mg / L; or about 15.0 mg / L to about 20 mg / L.

[0078] In some embodiments, the cleaning composition includes HEPES (acid). HEPES (acid) may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.001 g / L, 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 0.1 g / L, 0.2 g / L, 0. .3g / L, 0.4g / L, 0.5g / L, 0.6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9 .0g / L, 10.0g / L, 20.0g / L, 30.0g / L, 40.0g / L, 50.0g / L, 60.0g / L, 70.0g / L, 80.0g / L, 90.0g / L, 100.0g / L, 110.0g / L, 120.0g / L, 1 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9.0g / L, 10.0g / L, 20.0g / L, 30.0 g / L, 40.0g / L, 50.0g / L, 60.0g / L, 70.0g / L, 80.0g / L, 90.0g / L, 100.0g / L, 110.0g / L, 120.0g / L, 130.0g / L, 140.0g / L and 150.0g / L.For example, in some embodiments, HEPES (acid) is present in an amount of about 0.0001 g / L to about 150.0 g / L; about 0.001 g / L to about 150.0 g / L; about 0.01 g / L to about 150.0 g / L; about 0.1 g / L to about 150.0 g / L; about 1.0 g / L to about 150.0 g / L, about 1.0 g / L to about 140.0 g / L; about 1.0 g / L to about 120.0 g / L; about 1.0 g / L to about 100.0 g / L; about 1.0 g / L to about 80.0 g / L; about 1.0 g / L to about 60.0 g / L; about 1.0 g / L to about 40.0 g / L; about 1.0 g / L to about 20.0 g / L. / L; about 1.0 g / L to about 19.0 g / L; about 1.0 g / L to about 18.0 g / L; about 1.0 g / L to about 17.0 g / L; about 1.0 g / L to about 16.0 g / L; about 1.0 g / L to about 14.0 g / L; about 1.0 g / L to about 13.0 g / L; about 1.0 g / L to about 12.0 g / L; about 1.0 g / L to about 11.0 g / L; about 10.0 g / L to about 20.0 g / L; about 10.0 g / L to about 15.0 g / L, about 10.0 g / L to about 14.0 g / L; about 10.0 g / L to about 13.0 g / L; about 10.0 g / L to about 12.0 g / L; or about 10 g / L to about 11 g / L.

[0079] In some embodiments, the cleaning composition includes sodium HEPES. Sodium HEPES may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.001 g / L, 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.10 g / L, 0.11 g / L, 0.12 g / L, 0.13 g / L, 0.14 g / L, 0.15 g / L, 0.16 g / L, 0.17 g / L, 0.18 g / L, 0.19 g / L, 0.20 g / L, 0.21 g / L, 0.22 g / L, 0.23 g / L, 0.24 g / L, 0.25 g / L, 0.26 g / L L, 0.07g / L, 0.08g / L, 0.09g / L, 0.1g / L, 0.2g / L, 0.3g / L, 0.4g / L, 0.5g / L, 0.6g / L, 0.7g / L, 0.8g / L, 0. 9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9.0g / L, 10.0g / L, 20.0g / L, 30.0 g / L and 40.0 g / L, and an upper limit selected from the group consisting of 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L L, 0.1g / L, 0.2g / L, 0.3g / L, 0.4g / L, 0.5g / L, 0.6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9.0g / L, 10.0g / L, 20.0g / L, 30.0g / L, 40.0g / L and 50.0g / L.For example, in some embodiments, sodium HEPES may be present in an amount ranging from about 0.0001 g / L to about 50.0 g / L; about 0.001 g / L to about 50.0 g / L; about 0.01 g / L to about 50.0 g / L; about 0.1 g / L to about 50.0 g / L; about 0.1 g / L to about 40.0 g / L; about 0.1 g / L to about 30.0 g / L; about 0.1 g / L to about 20.0 g / L; about 0.1 g / L to about 15.0 g / L; about 0.1 g / L about 0.25 g / L to about 4.5 g / L; about 0.25 g / L to about 4.0 g / L; about 0.25 g / L to about 3.5 g / L; about 0.25 g / L to about 3.0 g / L; about 1.0 g / L to about 10.0 g / L; about 1.0 g / L to about 5.0 g / L; about 1.0 g / L to about 4.0 g / L, or about 1.0 g / L to about 3.5 g / L.

[0080] In some embodiments, the cleaning composition includes streptomycin sulfate and / or gentamicin sulfate. Streptomycin sulfate and / or gentamicin sulfate may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 0.10 g / L, 0.11 g / L, 0.12 g / L, 0.13 g / L, 0.14 g / L, 0.15 g / L, 0.16 g / L, 0.17 g / L, 0.18 g / L, 0.19 g / L, 0.20 g / L, 0.21 g / L, 0.22 g / L, 0.23 g / L, 0.24 g / L, 0.25 g / L, 0.26 g / L, 0.27 g / L, 0.28 g / L, 0.29 g / L, 0.30 g / L, 0.31 g / L, 0.32 g / L, 0.33 g / L, 0.34 g / L, 0.35 g / L, 0.36 g / L, 0.37 g / L, 0.38 g / L, 0.39 g / L, 0.40 g / L, 0.41 g / L, 0.42 g / L, / L, 0.6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9.0g / L, 10.0g / L, 11.0g / L, 12.0g / L, 13.0g / L, 14.0g / L, 15.0g / L, 16.0g / L, 17.0 g / L, 18.0 g / L and 19.0 g / L, and an upper limit selected from the group consisting of 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 6.0g / L, 7.0g / L, 8.0g / L, 9.0g / L, 10.0g / L, 11.0g / L, 12.0g / L, 13.0g / L, 14.0g / L, 15.0g / L, 16.0g / L, 17.0g / L, 18.0g / L, 19.0g / L and 20.0g / L.For example, in some embodiments, streptomycin sulfate and / or gentamicin sulfate may be present in amounts as follows: about 0.01 g / L to about 20.0 g / L; about 0.01 g / L to about 10.0 g / L; about 0.01 g / L to about 9.0 g / L; about 0.01 g / L to about 8.0 g / L; about 0.01 g / L to about 7.0 g / L; about 0.01 g / L to about 6.0 g / L; about 0.01 g / L to about 5.0 g / L; about 0.01 g / L to about 4.0 g / L; about 0.01 g / L to about 3.0 g / L; about 0.01 g / L to about 2.0 g / L; about 0.01 g / L to about 1.0 g / L; about 0.01 g / L to about or about 0.11 g / L to about 0.12 g / L.

[0081] In some embodiments, the cleaning composition includes amphotericin B. Amphotericin B may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 2.5 mg / L, 3.0 mg / L, 4.0 mg / L, 5.0 mg / L, 10 mg / L, 20 mg / L, 30 mg / L, 40 mg / L, 50 mg / L, 60 mg / L, 70 mg / L, 80 mg / L, 90 mg / L, 100 mg / L, 150 mg / L, 2 00mg / L and 250mg / L, and an upper limit selected from the group consisting of: 3.0mg / L, 4.0mg / L, 5.0mg / L, 10mg / L, 20mg / L, 30mg / L, 40mg / L, 50mg / L, 60mg / L, 70mg / L, 80mg / L, 90mg / L, 100mg / L, 150mg / L, 200mg / L, 250mg / L and 300mg / L. For example, in some embodiments, amphotericin B may be present in an amount as follows: about 2.5 mg / L to about 300.0 mg / L; about 2.5 mg / L to about 250.0 mg / L; about 2.5 mg / L to about 200.0 mg / L; about 2.5 mg / L to about 150.0 mg / L; about 2.5 mg / L to about 100.0 mg / L; about 2.5 mg / L to about 50.0 mg / L; about 2.5 mg / L to about 40.0 mg / L; about 2.5 mg / L to about 30.0 mg / L; about 5 mg / L to about 200.0 mg / L; about 5 mg / L to about 150.0 mg / L; about 5 mg / L to about 100.0 mg / L g / L; about 5 mg / L to about 50.0 mg / L; about 5 mg / L to about 40.0 mg / L; about 5 mg / L to about 30.0 mg / L; about 10 mg / L to about 200.0 mg / L; about 10 mg / L to about 150.0 mg / L; about 10 mg / L to about 100.0 mg / L; about 10 mg / L to about 50.0 mg / L; about 10 mg / L to about 40.0 mg / L; about 10 mg / L to about 30.0 mg / L; about 5 mg / L to about 90.0 mg / L; about 5 mg / L to about 80.0 mg / L; about 5 mg / L to about 70.0 mg / L; or about 5 mg / L to about 60.0 mg / L.

[0082] In some embodiments, the cleaning composition includes clotrimazole. Clotrimazole may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of 1.5 mg / L, 2.0 mg / L, 3.0 mg / L, 4.0 mg / L, 5.0 mg / L, 10 mg / L, 20 mg / L, 30 mg / L, 40 mg / L, 50 mg / L, 60 mg / L, 70 mg / L, 80 mg / L, 90 mg / L, 100 mg / L, 15 0mg / L and 190mg / L, and an upper limit selected from the group consisting of 2.0mg / L, 3.0mg / L, 4.0mg / L, 5.0mg / L, 10mg / L, 20mg / L, 30mg / L, 40mg / L, 50mg / L, 60mg / L, 70mg / L, 80mg / L, 90mg / L, 100mg / L, 150mg / L, 190mg / L, and 200mg / L. For example, in some embodiments, clotrimazole may be present in the following amounts: about 1.5 mg / L to about 200.0 mg / L; about 1.5 mg / L to about 150.0 mg / L; about 1.5 mg / L to about 100.0 mg / L; about 1.5 mg / L to about 80.0 mg / L; about 1.5 mg / L to about 60.0 mg / L; about 1.5 mg / L to about 40.0 mg / L; about 1.5 mg / L to about 20.0 mg / L; about 5.0 mg / L to about 150.0 mg / L; about 5.0 mg / L to about 100.0 mg / L; about 5.0 mg / L to about 80.0 mg / L; about 5.0 mg / L g / L to about 60.0 mg / L; about 5.0 mg / L to about 40.0 mg / L; about 10.0 mg / L to about 100.0 mg / L; about 10.0 mg / L to about 80.0 mg / L; about 10.0 mg / L to about 60.0 mg / L; about 10.0 mg / L to about 40.0 mg / L; about 10.0 mg / L to about 20.0 mg / L; about 15 mg / L to about 20.0 mg / L; about 16 mg / L to about 20.0 mg / L; about 17 mg / L to about 20.0 mg / L; about 17 mg / L to about 19.0 mg / L; or about 17 mg / L to about 18.0 mg / L.

[0083] In some embodiments, the cleaning composition includes bovine albumin. Bovine albumin may be present in the cleaning composition in an amount within a range having a lower limit selected from the group consisting of: 0.001 g / L, 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 g / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 ... .5g / L, 0.6g / L, 0.7g / L, 0.8g / L, 0.9g / L, 1.0g / L, 2.0g / L, 3.0g / L, 4.0g / L, 5.0g / L, 10g / L, 20g / L, 30g / L, 40g / L, 50g / L, 60g / L, 70g / L , 80g / L, 90g / L, 100g / L, 110g / L, 120g / L, 130g / L, 140g / L, 150g / L, 160g / L, 170g / L, 180g / L, 190g / L, 200g / L, 300g / L, 400g / L, 500g / L, 600 g / L and 700 g / L, and an upper limit selected from the group consisting of 0.002 g / L, 0.003 g / L, 0.004 g / L, 0.005 g / L, 0.006 g / L, 0.007 mg / L, 0.008 g / L, 0.009 g / L, 0.01 g / L, 0.02 g / L, 0.03 g / L, 0.04 g / L, 0.05 g / L, 0.06 g / L, 0.07 g / L, 0.08 g / L, 0.09 g / L, 0.1 g / L, 0.2 g / L, 0.3 g / L, 0.4 g / L, 0.5 g / L, 0.6 mg / L, 0.7 g / L, 0. 8g / L、0.9g / L、1.0g / L、2.0g / L、3.0g / L、4.0g / L、5.0g / L、10g / L、20g / L、30g / L、40g / L、50g / L、60g / L、70g / L、80g / L、90g / L、100g / L、11 0g / L, 120g / L, 130g / L, 140g / L, 150g / L, 160g / L, 170g / L, 180g / L, 190g / L, 200g / L, 300g / L, 400g / L, 500g / L, 600g / L, 700g / L and 800.g / L.For example, in some embodiments, bovine albumin may be present in the following amounts: about 0.001 g / L to about 800.0 g / L; about 0.01 g / L to about 800.0 g / L; about 0.1 g / L to about 800.0 g / L; about 0.1 g / L to about 500.0 g / L; about 1 g / L to about 500.0 g / L; about 1 g / L to about 250.0 g / L; about 1.0 g / L to about 100.0 g / L; about 6 g / L to about 500.0 g / L; about 6 g / L / L to about 250.0g / L; about 6.0g / L to about 100.0g / L; about 6.0g / L to about 95.0g / L; about 6.0g / L to about 90.0g / L; about 6.0g / L to about 85.0g / L; about 6.0g / L to about 80.0g / L; about 6.0g / L to about 75.0g / L; about 6.0g / L to about 70.0g / L; about 6.0g / L to about 65.0g / L; about 6.0g / L to about 60.0g / L; about 6. 0g / L to about 50.0g / L; about 10g / L to about 500.0g / L; about 10g / L to about 250.0g / L; about 10.0g / L to about 100.0g / L; about 10.0g / L to about 90.0g / L; about 10.0g / L to about 80.0g / L; about 10.0g / L to about 70.0g / L; about 10.0g / L to about 60.0g / L; about 10.0g / L to about 50.0g / L; about 20.0g / L to about 100.0g / L .0g / L; about 30.0g / L to about 100.0g / L; about 40.0g / L to about 100.0g / L; about 50.0g / L to about 100.0g / L; about 60.0g / L to about 100.0g / L; about 50.0g / L to about 90.0g / L; about 60.0g / L to about 90.0g / L; about 60.0g / L to about 80.0g / L; about 60.0g / L to about 70.0g / L; or about 60.0g / L to 75g / L.

[0084] In some embodiments, the cleaning composition comprises:

[0085] Components concentration Magnesium chloride hexahydrate About 0.001 to about 6.0 g / L zinc chloride About 0.001 to about 200 mg / L HEPES (acid) About 0.001 to about 150g / L HEPES sodium About 0.001 to about 50g / L Streptomycin sulfate About 0.01 to about 20g / L Gentamycin sulfate About 0.01 to about 20g / L Amphotericin B About 2.5 to about 300 mg / L Clotrimazole About 1.5 to about 200 mg / L bovine albumin About 0.001 to about 800g / L

[0086] In some embodiments, the cleaning composition comprises:

[0087]

[0088]

[0089] In some embodiments, the cleaning composition comprises:

[0090] Components concentration lipase About 1562U / L amylase About 725U / L Pseudocholinesterase (PCHE) About 14.7 U / mL γ-Glutamyl transpeptidase (GGT) About 840U / L Lactate dehydrogenase (LDH) About 650U / L Magnesium chloride hexahydrate About 0.468g / L zinc chloride About 15.7 mg / L HEPES (acid) About 10.9g / L HEPES sodium About 2.99g / L Streptomycin sulfate About 0.115g / L Gentamycin sulfate About 0.115g / L Amphotericin B About 28.7 mg / L Clotrimazole About 17.68 mg / L bovine albumin About 69g / L

[0091] In some embodiments, the electrode subsystem is placed inside a clinical analyzer or a chemistry analyzer.

[0092] According to the present disclosure, the electrode subsystem may contain one or more sensors. For example, the electrode subsystem may contain one sensor, two sensors, three sensors, four sensors, or five sensors. When there are two or more sensors in the electrode subsystem, these sensors may be the same or different.

[0093] Suitable sensors that may be present in the electrode subsystem include, but are not limited to, electrolyte sensors, gas sensors, metabolite sensors, potentiometric sensors, amperometric sensors, optical sensors, conductivity sensors, biosensors made from biomolecules (e.g., enzymes, antibodies, peptides, nucleic acids, etc.), independent of the analyte or substance to be measured. In one embodiment, the sensor is a selective sensor for sensing other types of ions, including but not limited to potassium ions (K + ), sodium ion (Na + ), chloride ion (Cl - ), bicarbonate ion (HCO3 - ), calcium ions (Ca 2+ ), magnesium ions (Mg 2+ ), ammonium (NH4 + ) and / or pH levels.

[0094] The Integrated Multi-Sensor Technology (IMT) system constantly generates a pattern of fluid and air slugs in the IMT manifold when handling samples or IMT Standards A and B during calibration. An air cushion exists on each multi-sensor cartridge to generate a signal related to the air slug. The air reading signal is based on a conductivity measurement.

[0095] As samples are processed over time, deposits (proteins, lipids, etc.) can form in the IMT system (including the manifold, tubing, and / or sensor cartridge). The buildup of deposits changes the surface of the air cushion and affects the conductivity measurement. IMT cleanliness-related calibration failures are often observed with significantly reduced air readings with a significantly reduced K slope. For example, a K slope of less than 50 mV / dec.

[0096] Each sensor has a useful life (sensor in-use life) during which the sensor's calibration remains within acceptable standards (the sensor does not perform with calibration failures). Towards the end of a sensor's useful life, a significantly lower air reading and / or a significantly reduced K slope is observed.

[0097] In some embodiments, cleaning the electrode subsystem with the cleaning composition extends the useful life of the sensor. In some embodiments, cleaning the electrode subsystem with the cleaning composition results in a return of the air reading to baseline. In some embodiments, cleaning the electrode subsystem with the cleaning composition results in an increase in the K slope.

[0098] In some embodiments, the sensor is used for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 day, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, at least 30 days, at least 2 months, at least 3 months, at least 4 months, or longer.

[0099] In some embodiments, the fluid flow path comprises one or more tubes or channels in a manifold.

[0100] In some instances, the techniques described and illustrated herein include methods for cleaning an electrode subsystem within a chemical analyzer system. In some instances, the subsystem includes an inlet port, one or more sensors, an outlet port, and / or a fluid flow channel connecting the inlet port, one or more sensors, and the outlet port, although in other instances, the subsystem may include other components. The subsystem is also referred to herein as an integrated multi-sensor technology (IMT) system. Cleaning may include generating or providing a cleaning composition or solution that includes one or more cleaning enzymes (e.g., amylases and / or lipases), one or more pH adjusting agents, one or more matrix components, one or more buffer components, and / or one or more preservatives. In some instances, the sensor is an ion selective sensor. The cleaning composition is also referred to herein as IMT cleaners and may have a pH range of about 7.2 to about 7.4, although other pH values ​​may be used in other embodiments. Figures 8A-8D Proceed as shown in .

[0101] The cleaning operation may further include flowing a cleaning composition through the subsystem and / or flowing a rinsing solution through the subsystem. The flow of the rinsing solution effectively removes any residual cleaning composition from the subsystem. In addition, cleaning may include calibrating the sensor to prepare for subsequent sample analysis. The following examples are presented to illustrate various aspects of the technology herein, but are not intended to limit the scope of the claimed technology.

[0102] The following is a list of non-limiting illustrative embodiments disclosed herein:

[0103] Illustrative embodiments 1. A method for cleaning an electrode subsystem, the method comprising: (a) providing a cleaning composition comprising: (i) one or more cleaning enzymes; (ii) one or more pH adjusters; (iii) one or more matrix components; (iv) one or more buffer components; and (v) one or more preservatives, wherein the cleaning composition has a pH range of about 7.2 to about 7.4; and (b) flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem comprises an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

[0104] Illustrative Embodiment 2. The method of Illustrative Embodiment 1, further comprising: (c) flowing a rinse solution through the electrode subsystem, wherein flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.

[0105] Illustrative Embodiment 3. The method of any of Illustrative Embodiments 1-2, wherein the cleaning composition is substantially free of sodium hypochlorite.

[0106] Illustrative Embodiment 4. The method of any of Illustrative Embodiments 1-3, wherein the one or more cleaning enzymes are selected from the group consisting of amylases, lipases, and combinations thereof.

[0107] Illustrative embodiment 5. The method of any of illustrative embodiments 1-4, wherein the one or more pH adjusters are selected from hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, phosphoric acid, tetramethylammonium hydroxide, CAPSO free acid, citric acid, acetic acid, CHES, borates, and combinations thereof.

[0108] Illustrative Embodiment 6. The method of any one of Illustrative Embodiments 1-5, wherein the one or more matrix components are selected from the group consisting of bovine serum albumin, human serum albumin, zinc chloride, and magnesium chloride hexahydrate.

[0109] Illustrative embodiment 7. The method of any one of illustrative embodiments 1-6, wherein the one or more buffer components are selected from HEPES free acid, HEPES Na salt, phosphate, Tris, TES, MOPS, PIPES, TAPS, Bicine, Tricine, CAPSO, cacodylate and MES.

[0110] Illustrative embodiment 8. The method of any of illustrative embodiments 1-7, wherein the one or more preservatives are selected from the group consisting of streptomycin sulfate, gentamicin sulfate, amphotericin B, clotrimazole, chloramphenicol, ampicillin, neomycin sulfate, isothiazolinone, and sodium gallate.

[0111] Illustrative Embodiment 9. The method of any one of Illustrative Embodiments 1-8, wherein the cleaning composition further comprises a diluent.

[0112] Illustrative embodiment 10. The method of illustrative embodiment 9, wherein the diluent is selected from the group consisting of water, buffer, saline-based solutions, preservatives, pH adjusters, and albumin.

[0113] Illustrative Embodiment 11. The method of any of Illustrative Embodiments 1-10, further comprising: (d) calibrating the sensor.

[0114] Illustrative embodiment 12. A method for cleaning an electrode subsystem, the method comprising: (a) providing a cleaning composition comprising: (i) a lipase; (ii) an amylase; (iii) one or more pH adjusters selected from hydrochloric acid and sodium hydroxide; (iv) one or more matrix components selected from bovine serum albumin, zinc chloride, and magnesium chloride hexahydrate; (v) a HEPES buffer; and (vi) one or more preservatives selected from streptomycin sulfate, gentamicin sulfate, amphotericin B, and clotrimazole; wherein the cleaning composition has a pH range of about 7.2 to about 7.4; and (b) flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem comprises an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

[0115] Illustrative Embodiment 13. The method of Illustrative Embodiment 12, further comprising: (c) flowing a rinse solution through the electrode subsystem, wherein flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.

[0116] Illustrative Embodiment 14. The method of any one of Illustrative Embodiments 12-13, wherein the cleaning composition further comprises a diluent.

[0117] Illustrative embodiment 15. The method of illustrative embodiment 14, wherein the diluent is selected from the group consisting of water, buffer, saline-based solutions, preservatives, pH adjusters, and albumin.

[0118] Illustrative Embodiment 16. The method of any of Illustrative Embodiments 12-15, further comprising: (d) calibrating the sensor.

[0119] Illustrative Embodiment 17. The method of any of Illustrative Embodiments 1-16, wherein the amylase is present in the cleaning composition in an amount of at least 60 U / L.

[0120] Illustrative Embodiment 18. The method of any of Illustrative Embodiments 1-17, wherein the lipase is present in the cleaning composition in an amount of at least 100 U / L.

[0121] Illustrative Embodiment 19. The method of any one of Illustrative Embodiments 12-16, wherein the cleaning composition comprises:

[0122] Components concentration lipase About 100 to about 16,000 U / L amylase About 50 to about 8000 U / L Pseudocholinesterase (PCHE) About 1 to about 200 U / mL γ-Glutamyl transpeptidase (GGT) About 50 to about 9000 U / L Lactate dehydrogenase (LDH) About 50 to about 7000 U / L

[0123] Illustrative Embodiment 20. The method of any one of Illustrative Embodiments 12-16, wherein the cleaning composition comprises:

[0124]

[0125]

[0126] Illustrative Embodiment 21. The method of any one of Illustrative Embodiments 12-16, wherein the cleaning composition comprises:

[0127] Components concentration lipase About 1562U / L amylase About 725U / L Pseudocholinesterase (PCHE) About 14.7 U / mL γ-Glutamyl transpeptidase (GGT) About 840U / L Lactate dehydrogenase (LDH) About 650U / L Magnesium chloride hexahydrate About 0.468g / L zinc chloride About 15.7 mg / L HEPES (acid) About 10.9g / L HEPES sodium About 2.99g / L Streptomycin sulfate About 0.115g / L Gentamycin sulfate About 0.115g / L Amphotericin B About 28.7 mg / L Clotrimazole About 17.68 mg / L bovine albumin About 69g / L

[0128] Illustrative embodiment 22. The method of any of illustrative embodiments 1-21, wherein the electrode subsystem is placed inside a clinical analyzer or a chemistry analyzer.

[0129] Illustrative Embodiment 23. The method of any of Illustrative Embodiments 1-22, wherein the one or more sensors present in the electrode subsystem each have a useful life, and wherein cleaning the electrode subsystem with the cleaning composition extends the useful life of the sensors.

[0130] Illustrative Embodiment 24. The method of any one of Illustrative Embodiments 1-23, wherein the sensor is an ion-selective sensor.

[0131] Illustrative embodiment 25. The method of any of illustrative embodiments 1-24, wherein the fluid flow path comprises one or more tubes or channels in a manifold. Example

[0132] Example 1 - Materials

[0133] Integrated multi-sensor (IMT Na K Cl), IMT Standard A, IMT standard B+ salt bridge and IMT thinner.

[0134] The composition of the IMT detergent product is shown in Table 1 below:

[0135] Table 1

[0136] Components concentration lipase 1562U / L amylase 725U / L Pseudocholinesterase (PCHE) 14.7 U / mL γ-Glutamyl transpeptidase (GGT) 840U / L Lactate dehydrogenase (LDH) 650U / L Magnesium chloride hexahydrate 0.468g / L zinc chloride 15.7mg / L HEPES (acid) 10.9g / L HEPES sodium 2.99g / L Streptomycin sulfate 0.115g / L Gentamycin sulfate 0.115g / L Amphotericin B 28.7mg / L Clotrimazole 17.68mg / L bovine albumin 69g / L

[0137] The CH system consists of a Direct Load (DL) or Sample Handler (SH) connected to the Clinical Chemistry (CH) module.

[0138] Example 2 - IMT System Cleanliness and Calibration Stability

[0139] When handling samples or IMT Standards A and B during calibration, the IMT system always has the IMT manifold ( Figure 7 ) to generate a pattern of fluid and air masses in the multi-sensor cartridge. An air cushion is present on each multi-sensor cartridge to generate a signal about the air mass. The air reading signal is based on conductivity measurements.

[0140] As samples are processed over time, deposits (proteins, lipids, etc.) can form in the IMT system, including the manifold, tubing, and sensor cartridge. The buildup of deposits changes the surface of the air cushion and affects the conductivity measurement. It is important to note that IMT cleanliness-related calibration failures are consistently observed as significantly reduced air readings, sometimes accompanied by a significantly reduced K slope.

[0141] Example 3 - Cleaning Effect of Enzymes

[0142] Reagents: Integrated Multisensor (IMT Na K Cl).

[0143] The operating life of the sensor was tested by carrying the sensor onboard for 14 days or 5000 samples. Calibration occurred automatically every 4 hours or every 250 samples (whichever came first). Successful operating life was shown when the calibration remained within its acceptance criteria for the duration of the study:

[0144] Na slope: 50–63 mV / dec;

[0145] K slope: 50–63 mV / dec;

[0146] Cl slope: (-40)–(-60) mV / dec; and

[0147] Standard A and Standard B air readings: ≥0.45V.

[0148] Some immunoassay and clinical chemistry analyzers, e.g. CH analyzers are currently cleaned using harsh cleaning agents (e.g., sodium hypochlorite or bleach). These harsh cleaning agents are known to damage IMT sensors. Therefore, to find an alternative cleaning solution for IMT sensors, the effectiveness of enzymes for cleaning IMT sensors and chemical analyzers was investigated.

[0149] Pancreatic enzymes from porcine pancreas have been found to be effective in restoring air readings to baseline and sometimes increasing the K slope if there is any decrease in the K slope due to residuals. Figure 1A As shown in , the air readings of both Standard A and Standard B all keep reducing, with the pattern of steep decline. K slope reduces together with air reading, and causes K drift error when the 8th day. After being processed by the 17mg / mL pancreatic enzyme solution that runs as 10 repeated samples, air reading and K slope all return to higher level. In order to identify the effective enzyme in the pancreatic enzyme mixture, trypsin, lipase and amylase from porcine pancreas were selected. Figures 1B-1D It was shown that, when tested individually, both lipase and amylase exhibited similar effects in cleaning the IMT system, whereas trypsin was not as effective as the other two.

[0150] Example 4 IMT Cleaner

[0151] Reagents: Integrated Multisensor (IMT NaK Cl). Samples: Bio-Rad Liquid Assayed Multiqual (86901, 86903) and Bio-Rad Liquidcheck Urine Chemistry Control (68561, 68562).

[0152] The operating life of the sensor is tested by airborne sensors for 14 days or 5000 samples. IMT Cleaner was used to clean the instrument and demonstrated extended onboard stability (>14 days or >5000 samples) for some sensors. Successful service life was shown as calibration remaining within its acceptance criteria for the duration of the study:

[0153] Na slope: 50–63 mV / dec;

[0154] K slope: 50–63 mV / dec;

[0155] Cl slope: (-40)–(-60) mV / dec; and

[0156] Standard A and Standard B air readings: ≥0.45V.

[0157] The stability of the sensor working life was evaluated. On each test day, one run was performed and N=5 replicates were collected for each test sample. Quality control (QC) materials were used as samples during the study. On each test day, new aliquots were thawed. Over the duration of the study, plasma and serum samples were loaded into the instrument to increase the overall number of total tests performed by the sensor. The QC materials were processed according to the manufacturer's instructions. Using linear regression (results versus time), the average results were evaluated with Minitab 18 for statistically significant drift within the service life. For linear regression, a slope with a p-value of ≥0.05 was considered a "pass" result, and there was no significant drift. For linear regression slopes with p-values ​​<0.05, the service life achieved was estimated based on the confidence interval of the linear regression fit and the dichotomy of the time in which the tolerance was exceeded.

[0158] Figures 2A-2B The calibration stability of the air reading and K slope is shown for two sensors tested with medium capacity over approximately two months of sensor life as performed by an enzymatic cleaner. IMT Cleaner. Figure 2A The sensor in the is cleaned approximately every two weeks and has stable air readings for the life of the sensor. Figure 2B The sensor in had its first enzymatic cleaning at day 28, and there was some observed drop in air readings before the first cleaning. After the first enzymatic cleaning, the air readings improved slightly. With the next regular enzymatic cleaning event, the air readings improved further, approaching the original values ​​at the beginning of the sensor's life.

[0159] In two studies, The IMT detergents were run as samples with either 10 or 20 replicates. There were no significant differences with increasing the number of replicates from 10 to 20. Figure 2C The calibration stability of air readings and K-slope is shown for a tested sensor with bulk capacity, enzymatic cleaning performed approximately weekly, and demonstrated stability over 28 hours and over 8,000 samples. IMT detergent was run as a sample with 10 replicates each. Figure 2D The calibration stability of the air reading and K slope of the sensor with the largest capacity tested by running plasma samples overnight is shown. Enzymatic cleaning was performed after 5000 samples, and the IMT system, which was able to maintain the cleanliness, kept the sensor on board for a longer period, with nearly 10,000 samples tested. The IMT cleaner was run as a sample with 10 replicates. Table 2 summarizes some additional sensors that were tested with different onboard days and sample volumes and with different frequencies of enzyme cleaning activity. All demonstrated extended sensor onboard stability in terms of both onboard days and number of samples tested.

[0160] Table 2. Summary of Additional Sensor Calibration Stability Studies with IMT Cleaners

[0161]

[0162] QC regression analysis was performed to assess whether there was any impact on sample results from periodic enzyme cleaning. QC recoveries were stable over a 28-day lifespan (Table 3), confirming the feasibility of using enzyme cleaning as a preventative treatment to extend sensor lifespan.

[0163] Table 3. QC regression analysis of sensor #3394 from batch 100001 over the sensor's service life.

[0164]

[0165]

[0166] Example 5 - Stress Testing and Residue Studies

[0167] Reagents: Integrated Multisensor (IMT Na K Cl). Samples: Bio-Rad Liquid Assayed Multiqual (86901, 86903) and Bio-Rad Liquicheck Urine Chemistry Control (68561, 68562).

[0168] To evaluate any potential negative effects on the sensor, an excess of A- IMT cleaners are pressure tested. Figure 3 Stable calibration slopes for Na, K, and Cl are shown for a total of 90 replicates with enzymatic cleaning over a 3-hour period. Testing was performed on three additional sensor cartridges, with 50 replicates for each, and all Na, K, and Cl remained stable and showed healthy slopes after stress enzymatic cleaning ( Figure 4 ).

[0169] Run QC sample immediately after enzyme cleaning, to evaluate whether cleaning can cause any residual problem.Five repetitions of each QC sample are run after cleaning.The result of the first repetition is compared with the mean value of remaining four repetitions.The first repetition of each level of every kind of analyte is all within the 3SD scope of data set (Table 4), has pointed out that after enzyme cleaning, residual is not observed.

[0170] Table 4. In use QC recoveries after IMT detergent treatment

[0171]

[0172]

[0173] The data provided in this disclosure support the use of enzymes as cleaning agents in IMT systems. When tested individually, lipase and amylase from porcine pancreatic enzymes showed excellent cleaning effects.

[0174] Example 6- Storage temperature and shelf life stability of IMT cleaners

[0175] Amylase catalyzes the hydrolysis of carbohydrates into monosaccharides, while lipase catalyzes the hydrolysis of fats into fatty acids and glycerol. The active enzymes in IMT detergents include amylase and lipase.

[0176] A shelf-life stability study was conducted to determine the shelf life of the product in its final customer packaging. The shelf life covers the interval from product manufacture to storage under recommended conditions until the last day of use. For this analysis, shelf-life stability was determined by calculating a linear regression for each analyte. If the p-value for the regression slope was not significant (>0.05), stability was determined as of the penultimate day of the study. If the p-value for the regression slope was significant (≤0.05), the observed drift was compared to the acceptance criteria.

[0177] The Dimension Amylase and Dimension Lipase assays were calibrated using calibrants stored at -70°C to ensure that drift in the test calibrants (stored refrigerated at 2-8°C) was independent of drift in the analytical system. Batches 5DD073 (Table 5), 5KD042 (Table 6), and 6GD078 (Table 7) represent the final formulation design for this calibrant and have been used to determine real-time shelf life. The data generated for the three validation batches are sufficient to support the determination of the IMT Cleaner has a shelf life of 12 months.

[0178] Table 5. Batch 5DD073

[0179]

[0180]

[0181] Table 6. Batch 5KD042

[0182]

[0183]

[0184] Table 7. Batch 6GD078

[0185]

[0186] Since the p-value for the amylase sample in batch 6GD078 was less than 0.05, the drift across the duration of the study was analyzed. Figure 5 The linear regression in shows that the drift is less than 5% of the initial recovery and thus the amylase in batch 6GD078 meets the requirements.

[0187] All shelf-life stability results for amylase and lipase met the acceptance criteria and supported IMT cleaning products have a shelf life of 12 months when stored at 2 to 8°C.

[0188] Example 7 - Working Life Stability of Opened Vials

[0189] Stability testing is performed to determine how long a product remains stable for its intended use under defined storage and handling conditions. Products may demonstrate multiple types of stability behavior. Working life stability is the period of time after a product is placed in service that it remains active.

[0190] On each test day, the open and recapped vials stored at 2 to 8°C were measured to determine the normalized The stability of the opened vials was verified by measuring the amylase and lipase activity of the IMT detergent vials. For this analysis, stability was determined by calculating the linear regression for each analyte. If the p-value for the regression slope was not significant (>0.05), the stability was determined as the penultimate day of the study. If the p-value for the regression slope was significant (≤0.05), the observed drift was compared with the acceptance criteria. The acceptance criteria were ≥30 days after opening, reopening, and storing at 2 to 8°C, with an allowed drift of ≤3% for amylase and ≤5% for lipase.

[0191] Reagents: Dimension Vista AMY, Dimension Vista LIPL and

[0192] IMT Cleaner. Sample: IMT Cleaner. Acceptance criteria: The product should be stable for ≥30 days when reopened and stored at 2 to 8°C. It should have an acceptable drift of ≤3% for amylase and ≤5% for lipase.

[0193] The results obtained support IMT Cleaner products have a 30-day working life stability in opened vials when recapped and stored at 2 to 8°C.

[0194] Example 8 - Bioburden

[0195] Bioburden testing is used to determine the level of microbial contamination in a sample.

[0196] The IMT cleaner is composed of several antimicrobial agents to limit bioburden, including streptomycin sulfate, gentamicin sulfate, amphotericin B, and clotrimazole solution.

[0197] Bioburden testing was completed on randomly sampled filled vials from across the batches. A sample size of 35 vials was used for each level. The 7 samples submitted were each A combined mixture of five vials of IMT detergent, Level B. Samples were plated onto letheen agar plates and incubated as follows: half of the plates were incubated at 23–27°C for at least two days, then moved to 33–37°C for at least one day. The other half were kept at 23–27°C for at least three days. Bacterial colonies were counted on the plates incubated at 33–37°C, and fungi were counted on the plates incubated at 23–27°C. Final results were reported as the number of bacteria and fungi per milliliter or gram of product. If no colonies appeared on the plate, the count was reported as <10 CFU / mL. The results are shown in Tables 8–10 below.

[0198] Table 8

[0199]

[0200] Table 9

[0201]

[0202]

[0203] Table 10

[0204]

[0205]

[0206] The bioburden of all samples across all 3 batches tested reported <10 CFU / mL of bacteria and fungi. Therefore, the bioburden test met the acceptance criteria of <100 CFU / mL of microbial growth.

[0207] Example 9 - Atellica Sample Processor Onboard Stability

[0208] Reagents: CH Amylase, Atellica CH Lipase, Atellica CH SPCL CHEM CAL batch 58103, and Atellica CH ENZ 1Cal batch 1MD033. Samples: IMT Cleaner.

[0209] The activity of amylase and lipase was measured in freshly opened vials after refrigerated storage of the material on an Atellica sample processor. The stability of IMT detergents when stored onboard the Atellica sample processor. Data were standardized for newly opened vials stored at 2 to 8°C on each test day. For this analysis, stability was determined by calculating the linear regression for each analyte. If the p-value for the regression slope was not significant (>0.05), stability was determined as the last day of the study minus one day. If the p-value for the regression slope was significant (≤0.05), the observed drift was compared with the acceptance criteria.

[0210] Stability should be > 7 days as determined by allowing a + / - 15% drift for amylase and + / - 15% drift for lipase activity after the vial is freshly opened and the material is placed under refrigerated storage on an Atellica sample processor.

[0211]

[0212] Regression Statistics:

[0213] amylase lipase Until the following return Day 31 Day 31 Slope: -0.000184 -0.000039 Slope P value: 0.261 0.734 Is the P value > 0.05? yes yes % drift within limits yes yes Pass / Fail pass pass Stable days 31 31

[0214] The results meet the acceptance criteria and are IMT Cleaner products support a 30-day stability duration after the vial is freshly opened and the material is placed on the Atellica Sample Processor ( Figures 6A-6B ).

[0215] While the preferred embodiments have been depicted and described herein in detail, it will be apparent to those skilled in the relevant arts that various modifications, additions, substitutions etc. are possible without departing from the spirit of the invention, and these are therefore considered to fall within the scope of the invention as defined in the claims that follow.

Claims

1. A method for cleaning an electrode subsystem, the method comprising: (a) providing a cleaning composition comprising: (i) one or more cleaning enzymes; (ii) one or more pH adjusting agents; (iii) one or more matrix components; (iv) one or more buffer components; and (v) one or more preservatives, wherein the cleaning composition has a pH range of about 7.2 to about 7.4; and (b) flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

2. The method according to claim 1, further comprising: (c) flowing a rinse solution through the electrode subsystem, wherein said flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.

3. The method of claim 1 or claim 2, wherein the cleaning composition is substantially free of sodium hypochlorite.

4. The method of any one of claims 1 to 3, wherein the one or more cleaning enzymes are selected from the group consisting of amylases, lipases, and combinations thereof.

5. The method of any one of claims 1 to 4, wherein the one or more pH adjusting agents are selected from the group consisting of hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, phosphoric acid, tetramethylammonium hydroxide, CAPSO free acid, citric acid, acetic acid, CHES, borates, and combinations thereof.

6. The method according to any one of claims 1 to 5, wherein the one or more matrix components are selected from bovine serum albumin, human serum albumin, zinc chloride and magnesium chloride hexahydrate.

7. The method of any one of claims 1 to 6, wherein the one or more buffer components are selected from HEPES free acid, HEPES Na salt, phosphate, Tris, TES, MOPS, PIPES, TAPS, Bicine, Tricine, CAPSO, cacodylate, and MES.

8. The method according to any one of claims 1 to 7, wherein the one or more preservatives are selected from the group consisting of streptomycin sulfate, gentamicin sulfate, amphotericin B, clotrimazole, chloramphenicol, ampicillin, neomycin sulfate, isothiazolinone and sodium gallate.

9. The method of any one of claims 1 to 8, wherein the cleaning composition further comprises a diluent.

10. The method of claim 9, wherein the diluent is selected from the group consisting of water, buffers, saline-based solutions, preservatives, pH adjusters, and albumin.

11. The method according to claim 1 , further comprising: (d) Calibrate the sensor.

12. A method for cleaning an electrode subsystem, the method comprising: (a) providing a cleaning composition comprising: (i) lipase; (ii) amylase; (iii) one or more pH adjusters selected from hydrochloric acid and sodium hydroxide; (iv) one or more matrix components selected from bovine serum albumin, zinc chloride, and magnesium chloride hexahydrate; (v) HEPES buffer; and (vi) one or more preservatives selected from the group consisting of streptomycin sulfate, gentamicin sulfate, amphotericin B and clotrimazole; wherein the cleaning composition has a pH range of from about 7.2 to about 7.4; and (b) flowing the cleaning composition through the electrode subsystem, wherein the electrode subsystem includes an inlet port, one or more sensors, an outlet port, and a fluid flow channel connecting the inlet port, the one or more sensors, and the outlet port.

13. The method according to claim 12, further comprising: (c) flowing a rinse solution through the electrode subsystem, wherein said flowing the rinse solution is effective to remove any residual cleaning composition from the electrode subsystem.

14. The method of any one of claims 12 to 13, wherein the cleaning composition further comprises a diluent.

15. The method of claim 14, wherein the diluent is selected from the group consisting of water, buffers, saline-based solutions, preservatives, pH adjusters, and albumin.

16. The method of claim 12, further comprising: (d) Calibrate the sensor.

17. The method of any one of claims 1 to 16, wherein the amylase is present in the cleaning composition in an amount of at least 60 U / L.

18. The method of any one of claims 1 to 17, wherein the lipase is present in the cleaning composition in an amount of at least 100 U / L.

19. The method of any one of claims 12 to 16, wherein the cleaning composition comprises:

20. The method of any one of claims 12 to 16, wherein the cleaning composition comprises:

21. The method of any one of claims 12 to 16, wherein the cleaning composition comprises:

22. The method of any one of claims 1 to 21, wherein the electrode subsystem is placed inside a clinical analyzer or a chemical analyzer.

23. The method of any one of claims 1 to 22, wherein one or more sensors present in the electrode subsystem each have a useful life, and wherein cleaning the electrode subsystem with the cleaning composition extends the useful life of the sensors.

24. The method of any one of claims 1 to 23, wherein the sensor is an ion-selective sensor.

25. The method of any one of claims 1 to 24, wherein the fluid flow path comprises one or more pipes or channels in a manifold.

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