Liquid composition for measuring ATP, AMP, and / or ADP in a sample

Abstract

In one embodiment, the present invention addresses the problem of providing a highly stable liquid cycling luminescence reagent.　In one embodiment, the present invention provides a liquid composition for measuring ATP, and AMP and / or ADP in a sample after storage. (i) The liquid composition contains luciferase, luciferin, an enzyme that catalyzes a reaction that produces ATP from AMP, a substrate for the enzyme that catalyzes a reaction that produces ATP from AMP, and cofactors, or, when at least one of these components is not present in the liquid composition, said component or components not present in the liquid composition are added to the liquid composition prior to measurement or when measurement is carried out. (ii) The relative amount of light emission for the liquid composition during storage is not more than 5,500 RLUs, where the relative amount of light emission is the value provided by subtracting a control value from a measured value.

Description

[Technical Field]

[0001] In one embodiment, the present invention relates to a liquid composition for measuring ATP, AMP, and / or ADP in a sample after storage, a kit for measuring ATP in a sample comprising the liquid composition, and a method for measuring ATP, AMP, and / or ADP in a sample, comprising using the liquid composition. [Background technology]

[0002] Adenosine triphosphate (hereinafter referred to as ATP) is a nucleotide found in all living organisms and is used by cells as a substrate for storing and releasing energy. Because ATP is contained in substances of biological origin, kits and methods for measuring the cleanliness of biological samples and biological equipment, as well as kits for measuring the degree of contamination of cooking equipment, have been reported (Patent Documents 1-2).

[0003] A representative method for measuring ATP involves reacting ATP with the substrate luciferin in the presence of luciferase and measuring the luminescence (Non-Patent Literature 1). This reaction is catalyzed by luciferase and proceeds as follows in the presence of divalent metal ions. Luciferin + ATP + O2 → Oxyluciferin + Adenosine monophosphate (AMP) + Pyrophosphate (PPi) + CO2 + Light

[0004] ATP can be relatively easily dephosphorylated into ADP, and ADP can also be dephosphorylated into AMP in some cases. Therefore, by measuring ATP and ADP, or ATP, ADP, and AMP, rather than ATP alone, it is possible to stably measure ATP (or its decomposition products) contained in biologically derived substances and determine the degree of cleanliness more accurately. For example, Patent Document 1 describes that by measuring ATP and ADP, or ATP, ADP, and AMP, rather than ATP alone, it is possible to accurately detect residual blood and adhering blood on blood-related devices, etc. [Prior art documents]

Patent Document

[0005]

Patent Document 1

Patent Document 2

Non-Patent Document

[0006]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] A luminescent reagent used in a reaction system (cycling reaction) that directly or indirectly converts AMP to ATP and measures ADP and / or AMP in addition to ATP is called a "cycling luminescent reagent". In existing cycling luminescent reagents such as Lucipac Pen (ATP+AMP measurement) (manufactured by Kikkoman Biochemifa Co., Ltd.) and Lucipac A3 (ATP+ADP+AMP measurement) (manufactured by Kikkoman Biochemifa Co., Ltd.), all luminescent reagents are designed and manufactured in a powder state, and there is no liquid cycling luminescent reagent. However, the production of powder reagents requires processes such as drying and pulverization, and it is difficult to fill them quickly and accurately, so the production method is complicated and costly. In addition, the powder has the drawback that measures against moisture absorption, etc. are also required.

[0008] Therefore, the present inventor newly attempted to design a liquid cycling luminescent reagent. And the present inventor newly found that the stability of the liquid cycling luminescent reagent is not necessarily sufficient.

[0009] In one embodiment, an object of the present invention is to provide a liquid cycling luminescent reagent having excellent stability. In one embodiment, an object of the present invention is to provide a kit containing the cycling luminescent reagent, or a method for measuring ATP, AMP and / or ADP in a sample using the cycling luminescent reagent or the kit.

Means for Solving the Problems

[0010] The present inventors have surprisingly found that in a cycling luminescence reaction using a luciferin-luciferase reaction, the stability of the liquid cycling luminescent reagent is improved by reducing the relative luminescence amount of the liquid cycling reagent during storage.

[0011] The present invention includes the following embodiments. [1] A liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) Contains luciferase, luciferin, an enzyme that catalyzes the reaction to generate ATP from AMP, a substrate of the enzyme that catalyzes the reaction to generate ATP from AMP, and a cofactor, or when at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added to the liquid composition before or during measurement, and (ii) The relative luminescence amount of the liquid composition during storage is 5500 RLU or less, The relative luminescence amount is a value obtained by subtracting the control value from the measured value, The measured value is obtained by adding 0.35 mL of the liquid composition to a measurement tube of a Lucipac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.), and then adding 0.01 mL of a 1 × 10 -7 M ATP (manufactured by Oriental Yeast Co., Ltd.) solution, allowing to stand at 25 ° C for 1 hour, and measuring with a luminometer Smart (manufactured by Kikkoman Biochemifa Co., Ltd.), The control value is a value obtained by measuring the luminescence amount under the same conditions as those for obtaining the measured value except that sterilized ultrapure water is added instead of the ATP solution. The liquid composition. [2] The liquid composition according to [1], further comprising at least one component selected from an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, an enzyme that catalyzes the reaction of producing AMP from ADP, or a substrate for an enzyme that catalyzes the reaction of producing AMP from ADP, or at least one of these being added before or during measurement. [3] A liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added before or at the time of measurement, and (ii) The relative luminescence of the liquid composition during storage is 5500 RLU or less, The aforementioned relative luminescence is the value obtained by subtracting the control value from the measured value. The above measurement was obtained by adding 0.35 mL of the liquid composition to the measuring tube of a LuciPac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.), and then 1 × 10⁻⁶ -7 The value was obtained by adding 0.01 mL of ATP solution M (manufactured by Oriental Yeast Co., Ltd.), allowing it to stand at 25°C for 1 hour, and then measuring it with a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd.). The aforementioned control value is the value obtained when the amount of luminescence is measured under the same conditions as those used to obtain the aforementioned measurement, except that sterile ultrapure water is added instead of ATP solution. The aforementioned liquid composition. [4] The liquid composition according to any one of [1] to [3], wherein the relative luminescence is 2300 RLU or less. [5] A liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction that produces ATP from AMP, a substrate for the enzyme that catalyzes the reaction that produces ATP from AMP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added to the liquid composition before or at the time of measurement, and (ii) At least one of the following is satisfied: The concentration of luciferin in the liquid composition is 0.4 mM or less; The concentration of luciferase in the liquid composition according to the Bradford method is 0.3 mg / mL or less; The concentration of the enzyme that catalyzes the reaction to produce ATP from AMP in the liquid composition is 1 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP in the liquid composition is 0.1 mM or less; The concentration of the cofactor in the liquid composition is 6 mM or less; The aforementioned liquid composition. [6] The liquid composition according to [5], further comprising at least one component selected from an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, an enzyme that catalyzes the reaction of producing AMP from ADP, or a substrate for an enzyme that catalyzes the reaction of producing AMP from ADP, or at least one of these being added before or during measurement. [7] A liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added before or at the time of measurement, and (ii) At least one of the following is satisfied: The concentration of the enzyme that catalyzes the reaction to produce ADP from AMP in the liquid composition is 450 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP in the liquid composition is 0.1 mM or less; The concentration of the enzyme that catalyzes the reaction to produce ATP from ADP in the liquid composition is 20 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP is 1.2 mM or less; The concentration of the cofactor in the liquid composition is 6 mM or less; The aforementioned liquid composition. [8] A liquid composition according to any one of [1] to [7], wherein the shelf life is one day or longer. [9] The liquid composition according to [8], wherein the shelf life is 30 days or more.

[10] A liquid composition according to any one of [1] to [9], which does not contain at least one component of luciferase, luciferin, an enzyme that catalyzes the reaction of producing ATP from AMP, a substrate of an enzyme that catalyzes the reaction of producing ATP from AMP, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate of an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate of an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the component not included in the liquid composition is added before or during measurement.

[11] The liquid composition according to any one of [1] to

[10] , wherein the concentration of luciferin in the liquid composition is 0.4 mM or less, and / or the concentration of luciferase based on the Bradford method is 0.3 mg / mL or less.

[12] The liquid composition according to any one of [1] to

[11] , wherein the concentration of luciferin in the liquid composition is 0.1 mM or less.

[13] The liquid composition according to any one of [1] to

[12] , wherein the concentration of luciferase in the liquid composition according to the Bradford method is 0.1 mg / mL or less. A kit for measuring ATP in a sample, comprising any of the liquid compositions described in

[14] [1] to

[13] . A method for measuring ATP, AMP and / or ADP in a sample, comprising using a liquid composition described in any of

[15] [1] to

[13] or a kit described in

[14] .

[16] The method described in

[15] , without using ATP standard solution. This specification includes the disclosures of Japanese Patent Application No. 2020-023442, which forms the basis of the priority claim of this application. [Effects of the Invention]

[0012] In one embodiment, the present invention provides a liquid cycling luminescence reagent with excellent stability. [Brief explanation of the drawing]

[0013] [Figure 1] Figure 1 shows the change in the amount of luminescence of a non-cycling luminescent reagent over time. [Figure 2] Figure 2 shows the stability of cycling luminescence reagents containing luciferin at various concentrations. [Figure 3] Figure 3 shows the luminescence output after 9 hours for cycling luminescence reagents containing luciferin at various concentrations, as shown in Figure 2. [Figure 4] Figure 4 shows the stability of cycling luminescence reagents with and without luciferin. [Figure 5] Figure 5 shows the stability of luminescent reagents that are not cycled and those that are cycled. Results are shown for both cases, with and without luciferin. [Figure 6] Figure 6 shows the stability of cycling luminescence reagents containing luciferase at various concentrations. [Figure 7] Figure 7 shows the luminescence output after 9 hours for cycling luminescence reagents containing luciferase at various concentrations. [Figure 8] Figure 8 shows the ATP concentration dependence of the decrease in luminescence in the cycling luminescent reagent. [Figure 9] Figure 9 shows the stability (change in luminescence over time) of luciferin-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁵ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 10] Figure 10 shows the luminescence output after 1 hour when 0.01 mL of 1 × 10⁻⁵ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferin-containing reagent. [Figure 11] Figure 11 shows the stability (change in luminescence over time) of luciferin-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁶ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 12] Figure 12 shows the luminescence output after 1 hour when 0.01 mL of 1 × 10⁻⁶ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferin-containing reagent. [Figure 13] Figure 13 shows the stability (change in luminescence over time) of luciferin-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁷ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 14] Figure 14 shows the luminescence output after 1 hour when 0.01 mL of 1 × 10⁻⁷ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferin-containing reagent. [Figure 15] Figure 15 shows the stability (change in luminescence over time) of luciferase-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁵ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 16] Figure 16 shows the luminescence output after 1 hour when 0.01 mL of 1 × 10⁻⁵ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferase-containing reagent. [Figure 17] Figure 17 shows the stability (change in luminescence over time) of luciferase-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁶ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 18] Figure 18 shows the luminescence output after 1 hour when 0.01 mL of 1 × 10⁻⁶ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferase-containing reagent. [Figure 19]Figure 19 shows the stability (change in luminescence over time) of luciferase-containing luminescent reagents at various concentrations when 0.01 mL of 1 × 10⁻⁷ M ATP is added to 0.35 mL of the luminescent reagent. [Figure 20] Figure 20 shows the amount of luminescence after 1 hour when 0.01 mL of 1 × 10⁻⁷ M ATP is added to 0.35 mL of luminescent reagent, for each concentration of luciferase-containing reagent. [Figure 21] Figure 21 shows the amount of luminescence obtained when each component is removed from the luminescent reagent, the removed components are "mixed and stored" or "mixed after storage," and 0.1 mL of 1 × 10⁻⁶ M ATP solution is added. The amount of luminescence obtained when 0.1 mL of 1 × 10⁻⁶ M ATP is added without storage (before storage) is also shown. [Modes for carrying out the invention]

[0014] [Liquid composition] In a first aspect, the present invention relates to a liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction that produces ATP from AMP, a substrate for the enzyme that catalyzes the reaction that produces ATP from AMP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added to the liquid composition before or at the time of measurement, and (ii) The relative luminescence of the liquid composition during storage is 5500 RLU or less, and the relative luminescence is the value obtained by subtracting the control value from the measured value.

[0015] In a second aspect, the present invention relates to a liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added before or at the time of measurement, and (ii) The relative luminescence of the liquid composition during storage is 5500 RLU or less, and the relative luminescence is the value obtained by subtracting the control value from the measured value.

[0016] In the compositions of the first and second embodiments, the measurement is obtained by adding 0.35 mL of the liquid composition to a measuring tube of a Lucipac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.), and then measuring 1 × 10⁻¹⁴ of the liquid composition. -7 The values ​​shown are those obtained by adding 0.01 mL of ATP solution M (manufactured by Oriental Yeast Co., Ltd.), allowing it to stand at 25°C for 1 hour, and then measuring it with a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd.). The control values ​​are those obtained by measuring the luminescence under the same conditions as the above measurement, except that sterile ultrapure water is added instead of ATP solution. Note that the LuciPac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.) measurement tubes contain a luminescence reagent, so these should be removed by washing to the extent that they do not affect the measurement system before use. If LuciPac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.) measurement tubes are difficult to obtain, equivalent LuciPac A3 (manufactured by Kikkoman Biochemifa Co., Ltd.) measurement tubes may be used. In principle, ATP manufactured by Oriental Yeast Co., Ltd. should be used, but if it is difficult to obtain, equivalent ATP may be used. To avoid high background levels that could affect the measurement results, sterile ultrapure water is preferably contaminated with minimal ATP, ADP, and AMP. For example, the sum of the concentrations of ATP, ADP, and AMP should be 1 × 10⁻⁶. -9 M or less, or 1 × 10 -10 Any water with a molecular weight of M or less may be used. Sterile ultrapure water should be used for ATP dilution, and the same sterile ultrapure water used for background measurements should be used.

[0017] When measuring the relative luminescence of a liquid composition during storage, if the total volume of the liquid composition (e.g., a liquid composition in one kit) is less than 0.35 mL, multiple equivalent liquid compositions (e.g., other liquid compositions in the same type of kit) may be mixed, and the relative luminescence of the mixed liquid composition may be measured.

[0018] In this specification, the relative luminescence is, in principle, the value obtained when the luminescence is measured under the above conditions. However, if the above-mentioned Lucipac Pen is difficult to obtain, the following conditions may be substituted: the measured value is obtained by adding 0.35 mL of the liquid composition to a Lumina tube (manufactured by Kikkoman Biochemifa Co., Ltd., 12φ × 54 mm), and then measuring 1 × 10⁻⁶. -7 The value obtained by adding 0.01 mL of ATP solution M and letting it stand at 25°C for 1 hour, then measuring the luminescence using a Lumitester C-110 (manufactured by Kikkoman Biochemifa Co., Ltd.), was divided by 400. The control value was obtained by dividing the value obtained by dividing by 400 the luminescence measured under the same conditions as the above measurement, except that sterile ultrapure water was added instead of ATP solution.

[0019] In one embodiment, the relative luminescence of the liquid composition during storage may be 5500 RLU or less, 5000 RLU or less, 4500 RLU or less, 4000 RLU or less, 3500 RLU or less, or 3000 RLU or less. For example, the relative luminescence of the liquid composition during storage may be 2900 RLU or less, 2800 RLU or less, 2700 RLU or less, 2600 RLU or less, 2500 RLU or less, 2400 RLU or less, 2300 RLU or less, 2200 RLU or less, 2100 RLU or less, 2000 RLU or less, 1900 RLU or less, 1800 RLU or less, 1700 RLU or less, 1600 RLU or less, 1500 RLU or less, 1400 RLU or less, 1300 RLU or less, 1200 RLU or less, 1100 RLU or less, 1000 RLU or less, 900 RLU or less, 800 RLU or less, 700 RLU or less, 600 RLU or less, 500 RLU or less, 400 RLU or less, 300 RLU or less, 200 RLU or less, or 100 RLU or less. Examples have shown that the lower the relative luminescence of the liquid composition during storage, the greater the stability of the liquid composition. Furthermore, the stability of the liquid composition may be particularly excellent when the relative luminescence of the liquid composition during storage is 2500 RLU or less or 2300 RLU or less. In this specification, "excellent stability" of a liquid composition means, for example, that there is little or no decrease in the luminescence of the liquid composition.

[0020] Methods for reducing the relative luminescence of a liquid composition during storage are not limited to those mentioned above, and include methods such as changing the pH during storage from the optimal pH for the enzyme, adding ATP-degrading enzymes to decompose ATP and prevent luminescence, adding reaction inhibitors, and lowering the concentration of components necessary for the cycling reaction, or removing components and then adding the removed components before or during measurement, or a combination thereof.

[0021] For example, in a method of changing the pH during storage from the optimal pH, the pH of the liquid composition may be raised or lowered from the optimal pH to the extent that the enzymatic reaction does not proceed or is delayed, and the enzyme does not denature, and the pH of the liquid composition may be returned to the optimal pH before or during measurement. When making it acidic, the pH during storage may be, for example, 6 or less, 5 or less, or 4 or less, or 2 or more, or 3 or more. When making it basic, the pH during storage may be, for example, 9 or more, 10 or more, or 11 or more, or 13 or less, or 12 or less. A person skilled in the art can easily determine the pH at which the enzyme does not denature and the relative luminescence of the liquid composition is reduced, and can easily adjust the pH using an acid or base to reach the determined pH. For example, with HLK described in Japanese Patent Publication No. 11-239493, the relative luminescence can be reduced to about 1 / 3 or less by setting the pH to 6.5 or less, and the relative luminescence can be reduced to about 1 / 10 or less by setting the pH to 6 or less. The pH before or at the time of measurement may be 6-9, 7.5-8.5, or approximately 8. In another embodiment, the pH during storage and the pH before or at the time of measurement may be the same or nearly the same (for example, the difference between the pH during storage and the pH before or at the time of measurement may be 1 or less).

[0022] One method for decomposing ATP by adding an ATP-degrading enzyme is to add adenosine phosphate deaminase during storage. The ATP-degrading enzyme may be used at a concentration that does not affect the ATP measurement system, and the effect of the ATP-degrading enzyme may be reduced by diluting the liquid composition before or during measurement. The concentration and type of ATP-degrading enzyme can be easily determined by those skilled in the art.

[0023] When reaction inhibitors are added, examples of reaction inhibitors include metal salts such as NaCl and surfactants such as benzalkonium chloride. The effect of the reaction inhibitor may be reduced by diluting the liquid composition before or during measurement. Alternatively, the reaction inhibitor may be removed before or during measurement; for example, metal salts can be removed with a chelating agent, and benzalkonium chloride can be removed with cyclodextrin. The concentration and type of reaction inhibitor can be easily determined by those skilled in the art.

[0024] Methods for reducing the concentration of components necessary for the cycling response, or for removing components and then adding the removed components before or during measurement, are as described herein.

[0025] In a third aspect, the present invention relates to a liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction that produces ATP from AMP, a substrate for the enzyme that catalyzes the reaction that produces ATP from AMP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added to the liquid composition before or at the time of measurement, and (ii) At least one of the following is satisfied: The concentration of luciferin in the liquid composition is 0.4 mM or less; The concentration of luciferase in the liquid composition according to the Bradford method is 0.3 mg / mL or less; The concentration of the enzyme (e.g., PPDK) that catalyzes the reaction to produce ATP from AMP in the liquid composition is 1 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP in the liquid composition (for example, pyrophosphate or a salt thereof and / or phosphoenolpyruvic acid or a salt thereof, if the enzyme is PPDK) is 0.1 mM or less; The concentration of the cofactor (e.g., magnesium salt) in the liquid composition is 6 mM or less; The present invention relates to the aforementioned liquid composition.

[0026] In a fourth aspect, the present invention relates to a liquid composition for measuring ATP, AMP and / or ADP in a sample after storage, (i) If the liquid composition contains luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, or if at least one of these components is not included in the liquid composition, the component not included in the liquid composition is added before or at the time of measurement, and (ii) At least one of the following is satisfied: The concentration of the enzyme (e.g., ADK) that catalyzes the reaction to produce ADP from AMP in the liquid composition is 450 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP in the liquid composition is 0.1 mM or less (for example, in the case of ADK, no substrate is required); The concentration of the enzyme (e.g., PK) that catalyzes the reaction of producing ATP from ADP in the liquid composition is 20 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP (for example, phosphoenolpyruvate or its salt if the enzyme is PK) is 1.2 mM or less; The concentration of the cofactor (e.g., magnesium salt) in the liquid composition is 6 mM or less; The present invention relates to the aforementioned liquid composition.

[0027] In one embodiment, the liquid compositions of the first and third embodiments further comprise at least one component selected from an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, an enzyme that catalyzes the reaction of producing AMP from ADP, or a substrate for an enzyme that catalyzes the reaction of producing AMP from ADP, or at least one of these components is added before or during measurement.

[0028] The liquid compositions of the first to fourth embodiments (collectively referred to as "the liquid compositions described herein" in this specification) and their constituent components will be described in more detail below.

[0029] In one embodiment, the liquid composition described herein is for measuring ATP in addition to AMP and / or ADP (i.e., ATP and ADP; ATP and AMP; or ATP, ADP and AMP). Although biological substances contain ATP, ATP can be relatively easily dephosphorylated to become ADP, and ADP can also be dephosphorylated to become AMP in some cases. Therefore, by measuring two components, ATP and ADP or AMP, or three components, ATP, ADP and AMP, the amount of ATP (or its decomposition products) contained in biological substances can be stably measured. Consequently, by measuring two components, ATP and ADP or AMP, or three components, the cleanliness can be determined more accurately without overlooking any contamination.

[0030] [luciferase] Luciferase is a general term for oxidases that produce bioluminescence. In one embodiment, luciferase catalyzes the conversion of ATP, O2, and luciferin to AMP, pyrophosphate, CO2, and oxyluciferin, which produces luminescence. The luciferase may be a natural luciferase or a genetically engineered recombinant luciferase mutant. The luciferase mutant may be a site-directed mutagenesis or a random mutagenesis. It may also be a fusion protein with another functional protein. The luciferase mutant may have desired properties, such as improved heat resistance or improved surfactant resistance.

[0031] The luminescence of luciferase can be evaluated using the relative luminescence intensity (RLU) obtained with a suitable luminescence measuring device, such as a luminometer (e.g., Kikkoman Biochemifa's Lumitester Smart, Lumitester PD-20, Lumitester PD-30) or a device equipped with a photodiode (e.g., Hygiena's SystemSURE Plus, EnSURE, Neogen's AccuPoint Advanced). Typically, the luminescence produced during the conversion of luciferin to oxyluciferin is measured. As a luminescence measuring device, a device equipped with a photomultiplier tube that allows for high-sensitivity measurement (e.g., 3M's CleanTrace LM1, CleanTrace UNG3; Kikkoman Biochemifa's Lumitester C-110, Lumitester C-100; or Berthold's Junior LB9509, CentroLB960, or Lumat3 LB9508) can also be used. A device capable of high-sensitivity measurement is particularly useful for accurate measurements when the amount of light emitted is reduced.

[0032] Luciferase can be derived from bacteria, protozoa, animals, mollusks, or insects, as long as it uses ATP as a substrate. Examples of insect-derived luciferases include those from beetles, such as the genus Photinus (e.g., North American firefly Photinus pyralis), the genus Photuris (e.g., Photuris lucicrescens, Photuris pennsylvanica), the genus Luciola (e.g., fireflies Luciola cruciata, Luciola lateralis, Luciola parvula, Pyrocoelia, Lucidina biplagiata), and click beetles of the genus Pyrophorus. Numerous luciferase genes have been reported, and their nucleotide and amino acid sequences can be obtained from publicly known databases such as GeneBank.

[0033] The luciferase gene may be wild-type or mutated. The mutation may be site-specific or random. Known mutations include, but are not limited to, mutations that improve the amount of luminescence, such as those described in Japanese Patent Publication No. 2011-188787; mutations that improve the duration of luminescence, such as those described in Japanese Patent Publication No. 2000-197484; mutations that change the emission wavelength, such as those described in Japanese Patent No. 2666561 or Japanese Patent Publication No. 2003-512071; mutations that improve surfactant resistance, such as those described in Japanese Patent Publication No. 11-239493; mutations that improve substrate affinity, such as those described in International Publication No. 99 / 02697, Japanese Patent Publication No. 10-512750 or Japanese Patent Publication No. 2001-518799; and mutations that improve stability, such as those described in Japanese Patent Publication No. 3048466, Japanese Patent Publication No. 2000-197487, Japanese Patent Publication No. 9-510610 and Japanese Patent Publication No. 2003-518912.

[0034] Luciferase genes and their recombinant DNA can be prepared by conventional methods. For example, Japanese Patent Publication No. 7-112434 describes the luciferase gene for the firefly (Luciola cruciata). Japanese Patent Publication No. 1-51086 describes the luciferase gene for the firefly (Luciola cruciata).

[0035] The luciferase gene can be incorporated into vectors such as plasmids, bacteriophages, or cosmids, which can then be used to transform or transduce a suitable host. The host can be a microorganism, such as bacteria (e.g., E. coli), or yeast. The transformed host, capable of producing luciferase, can be cultured using various known methods.

[0036] Examples of culture media include one or more nitrogen sources such as tryptone, yeast extract, meat extract, peptone, corn steep liquor, or soybean or wheat bran extract, to which one or more inorganic salts such as sodium chloride, monopotassium phosphate, dipotassium phosphate, magnesium chloride, ferric chloride, magnesium sulfate, or manganese sulfate are added, with carbohydrate raw materials, vitamins, etc. added as needed.

[0037] The initial pH of the culture medium can be set to, for example, 7-9. Culturing can be carried out, for example, at 30-40°C for 2-24 hours by aerated stirring, shaking, or static culture. After culturing, luciferase is recovered from the culture using a known method.

[0038] Specifically, the bacterial cells are subjected to ultrasonic disruption, grinding, etc., according to conventional methods, or luciferase is extracted using a lytic enzyme such as lysozyme. The resulting extract is filtered, centrifuged, etc., and nucleic acids are removed as necessary with streptomycin sulfate, etc. Ammonium sulfate, alcohol, acetone, etc. are added to the extract for fractionation, and crude enzyme can be obtained.

[0039] The crude enzyme may be further purified by various gel filtration and chromatographic methods. Commercially available luciferases can also be used; for example, luciferase from Kikkoman Biochemifa Co., Ltd., catalog number 61314, can be used. This luciferase is described in Japanese Patent Publication No. 11-239493 (Japanese Patent No. 3749628) (Sequence ID 1 in the said document). Alternatively, commercially available molecular probe luciferases from Sigma-Aldrich, Promega, and Life Technologies can also be used.

[0040] In one embodiment, the luciferase concentration in the liquid composition described herein may be a concentration based on the Bradford method, for example, 0.3 mg / mL or less, 0.25 mg / mL or less, 0.2 mg / mL or less, 0.1 mg / mL or less, 0.05 mg / mL or less, 0.01 mg / mL or less, 0.005 mg / mL or less, 0.001 mg / mL or less, or 0.0005 mg / mL or less. The concentration based on the Bradford method can be measured using the Coomassie (Bradford) Protein Assay Kit (Thermo Scientific) with BSA solution as a standard, as described in the Examples. If this kit is difficult to obtain, the luciferase concentration can be measured by the Bradford method, which is known to those skilled in the art and uses BSA solution as a standard, to obtain an equivalent value. Alternatively, the absorbance can be determined according to the 280 nm absorbance method as described in the Examples, and the concentration based on the Bradford method can be measured by conversion. Lower luciferase concentrations can improve the stability of the liquid composition, but they also reduce the overall luminescence. If the luminescence is too low, luciferase may be added before or during measurement. The luciferase concentration in the liquid composition during storage, or after adding luciferase before or during measurement, may be, for example, 0.00001 mg / mL or higher, 0.0001 mg / mL or higher, 0.001 mg / mL or higher, or 0.01 mg / mL or higher, based on the Bradford method.

[0041] In this specification, luciferase concentrations are generally based on the Bradford method. However, if a liquid composition is prepared containing proteins other than luciferase, the concentration of luciferase alone in such a prepared liquid composition cannot be directly measured by the Bradford method. In this case, the luciferase concentration can be indirectly measured based on the Bradford method, according to the activity of luciferase, as described below.

[0042] Dilute the liquid composition containing luciferase with an enzyme diluent (5.0% Glycerol, 1.0 mM EDTA·2Na·2H2O, 1.0 mM 2-Mercaptoethanol, 50 mM Tricine, 1.0% Bovine serum albumin (BSA) (pH 7.8)) so that the luminescence amount becomes 100,000 - 1,000,000 RLU. Collect 100 μL of the liquid composition diluted with the enzyme diluent in a pre-warmed (at 25°C) Eppendorf tube (manufactured by Sarstedt), and add 100 μL of a luminescence reagent for luciferase activity measurement (50 mM Tricine, 4.0 mM ATP·2Na, 2.0 mM D-Luciferin, 10 mM MgSO4·7H2O (pH 7.8)) thereto with an injector. Measure the luminescence amount from 0.5 seconds to 20 seconds with a LUMAT LB9507 (manufactured by Berthold), and set the luminescence amount at that time as the sample luminescence amount (Es). The measurement is carried out at 25°C. Similarly, measure the blank luminescence amount (E0) using the enzyme diluent instead of the luciferase solution. Luciferase activity (LU / mL) = (Es - E0) × dilution factor ÷ sample liquid volume Sample liquid volume: 0.1 mL

[0043] In addition to the above experiment, when the luciferase confirmed to have a single band by SDS-PAGE was used to measure its activity value and protein concentration, the luciferase activity was 8.4×10 14 LU / mL, and the value based on the Bradford method was 39.4 mg / mL. That is, the specific activity was 2.1×10 13 LU / mg. By using this numerical value of the specific activity, the protein concentration can be converted from the luciferase activity. That is, Protein concentration (mg / mL) based on the Bradford method = luciferase activity (LU / mL) ÷ (2.1×10 13 LU / mg)

[0044] This allows for the determination of luciferase protein concentration even in reagents containing proteins used as stabilizers, such as BSA, or enzymes for cycling (e.g., PPDK and PK). While this is a conversion value based on a specific luciferase (HLK as described in Japanese Patent Publication No. 11-239493), the same method can be used to calculate conversion values ​​when using different luciferases, and the luciferase concentration can be measured based on these values.

[0045] If the liquid composition contains proteins other than luciferase, the luciferase concentration can also be measured by fractionating the liquid composition using chromatography such as HPLC, and then measuring the amount of separated luciferase protein using the Bradford method, in addition to the activity measurement described above.

[0046] [Luciferin] Luciferin can be any substance that is recognized as a substrate by the luciferase used, and may be natural or chemically synthesized. Known luciferin derivatives can also be used. The basic structure of luciferin is imidazopyrazinon, and many tautomers exist. Firefly luciferin is an example of luciferin. Firefly luciferin is a substrate of firefly luciferase (EC 1.13.12.7). Luciferin derivatives may be those described in Japanese Patent Publication No. 2007-91695, Japanese Patent Publication No. 2010-523149 (International Publication No. 2008 / 127677), etc.

[0047] In one embodiment, the concentration of luciferin or its derivative in the liquid composition described herein may be, for example, 0.4 mM or less, 0.35 mM or less, 0.3 mM or less, 0.25 mM or less, 0.15 mM or less, 0.1 mM or less, 0.05 mM or less, 0.02 mM or less, 0.01 mM or less, 0.005 mM or less, 0.001 mM or less, or 0.0001 mM or less. Lower luciferin concentrations can improve the stability of the liquid composition, but the overall luminescence decreases. If the luminescence is too low, luciferin or its derivative may be added before or during measurement. The concentration of luciferin or its derivative in the liquid composition during storage, or after adding luciferin before or during measurement, may be, for example, 0.00001 mM or more, 0.0001 mM or more, 0.001 mM or more, or 0.01 mM or more.

[0048] The concentration of luciferin or its derivatives can be measured based on the amount of luminescence, in accordance with the method described above for luciferase. For example, the concentration of luciferin can be measured by diluting the luminescent reagent to avoid the influence of other components such as enzymes, preparing reagents containing luciferin of different concentrations under luciferase excess, and comparing the amount of luminescence with a standard substance containing a known concentration of luciferin. Alternatively, the concentration of luciferin can be measured by fractionating the liquid composition by chromatography such as HPLC, detecting the peak corresponding to luciferin, and comparing the peak intensity with a standard substance containing a known concentration of luciferin.

[0049] It was unexpected, as described below, that the stability of the liquid composition improved as the luciferin concentration decreased. In other words, in measurement systems using enzymatic reactions, the substrate is usually added at a high concentration so that the reaction rate is not affected even as the reaction progresses and the substrate decreases. Especially in cycling reactions, since the substrate is continuously consumed, it is reasonable for those skilled in the art to assume that designing the substrate concentration to be higher will lead to the sustained luminescence of the reagent and its stability during storage. However, from the results of the examples described herein, it became clear that in cycling luminescence reagents utilizing the luciferin-luciferase reaction, conversely, the luminescence of the cycling luminescence reagent can be stabilized by lowering the luciferin concentration. Although not theoretically bound, the decrease in luminescence stability that occurs when the cycling luminescence reagent is stored in liquid form may not be primarily due to a decrease in luciferin due to luciferin consumption, but rather to luminescence inhibition by oxyluciferin generated during the luminescence reaction. That is, this may be a phenomenon unique to liquid cycling luminescence reagents using the luciferin-luciferase reaction, unlike phenomena that occur in other enzyme-based cycling methods.

[0050] [An enzyme that catalyzes the reaction that produces ATP from AMP] In one embodiment, the liquid composition described herein contains an enzyme that catalyzes the reaction that produces ATP from AMP. The enzyme catalyzes the reaction that produces ATP from AMP, converting AMP present in the system to ATP. Then, ATP is converted back to AMP by luciferase, and luminescence occurs. Therefore, in this embodiment, AMP can be measured in addition to ATP. Known enzymes can be used to catalyze the reaction that produces ATP from AMP. Examples include, but are not limited to, pyruvate-phosphate dikinase (PPDK), pyruvate water dikinase (PWDK), and combinations thereof.

[0051] [Pyruvate-phosphate dikinase (PPDK)] Pyruvate-phosphate dikinase (EC 2.7.9.1) catalyzes the reaction between ATP, pyruvate, and orthophosphate and adenosine monophosphate (AMP), phosphoenolpyruvate (PEP), and pyrophosphate (PPi): ATP + pyruvate + phosphate ←→ AMP + PEP + PPi

[0052] Pyruvate-phosphate dikinase (PPDK) is also known as ATP:pyruvate,phosphate phosphotransferase, pyruvate orthophosphate dikinase, and pyruvate phosphate ligase. These terms are interchangeable in this specification. PPDK typically converts pyruvate to PEP, consuming one molecule of ATP and converting it to AMP in the process. The reaction can be divided into three reversible reactions. 1. PPDK binds to ATP, producing AMP and diphosphorylated PPDK. 2. Diphosphorylated PPDK binds to inorganic phosphate, producing diphosphorylated PPDK and monophosphorylated PPDK. 3. Monophosphorylated PPDK binds to pyruvate, producing PEP and PPDK. In this case, if the PEP concentration in the system is high, the reaction proceeds in the reverse direction as follows.

[0053] [ka]

[0054] For convenience, the reaction steps will be explained using the same numbers as above. 3. PEP binds to PPDK, producing monophosphorylated PPDK and pyruvate. 2. From diphosphate and monophosphorylated PPDK, diphosphorylated PPDK and inorganic phosphate are produced. 1. Diphosphorylated PPDK and AMP produce PPDK and ATP.

[0055] PPDKs are not particularly limited, but examples include those derived from microorganisms such as Microbispora thermorosea, Propionibacterium shremanii, Bacteroides symbiosus, Entamoeba histolytica, Acetobacter xylinum, and Propionibacter shermanii as described in Japanese Patent Publication No. 8-168375, as well as those derived from plants such as corn and sugarcane.

[0056] [Water dikinase pyruvate (PWDK)] Pyruvate water dikinase (EC 2.7.9.2) catalyzes the following reaction: ATP + pyruvate + H2O ↔ AMP + phosphoenolpyruvate (PEP) + phosphate (P) Pyruvate water dikinase is also known as phosphoenolpyruvate synthase; phosphorylated pyruvate water dikinase; PEP synthetase; phosphoenolpyruvate synthetase; phosphoenolpyruvic synthetase; or phosphopyruvate synthetase. These terms are interchangeable in this specification.

[0057] PWDKs are not limited to any specific species, but examples include those derived from Escherichia coli, Pseudomonas fluorescens, Pyrococcus furiosus, Staphylothermus marinus, Sulfolobus solfataricus, Thermococcus kodakarensis, Thermoproteus tenax, and maize (Zea mays).

[0058] By using PWDK together with PEP, ATP production from AMP and PEP can be promoted. When an enzyme that catalyzes the reaction that produces ATP from AMP is combined with an enzyme that catalyzes the reaction that produces ATP from ADP as described herein, ADP is converted to ATP, and as a result, ATP, ADP, and AMP can be measured.

[0059] [An enzyme that catalyzes the reaction that produces ATP from ADP] In one embodiment, the liquid composition described herein contains an enzyme that catalyzes the reaction that produces ATP from ADP. The enzyme that catalyzes the reaction that produces ATP from ADP converts ADP present in the system to ATP. Then, ATP is converted to AMP by luciferase, and luminescence occurs. Therefore, in this embodiment, ADP can be measured in addition to ATP.

[0060] As enzymes that catalyze the reaction to produce ATP from ADP, known enzymes can be used, such as kinases that have ATP-producing ability. Examples of kinases that have ATP-producing ability include, but are not limited to, pyruvate kinase, acetate kinase, creatine kinase, polyphosphate kinase, riboflavin kinase, phosphofructokinase, fructose bisphosphatase, hexokinase, glucokinase, glycerol kinase, fructokinase, and combinations thereof.

[0061] [Pyruvate kinase (PK)] Pyruvate kinase (EC 2.7.1.40) converts phosphoenolpyruvate to pyruvate in glycolysis, in which case ADP is converted to ATP. This reaction is a negative Gibbs free exergonic reaction and is irreversible under natural conditions. PEP + ADP → Pyruvate + ATP In the reverse reaction, gluconeogenesis, pyruvate carboxylase and phosphoenolpyruvate carboxykinase catalyze the production of PEP and ADP from ATP and pyruvate. When cell extraction is performed, various enzymes are present in the system, and the above reactions can proceed in both directions. In this case, if phosphoenolpyruvate is present at a high concentration, ADP can be converted to ATP. Furthermore, if pyruvate kinase is present in addition to phosphoenolpyruvate, it is thought that ADP will be converted to ATP more readily. The PK is not particularly limited, but for example, those derived from animals such as rabbits, rats, and chickens, or from microorganisms such as yeast and Bacillus stearothermophilus can be used.

[0062] [Acetate kinase (AK)] Acetate kinase (EC 2.7.2.1) catalyzes the conversion between ATP and acetate and ADP and acetylated phosphate in the presence of cations: ATP + Acetate ↔ ADP + Acetylated Phosphate Acetate kinase (AK) is also known as ATP:acetate phosphotransferase or acetyl kinase. These terms are interchangeable in this specification. In vivo, it facilitates the reaction that produces ADP and acetylated phosphate from ATP and acetic acid, ultimately generating acetyl-CoA. If acetylated phosphate and ADP, derived from acetyl-CoA, are present in the system, they can be converted to acetic acid and ATP. AK is not particularly limited, but AKs derived from microorganisms such as Escherichia coli, Bacillus stearothermophilus, Costridium pasteurianum, Lactobacillus delbruckii, and Veillonella alcalescence can be used.

[0063] [Creatine kinase (CK)] Creatine kinase (EC 2.7.3.2) mediates the conversion reaction between creatine and ATP, and between creatine phosphate and ADP: Creatine + ATP ↔ Creatine phosphate + ADP Creatine kinase (CK) is also known as creatine phosphokinase (CPK) or phosphocreatine kinase. These terms are interchangeable in this specification. Normally, in animal muscle tissue, creatine and ATP produce creatine phosphate and ADP. However, this reaction is reversible; if high concentrations of creatine phosphate and ADP are present in the system, the reaction can proceed in the reverse direction, producing creatine and ATP. In vivo, cytoplasmic CK is composed of two subunits, B or M. Therefore, three isozymes, CK-MM, CK-BB, and CK-MB, can exist depending on the combination of subunits. While the isozyme pattern varies depending on the tissue, any combination is usable in this invention. CK is not particularly limited, but animal-derived CKs can be used, such as those from rabbits, chickens, cattle, pigs, carp, catfish, and frogs.

[0064] [Polyphosphate kinase (PPK)] Polyphosphate kinase (EC 2.7.4.1) catalyzes the reaction that converts polyphosphate (PolyPn) and ADP to polyphosphate (PolyPn-1) and ATP: ADP+PolyPn ←→ ATP+PolyPn-1 Polyphosphate kinase (PPK) is also known as ATP:polyphosphate phosphotransferase. These terms are interchangeable in this specification. In vivo, PPK is involved in oxidative phosphorylation. When polyphosphate (n) and ADP are present in the system, PPK can convert them to polyphosphate (n-1) and ATP. PPK is not particularly limited, but can be derived from microorganisms such as Escherichia coli, yeast, and Corynebacterium xerosis.

[0065] [Riboflavin kinase (FMNK)] Riboflavin kinase (EC 2.7.1.26), also known as FMNK, catalyzes the conversion of riboflavin and ATP to riboflavin phosphate (FMN) and ADP. ATP + Riboflavin ↔ ADP + FMN Riboflavin kinase belongs to the ATP:riboflavin 5'-phosphotransferase (also called flavokinase). FMNK is not particularly limited, but can be derived from microorganisms or animals, such as yeast, rats, or beans (Phaseolus radiatus).

[0066] [Phosphofructokinase 1 (PFK1)] Phosphofructokinase 1 (EC 2.7.1.11), also known as PFK1, catalyzes the conversion of fructose-6-phosphate (Fru6P) and ATP to fructose-1,6-bisphosphate (Fru1,6-BP) and ADP. Fru6P+ATP ←→ Fru1,6-BP+ADP Phosphofructokinase 1 belongs to the phosphofructokinase group. In this specification, phosphofructokinase 1 may be referred to as Fru-1,6BPK. PFK1 is not particularly limited, but can be derived from animals or microorganisms. Examples of microbial sources include baker's yeast, brewer's yeast, Clostridium pasteurianum, Escherichia coli, and Bacillus licheniformis.

[0067] [Fructose bisphosphatase (FBPase)] Fructose bisphosphatase (EC 3.1.3.11), also known as FBPase, catalyzes the conversion of fructose-1,6-bisphosphate (Fru1,6-BP) and ADP to fructose-6-phosphate (Fru6P) and ATP. Fru1,6-BP+ADP ←→ Fru6P+ATP FBPase is sometimes written as FBP or FBP1. FBPase is not particularly limited, but can be derived from animals, plants, or microorganisms, for example, rabbit or chicken-derived FBPase.

[0068] [An enzyme that catalyzes the reaction that produces AMP from ADP] In one embodiment, the liquid composition described herein includes an enzyme that catalyzes a reaction to produce AMP from ADP. The enzyme catalyzes the reaction to produce AMP from ADP, converting ADP present in the system to AMP. By combining the enzyme that produces AMP from ADP with an enzyme that produces ATP from AMP (e.g., PPDK), ADP is converted to AMP and AMP is converted to ATP, so that ATP, ADP, and AMP can be measured as a result. Known enzymes can be used to catalyze the reaction that produces AMP from ADP. Examples include, but are not limited to, ADP-dependent hexokinase, apirase, and combinations thereof.

[0069] [ADP-dependent hexokinase] ADP-dependent hexokinase (EC 2.7.1.147), also known as ADP-specific hexokinase, catalyzes the following reactions: D-glucose + ADP ↔ D-glucose-6-phosphate + AMP

[0070] [Apirase] Apirase (EC 3.6.1.5), also known as adenosine diphosphatase, ADPase, ATP diphosphatase, or ATP diphosphohydrolase, catalyzes the following two reactions: ATP + H2O → ADP + Phosphate (P) ADP + H2O → AMP + Phosphate (P)

[0071] [An enzyme that catalyzes the reaction that produces ADP from AMP] In one embodiment, the liquid composition described herein includes an enzyme that catalyzes the reaction of producing ADP from AMP. The enzyme that catalyzes the reaction of producing ADP from AMP converts AMP present in the system to ADP. Furthermore, by combining the enzyme that produces ADP from AMP with an enzyme that produces ATP from ADP (e.g., PK), AMP is converted to ADP and ADP is converted to ATP, so that as a result, ATP, ADP, and AMP can be measured. Any known enzyme can be used to catalyze the reaction that produces ADP from AMP. For example, adenylate kinase (ADK) is one example, but it is not limited to ADK.

[0072] [Adenylate Kinase (ADK)] Adenylate kinase (EC 2.7.4.3), also known as adenylate kinase, catalyzes the following reactions in the presence of metal ions: ATP+AMP ↔ 2ADP This reaction is reversible. ADK is an example of an enzyme that catalyzes the reaction that produces ADP from AMP. ADKs are not particularly limited, but examples include those derived from microorganisms such as yeast, or from animals such as rabbits, pigs, cows, rats, and other animals.

[0073] [RNA-degrading enzyme] In one embodiment, the kit of the present invention may contain an RNA-degrading enzyme. In another embodiment, the method of the present invention may use an RNA-degrading enzyme. The RNA-degrading enzyme referred to herein means an RNA-degrading enzyme that does not originate from the sample.

[0074] In one embodiment, the liquid composition described herein may contain an RNA-degrading enzyme. In this specification, RNA-degrading enzyme means an RNA-degrading enzyme that does not originate from the sample. By using an RNA-degrading enzyme, RNA can be broken down into AMP, and the cleanliness of a wide range of samples, including RNA, can be measured.

[0075] In this specification, RNA-degrading enzymes mean enzymes that catalyze the reaction that produces 5'-mononucleotides (AMP, GMP, CMP, and UMP) from RNA, and include, for example, the following: (1) Endonuclease S1 (EC3.1.30.1), (2) Venom exonuclease (EC3.1.15.1), and (3) Phospho diesterase 1 (EC3.1.4.1). Note that Endonuclease S1 includes Nuclease P1, Mung bean nuclease, and Neurospora crassa nuclease.

[0076] In this specification, enzymes that catalyze the reaction that produces ATP from AMP (e.g., PPDK, PWDK), enzymes that catalyze the reaction that produces ATP from ADP, enzymes that catalyze the reaction that produces AMP from ADP, and enzymes that catalyze the reaction that produces ADP from AMP (e.g., ADK) may be collectively referred to as enzymes that have ATP-producing ability.

[0077] The enzyme capable of producing ATP can be any known enzyme, such as those derived from microorganisms, bacteria, eukaryotes, protists, plants, or animals; for example, commercially available enzymes can be used. The amount of enzyme added can be appropriately set according to the desired concentration and reaction system.

[0078] Various enzymes capable of producing ATP are known. In this specification, we focus on the ATP-producing ability of enzymes and define the active unit (U) of an ATP-producing enzyme as the amount of enzyme that converts 1.0 μmol of substrate into ATP per minute at 37°C and pH 7.8 (1U = 1 μmol ATP / min, pH 7.8, 37°C). In principle, the active unit (U) of an ATP-producing enzyme is defined as above, but exceptionally, for enzymes that catalyze the reaction to produce ATP from ADP (e.g., PK), the active unit (U) of the enzyme is defined as the amount of enzyme that converts 1.0 μmol of substrate into ATP per minute at 25°C and pH 7.4 (1U = 1 μmol ATP / min, pH 7.4, 25°C). In one embodiment, an enzyme having ATP-producing ability can be added such that the active units in the measurement system are 0.001 U or more, 0.01 U or more, 0.1 U or more, 1 U or more, 2 U or more, 3 U or more, 4 U or more, or 5 U or more. In another embodiment, an enzyme having ATP-producing ability can be added such that the active units in the measurement system are 10,000 U or less, 1,000 U or less, 100 U or less, 50 U or less, 10 U or less, 9 U or less, 8 U or less, 7 U or less, or 6 U or less. A person skilled in the art can appropriately determine the amount of enzyme to add. In one embodiment, the concentration of the enzyme having ATP-producing ability in the liquid composition described herein (if multiple enzymes are included, the concentration of each enzyme or the total concentration of the enzymes, the same applies hereinafter) may be, for example, 20 U / mL or less, 10 U / mL or less, 5 U / mL or less, 1 U / mL or less, 0.5 U / mL or less, 0.1 U / mL or less, 0.05 U / mL or less, 0.01 U / mL or less, or 0.001 U / mL or less. For example, the concentration of the enzyme that catalyzes the reaction to produce ATP from AMP (e.g., PPDK) may be 1 U / mL or less, 0.5 U / mL or less, 0.1 U / mL or less, 0.05 U / mL or less, 0.01 U / mL or less, or 0.001 U / mL or less, and the concentration of the enzyme that catalyzes the reaction to produce ATP from ADP (e.g., PK) may be 20 U / mL or less, 10 U / mL or less, 5 U / mL or less, 1 U / mL or less, 0.5 U / mL or less, 0.1 U / mL or less, 0.05 U / mL or less, 0.01 U / mL or less, or 0.001 U / mL or less.The lower the concentration of the enzyme capable of ATP production, the more stable the liquid composition may become, but the overall luminescence will decrease. Therefore, if the luminescence is too low, the enzyme capable of ATP production may be added before or during measurement. The concentration of the enzyme capable of ATP production (e.g., an enzyme that catalyzes the reaction of producing ATP from AMP (e.g., PPDK) and / or an enzyme that catalyzes the reaction of producing ATP from ADP (e.g., PK)) in the liquid composition during storage or after the addition of the enzyme capable of ATP production before or during measurement may be, for example, 0.00001 U / mL or higher, 0.0001 U / mL or higher, 0.001 U / mL or higher, 0.01 U / mL or higher, 0.1 U / mL or higher, 1 U / mL or higher, or 10 U / mL or higher.

[0079] When using enzymes capable of producing ATP, substrates for each enzyme (for example, substrates for enzymes that catalyze the reaction of producing ATP from AMP, substrates for enzymes that catalyze the reaction of producing ATP from ADP, substrates for enzymes that catalyze the reaction of producing AMP from ADP, or substrates for enzymes that catalyze the reaction of producing ADP or ATP from AMP) can be added. Note that substrates for different enzymes (for example, enzymes that catalyze the reaction of producing ATP from AMP and enzymes that catalyze the reaction of producing ATP from ADP) may be common. Also, depending on the type of enzyme, it may not be necessary to add additional components equivalent to the substrate. For example, if the enzyme that catalyzes the reaction of producing ADP from AMP is ADK, then since this enzyme reaction produces ADP from ATP and AMP, it is not necessary to include any further substrates for this enzyme reaction in the liquid composition. The substrates are not particularly limited, but for example, for PPDK, examples include phosphoenolpyruvic acid or its salt and pyrophosphate or its salt; for PK, AK, CK, PPK, and FMNK, examples include phosphoenolpyruvic acid or its salt, acetyl phosphate or its salt, creatine phosphate or its salt, polyphosphate or its salt, and riboflavin phosphate or its salt, respectively. For PFK1 and FBPase, examples include fructose-1,6-bisphosphate or its salt. For PWDK, examples include phosphoenolpyruvic acid or its salt and phosphate or its salt; and for ADP-dependent hexokinase, example is glucose. In one embodiment, the liquid composition described herein further comprises these substrates. In one embodiment, the concentration of the substrate (e.g., phosphoenolpyruvic acid, pyrophosphate, or a salt thereof) in the liquid composition described herein (if multiple substrates are included, the concentration of each substrate or the total concentration of the substrates) may be, for example, 4 mM or less, 3 mM or less, 2.5 mM or less, 2 mM or less, 1.5 mM or less, 1.2 mM or less, 1 mM or less, 0.5 mM or less, 0.1 mM or less, 0.05 mM or less, 0.01 mM or less, 0.001 mM or less, or 0.0001 mM or less. Lowering the substrate concentration can improve the stability of the liquid composition, but it will reduce the overall luminescence. Therefore, if the luminescence is too low, substrate may be added before or during measurement.The substrate during storage, or before or during measurement. Add The concentration of the substrate in the liquid composition after the preparation may be, for example, 0.00001 mM or more, 0.0001 mM or more, 0.001 mM or more, 0.01 mM or more, 0.1 mM or more, or 1 mM or more.

[0080] The concentration of a substrate (e.g., phosphoenolpyruvic acid, pyrophosphate, or its salts) contained in a liquid composition can be measured based on an enzymatic reaction. For example, the concentrations of phosphoenolpyruvic acid and pyrophosphate can be measured by generating pyruvate using AMP, phosphoenolpyruvic acid, and pyrophosphate as substrates with PPDK, reacting with lactate dehydrogenase and β-NADH, and measuring the absorbance at 340 nm. Alternatively, the concentrations of phosphoenolpyruvic acid and pyrophosphate can also be measured by generating ATP using AMP, phosphoenolpyruvic acid, and pyrophosphate as substrates with PPDK, and measuring the emission using luciferase. For example, the concentration of pyrophosphate can be measured by generating ATP using pyrophosphate as a substrate with ATP sulfurylase, and measuring the amount of emission using luciferase.

[0081] [Phosphoenolpyruvic acid (PEP)] In one embodiment, the liquid composition described herein comprises phosphoenolpyruvic acid (PEP) or a salt thereof. Optionally, adding an excess amount of PEP or a salt thereof to the system may facilitate the measurement of ATP and AMP present in the system.

[0082] [Pyrophosphate (PPi)] In one embodiment, the liquid composition described herein contains pyrophosphate (PPi) or a salt thereof. Optionally, adding an excess amount of PPi or a salt thereof to the system may facilitate the measurement of ATP and AMP present in the system.

[0083] [Cofactor] In one embodiment, the liquid composition described herein contains a cofactor. A cofactor refers to a chemical substance other than a protein necessary for the catalytic activity of an enzyme. Examples of cofactors, but not limited to, include metal salts, vitamins and their derivatives, non-vitamin coenzymes, and organic prosthetic molecules, such as metal salts.

[0084] For example, cofactors for luciferase include metal salts, such as divalent metal ions like magnesium and calcium, or salts of manganese (e.g., magnesium acetate). Similarly, cofactors for PPDK include metal salts, such as magnesium. Those skilled in the art can determine the type and concentration of the cofactor (e.g., metal salt) depending on the enzyme used.

[0085] In one embodiment, the concentration of the cofactor (e.g., a metal salt such as magnesium) in the liquid composition described herein may be, for example, 30 mM or less, 25 mM or less, 20 mM or less, 15 mM or less, 10 mM or less, 8 mM or less, 6 mM or less, 4 mM or less, 2 mM or less, 1 mM or less, 0.5 mM or less, 0.1 mM or less, or 0.05 mM or less. The lower the concentration of the cofactor, the more the stability of the liquid composition may improve, but the overall amount of luminescence will decrease, so if the amount of luminescence is too low, the cofactor may be added before or during measurement. The concentration of the cofactor in the liquid composition during storage, or after adding the cofactor before or during measurement, may be, for example, 0.0001 mM or more, 0.001 mM or more, 0.01 mM or more, 0.1 mM or more, 1 mM or more, or 5 mM or more.

[0086] The concentration of cofactors contained in a liquid composition can be measured by general methods known to those skilled in the art. For example, the concentration of a cofactor can be measured by fractionating the liquid composition by chromatography such as HPLC, detecting the peak corresponding to the cofactor, and comparing the peak intensity with that of a standard substance containing a known concentration of the cofactor. Furthermore, if the cofactor is a metal salt, its concentration can be measured by ICP emission spectroscopy.

[0087] In one embodiment, the liquid composition described herein includes an enzyme stabilizer such as bovine serum albumin or gelatin that protects a reporter molecule such as luciferase from degradation. In one embodiment, the liquid composition described herein includes a substance that adjusts pH or improves shelf life. Examples of such substances include pH buffers (HEPES, Tricin, Tris, phosphate buffer, acetate buffer, etc.), reducing agents (dithiothreitol (DTT), 2-mercaptoethanol, etc.), sugars (glucose, sucrose, trehalose, etc.).

[0088] [Addition of ingredients before or during measurement] In one embodiment, the liquid composition does not contain at least one component necessary for the cycling reaction, and the component not included in the liquid composition is added to the liquid composition before or during measurement. In another embodiment, the liquid composition contains at least one component necessary for the cycling reaction at a low concentration such that the cycling reaction hardly or not proceeds at all, and the component included in the liquid composition at a low concentration is added to the liquid composition before or during measurement.

[0089] In this specification, "cycling reaction" means a reaction system that directly or indirectly converts ADP and / or AMP to ATP and measures ADP and / or AMP in addition to ATP.

[0090] In this specification, "components necessary for the cycling reaction" include, for example, in the liquid compositions of the first and third embodiments, luciferase, luciferin, an enzyme or its substrate that catalyzes the reaction to produce ATP from AMP, and cofactors. In the liquid compositions of the second and fourth embodiments, "components necessary for the cycling reaction" include luciferase, luciferin, an enzyme or its substrate that catalyzes the reaction to produce ADP from AMP, an enzyme or its substrate that catalyzes the reaction to produce ATP from ADP, and cofactors.

[0091] In one embodiment, the composition described herein does not contain at least one of these components (for example, one, two, three, four, five, or all of them), but contains other components, and the components not included in the liquid composition are added to the liquid composition before or at the time of measurement.

[0092] In this specification, “before measurement” is not limited as long as the stability of the liquid composition is improved, but may be, for example, 30 minutes, 10 minutes, 5 minutes, 1 minute, 30 seconds, 10 seconds before measuring ATP, AMP, and / or ADP, or immediately before measurement. “At measurement” means simultaneously with the measurement. The shorter the time between adding the components necessary for the cycling reaction and measurement, the less time the cycling reaction has to occur, and the more the stability of the liquid composition may be improved.

[0093] [sample] In this specification, the type of "sample" is not limited, but may include, for example, a biological sample or biological device, a blood sample or blood device, or a cooking device.

[0094] In this specification, a biological sample includes any sample that may have biological substances attached to it. In this specification, a biological device includes any device that may have biological substances attached to it or remain on it. In this specification, an environment from which a biological sample or biological device originates includes an environment from which biological fluids may be attached or remain. Such environments include, but are not limited to, clothing, protective equipment such as gloves, hands, fingers, beds, switches, doorknobs, bed rails, nurse call buttons, handrails, washrooms, washbasins, toilets, and toilet bowls. Biological substances may be of human or animal origin. In one embodiment, the biological substance is of human origin. In one embodiment, a biological sample includes human-derived samples but does not include non-human animal-derived samples. In one embodiment, a biological device includes human-related devices but does not include non-human animal-derived devices.

[0095] Substances of biological origin include liquids and solids. Liquids include, but are not limited to, body fluids, blood, lymph, sweat, nasal mucus, tears, saliva, digestive fluids, tissue fluid, ascites, amniotic fluid, cerebrospinal fluid, urine, feces, vomit, and sebum. Solids include, but are not limited to, tissue fragments, flesh fragments, cells, etc., as well as solidified liquids, coagulated blood, excrement, dead skin cells, eye discharge, and scabs.

[0096] Examples of biomedical devices include medical instruments, such as surgical instruments, endoscopes (e.g., upper endoscopes used for examining the esophagus, stomach and duodenum, lower endoscopes used for examining the rectum and large intestine, or double-balloon enteroscopes, preferably lower endoscopes), catheters, scalpels, tubes inserted into the patient's body, instruments inserted into the patient's body, surgical instrument washing tanks, and medical instrument washing environments.

[0097] In this specification, a blood-related sample includes any sample that may have blood on it. In this specification, a blood-related device means any device that may have blood on it or residual blood on it. Examples of blood-related devices include medical devices that may have blood on them or residual blood on them. These examples include surgical instruments, endoscopes (e.g., upper endoscopes used for examining the esophagus, stomach and duodenum, lower endoscopes used for examining the rectum and large intestine, or double-balloon enteroscopes, preferably lower endoscopes), catheters, scalpels, tubes inserted into a patient's body, instruments inserted into a patient's body, surgical instrument washing tanks, and medical instrument washing environments. In this specification, an environment from which a blood-related sample or blood-related device originates includes an environment from which blood may have blood on it or residual blood. Such environments include operating tables, washing tanks, protective equipment such as clothing and gloves, hands, fingers, beds, handrails, washrooms, washbasins, and medical facilities. Other examples include accident scenes, injury scenes, and sites where bloodstain searches are conducted. The blood may be of human or animal origin. In one embodiment, the blood is of human origin. In one embodiment, the blood does not include blood derived from animal or fish meat related to the food.

[0098] Blood includes whole blood, serum, plasma, blood for transfusion, primary blood collected, and diluted solutions of primary blood. Blood-related samples also include solutions containing blood cells (white blood cells, red blood cells, platelets), or samples that may have been contaminated with such solutions.

[0099] In one embodiment, a blood-related sample does not include the collected blood itself (referred to as the primary sample for convenience). For example, in this embodiment, the "solution containing blood cells" included in the blood-related sample does not include the blood itself. In one embodiment, a blood-related sample refers to a secondary sample derived from equipment or the environment that came into contact with the primary sample. A secondary sample can be obtained by wiping equipment or the environment that may have come into contact with the primary sample with a cotton swab or the like. In one embodiment, the method of the present invention examines the secondary sample to see if blood is attached to it or if blood remains. In one embodiment, a blood-related sample may be a sample in which the existing blood has been diluted by washing or the like.

[0100] In this specification, "cooking-related utensils" refers to cooking utensils and the environment of a cooking site or anything in that environment that may be contaminated. Examples of cooking utensils include, but are not limited to, cutting boards, pots, frying pans, pressure cookers, griddles, plates, knives, chopsticks, spoons, forks, knives and other tableware, ladles, strainers, colanders, racks, cutting board stands, containers for storing cooking utensils, packaging containers, packaging sheets, and other utensils used for cooking and related equipment. The environment of a cooking site refers to the environment of a cooking site, food processing plant, food serving facility, etc. Examples of things in that environment include, but are not limited to, mixing tanks, piping, filling nozzles, conveyor belts and other equipment in food processing plants, containers, doorknobs, handles on appliances such as refrigerators and ovens, switches, telephone receivers and other parts or places that are frequently touched by people.

[0101] [Storage period] The liquid compositions described herein are for measuring ATP, AMP, and / or ADP in a sample after storage. Storage as described herein includes not only the period from the preparation of the liquid composition until its use in measurement, but also the storage period of the liquid composition if it is produced during the manufacturing process of a powder composition. In this case, the liquid composition described herein may be stored for a certain period after manufacturing, converted to a powder composition by a drying process, and then converted back to a liquid composition (after optionally being stored again) for use in measuring ATP, AMP, and / or ADP in a sample. The storage period of the liquid composition (or the total period if there are multiple storage periods) is not limited, but may be, for example, 6 hours or more, 12 hours or more, 18 hours or more, 1 day or more, 2 days or more, 3 days or more, 7 days or more, 14 days or more, 30 days or more, 60 days or more, 90 days or more, 120 days or more, 150 days or more, 180 days or more, 210 days or more, 240 days or more, 270 days or more, or 300 days or more. Furthermore, the storage period may be 600 days or less, 500 days or less, or 400 days or less. Since the liquid compositions described herein may have improved stability, the effect of this improved stability may be more clearly demonstrated when the storage period is longer.

[0102] [kit] In a fifth embodiment, the present invention relates to a kit for measuring ATP in a sample, comprising the liquid composition described herein. The kit of this embodiment may, in addition to the liquid composition described herein, include at least one of an extract (e.g., water or buffer solution, or water or buffer solution containing a surfactant such as benzalkonium chloride), a buffer solution, equipment necessary for the test, a control, and instructions for use.

[0103] In one embodiment, the kit may include a sample collection section and a reaction section. The sample collection section is not particularly limited as long as it can collect a sample, but examples include cotton swabs, sponges, porous plastics, filter paper, nonwoven fabrics, and droppers. For ease of sample collection, the sample collection section is preferably rod-shaped, and particularly preferably rod-shaped with a fibrous or sponge-like wiping portion, such as a cotton swab.

[0104] The reaction section is the site where a reaction occurs when ATP or its decomposition products are present in the sample collected by the sampling section. In one embodiment, the reaction section contains the liquid composition described herein. The reaction section is preferably a transparent container, which allows for direct measurement of the amount of luminescence.

[0105] In one embodiment, the kit may include other parts in addition to the sample collection section and reaction section, such as a storage section or an extraction section. The storage section is for storing components not included in the liquid composition (e.g., luciferin) if the liquid composition described herein does not contain at least one component necessary for the cycling reaction. The extraction section is for extracting ATP or its degradation products into an extractant if ATP or its degradation products are present in the sample collected by the sample collection section. In one embodiment, the extraction section may include an extractant. The sample extracted in the extraction section can be transferred to the reaction section to carry out the reaction.

[0106] If the liquid composition described herein does not contain at least one component necessary for the cycling reaction, the kit may contain the component not included in the liquid composition. In this case, the liquid composition and the component not included in the liquid composition may be stored separately. For example, the liquid composition may be contained in the reaction section, and the component not included in the liquid composition may be contained in the sampling section, storage section, extraction section, or other section isolated from the liquid composition.

[0107] [method] In a sixth aspect, the present invention relates to a method for measuring ATP and AMP and / or ADP in a sample, or to the use of a liquid composition or kit described herein for measuring ATP and AMP and / or ADP in a sample.

[0108] For example, the amount of ATP, AMP, and / or ADP in a sample can be measured by adding a sample solution containing ATP to the liquid composition described herein and measuring the luminescence. The amounts of the liquid composition and the sample solution may be the same or different. The amounts of the liquid composition and the sample solution are not limited, but may be, for example, 0.01 mL to 10 mL, 0.25 mL to 4 mL, 0.5 mL to 2 mL, or 0.1 mL. The sample solution is not limited, but may be a suspension of a cotton swab or the like used to wipe the sample in an extract.

[0109] The amount of luminescence can be measured using a known luminometer (such as Kikkoman Biochemifa's Lumitester Smart, Lumitester PD-20, Lumitester PD-30, etc.), a device equipped with a photodiode (such as Hygiena's SystemSURE Plus, EnSURE, Neogen's AccuPoint Advanced, etc.), or a device equipped with a photomultiplier tube (such as 3M's CleanTrace LM1, CleanTrace UNG3, Kikkoman Biochemifa's Lumitester C-110, Lumitester C-100; or Berthold's Junior LB9509, CentroLB960, or Lumat3 LB9508, etc.). The luminescence can be expressed as relative luminescence units (RLU) relative to a defined standard. (For example, when taking a sample in a rod-shaped form with a wipe-off portion,) the value of the relative luminescence units may be used directly for cleanliness control, etc. In this case, a standard solution with a known ATP concentration is not used. In one embodiment, the method described herein does not use any ATP standard solution, ADP standard solution, or AMP standard solution. When the relative luminescence units obtained by measuring only the sample without using standard solutions of ATP, ADP, and / or AMP (hereinafter also referred to as ATP, etc.) are directly used for cleanliness control, etc., the decrease in luminescence due to the instability of the liquid composition directly affects the test results, so the advantage of using the composition described herein, which has excellent stability, is particularly great.

[0110] In another embodiment, a calibration curve may be created using a substrate solution with a known concentration of ATP, etc. Then, the concentration of ATP, etc. in the sample solution may be measured by adding the liquid composition described herein to a sample solution with an unknown concentration of ATP, etc. and measuring the luminescence under the same conditions. In this embodiment, even if the amount of luminescence decreases due to the instability of the liquid composition, the degree to which the decrease in luminescence becomes a problem can be relatively reduced by creating a calibration curve for ATP, etc. using the liquid composition under the same conditions each time. [Examples]

[0111] The present invention will be described in more detail below using examples. However, the technical scope of the present invention is not limited in any way by these examples.

[0112] <Example 1: Measurement of luciferase concentration> (280nm absorbance method) The absorbance at 280 nm of the sample solution, appropriately diluted with PBS, was measured using a U-3900 spectrophotometer (Hitachi High-Tech Science Corporation), and the luciferase concentration (mg protein / mL) was determined. (Bradford Procedure) Protein concentration was measured using the Coomassie (Bradford) Protein Assay Kit (Thermo Scientific), based on the Bradford method. Specifically, 100 μL of protein assay reagent (Quick Start Bradford 1× Dye Reagent, Thermo Scientific) was added to 100 μL of sample solution diluted appropriately with PBS, and the absorbance at 595 nm was measured using a MICROPLATE READER SH-9000 (Corona Electric). Instead of the sample solution, Albumin Standard Ampules, 2 mg / mL, included in the kit, were used as a standard protein for measurement, and a calibration curve was created to determine the amount of luciferase. (Conversion between 280nm absorbance method and Bradford method) The measurement results showed that 1 mg protein / mL using the 280 nm absorbance method was equivalent to 1.77 mg / mL using the Bradford method.

[0113] <Example 2: Preparation of Cycling Luminescence Reagent and Background Luminescence Amount> Based on the alternative composition of Lucipak Pen (manufactured by Kikkoman Biochemifa Co., Ltd. (hereinafter the same), a kit used by adding an extraction reagent (solution) to a powdered luminescence reagent) described in

[0094] of International Publication No. 2018 / 147443, a new basic composition solution was designed. The alternative composition of Lucipak Pen is as follows:

[0114] <Alternative composition of LuciPac Pen> 7 mM magnesium acetate, 0.5 mM luciferin, 25 mM tricine, 0.2 mg protein / mL luciferase (value based on absorbance at 280 nm; hereafter, this will be expressed as 0.35 mg / mL, which is the value obtained by the Bradford method based on Example 1), 0.2 mM potassium pyrophosphate, 1.4 mM potassium phosphoenolpyruvate, 1.3 U / mL PPDK Following the instructions for the Lucipac Pen, the stainless steel surface was wiped with a water-moistened cotton swab, and then the swab was pressed in to dissolve the powdered luminescence reagent in the resulting extraction reagent (solution). The volume of the solution was 0.35 mL, and the pH was 7.8. Based on these results and the composition of the Lucipac Pen described above, a new solution with the following basic composition was designed.

[0115] <Basic composition> 7 mM magnesium acetate, 0.5 mM luciferin (manufactured by Biosynth, hereafter the same), 25 mM trichine, 0.35 mg / mL (Bradford method) luciferase (HL as described in Japanese Patent Publication No. 11-239493) K、 (The same applies hereafter), 0.2 mM potassium pyrophosphate, 1.4 mM potassium phosphoenolpyruvate, 1.3 U / mL PPDK (PPDK as described in Japanese Patent Publication No. 8-168375, manufactured by Kikkoman Biochemifa Co., Ltd., the same applies hereafter), pH 7.8, liquid volume per luminescence measurement container: 0.35 mL A luminescent reagent with the basic composition described above was prepared, and 0.35 mL was measured into the luminescent reagent container of the LuciPac Pen (measuring tube, 10φ top × 35 mm height, hereafter the same). This container was attached to the main unit equipped with a cotton swab holder, and measured using a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd., hereafter the same). The amount of luminescence at this time was defined as the background luminescence. To convert the background luminescence to ATP concentration, 0.01 mL of a 1 × 10⁻⁵ M ATP (manufactured by Oriental Yeast Co., Ltd., hereafter the same) solution was added as a control. The amount of luminescence 10 seconds after addition was measured using the Lumitester Smart, and this amount of luminescence was defined as the luminescence at the time of ATP addition. The Δ luminescence was calculated by subtracting the background luminescence from the luminescence at the time of ATP addition.

[0116] 1 x 10 -5 When 0.01 mL of ATP solution M is added, the ATP concentration (M) in the solution (total 0.36 mL) is 2.77 × 10⁻¹⁴. -7 Therefore, the background ATP+AMP concentration was calculated based on the following formula. Background ATP+AMP concentration (M) = Background luminescence (RLU) / Δluminescence (RLU) × 2.77 × 10 -7 (M) Table 1 shows the background luminescence (RLU), luminescence with ATP addition (RLU), Δ luminescence (RLU), and background ATP+AMP concentration (M). RLU stands for Relative Light Units.

[0117] [Table 1]

[0118] The background luminescence is thought to be due to ATP or AMP contamination from reagents, containers, and equipment during preparation. When prepared with the usual care of a person skilled in the art, the luminescence is approximately 500 RLU, which, as shown in Table 1, corresponds to 2.7 × 10⁻¹⁶ ATP + AMP concentration in the luminescent reagent. -10This corresponds to M (0.27 nM). Note that this concentration is approximately 1 × 10⁻¹⁶ in 0.35 mL of reagent. -8 This corresponds to the concentration obtained when 0.01 mL of M ATP solution is added.

[0119] Furthermore, in reagents that measure the three components ATP+ADP+AMP by adding an enzyme that converts ADP to ATP or AMP, the ADP mixed into the reagent will also be measured, and since an enzyme that may cause contamination of ATP, ADP, and AMP is added, it is expected that the background luminescence will be even higher.

[0120] <Example 3: Change in luminescence over time in a non-cycling luminescent reagent> To prepare a non-cycling luminescent reagent, prepare a reagent by removing PPDK, an enzyme necessary for cycling, from the basic composition. Measure 0.35 mL of the prepared solution into a LuciPac Pen luminescent reagent container and set it to 1 × 10⁻⁶. -5 0.01 mL of ATP solution M was added, the swab was attached to the main unit with a cotton swab holder, and measured using the Lumitester Smart. Figure 1 shows the change in luminescence over time for non-cycling luminescent reagents. As shown in Figure 1, in non-cycling luminescent reagents, the added ATP is rapidly consumed in the luciferin-luciferase reaction, the luminescence decreases rapidly, and in the basic composition without PPDK, it is almost quenched in about 2 minutes.

[0121] <Example 4: Stability of cycling luminescence reagents containing luciferin at various concentrations> Following the basic composition, only the luciferin concentration was changed to prepare cycling luminescence reagents containing each concentration of luciferin, and 0.1 mL of 1 × 10⁶ reagent was used, assuming contamination with ATP. -6 M ATP solution was added to 3.5 mL of cycling luminescence reagent (various luciferin concentrations) and allowed to stand at 25°C. At each time interval, 0.36 mL was measured into a Lucipak Pen luminescence reagent container, attached to the main unit with a cotton swab holder, and measured with a Lumitester Smart. The amount of luminescence at this time was defined as the background luminescence. Furthermore, to confirm the stability of the luminescence, 1 × 10⁻⁶-5 0.01 mL of ATP solution M was added, and the amount of luminescence 10 seconds after addition was measured using a Lumitester Smart. The amount of luminescence at this time was defined as the luminescence upon ATP addition, and the difference obtained by subtracting the background luminescence from this amount was defined as the Δ luminescence.

[0122] Figure 2 shows the time course of luminescence for cycling luminescent reagents containing luciferin at various concentrations. Furthermore, Figure 3 shows the luminescence of cycling reagents containing luciferin at 9 hours after obtaining the data from Figure 2.

[0123] In the basic composition, a phenomenon was observed in which the Δluminescence amount decreased over time when ATP was added. In other words, it became clear that the cycling reagent had low stability. Furthermore, the decrease in Δluminescence amount when ATP was added was greater with increasing luciferin concentration, and it was observed that lowering the luciferin concentration from that of the basic composition tended to suppress the decrease in luminescence over time. Normally, in measurement systems using enzymatic reactions, the substrate is added at a high concentration so that the reaction rate is not affected even if the substrate decreases as the enzymatic reaction proceeds. In particular, in cycling reactions, the substrate is consumed continuously, so it is considered appropriate to use a higher concentration of substrate to stabilize the reagent. However, surprisingly, the results of this example revealed that in a cycling luminescence reagent using the luciferin-luciferase reaction, the luminescence amount of the cycling luminescence reagent can be stabilized by lowering the luciferin concentration.

[0124] <Example 5: Stability of a cycling luminescence reagent that does not contain luciferin> Next, we investigated the effect of improving stability in the reagent form in which luciferin is added immediately before the reaction, after being stored without luciferin. Following the basic composition, a cycling luminescence reagent without luciferin was prepared, and assuming contamination with ATP, 0.1 mL of 1 × 10⁶ solution was added to 3.5 mL. -6 M ATP solution was added (hereinafter referred to as the mixed solution).

[0125] (1) In the "Storage with Luciferin" case, 0.1 mL of 17.5 mM luciferin solution (pH 7.8) (final concentration 0.5 mM) was added to 3.6 mL of the above mixture, and the mixture was then stored at 25°C. After each storage period, 0.37 mL of the mixture was measured into the luminescence reagent container of the Lucipak Pen, attached to the main unit equipped with a cotton swab holder, and the background luminescence was measured using a Lumitester Smart. Furthermore, to confirm the stability of the luminescence, 1 × 10⁶ samples were used as a control. -5 0.01 mL of ATP solution M was added, and the amount of luminescence after 10 seconds was measured using a Lumitester Smart, which was defined as the luminescence at the time of ATP addition. The difference between the luminescence at the time of ATP addition and the background luminescence was defined as the luminescence at the time of ATP addition.

[0126] (2) In the "Storage without luciferin" case, 3.6 mL of the above mixture was stored at 25°C without adding luciferin solution. After storage for each time period, 0.36 mL was measured into a Lucipak Pen luminescence reagent container, and 0.01 mL of 17.5 mM luciferin solution (pH 7.8) (final concentration 0.5 mM) stored at 25°C was added. The background luminescence was measured, and then 1 × 10⁻⁶ -5 0.01 mL of ATP solution M was added, and the amount of luminescence 10 seconds after addition was measured using a Lumitester Smart, and this was defined as the luminescence at the time of ATP addition. The difference between the luminescence at the time of ATP addition and the background luminescence was defined as the Δ luminescence.

[0127] Figure 4 shows the stability of luminescent reagents with and without luciferin. As shown in Figure 4, the reagent stored with luciferin underwent a cycling reaction during storage, resulting in a decrease in luminescence. However, the reagent stored without luciferin did not experience a decrease in luminescence during storage and remained constant, demonstrating a significant improvement in stability.

[0128] <Example 6: Stability of luciferin-free reagents in non-cycling luminescent reagents> For reagents that do not contain PPDK in their basic composition, i.e., non-cycling luminescent reagents, (1) RuThe stability of luminescence was confirmed when (1) the sample was stored with luciferin and (2) without luciferin, and the remaining luminescence after 3 hours of storage was shown. The remaining luminescence after 3 hours of storage with cycling (Example 5) was also shown. The results are shown in Figure 5. No decrease in luminescence was observed in the luminescent reagents that were stored without luciferin and to which luciferin was added immediately before measurement. However, in the reagents stored with luciferin, a decrease in luminescence was observed only in the case of the luminescent reagent that cycles and contains PPDK, and no decrease in luminescence was observed in the non-cycling reagent that does not contain PPDK. In other words, the decrease in luminescence observed in this example is a phenomenon that does not occur in luminescent reagents that utilize the luciferin-luciferase reaction and measure only non-cycling ATP, and is considered to be a phenomenon that occurs only when the luminescent reagent that utilizes the cycling reaction is stored in liquid form.

[0129] <Example 7: Luminescence stability in cycling luminescence reagents containing luciferase at various concentrations> Examples 3-6 showed that suppressing the amount of luminescence is important for improving the stability of the luminescence of cycling luminescent reagents. Since it is also possible to suppress the amount of luminescence by reducing the luciferase concentration, we investigated the relationship between the stability of the luminescence in cycling luminescent reagents and the luciferase concentration.

[0130] According to the basic composition, however, the luciferase concentration was changed to prepare cycling luminescence reagents containing luciferase at each concentration, and assuming ATP contamination, 0.1 mL of 1 × 10⁶ solution was used. -6 M ATP solution was added to 3.5 mL of cycling luminescence reagent and allowed to stand at 25°C. At each time interval, 0.36 mL was measured into a LuciPac Pen luminescence reagent container, attached to the main unit with a cotton swab holder, and measured with a Lumitester Smart. The amount of luminescence at this time was defined as the background luminescence. Furthermore, to confirm the stability of the luminescence, 1 × 10⁶ was used as a control. -50.01 mL of ATP solution M was added, and the amount of luminescence 10 seconds after addition was measured using a Lumitester Smart. The amount of luminescence at this time was defined as the luminescence upon ATP addition, and the difference obtained by subtracting the background luminescence from this amount was defined as the Δ luminescence.

[0131] Figure 6 shows the residual luminescence of cycling luminescence reagents containing luciferase at various concentrations. Furthermore, Figure 7 shows the luminescence of cycling reagents with each luciferase concentration after 9 hours, as shown in Figure 6.

[0132] As shown in Figure 6, the higher the luciferase concentration, the greater the decrease in luminescence over time, and the lower the luciferase concentration was compared to the basic composition, the more the decrease in luminescence tended to be suppressed.

[0133] <Example 8: ATP concentration dependence of luminescence decrease in cycling luminescence reagent> In cycling luminescence reagents, if ATP is present in the measurement system, luminescence should continue at a constant level as long as the substrate, luciferin, is not depleted. As shown in Examples 4-7, even without adding ATP after storage, similar experimental results can be obtained by adding ATP before storage and observing the change in luminescence over time, thus allowing for a simple investigation of the stability of the luminescence reagent. In this example, in order to construct an experimental system that does not require the addition of ATP after storage, we decided to investigate the appropriate ATP concentration when ATP solution is not added after storage.

[0134] Prepare the cycling luminescence reagent according to the basic composition, measure 0.35 mL into the luminescence reagent container of the LuciPac Pen, and then add 1 × 10⁻⁶ -5 ~1 × 10 -8 0.01 mL of ATP solution M or sterile ultrapure water was added, and the luminescence was measured over time using a Lumitester Smart. Δluminescence was calculated by subtracting the luminescence of the sample with sterile ultrapure water from the luminescence of the sample with ATP at each concentration, and these results are shown in the respective graphs.

[0135] The results are shown in Figure 8. The attenuation of luminescence was correlated with ATP concentration, with a tendency for greater attenuation at higher ATP concentrations and less attenuation at lower ATP concentrations.

[0136] The amount of ATP assumed to be mixed in with the cycling luminescence reagent prepared in Example 2 is approximately 1 × 10⁻⁶ -8 This is equivalent to adding 0.01 mL of M, and the presence of ATP at that concentration level means that no decrease in luminescence is observed after 2 hours. Therefore, while the decrease in luminescence is not a major problem when the cycling luminescence reagent is used up in a short period, the degree to which it becomes a problem may increase when stored for a long period. For example, if the decrease in luminescence is proportional to the amount of luciferin consumed, i.e., the amount of luminescence, then 1 × 10⁻⁶ -5 When M ATP was added, the luminescence decreased to 30% in 2 hours, therefore, calculated to be 1 × 10 -6 If M ATP is present, 20 hours, 1 × 10 -7 If M ATP is present, the reaction time is 200 hours (8.3 days), 1 × 10⁻¹⁶ -8 If M's ATP is mixed in, the amount of luminescence is expected to decrease to the same level in 2000 hours (83 days).

[0137] In the examples described herein, a high-concentration ATP solution was added to obtain results in a short time. While the stability of the measurement kit may be affected by the stability of the enzyme and the substrate itself, the luminescence does not decrease with low concentrations of ATP, so it is considered possible to evaluate the results without being affected by the stability of the enzyme or substrate, at least for a short time.

[0138] <Example 9: Luminescence during storage and reagent stability of cycling luminescence reagents containing luciferin at various concentrations> As shown in Example 8, the stability of a cycling luminescence reagent can be investigated by adding ATP to the reagent and examining the change in luminescence over time. It was also found that results could be obtained in a short time by adding a high concentration of ATP. Furthermore, from Examples 3 to 6, it became clear that it is important to suppress the luminescence reaction during storage. In this example, in order to suppress the luminescence reaction during storage, experiments were conducted to define the amount of luminescence under standard storage conditions. First, the definition of the amount of luminescence under storage conditions is presented, and then the experimental results that formed the basis of this definition are presented.

[0139] The luminescence luminescence (RLU) under storage conditions is measured by adding 0.35 mL of the luminescence reagent under storage conditions to a measurement tube, and then measuring 1 × 10⁻⁶ -7 The luminescence (RLU) is defined as the amount of light emitted when 0.01 mL of ATP solution M is added, the mixture is allowed to stand at 25°C for 1 hour, and then measured using a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd.).

[0140] The experiment to establish the definition is as follows: Prepare cycling luminescence reagents containing luciferin at various concentrations (components other than luciferin are the same as the basic composition), measure 0.35 mL into the luminescence reagent container of Lucipak Pen, and then further measure 1 × 10⁻⁶ -5 ~1 × 10 -8 0.01 mL of ATP solution M or sterile ultrapure water was added, and the luminescence was measured over time using a Lumitester Smart. The Δ luminescence was calculated by subtracting the luminescence of the sample with sterile ultrapure water from the luminescence when ATP was added at each concentration, and is shown in Figures 9-14.

[0141] As shown in Figures 9-10, 1 × 10 -5 When ATP M was added, a decrease in luminescence was observed, yielding results similar to those in Example 4. This method confirmed that, by conducting short-term tests, it is possible to predict long-term storage stability without being affected by the degradation of the enzyme or the substrate itself.

[0142] When defining the amount of luminescence during storage, for example, when stopping cycling, the amount of luminescence immediately after adding ATP is high, as shown in Figure 1 of Example 3. Therefore, simply measuring the amount of luminescence immediately after adding ATP does not allow for a proper evaluation of the effect of stopping cycling. In contrast, for example, if ATP is broken down by luciferase one hour after ATP addition, the amount of luminescence one hour later can be examined to determine the amount of luminescence during storage, including the effect of stopping cycling. However, as shown in Figures 9-12, 1 × 10⁻⁶ -5 M or 1×10 -6 When adding M ATP solution, a decrease in luminescence over time is observed, making it impossible to accurately measure the amount of luminescence during storage. On the other hand, as shown in Figures 13-14, 1 × 10 -7 Since no decrease in luminescence is observed in M ​​for about 2 hours, it is possible to investigate the luminescence during stable storage. On the other hand, 1 × 10 -8 In M, the Δ emission amount is about the same as the background emission amount shown in Example 2, and is therefore susceptible to its influence, making it unsuitable (data not shown).

[0143] Based on the above results, the luminescence luminescence (RLU) under storage conditions was defined as described above. The luminescence luminescence (RLU) under storage conditions according to this definition is shown in Table 2 below.

[0144] [Table 2]

[0145] Figure 10 shows that lowering the luciferin concentration to below 0.5 mM (6000 RLU in storage conditions, according to Table 2) results in less decrease in luminescence compared to the basic composition and a tendency towards improved stability. Furthermore, Figure 10 shows that stability can be significantly improved, especially when the luciferin concentration is 0.1 mM or less (2300 RLU or less in storage conditions, according to Table 2).

[0146] <Example 10: Luminescence and stability during storage of cycling luminescence reagents containing luciferase at various concentrations> Prepare cycling luminescence reagents containing luciferase at various concentrations (components other than luciferase are the same as the basic composition), measure 0.35 mL into the luminescence reagent container of the Lucipak Pen, and then further measure 1 × 10⁻⁶ -5 ~1 × 10 -8 0.01 mL of ATP solution M or sterile ultrapure water was added, and the luminescence was measured over time using a Lumitester Smart. The Δluminescence was calculated by subtracting the luminescence of the sample with sterile ultrapure water from the luminescence when ATP was added at each concentration, and is shown in Figures 15-20.

[0147] 1 x 10 -5 A decrease in luminescence was observed when ATP solution M was added, yielding the same trend as in Example 7. This method confirmed that it is possible to investigate long-term storage stability in a short time without being affected by the degradation of the enzyme or the substrate itself. Furthermore, as shown in Figures 19-20, 1 × 10⁻⁶ -7 Since no decrease in luminescence was observed for about 2 hours after adding ATP solution M, the validity of the definition of luminescence under the storage conditions shown in Example 9 is also supported by this example. The luminescence (U) under the storage conditions according to this definition is shown in Table 3 below.

[0148] [Table 3]

[0149] As shown in Figure 15, lowering the luciferase concentration below 0.35 mg / mL (which corresponds to a luminescence of 6000 RLU or less in storage conditions, as shown in Table 3) results in less luminescence reduction and a tendency towards improved stability compared to the basic composition. Furthermore, as shown in Table 3, at the improved concentration (0.07 mg / mL or less), the luminescence was 1 × 10⁻⁶. -7 The luminescence of M after 1 hour following the addition of ATP solution was shown to be less than 2300 RLU.

[0150] <Example 11: Stability of a luminescent reagent that does not contain cycling components> We investigated whether modifying the basic composition, excluding some cycling-related substrates and enzymes, and adding them at the time of measurement could improve stability.

[0151] The luminescence reagent was divided into solution A and solution B. One of the components necessary for the luminescence reaction and the cycling reaction (magnesium acetate, potassium phosphoenolpyruvate, potassium pyrophosphate, luciferin, luciferase, PPDK) was transferred to solution B to prepare the mixture. These were stored separately, and 0.05 mL of each was mixed immediately before the reaction. 0.1 mL of ATP solution was added to this mixture, and the amount of luminescence was measured.

[0152] Luminescent reagent A was prepared with 50 mM Tricine containing the remaining components after removing one of the following: 24 mM magnesium acetate, 1.6 mM luciferin, 4 mM potassium phosphoenolpyruvate (PEP), 0.4 mM potassium pyrophosphate (PPi), 1.0 mg / mL (Bradford method) luciferase, and 4.3 U / mL PPDK (pH 7.8). Luminescent reagent B was prepared with 50 mM Tricine containing one of the following components after removing one of the components removed in solution A: 24 mM magnesium acetate, 4 mM PEP, 0.4 mM PPi, 1.6 mM luciferin, 1.0 mg / mL (Bradford method) luciferase, and 4.3 U / mL PPDK (pH 7.8).

[0153] The compositions of Solution A and Solution B for reagents without luciferase, PPDK, luciferin, magnesium acetate, PEP, and PPi are shown in Tables 4 to 9 below.

[0154] [Table 4]

[0155] [Table 5]

[0156] [Table 6]

[0157] [Table 7]

[0158] [Table 8]

[0159] [Table 9]

[0160] For "mix and store," add 0.5 mL of solution B to 0.5 mL of solution A, and assuming the ATP that was mixed in during preparation, 1 × 10⁻¹⁶ -5 0.01 mL of ATP solution M was added and stored at 25°C for 40 hours. After storage, 0.1 mL of the sample was taken and added to it, along with 0.1 mL of 1 × 10⁶ solution. -6 M ATP was added, and the amount of light emitted 10 seconds after addition was measured using a Lumitester Smart.

[0161] In the "mix after storage" section, 0.5 mL of solution A is mixed with 1 × 10¹⁶ ATP, assuming that ATP was introduced during preparation. -5 0.01 mL of ATP solution M was added, and nothing was added to solution B. The mixture was stored at 25°C for 40 hours. After storage, 0.05 mL of solution B was added to 0.05 mL of solution A containing ATP, and 0.1 mL of 1 × 10⁶ solution was added to this mixture. -6 M ATP was added, and the amount of light emitted 10 seconds after addition was measured using a Lumitester Smart.

[0162] For comparison, the luminescence before storage was measured by mixing 0.5 mL of solution A and 0.5 mL of solution B, resulting in 1 × 10⁻⁶ values. -5 0.01 ml of ATP solution of M L attachment In addition, take 0.1 mL of the sample without preserving it, and add 0.1 mL of 1 × 10⁻¹⁶ to it. -6 The amount of light emitted when M ATP was added is also shown in Figure 21.

[0163] It was found that when luciferase, PPDK, luciferin, magnesium acetate (Mg acetate), PEP, and PPi were "stored mixed together," the amount of luminescence upon ATP addition decreased, while when they were "mixed after storage," a high amount of luminescence was maintained.

[0164] When luciferase, which is involved in the luminescence reaction, and PPDK, which is involved in the cycling reaction, were removed, the cycling reaction did not proceed, and stability improved. Stability also improved when cofactors or substrates such as magnesium acetate, phosphoenolpyruvate, and pyrophosphate were removed. The roles of magnesium acetate, phosphoenolpyruvate, and pyrophosphate in the cycling reaction are as follows:

[0165] The magnesium ions in magnesium acetate are essential for the luciferase and PPDK reactions; without them, the luminescence and cycling reactions will not proceed. Phosphoenolpyruvate is a substrate required for the PPDK reaction, and pyrophosphate is also a substrate required for the PPDK reaction. acid If the ATP is removed, the luminescence reaction proceeds for the amount of ATP present, but it is quenched once the ATP is consumed, and the luminescence reaction does not proceed further.

[0166] These results indicate that separating and storing the components necessary for the luciferase reaction and cycling reaction is an effective way to stop the reaction and improve its stability. All publications, patents, and patent applications cited herein shall be incorporated herein by direct reference.

Claims

1. A liquid composition for measuring ATP, AMP, and / or ADP in a sample after storage, (i)-1 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein luciferin is added to the liquid composition before or during the measurement, or (i)-2 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the luciferase is added to the liquid composition before or during the measurement, or (i)-3 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from AMP is added to the liquid composition before or during measurement, or (i)-4 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP is added to the liquid composition before or during measurement, or (i)-5 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactor is added to the liquid composition before or during measurement. (i)-6 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein luciferin and luciferase are added to the liquid composition before or during the measurement, or (i)-7 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from luciferin and AMP is added to the liquid composition before or during measurement, or (i)-8 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrates of the enzyme that catalyzes the reaction to produce ATP from luciferin and AMP are added to the liquid composition before or during the measurement, or (i)-9 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and luciferin and cofactors are added to the liquid composition before or during the measurement, or (i)-10 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-11 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrates of the luciferase and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-12 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, wherein the luciferase and cofactors are added to the liquid composition before or during the measurement, or (i)-13 The liquid composition comprises luciferase, luciferin, and cofactors, wherein the enzyme that catalyzes the reaction to produce ATP from AMP and the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, (i)-14 The liquid composition comprises luciferase, luciferin, and a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, wherein the enzyme and cofactor that catalyze the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-15 The liquid composition comprises luciferase, luciferin, and an enzyme that catalyzes the reaction to produce ATP from AMP, wherein the substrate and cofactors of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-16 The liquid composition comprises luciferin and luciferase, and the enzyme that catalyzes the reaction to produce ATP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-17 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from luciferin and AMP, and the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactors are added to the liquid composition before or during the measurement, or (i)-18 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from luciferin and AMP, and the luciferase, the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactor are added to the liquid composition before or during the measurement, or (i)-19 The liquid composition comprises luciferin and cofactors, and luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, or (i)-20 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ATP from AMP, and luciferin, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor are added to the liquid composition before or during the measurement, or (i)-21 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from luciferase and AMP, and luciferin, the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-22 The liquid composition comprises luciferase and cofactors, and luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, or (i)-23 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from AMP and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and luciferase, luciferin, and cofactors are added to the liquid composition before or during the measurement, or (i)-24 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ATP from AMP, and the luciferase, luciferin, and substrates of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-25 The liquid composition contains substrates and cofactors of an enzyme that catalyzes the reaction to produce ATP from AMP, and the luciferase, luciferin, and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-26 The liquid composition contains luciferin, and luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-27 The liquid composition contains luciferase, and luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-28 The liquid composition contains an enzyme that catalyzes the reaction that produces ATP from AMP, and luciferase, luciferin, a substrate of the enzyme that catalyzes the reaction that produces ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-29 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and luciferase, luciferin, the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-30 The liquid composition contains cofactors, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement. and (ii) The relative luminescence of the liquid composition during storage is 5500 RLU or less, The aforementioned relative luminescence is the value obtained by subtracting the control value from the measured value. The above measurement was obtained by adding 0.35 mL of the liquid composition to the measuring tube of a Lucipac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.), and then 1 × 10⁻⁶ -7 The value was obtained by adding 0.01 mL of ATP solution M (manufactured by Oriental Yeast Co., Ltd.), allowing it to stand at 25°C for 1 hour, and then measuring it with a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd.). The aforementioned control value is the value obtained when the amount of luminescence is measured under the same conditions as those used to obtain the aforementioned measurement, except that sterile ultrapure water is added instead of ATP solution. The shelf life is one day or longer. The aforementioned liquid composition.

2. The liquid composition according to claim 1, further comprising at least one component selected from an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, an enzyme that catalyzes the reaction of producing AMP from ADP, or a substrate for an enzyme that catalyzes the reaction of producing AMP from ADP, or at least one of these components being added before or during measurement.

3. A liquid composition for measuring ATP, AMP, and / or ADP in a sample after storage, (i)-1 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin is added before or during the measurement, or (i)-2 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase is added before or during the measurement, or (i)-3 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP is added before or during the measurement, or (i)-4 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP is added before or during the measurement, or (i)-5 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ATP from ADP is added before or during the measurement, or (i)-6 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP is added before or during the measurement, or (i)-7 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor is added before or during the measurement. (i)-8 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin and luciferase are added before or during the measurement, (i)-9 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, or (i)-10 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-11 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-12 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-13 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin and cofactors are added before or at the time of measurement, (i)-14 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, or (i)-15 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-16 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or at the time of measurement, (i)-17 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-18 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase and cofactors are added before or during the measurement, (i)-19 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-20 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ADP from AMP and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-21 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-22 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme and cofactors that catalyze the reaction to produce ADP from AMP are added before or during the measurement, (i)-23 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP and the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-24 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrates of the enzyme that catalyzes the reaction to produce ADP from AMP and the substrates of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-25 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate and cofactors for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, or (i)-26 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from ADP and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-27 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme and cofactors that catalyze the reaction to produce ATP from ADP are added before or during the measurement, (i)-28 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate and cofactors for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-29 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, or (i)-30 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-31 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or at the time of measurement, (i)-32 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-33 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, luciferase, and cofactors are added before or at the time of measurement, (i)-34 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-35 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-36 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-37 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and cofactors are added before or during the measurement, (i)-38 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-39 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-40 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor are added before or during the measurement, or (i)-41 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-42 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-43 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-44 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-45 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, or (i)-46 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-47 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-48 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-49 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-50 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-51 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ATP from ADP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, or (i)-52 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ATP from ADP, and the cofactors are added before or during the measurement, (i)-53 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-54 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-55 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-56 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and cofactors are added before or during the measurement, or (i)-57 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-58 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor are added before or at the time of measurement, (i)-59 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-60 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-61 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-62 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-63 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-64 The liquid composition comprises luciferin, luciferase, and an enzyme that catalyzes the reaction to produce ADP from AMP, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-65 The liquid composition comprises luciferin, luciferase, and a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ADP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-66 The liquid composition comprises luciferin, luciferase, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-67 The liquid composition comprises luciferin, luciferase, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor are added before or at the time of measurement, (i)-68 The liquid composition comprises luciferin, luciferase, and cofactors, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-69 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, or (i)-70 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-71 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-72 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-73 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-74 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-75 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-76 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-77 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate of the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate of the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-78 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-79 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, or (i)-80 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-81 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor are added before or during the measurement, or (i)-82 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-83 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-84 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-85 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-86 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-87 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-88 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ATP from luciferase and ADP, and a cofactor, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-89 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-90 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-91 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-92 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-93 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-94 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-95 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-96 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-97 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-98 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-99 The liquid composition comprises luciferin and luciferase, wherein an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-100 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from luciferin and AMP, and the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-101 The liquid composition comprises luciferin and a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-102 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from luciferin and ADP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-103 The liquid composition comprises luciferin and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-104 The liquid composition comprises luciferin and cofactors, wherein luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during measurement, (i)-105 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-106 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction to produce ADP from luciferase and AMP, and the luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-107 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ATP from ADP, and luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-108 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ATP from luciferase and ADP, and the luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-109 The liquid composition comprises luciferase and cofactors, wherein luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during measurement, (i)-110 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-111 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-112 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor are added before or during the measurement, or (i)-113 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ADP from AMP, and the luciferase, luciferin, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, enzyme that catalyzes the reaction to produce ATP from ADP, and substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-114 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-115 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and includes luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor. It is added before or during measurement, or (i)-116 The liquid composition comprises a substrate and cofactor of an enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-117 The liquid composition comprises an enzyme that catalyzes the reaction of producing ATP from ADP and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-118 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ATP from ADP, and the luciferase, luciferin, enzyme that catalyzes the reaction to produce ADP from AMP, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-119 The liquid composition comprises a substrate and cofactor of an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, luciferin, enzyme that catalyzes the reaction to produce ADP from AMP, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-120 The liquid composition comprises luciferin, and luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-121 The liquid composition comprises luciferase, and luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-122 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-123 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-124 The liquid composition contains an enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-125 The liquid composition contains a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-126 The liquid composition contains cofactors, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during measurement. and (ii) The relative luminescence of the liquid composition during storage is 5500 RLU or less, The aforementioned relative luminescence is the value obtained by subtracting the control value from the measured value. The above measurement was obtained by adding 0.35 mL of the liquid composition to the measuring tube of a Lucipac Pen (manufactured by Kikkoman Biochemifa Co., Ltd.), and then 1 × 10⁻⁶ -7 The value was obtained by adding 0.01 mL of ATP solution M (manufactured by Oriental Yeast Co., Ltd.), allowing it to stand at 25°C for 1 hour, and then measuring it with a Lumitester Smart (manufactured by Kikkoman Biochemifa Co., Ltd.). The aforementioned control value is the value obtained when the amount of luminescence is measured under the same conditions as those used to obtain the aforementioned measurement, except that sterile ultrapure water is added instead of ATP solution. The shelf life is one day or longer. The aforementioned liquid composition.

4. The liquid composition according to any one of claims 1 to 3, wherein the relative luminescence is 2300 RLU or less.

5. A liquid composition for measuring ATP, AMP, and / or ADP in a sample after storage, (i)-1 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein luciferin is added to the liquid composition before or during the measurement, or (i)-2 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the luciferase is added to the liquid composition before or during the measurement, or (i)-3 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from AMP is added to the liquid composition before or during measurement, or (i)-4 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP is added to the liquid composition before or during measurement, or (i)-5 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactor is added to the liquid composition before or during measurement. (i)-6 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein luciferin and luciferase are added to the liquid composition before or during the measurement, or (i)-7 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from luciferin and AMP is added to the liquid composition before or during measurement, or (i)-8 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrates of the enzyme that catalyzes the reaction to produce ATP from luciferin and AMP are added to the liquid composition before or during the measurement, or (i)-9 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and luciferin and cofactors are added to the liquid composition before or during the measurement, or (i)-10 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-11 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor, wherein the substrates of the luciferase and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-12 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, wherein the luciferase and cofactors are added to the liquid composition before or during the measurement, or (i)-13 The liquid composition comprises luciferase, luciferin, and cofactors, wherein the enzyme that catalyzes the reaction to produce ATP from AMP and the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, (i)-14 The liquid composition comprises luciferase, luciferin, and a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, wherein the enzyme and cofactor that catalyze the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-15 The liquid composition comprises luciferase, luciferin, and an enzyme that catalyzes the reaction to produce ATP from AMP, wherein the substrate and cofactors of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-16 The liquid composition comprises luciferin and luciferase, and the enzyme that catalyzes the reaction to produce ATP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-17 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from luciferin and AMP, and the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactors are added to the liquid composition before or during the measurement, or (i)-18 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from luciferin and AMP, and the luciferase, the enzyme that catalyzes the reaction to produce ATP from AMP, and the cofactor are added to the liquid composition before or during the measurement, or (i)-19 The liquid composition comprises luciferin and cofactors, and luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, or (i)-20 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ATP from AMP, and luciferin, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and a cofactor are added to the liquid composition before or during the measurement, or (i)-21 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from luciferase and AMP, and luciferin, the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-22 The liquid composition comprises luciferase and cofactors, and luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement, or (i)-23 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from AMP and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and luciferase, luciferin, and cofactors are added to the liquid composition before or during the measurement, or (i)-24 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ATP from AMP, and the luciferase, luciferin, and substrates of the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-25 The liquid composition contains substrates and cofactors of an enzyme that catalyzes the reaction to produce ATP from AMP, and the luciferase, luciferin, and the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during the measurement, or (i)-26 The liquid composition contains luciferin, and luciferase, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-27 The liquid composition contains luciferase, and luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-28 The liquid composition contains an enzyme that catalyzes the reaction that produces ATP from AMP, and luciferase, luciferin, a substrate of the enzyme that catalyzes the reaction that produces ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-29 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ATP from AMP, and luciferase, luciferin, the enzyme that catalyzes the reaction to produce ATP from AMP, and cofactors are added to the liquid composition before or during the measurement, or (i)-30 The liquid composition contains cofactors, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from AMP are added to the liquid composition before or during measurement. and (ii) At least one of the following is satisfied: The concentration of luciferin in the liquid composition is 0.4 mM or less; The concentration of luciferase in the liquid composition according to the Bradford method is 0.3 mg / mL or less; The concentration of the enzyme that catalyzes the reaction to produce ATP from AMP in the liquid composition is 1 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from AMP in the liquid composition is 0.1 mM or less; The concentration of the cofactor in the liquid composition is 6 mM or less; The shelf life is one day or longer. The aforementioned liquid composition.

6. The liquid composition according to claim 5, further comprising at least one component selected from an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, an enzyme that catalyzes the reaction of producing AMP from ADP, or a substrate for an enzyme that catalyzes the reaction of producing AMP from ADP, or at least one of these components being added before or during measurement.

7. A liquid composition for measuring ATP, AMP, and / or ADP in a sample after storage, (i)-1 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin is added before or during the measurement, or (i)-2 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase is added before or during the measurement, or (i)-3 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP is added before or during the measurement, or (i)-4 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP is added before or during the measurement, or (i)-5 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ATP from ADP is added before or during the measurement, or (i)-6 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP is added before or during the measurement, or (i)-7 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor is added before or during the measurement. (i)-8 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin and luciferase are added before or during the measurement, (i)-9 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, or (i)-10 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-11 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-12 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-13 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin and cofactors are added before or at the time of measurement, (i)-14 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, or (i)-15 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-16 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or at the time of measurement, (i)-17 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-18 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase and cofactors are added before or during the measurement, (i)-19 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-20 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ADP from AMP and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-21 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-22 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme and cofactors that catalyze the reaction to produce ADP from AMP are added before or during the measurement, (i)-23 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP and the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-24 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the substrates of the enzyme that catalyzes the reaction to produce ADP from AMP and the substrates of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-25 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate and cofactors for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, or (i)-26 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ATP from ADP and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-27 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme and cofactors that catalyze the reaction to produce ATP from ADP are added before or during the measurement, (i)-28 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate and cofactors for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-29 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, or (i)-30 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-31 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or at the time of measurement, (i)-32 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, luciferase, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-33 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, luciferase, and cofactors are added before or at the time of measurement, (i)-34 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-35 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-36 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-37 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and cofactors are added before or during the measurement, (i)-38 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-39 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-40 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor are added before or during the measurement, or (i)-41 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-42 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-43 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-44 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP are added before or during the measurement, (i)-45 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, or (i)-46 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-47 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-48 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-49 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-50 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-51 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ATP from ADP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, or (i)-52 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ATP from ADP, and the cofactors are added before or during the measurement, (i)-53 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-54 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-55 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-56 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and cofactors are added before or during the measurement, or (i)-57 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-58 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor are added before or at the time of measurement, (i)-59 The liquid composition comprises luciferase, luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-60 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-61 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-62 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-63 The liquid composition comprises luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-64 The liquid composition comprises luciferin, luciferase, and an enzyme that catalyzes the reaction to produce ADP from AMP, wherein the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-65 The liquid composition comprises luciferin, luciferase, and a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ADP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-66 The liquid composition comprises luciferin, luciferase, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-67 The liquid composition comprises luciferin, luciferase, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor are added before or at the time of measurement, (i)-68 The liquid composition comprises luciferin, luciferase, and cofactors, wherein the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-69 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, or (i)-70 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-71 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, wherein the luciferase, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-72 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-73 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-74 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-75 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-76 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-77 The liquid composition comprises luciferin, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate of the enzyme that catalyzes the reaction of producing ADP from AMP, and the substrate of the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-78 The liquid composition comprises luciferin, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-79 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, or (i)-80 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-81 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and luciferin, a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor are added before or during the measurement, or (i)-82 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-83 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-84 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-85 The liquid composition comprises luciferase, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and a cofactor, wherein luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-86 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-87 The liquid composition comprises luciferase, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-88 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ATP from luciferase and ADP, and a cofactor, wherein luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-89 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-90 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-91 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-92 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-93 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-94 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-95 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, (i)-96 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, (i)-97 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, and the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during the measurement, (i)-98 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and a cofactor, wherein the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, and the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP are added before or during the measurement, (i)-99 The liquid composition comprises luciferin and luciferase, wherein an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-100 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from luciferin and AMP, and the luciferase, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-101 The liquid composition comprises luciferin and a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-102 The liquid composition comprises an enzyme that catalyzes the reaction to produce ATP from luciferin and ADP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-103 The liquid composition comprises luciferin and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, the enzyme that catalyzes the reaction to produce ADP from AMP, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-104 The liquid composition comprises luciferin and cofactors, wherein luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP are added before or during measurement, (i)-105 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-106 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction to produce ADP from luciferase and AMP, and the luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, the substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-107 The liquid composition comprises a luciferase and an enzyme that catalyzes the reaction to produce ATP from ADP, and luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-108 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ATP from luciferase and ADP, and the luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-109 The liquid composition comprises luciferase and cofactors, wherein luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during measurement, (i)-110 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP and a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, or (i)-111 The liquid composition comprises an enzyme that catalyzes the reaction of producing ADP from AMP and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-112 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP and a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, luciferin, the substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the cofactor are added before or during the measurement, or (i)-113 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ADP from AMP, and the luciferase, luciferin, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, enzyme that catalyzes the reaction to produce ATP from ADP, and substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-114 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP and an enzyme that catalyzes the reaction of producing ATP from ADP, wherein luciferase, luciferin, the enzyme that catalyzes the reaction of producing ADP from AMP, the substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or during the measurement, (i)-115 The liquid composition comprises a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP and a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and includes luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and a cofactor. It is added before or during measurement, or (i)-116 The liquid composition comprises a substrate and cofactor of an enzyme that catalyzes the reaction to produce ADP from AMP, and the luciferase, luciferin, the enzyme that catalyzes the reaction to produce ADP from AMP, the enzyme that catalyzes the reaction to produce ATP from ADP, and the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-117 The liquid composition comprises an enzyme that catalyzes the reaction of producing ATP from ADP and a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, and cofactors are added before or during the measurement, or (i)-118 The liquid composition comprises an enzyme and cofactors that catalyze the reaction to produce ATP from ADP, and the luciferase, luciferin, enzyme that catalyzes the reaction to produce ADP from AMP, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and substrate of the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-119 The liquid composition comprises a substrate and cofactor of an enzyme that catalyzes the reaction to produce ATP from ADP, and the luciferase, luciferin, enzyme that catalyzes the reaction to produce ADP from AMP, substrate of the enzyme that catalyzes the reaction to produce ADP from AMP, and enzyme that catalyzes the reaction to produce ATP from ADP are added before or during the measurement, or (i)-120 The liquid composition comprises luciferin, and luciferase, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-121 The liquid composition comprises luciferase, and luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-122 The liquid composition comprises an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or during the measurement, (i)-123 The liquid composition contains a substrate for an enzyme that catalyzes the reaction to produce ADP from AMP, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, a substrate for an enzyme that catalyzes the reaction to produce ATP from ADP, and cofactors are added before or at the time of measurement, (i)-124 The liquid composition contains an enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for the enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-125 The liquid composition contains a substrate for an enzyme that catalyzes the reaction of producing ATP from ADP, and luciferase, luciferin, an enzyme that catalyzes the reaction of producing ADP from AMP, a substrate for an enzyme that catalyzes the reaction of producing ADP from AMP, an enzyme that catalyzes the reaction of producing ATP from ADP, and cofactors are added before or at the time of measurement, (i)-126 The liquid composition contains cofactors, and luciferase, luciferin, an enzyme that catalyzes the reaction to produce ADP from AMP, a substrate for the enzyme that catalyzes the reaction to produce ADP from AMP, an enzyme that catalyzes the reaction to produce ATP from ADP, and a substrate for the enzyme that catalyzes the reaction to produce ATP from ADP are added before or during measurement. and (ii) At least one of the following is satisfied: The concentration of the enzyme that catalyzes the reaction to produce ADP from AMP in the liquid composition is 450 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ADP from AMP in the liquid composition is 0.1 mM or less; The concentration of the enzyme that catalyzes the reaction to produce ATP from ADP in the liquid composition is 20 U / mL or less; The concentration of the substrate of the enzyme that catalyzes the reaction to produce ATP from ADP is 1.2 mM or less; The concentration of the cofactor in the liquid composition is 6 mM or less; The shelf life is one day or longer. The aforementioned liquid composition.

8. A liquid composition according to any one of claims 1 to 7, wherein the shelf life is 30 days or more.

9. The liquid composition according to any one of claims 1 to 8, wherein the concentration of luciferin in the liquid composition is 0.4 mM or less, and / or the concentration of luciferase based on the Bradford method is 0.3 mg / mL or less.

10. The liquid composition according to any one of claims 1 to 9, wherein the concentration of luciferin in the liquid composition is 0.1 mM or less.

11. The liquid composition according to any one of claims 1 to 10, wherein the concentration of luciferase in the liquid composition according to the Bradford method is 0.1 mg / mL or less.

12. A kit for measuring ATP in a sample, comprising the liquid composition according to any one of claims 1 to 11.

13. A method for measuring ATP, AMP, and / or ADP in a sample, comprising using the liquid composition described in any one of claims 1 to 11 or the kit described in claim 12.

14. The method according to claim 13, wherein an ATP standard solution is not used.

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