RU2800131C2 - Methods for colorimetric detection of endpoints and multiple titration systems - Google Patents

Abstract

FIELD: chemical industry.

SUBSTANCE: group of inventions relates to a system for the quantitative determination of the concentrations of one or more target analytes in a process solution. The automated titration system includes a reactor manifold containing a conditioning manifold and a second liquid mixer, while the reactor manifold is in fluid communication with a sample source and a titrant source for mixing a continuously flowing and renewed sample stream containing an unknown concentration of the first analyte with the first titrant and an unknown concentration of the second analyte with second titrant; a sample pump in fluid communication with the sample source and the reactor manifold, continuously pumping a sample stream from the sample source into the reactor manifold through the sample stream inlet; a first titrant pump in fluid communication with the first titrant source and the reactor manifold for pumping the first titrant into the reactor manifold through the first titrant inlet to contact a continuously flowing and renewing sample stream; a second titrant pump in fluid communication with the second titrant source and the reactor manifold for pumping the second titrant into the reactor manifold through the second titrant inlet to contact a continuously flowing and renewing sample stream; a multi-wavelength detector in fluid communication with the reactor manifold for detecting a first titration endpoint of the reaction between the first analyte and the first titrant and for detecting a second titration endpoint of the reaction between the second analyte and the second titrant, the detector being located downstream of the first and second inlets titrants and is located at a distance from the inputs of the first and second titrants; and a controller in communication with the sample pump, the first titrant pump, the second titrant pump, and the detector. In this case, the conditioning manifold contains the first liquid mixer, and the conditioning manifold is located downstream of the sample flow inlet, while the first titrant inlet and the second titrant inlet are located downstream of the conditioning manifold and upstream of the second liquid mixer, and the second liquid mixer located upstream of the detector. The controller controls the sample pump to set a continuous sample flow rate, controls the first titrant pump to set the flow rate of the first titrant, controls the second titrant pump to set the second titrant to a continuous flow rate, and receives data from the detector to detect the first titration endpoint for the reaction between the first analyte and the first titrant and determining the concentration of the first analyte at the first endpoint of the titration and detecting the second endpoint of the titration for the reaction between the second analyte and the second titrant and determining the concentration of the second analyte at the second endpoint of the titration. Also disclosed is a method for quantifying the concentration of a first target analyte and the concentration of a second target analyte in a sample stream.

EFFECT: group of inventions provides efficient and reliable automated titration for various target analytes.

15 cl, 7 dwg, 1 tbl

Description

FIELD OF TECHNOLOGY

[0001] Systems are provided for quantifying the concentrations of one or more target analytes in a process solution, which can be used, for example, in methods for quantifying the concentration of a target analyte. These systems and methods include continuous automated titration methods that use the titration chemistry to measure the concentration of a target analyte in a process solution. These methods provide efficient and reliable automated titration methods for various target analytes and may include methods that analyze more than one analyte and that provide a dynamic range for measuring the concentration of more than one target analyte.

BACKGROUND OF THE INVENTION

[0002] Titration is a well known and practiced method for determining the concentrations of the components of a solution. Titration is used with various chemical compositions, in which the titrant is usually added to a solution in which it reacts with the components selected for it. After all of the reacting component has reacted with said known titrant, a measurable or noticeable change occurs, indicating completion of the reaction. In some cases, the noticeable change includes a change in color. For example, color change can vary widely depending on the chemical regime of the titration.

[0003] Although titration is known from theory, it can be a tedious process requiring careful practice on the part of a chemist or other experienced operator. In some cases it may not be practical to have a chemist or other technician on hand to perform the titration, although data obtained by titration may be desirable. Automated titrators can be implemented which can be used to determine the point at which the reactions are completed and the corresponding titration calculations to determine the amount of a component in a solution. However, depending on the reaction, it can be difficult for an automated process to determine the end point of the reaction accurately enough. In addition, automated systems may take a long time to complete the process, which may be undesirable or unacceptable if the solution requires monitoring at regular intervals.

SUMMARY OF THE INVENTION

[0004] An automated titration system is provided, including a reactor manifold for mixing a continuously flowing and renewable sample stream containing an unknown concentration of one or more analytes with titrants; a sample pump for pumping a continuously current and renewable sample stream into the reactor manifold; a first titrant pump for pumping the first titrant into the reactor manifold to contact a continuously flowing and renewing sample stream; a multi-wavelength detector for detecting the first titration end point of the reaction between the analyte and the first titrant; and a controller communicatively connected to the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set the flow rate of the continuously current and updated sample flow, controls the first titrant pump to set the flow rate of the first titrant, and receives data from the detector to detect the first titration endpoint for the reaction between the analyte and the first titrant and determine the analyte concentration at the first titration endpoint.

[0005] An automated titration system is provided that includes a reactor manifold for mixing a sample stream containing an unknown analyte concentration with a first titrant; a sample pump for pumping a sample stream into the reactor manifold; a first titrant pump for pumping the first titrant into the reactor manifold for contact with the sample stream; a multi-wavelength detector for detecting the first titration end point of the reaction between the analyte and the first titrant; and a controller communicatively connected to the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set the sample flow rate, controls the first titrant pump to set the first titrant flow rate, and receives data from the detector to detect the first titration endpoint for the reaction between the analyte and the first titrant and determine the concentration of the analyte at the first titration endpoint.

[0006] In the automated titration systems described herein, the sample stream may contain two or more analytes.

[0007] In addition, the automated titration systems described herein may further comprise a second titrant pump for pumping the second titrant into the reactor manifold for contact with a sample batch stream or a continuously flowing and updated sample stream. The multiwavelength detector may further detect a second titration endpoint of the reaction between the analyte and the second titrant, the controller is further communicatively coupled to the second titrant pump, and the controller further controls the second titrant pump to set the second titrant flow rate and receives data from the detector to detect the second titration endpoint for the reaction between the analyte and the second titrant and determine the analyte concentration at the second titration endpoint.

[0008] In the automated titration systems described herein, the second titrant may react with the second analyte.

[0009] The automated titration systems described herein may further comprise a third titrant pump for pumping the third titrant into the reactor manifold for contact with a sample batch stream or a continuously flowing and updated sample stream. The multi-wavelength detector may further detect a third titration endpoint of the reaction between the analyte and the third titrant, wherein the controller is further communicatively connected to the third titrant pump, and the controller further controls the third titrant pump to set the third titrant flow rate and receives data from the detector to detect the third titration endpoint for the reaction between the analyte and the third titrant and determine the concentration of the analyte at the third titrant endpoint.

[0010] In the automated titration systems described herein, a third titrant may be reacted with a third analyte.

[0011] The automated titration systems described herein may have a multi-wavelength detector capable of detecting signals ranging from ultraviolet to visible light.

[0012] In addition, the automated titration systems described herein may have a multi-wavelength detector as a spectrometer.

[0013] The automated titration systems described herein may have a reactor manifold containing a liquid mixer located downstream of the titrant inlet and upstream of the detector.

[0014] The automated titration systems described herein may also optionally include a conditioning manifold upstream of the titrant inlet and downstream of the sample stream inlet.

[0015] The automated titration system described herein may have a conditioning manifold containing a liquid mixer.

[0016] The automated titration system described herein may have a conditioning manifold further comprising a mixing loop.

[0017] The automated titration systems described herein may further comprise a conditioning agent pump for pumping the conditioning agent into the conditioning manifold for mixing with a constantly flowing and renewing sample stream.

[0018] The automated titration system may include a pH buffer conditioning agent, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, a biobased chemical, or a combination thereof.

[0019] In the automated titration systems described herein, the conditioning agent may contain potassium iodide, sulfuric acid, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

[0020] The automated titration system may have a conditioning agent pump, further comprising a first conditioning agent pump for pumping the first conditioning agent and a second conditioning agent pump for pumping the second conditioning agent.

[0021] In an automated titration system, the first conditioning agent may be a metal iodide and the second conditioning agent an indicator.

[0022] In the automated titration systems described herein, a conditioning agent pump may introduce a conditioning agent into a current sample stream, wherein a controller is communicatively connected to the conditioning agent pump and configured to control the conditioning agent pump to set the flow rate of the conditioning agent that is injected into the sample batch stream or into a continuously flowing and updated sample stream.

[0023] The automated titration systems described herein can be used in methods for quantifying a target analyte.

[0024] For example, this document describes a method for quantifying the concentration of a target analyte in a sample stream, including: continuously passing and constantly updating the sample stream at a known flow rate through an analyzer containing a collector and a multi-wavelength detector; quantitative determination of the concentration of the target analyte by continuously adding a titrant to the analyzer and setting the change in the concentration of the titrant by changing the concentration of the titrant by increasing or decreasing the flow rate of the titrant in a given range; and determining a titration endpoint for a reaction between a target analyte in the sample stream and a titrant within a predetermined concentration range of the target analyte.

[0025] In addition, a method for quantifying the concentration of a target analyte in a sample stream may include adding a sample to an analyzer comprising a collector and a multiwavelength detector; quantifying the concentration of the target analyte by adding a titrant to the analyzer and setting the change in the concentration of the titrant by changing the concentration of the titrant by increasing or decreasing the flow rate of the titrant in a given range; and determining the end point of the titration for the reaction between the target analyte in the sample stream and the titrant within a predetermined concentration range of the target analyte; the sample stream contains two or more analytes.

[0026] Assay methods may include that the sample stream contains two or more analytes.

[0027] In this method, the sample stream may further comprise a second analyte.

[0028] The methods described herein may further include quantifying the second analyte by continuously adding the second titrant to a sample batch stream or to a continuously flowing and constantly updated sample stream.

[0029] In this method, the sample stream may further comprise a third analyte.

[0030] These quantitation methods may further include quantifying a third analyte by continuously adding a third titrant to a sample batch stream or to a continuously flowing and constantly updated sample stream.

[0031] These methods may have a known sample flow rate from about 1 μl/min to about 200 ml/min.

[0032] These methods may have a known sample flow rate from about 5 ml/min to about 25 ml/min.

[0033] These methods may further include continuously adding a conditioning agent to the sample stream at a concentration proportional to the concentration of the target analyte.

[0034] These quantification methods may further include determining the end point of the titration using a multi-wavelength detector that is at a certain distance from the titrant addition point, and calculating the concentration of the titrant using the distance between the detector and the titrant addition point, titrant flow rate, and system volume.

[0035] The methods described herein may further include changing the concentration of the titrant by adjusting its flow rate, wherein the detector signal from the titration reaction product correlates over time with the concentration of the titrant.

[0036] These methods may further include dosing a calibrant of known concentration into the sample stream, determining the concentration of the calibrant, and calculating the response.

[0037] These quantification methods may further include controlling the concentration of the titrant using a feedback loop that is responsive to a detector detecting a reaction between the titrant and the target analyte.

[0038] Described herein are methods in which a conditioning reagent treats a sample stream to improve detection of a target analyte.

[0039] These methods can improve the detection of the target analyte by increasing the sensitivity of the detection method.

[0040] In the methods described herein, the conditioning agent can be a pH buffer, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, a biobased chemical, or a combination thereof.

[0041] In assay methods, the conditioning agent may include potassium iodide, acetic acid, a starch indicator, or a combination thereof.

[0042] In the method described herein, the flow rate of a continuously current and constantly updated sample flow can increase or decrease depending on whether the endpoint of the titration can be detected within the specified concentration range of the target analyte.

BRIEF DESCRIPTION OF GRAPHICS

[0043] FIG. 1 is a diagram of an automated titration system having two analytes per sample and two titrant pumps, four conditioning reagent pumps, and a multiwavelength detector in the system.

[0044] FIG. 2 is a diagram of an automated titration system having three analytes per sample and three titrant pumps, three conditioning reagent pumps, and a multiwavelength detector in the system.

[0045] FIG. 3A is a plot of absorbance versus wavelength for a caustic titration with 0.1 N hydrochloric acid.

[0046] FIG. 3B is a plot of absorbance versus drop number for a caustic titration with 0.1 N hydrochloric acid.

[0047] FIG. 4A is spectrum images at each test concentration from 6 to 40 ppm for a peracid sample of approximately 15 ppm.

[0048] FIG. 4B is a plot of absorbance versus wavelength calculated from the spectra shown in FIG. 4A.

[0049] FIG. 5 is a plot of absorbance versus concentration and shows identical trends in the absorbance versus concentration curve.

[0050] FIG. 6 is a graph of absorbance versus wavelength, which shows that the detector gives results similar to the standard.

[0051] FIG. 7A is a plot of absorbance versus wavelength when titrated using the No. 307 hardness kit for titrating laboratory water with a hardness of 17 grains. Fig. 7B is an image showing the number of drops required for the same titration.

DETAILED DESCRIPTION OF THE INVENTION

[0052] The automated titration systems and methods described herein have been developed to analyze more than one analyte. These systems and methods have the advantage that the endpoint is determined by a multi-wavelength detector that allows detection of titration endpoints in the visible wavelength range. The use of a spectrometer and a broad spectrum source allows the titrator's detection system to select the optimal wavelength required for the upcoming titration. The optimal wavelength can be selected by performing an optical density scan of the desired molecule (eg starch-iodine complex). Typically, the wavelength with maximum absorption is used to determine the end point. However, when the absorption response exceeds the desired response, it may be advantageous to use the wavelength of the secondary absorption peak instead. If a reduced response is desired for a particular molecule, as if the concentration of the molecule makes the maximum absorption of the main absorption peak very high, the sensitivity of the instrument optics may be exceeded. In this case, the peak with the lower maximum absorbance will be used so that a high sample concentration at a lower absorbance can be measured more accurately.

[0053] This system configuration can also increase the dynamic range because lower concentration analytes can be measured using the main absorption peak and higher concentration analytes can be measured using the reduced peak without changing the detector system. Thus, an analyte with higher and lower concentrations can be measured within the range of the instrument. This system also allows the instrument to use the same detector system for different titrations that have different absorption peaks for the molecule being measured.

[0054] In addition, a number of titrant pumps can introduce titrants into the sample stream to react with more than one analyte and simultaneously determine the concentration of several analytes. One instrument that has the ability to add all the reagents needed to analyze a sample containing more than one analyte is capable of performing all tests using a single spectrometer as a detector. In contrast, multiple detectors are usually required due to differences in spectral response indicating that the end point of the titration has been reached.

[0055] An automated titration system is provided, comprising a reactor manifold for mixing a continuously flowing and renewable sample stream containing an unknown concentration of one or more analytes with titrants; a sample pump for pumping a continuously current and renewable sample stream into the reactor manifold; a first titrant pump for pumping the first titrant into the reactor manifold for contact with a continuously flowing and renewing sample stream; a multi-wavelength detector for detecting the first titration end point of the reaction between the analyte and the first titrant; and a controller communicatively connected to the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set the flow rate of the continuously current and updated sample flow, controls the first titrant pump to set the flow rate of the first titrant, and receives data from the detector to detect the first titration endpoint for the reaction between the analyte and the first titrant and determine the analyte concentration at the first titration endpoint.

[0056] Also provided is an automated titration system that includes a reactor manifold for mixing a sample batch stream containing an unknown analyte concentration with a first titrant; a sample pump for pumping a sample stream into the reactor manifold; a first titrant pump for pumping the first titrant into the reactor manifold for contact with the sample stream; a multi-wavelength detector for detecting the first titration end point of the reaction between the analyte and the first titrant; and a controller communicatively connected to the sample pump, the first titrant pump, and the detector, wherein the controller controls the sample pump to set the sample flow rate, controls the first titrant pump to set the first titrant flow rate, and receives data from the detector to detect the first titration endpoint for the reaction between the analyte and the first titrant and determine the concentration of the analyte at the first titration endpoint.

[0057] In the automated titration systems described herein, a sample stream may contain two or more analytes.

[0058] In addition, the automated titration systems described herein may further comprise a second titrant pump for pumping the second titrant into the reactor manifold for contact with a sample batch stream or a continuously flowing and updated sample stream. Said multi-wavelength detector can additionally detect the second titration endpoint of the reaction between the analyte and the second titrant, wherein the controller is additionally communicatively connected to the second titrant pump, and the controller additionally controls the second titrant pump to set the flow rate of the second titrant, and receives data from the detector to detect the second titration endpoint for the reaction between the analyte and the second titrant and determine the analyte concentration at the second titration endpoint.

[0059] In the automated titration systems described herein, the second titrant may be reacted with a second analyte.

[0060] The automated titration systems described herein may further comprise a third titrant pump for pumping the third titrant into the reactor manifold for contact with a sample batch stream or a continuously flowing and updated sample stream. Said multi-wavelength detector can additionally detect a third titration endpoint of the reaction between the analyte and the third titrant, wherein said controller is additionally communicatively connected to the third titrant pump, and the controller additionally controls the third titrant pump to set the flow rate of the third titrant, and receives data from the detector to detect the third titration endpoint for the reaction between the analyte and the third titrant and determine the analyte concentration at the third titration endpoint.

[0061] In the automated titration systems described herein, a third titrant may be reacted with a third analyte.

[0062] The automated titration systems described herein may have a multi-wavelength detector capable of detecting signals ranging from ultraviolet to visible light.

[0063] In addition, the automated titration systems described herein may have a multi-wavelength detector as a spectrometer.

[0064] The automated titration systems described herein may have a reactor manifold containing a liquid mixer located downstream of the titrant inlet and upstream of the detector.

[0065] The automated titration systems described herein may also optionally include a conditioning manifold upstream of the titrant inlet and downstream of the sample stream inlet.

[0066] The automated titration system described herein may have a conditioning manifold containing a liquid mixer.

[0067] The automated titration system described herein may have a conditioning manifold further comprising a mixing loop.

[0068] The automated titration systems described herein may further comprise a conditioning agent pump for pumping the conditioning agent into the conditioning manifold for mixing with a continuously flowing and renewing sample stream.

[0069] Said automated titration system may comprise a pH buffer conditioning agent, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, a biobased chemical, or a combination thereof.

[0070] In the automated titration systems described herein, the conditioning agent may contain potassium iodide, sulfuric acid, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

[0071] Said automated titration system may comprise a conditioning agent pump, further comprising a first conditioning agent pump for pumping the first conditioning agent and a second conditioning agent pump for pumping the second conditioning agent.

[0072] In said automated titration system, the first conditioning agent may be a metal iodide and the second conditioning agent an indicator.

[0073] In the automated titration systems described herein, a conditioning agent pump may introduce a conditioning agent into a sample batch stream or a running sample stream, wherein a controller is communicatively connected to the conditioning agent pump and configured to control the conditioning agent pump to set the flow rate of the conditioning agent introduced into the continuously flowing and updated sample stream.

[0074] The automated titration systems described herein can be used in methods for quantifying a target analyte.

[0075] For example, this document describes a method for quantifying the concentration of a target analyte in a sample stream, including: continuously passing and constantly updating the sample stream at a known flow rate through an analyzer containing a collector and a multi-wavelength detector; quantifying the concentration of the target analyte by continuously adding a titrant to the analyzer and setting the change in the concentration of the titrant by changing the concentration of the titrant by increasing or decreasing the flow rate of the titrant in a given range; and determining a titration endpoint for a reaction between a target analyte in the sample stream and a titrant within a predetermined concentration range of the target analyte.

[0076] Alternatively, this document describes a method for quantifying the concentration of a target analyte in a periodic sample stream, including adding a sample to an analyzer containing a collector and a multiwavelength detector; quantifying the concentration of the target analyte by adding a titrant to the analyzer and setting the change in the concentration of the titrant by changing the concentration of the titrant by increasing or decreasing the flow rate of the titrant in a given range; and determining the end point of the titration for the reaction between the target analyte in the sample stream and the titrant within a predetermined concentration range of the target analyte; the sample stream contains two or more analytes.

[0077] Assay methods may include that the sample stream contains two or more analytes.

[0078] This method may have a sample stream, which may additionally contain a second analyte.

[0079] The methods described herein may further include quantifying the second analyte by continuously adding the second titrant to a sample batch stream or to a continuously flowing and constantly updated sample stream.

[0080] In this method, the sample stream may further comprise a third analyte.

[0081] These quantitation methods may further include quantifying a third analyte by continuously adding a third titrant to a sample batch stream or to a continuously flowing and constantly updated sample stream.

[0082] These methods may have a known sample flow rate from about 1 μl/min to about 200 ml/min.

[0083] These methods may have a known sample flow rate of about 5 ml/min to about 25 ml/min.

[0084] These methods may further include continuously adding a conditioning agent to the sample stream at a concentration proportional to the concentration of the target analyte.

[0085] These quantification methods may further include determining the end point of the titration using a multi-wavelength detector that is at a certain distance from the titrant addition point, and calculating the concentration of the titrant using the distance between the detector and the titrant addition point, titrant flow rate, and system volume.

[0086] The methods described herein may further include changing the concentration of the titrant by adjusting its flow rate, wherein the detector signal from the titration reaction product correlates over time with the concentration of the titrant.

[0087] These methods may further include dosing a calibrant of known concentration into the sample stream, determining the concentration of the calibrant, and calculating the response.

[0088] These quantification methods may further include controlling the titrant concentration using a feedback loop that is responsive to a detector detecting a reaction between the titrant and the target analyte.

[0089] Methods are described herein in which a conditioning reagent treats a sample stream to improve detection of a target analyte.

[0090] These methods can improve the detection of the target analyte by increasing the sensitivity of the detection method.

[0091] In the methods described herein, the conditioning agent can be a pH buffer, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, a biobased chemical, or a combination thereof.

[0092] In assay methods, the conditioning agent may include potassium iodide, acetic acid, a starch indicator, or a combination thereof.

[0093] In the method described herein, the rate of a continuously flowing and constantly updated sample stream can increase or decrease depending on whether the end point of the titration can be detected within the specified concentration range of the target analyte.

[0094] FIG. 1 is a schematic diagram of an automated titrator 100. The controller can control parameters of a sample pump 10, a first conditioning pump 12, a second conditioning pump 14, a third conditioning pump 16, a fourth conditioning pump 18, a first 3-way valve 22, a second 3-way valve 24, a mixing valve 20, a 4-way valve 40, a first titrant pump 42 in fluid communication with a valve 44, a second titrant pump 48 in fluid communication with a valve 46, and a detector 60. The sample flows through the sample pump 10, through the line and through the mixing valve 20 to the first liquid mixer 30. The first conditioning agent flows through the first conditioning agent pump 12, through the line and through the mixing valve 20 to the first liquid mixer 30 . The second conditioning agent flows through the second conditioning agent pump 14, through the line and through the mixing valve 20 to the first liquid mixer 30. The third conditioning agent flows through the third conditioning agent pump 16, through the line and through the mixing valve 20 to the first liquid mixer 30 . The fourth conditioning agent flows through the fourth conditioning agent pump 18, through the line and through the mixing valve 20 to the first liquid mixer 30 . After the sample and the first to fourth conditioning reagents are mixed in the first fluid mixer 30, the mixture of sample and conditioning reagents becomes the conditioned sample and flows through the 4-way valve 40, where the titrant is added from the first titrant pump 42, the second titrant pump 44, or the titrant is added from both the first titrant pump 42 and the second titrant pump 44. After adding the titrant to the conditioned sample, a reactor mixture is formed which passes through the second liquid mixer 50 to the detector 60.

[0095] FIG. 2 is a schematic diagram of an automated titrator 200. This controller can control the parameters of a variable flow sample pump 210, a first conditioning agent pump 236, a second conditioning agent pump 238, a third conditioning agent pump 240, a first switching valve 230, a second switching valve 232, a third switching valve 234, a first 3-way valve 244, a mixture 242, first liquid mixer 246, 3-way valve 250, titrant pump 260, selector valve 262, second liquid mixer 270, and detector 280. The sample passes through the sample pump 210, through the line and through the mixing valve 242 to the first liquid mixer 246. One series of conditioning agents 212, 214, 216 is connected to the first switching valve 230 and then to the first reagent pump 236. The second series of conditioning agents 218, 220, 222 is connected to the second switching valve 232 and then to the pump 238 for the second conditioning agent. A third series of conditioning agents 224, 226, 228 is connected to a third switching valve 234 and then to a third conditioning agent pump 240. After the sample and a series of conditioning reagents are mixed in the first liquid mixer 246, the mixture of sample and conditioning reagents becomes the conditioned sample and passes through the second 3-way valve 250, in which the first titrant 264, the second titrant 266 or the third titrant 268 flows through the fourth switching valve 262 and the titrant pump 260 into the sample stream through the second 3-way valve 250. The conditioned sample then flows through the second liquid mixer 270 and enters the detector 280.

[0096] A wide range of reagents known for standard titration can be used, and a sufficient amount of titrant will result in sample change. However, in this continuous mode of operation, the determining factor "sufficient addition of titrant" corresponds to the rate of addition of titrant and concentration relative to the sample flow (and sample concentration). This is because sample is continuously flowing through the system, so fresh sample is continuously fed into a manifold containing a first fluid mixer 30 or 246, a selector valve 40 or 3-way valve 250, and a second fluid mixer 50 or 270.

[0097] Accordingly, if the titrant is added too slowly, it may not react adequately with the conditioned sample, and the conditioned sample may not change. In other words, for a given period of time, a certain volume of sample will pass through a certain point in the system. Thus, to achieve the desired change, an appropriate volume of titrant is needed, which also passes through this point in the same time, which corresponds to a sufficient flow rate.

[0098] The process can be automated using a controller, such as a programmable logic controller (PLC), using feedback mechanisms from the detector.

[0099] The flow rate of the titrant may vary non-linearly with time. An exponential increase in flow rate, for example, will start with small changes in flow rate at low concentrations. Over time, when a higher concentration is reached (as the flow rate continues to increase), small changes in the flow rate become overly accurate compared to the available concentrations, and the flow rate may increase by a large amount.

[00100] A low analyte concentration can be accurately determined by small concentration changes early in the process, while high analyte concentrations can be titrated in a shorter amount of time as the rate of titrant addition increases faster over time.

[00101] For example, low concentrations of peroxide and peracid can be accurately eliminated by small concentration changes early in the process, while high concentrations of peracid and/or peroxide can be titrated in a shorter amount of time as the rate of titrant addition increases faster with time.

[00102] The advantage of this method is that with a sufficiently fast optical design, analysis at each injection point can be performed very quickly. Thus, only a small amount of titrant needs to be added to each point to determine if the flow rate is sufficient for a complete titration, and a total small amount of titrant is needed to determine the end point. This process can be automated by a device such as a PLC using methods similar to those described in relation to the alternatives, where the controller can control the flow rates of the sample and titrants, determine the titration with an optical device, and calculate the concentration from the flow rate. In this embodiment, the controller performs the additional task of determining a "cut-off" point above which titration occurs and below which it does not.

[00103] A method for quantifying the concentration of a target analyte in a sample stream includes continuously passing and continuously updating a sample stream at a variable flow rate through an analyzer comprising a manifold and a detector; quantifying the concentration of the target analyte by continuously adding a titrant to the analyzer and setting the change in the concentration of the titrant by changing the concentration of the titrant by increasing or decreasing the flow rate of the titrant in a given range; and determining a titration end point for a reaction between the target analyte and the titrant within a specified concentration range of the target analyte.

[00104] The method described herein may further include a second titrant stream in which the concentration of titrant in the second titrant stream is different from the concentration of titrant in the first titrant stream.

[00105] The method described herein can have a variable sample flow rate from about 0.1 µl/min to about 1 ml/min. The method described herein may have a variable sample flow rate from about 0.1 µl/min to about 0.75 ml/min, from about 0.1 µl/min to about 0.5 ml/min, from about 0.1 µl/min to about 0.25 ml/min, from about 0.1 µl/min to about 0.1 ml/min, from about 0.1 µl/min to about 75 µl/min , from about 0.1 µl/min to about 50 µl/min, from about 0.1 µl/min to about 25 µl/min, from about 0.1 µl/min to about 10 µl/min, from about 1 µl/min to about 1 ml/min, from about 1 µl/min to about 0.75 ml/min, from about 1 µl/min to about 1 ml/min, from about 1 µl/min to about 25 ml/min, from about 1 µl/min to about 0.1 ml/min, from about 1 µl/min to about 75 µl/min, from about 1 µl/min to about 50 µl/min, from about 1 µl/min to about 25 µl/min, from about 1 µl/min to about 10 µl/min, from about 5 µl/min min to about 1 ml/min, from about 5 μl/min to about 0.75 ml/min, from about 5 μl/min to about 1 ml/min, from about 5 μl/min to about 25 ml/min, from about 5 μl/min to about 0.1 ml/min, from about 5 μl/min to about 75 μl/min, from about 5 μl/min to about 50 μl/min, from about 5 µl/min to about 25 µl/min; or from about 5 µl/min to about 10 µl/min.

[00106] The method described herein may have a variable sample flow rate from about 1 ml/min to about 200 ml/min.

[00107] The method described herein may have a variable sample flow rate from about 1 ml/min to about 175 ml/min, from about 1 ml/min to about 150 ml/min, from about 1 ml/min to about 125 ml/min, from about 1 ml/min to about 100 ml/min, from about 1 ml/min to about 75 ml/min, from about 1 ml/min to about 50 ml/min, from about 1 ml/min to about 30 ml/min, from about 2 ml/min to about 200 ml/min, from about 2 ml/min to about 175 ml/min, from about 2 ml/min to about 150 ml/min, from about 2 ml/min to about 125 ml/min, from about 2 ml/min to about 100 ml/min, from about 2 ml/min to about 75 ml/min, from about 2 ml/min to about 50 ml/min, from about 2 ml/min to about 30 ml/min, from about 5 ml/min to about 200 ml/min, from about 5 ml/min to about 175 ml/min, from about 5 ml/min to about 150 ml/min, from about 5 ml/min to about 125 ml/min, from about 5 ml/min to about 100 ml/min, from about 5 ml/minute to about 75 ml/min, from about 5 ml/min to about 50 ml/min, preferably from about 5 ml/min to about 30 ml/min.

[00108] The method described herein may have a variable sample flow rate from about 200 ml/min to about 100 l/min. The method described herein may have a variable sample flow rate from about 200 ml/min to about 75 L/min, from about 200 ml/min to about 50 L/min, from about 200 ml/min to about 25 L/min, from about 200 ml/min to about 10 L/min, from about 200 ml/min to about 5 L/min, from about 200 ml/min to about 2 l/min, from about 200 ml/min to about 1 l/min, from about 500 ml/min to about 100 l/min, from about 500 ml/min to about 75 l/min, from about 500 ml/min to about 50 l/min, from about 500 ml/min to about 25 l/min, from about 500 ml/min to about 10 l/min, from about 5 00 ml/min to about 5 L/min, from about 500 ml/min to about 2 L/min, from about 500 ml/min to about 2 L/min, from about 1 L/min to about 100 L/min, from about 1 L/min to about 75 L/min, from about 1 L/min to about 50 L/min, from about 1 L/min to about 25 L/min, from about 1 L/min to about 10 L/min, from about 1 L/min to about 8 L/min, or from about 1 L/min to about 5 L/min.

[00109] The method described herein may have an analyte concentration detection range that is larger at a lower sample flow rate and smaller at a higher sample flow rate.

[00110] The method described herein further comprises continuously adding a conditioning agent to the sample stream at a concentration proportional to the concentration of the target analyte.

[00111] The method described herein further includes determining the end point of the titration using a detector located at a certain distance from the titrant addition point, and calculating the titrant concentration using the distance between the detector and the titrant addition point, titrant flow rate, and system volume.

[00112] The method described herein further comprises varying the concentration of the titrant by adjusting its flow rate, wherein the detector signal from the titration reaction product correlates over time with the concentration of the titrant.

[00113] The method described herein further includes dispensing a calibrant of known concentration into the sample stream, determining the concentration of the calibrant, and calculating a response.

[00114] The method described herein may further include changing the concentration of the titrant using a mathematical function and determining the endpoint of the titration within a certain concentration range of the target analyte.

[00115] In the method described herein, the mathematical function may be a linear function, a step function, a sine function, a square wave function, an exponential function, or a combination thereof.

[00116] The method described herein may further include controlling the concentration of the titrant using a feedback loop that is responsive to a detector detecting a reaction between the titrant and the target analyte.

[00117] The method described herein may further include measuring the end point of the titration using a step change in the concentration of the titrant over a given concentration range of the target analyte.

[00118] In the method described herein, a conditioning reagent may treat the sample stream to improve detection of the target analyte.

[00119] The method described herein can improve the detection of a target analyte by increasing the sensitivity of the detection method.

[00120] In the method described herein, the conditioning agent can be a pH buffer, an acid, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, a biobased chemical, or a combination thereof.

[00121] In the method described herein, the end point of the titration can be determined using a light detector.

[00122] The endpoint of a titration can be indicated by a detectable change upon complete reaction of the target analyte with the titrant. Said detectable change may be spectrophotometric.

[00123] The titration system can be used to select the optimum wavelength for the intended titration. For example, depending on the identity of the analyte, titrant, and composition of the sample stream at the endpoint, the optimum wavelength can be determined to detect specific chemicals formed at the endpoint.

[00124] The light-based detector may be a spectrometer.

[00125] The spectrometer can pass light through a fixed optical cell where it can be detected by an image sensor.

[00126] Alternatively, the spectrometer can reflect light to and from the sample through the entrance slit, where the light can be detected by the image sensor.

[00127] In the method described herein, the conditioning agent may include potassium iodide, acetic acid, a starch indicator, molybdate, or a combination thereof.

[00128] In the method described herein, the flow rate of a continuously current and constantly updated sample flow can be increased or decreased depending on whether the endpoint of the titration can be detected within the specified concentration range of the target analyte.

[00129] The method described herein may include continuously passing the process solution through an analyzer containing a manifold and a detector; quantitative determination of the concentration of the target analyte by changing the flow rate and, consequently, the concentration of the titrant in a given range; and determining a titration end point for a reaction between the target analyte and the titrant within a specified concentration range of the target analyte.

[00130] Varieties of reagents that can be conditioning reagents are well known to one of ordinary skill in the art and can be used in a wide variety of titration systems.

[00131] For the methods described herein, the target analyte may contain hydrogen peroxide, peroxyacetic acid, performic acid, peroxyoctanoic acid, or a combination thereof. Preferably, the target analyte contains hydrogen peroxide, peroxyacid, or a combination thereof.

[00132] For the methods described herein, the titrant contains thiosulfate.

[00133] For the methods described herein, the conditioning agent contains potassium iodide, acetic acid, a starch indicator, ammonium molybdate, or a combination thereof.

[00134] In each method described herein, the actual concentration of the target analyte can be directly determined or the actual concentration of the target analyte can be calculated based on the determination of the concentration of the reaction product of the target analyte and the titrant.

[00135] The specified process is such that it can be implemented anywhere, for example, at a sampling point in a processing plant or other industrial or commercial establishment, not corresponding to the specifics of regularly performing standard titrations.

[00136] In addition, the entire specified process can be completed in a short time: about 2 minutes 40 seconds. Before flushing and preparing the system for another measurement, the amount can be determined in less time: approximately 1 minute 20 seconds.

[00137] The methods described herein may further include a calibration step. Calibration steps can be performed in real time, flow rate calibrations, measurements, and the like. Calibration can be performed before each titration to ensure improved measurement accuracy. Calibration may be performed after a predetermined number of measurements or may be suggested by the user. On-line calibration can be performed without significantly slowing down the analysis procedure. Such calibration may involve introducing a sample of known concentration and verifying that the system is accurately measuring the concentration. To the extent that the measurement is not entirely accurate; the system can self-adjust to accurately measure a sample of known concentration.

[00138] Alternatively, the optical sensor may signal transparency as soon as it detects any radiation from the light source. Such systems can be used if the color change is sufficiently abrupt, for example from blue-black to transparent, as described above. However, it should be noted that with proper optical equipment such a dramatic color change may not be necessary for the optical device to accurately determine the end point of the titration. Not all reagents may be needed. For example, the starch indicator can be eliminated by including certain optics in the optical system.

[00139] "Amount" in the context of this document refers to a general measurable quantity such as mass, concentration, volume, etc.

[00140] Upon reading the detailed description of the invention, it will become apparent that modifications and variations are possible without departing from the scope of the invention as defined in the appended claims.

EXAMPLES

[00141] To further illustrate the present invention, the following non-limiting examples are given.

[00142] The caustic-containing sample was titrated using the Ecolab Alkalinity Test Kit No. 301 using 0.1 N HCl as the titrant. The operator measured the end point at 10 drops. The spectra are shown in Fig. 3A and 3B.

[00143] The sharp inflection point at 10 drops in FIG. 3B illustrates that the endpoint of the titration was measured with a multi-wavelength detector (eg Hamamatsu C12666MA).

[00144] This Hamamatsu C12666MA instrument was connected to a laboratory prototype Fast Flow Titrator and was used to monitor the end point of the titration by collecting spectra at each test concentration from 6-40 ppm on a peracid sample of approximately 15 ppm.

[00145] The light from the LED source passed through the titrator sample stream at a fast flow immediately after the Banner sensor block. These spectra are shown in Fig. 4A, and the absorbance at each wavelength was calculated from the sample, reference, and dark signals using the following equation, which is shown in FIG. 4b.

[00146] It was observed that as the test concentration increased, the measured absorbance decreased. This is the measured transition of the blue triiodide starch complex to a brightly colored solution at the end point where the triiodide is completely reduced to iodide, at the end point of the titration.

[00147] The flow sensors used in the two Ecolab automated titrators use a sensor that measures light at a wavelength of 680 nm. The spectra above show that the optimum wavelength for the analysis performed is approximately 550 nm. The absorbance data for 550 and 680 nm collected by the C12666MA was then compared with the titration results measured by the Banner sensor.

[00148] The results in FIG. 5 showed an identical course of the absorbance curve as a function of concentration. The fact that the optical density values were not the same was due to the fact that none of the optical systems was optimized to minimize stray light. Scattered light introduced non-linearity in optical density measurements.

[00149] The Hamamatsu C12666MA is just one example of an array spectrometer that can be used to collect spectral data during a titration using the proposed tools.

[00150] The linearity of the C12666MA response was confirmed by comparing the absorbance obtained with the C12666MA to certified standards. HACH Spectra Detector/Check Standards in FIG. 6 were obtained using C12666MA.

[00151] The absorbance was then calculated as described above.

[00152] The absorbance values of the sample were then compared to certified absorbance values at published wavelengths.

λ (nm) Hach Company LED Radio Shack 276-0320 systematic error Std1 Std2 Std3 Std1 Std2 Std3 Std1 Std2 Std3 420 0.561 1.129 1.748 0.542 1.161 1.759 -3.4% 2.8% 0.6% 520 0.591 1.160 1.714 0.555 1.184 1.788 -6.0% 2.0% 4.3% 560 0.556 1.115 1.710 0.538 1.148 1.741 -3.2% 3.0% 1.8% 610 0.584 1.159 1.751 0.560 1.184 1.794 -4.1% 2.1% 2.5%

[00153] The white LED Radio Shack 276-0320 was used as the light source in this experiment. Note that the systematic error is less than 6%, indicating a good match between the certified standards and the data collected with the C12666MA. As stated above, response can be improved by optimizing the optical configuration.

[00154] These data indicated that the mini-spectrometer is a viable detector system for an automated titration system. Then, the use of a mini spectrometer makes it possible to measure titration with end point transitions other than 680 nm with a single broadband detector.

[00155] Hamamatsu C 12666MA was used to monitor spectral changes as several Ecolab field test kits were used to titrate samples. For these titrations, the sample setup described above was used. Hardness test set no. 307 was used to titrate 17-grain laboratory water. This sample was titrated manually and then in an optical test system. Spectra and drop response for testing are shown in FIG. 7A and 7B.

[00156] Two peaks, 525 and 620, show the inflection point at 17 drops, which is the end point measured by the operator.

[00157] When presenting elements of the present invention or its preferred embodiments, the articles "a", "an", "the" and the term "specified" are intended to indicate that there is one or more elements. The terms "comprising", "including" and "having" are intended to be inclusive and mean that there may be additional elements other than those listed.

[00158] In view of the foregoing, it becomes clear that several objectives of the invention are achieved, as well as other useful results.

[00159] Since various changes can be made to these methods without departing from the scope of the invention, it is intended that all of the foregoing contained in the above description and shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense.

Claims (32)

1. An automated titration system, comprising: a reactor manifold comprising a conditioning manifold and a second fluid mixer, wherein the reactor manifold is in fluid communication with the sample source and the titrant source for mixing a continuously flowing and renewing sample stream containing an unknown concentration of the first analyte with the first titrant and an unknown concentration of the second analyte with the second titrant; a sample pump in fluid communication with the sample source and the reactor manifold, continuously pumping a sample stream from the sample source into the reactor manifold through the sample stream inlet; a first titrant pump in fluid communication with the first titrant source and the reactor manifold for pumping the first titrant into the reactor manifold through the first titrant inlet to contact a continuously flowing and renewing sample stream; a second titrant pump in fluid communication with the second titrant source and the reactor manifold for pumping the second titrant into the reactor manifold through the second titrant inlet to contact a continuously flowing and renewing sample stream; a multi-wavelength detector in fluid communication with the reactor manifold for detecting a first titration endpoint of the reaction between the first analyte and the first titrant and for detecting a second titration endpoint of the reaction between the second analyte and the second titrant, the detector being located downstream of the first and second titrants inlets and spaced from the first and second titrants inlets; And a controller in communication with the sample pump, the first titrant pump, the second titrant pump and the detector, wherein the conditioning manifold comprises a first liquid mixer, and the conditioning manifold is located downstream of the sample flow inlet, wherein the first titrant inlet and the second titrant inlet are located downstream of the conditioning manifold and upstream of the second liquid mixer, and the second liquid mixer is located upstream of the detector, wherein the controller controls the sample pump to set a continuous sample flow rate, controls the first titrant pump to set the flow rate of the first titrant, controls the second titrant pump to set the second titrant to a continuous flow rate, and receives data from the detector to detect the first titration endpoint for the reaction between the first analyte and the first titrant, and determine the concentration of the first analyte in the first titration endpoint, and detect the second titration endpoint for the reaction between the second analyte and the second titrant trant and determine the concentration of the second analyte at the second endpoint of the titration. 2. An automated titration system according to claim 1, further comprising: a third titrant pump for pumping the third titrant into the reactor manifold for contact with the sample stream; wherein the multiwave detector additionally detects the third end point of the titration of the reaction between the third analyte and the third titrant, the controller is additionally communicatively connected to the pump for the third titrant, and the controller additionally controls the pump for the third titrant to set the flow rate of the third titrant and receives data from the detector to determine the third end point of the titration for the reaction between the third analyte and the third titrant and determine the concentration of the analyte in the third end point of the titration. 3. An automated titration system according to claim 1 or 2, wherein the multi-wavelength detector is capable of detecting signals ranging from ultraviolet to visible light. 4. The automated titration system of claim 3, wherein the multi-wavelength detector is a spectrometer. 5. The automated titration system of claim 1 or 2, wherein the reactor manifold further comprises a 4-way valve at the first titrant inlet and the second titrant inlet, which is located downstream of the conditioning manifold and upstream of the second liquid mixer. 6. Automated titration system according to claim 1 or 2, in which the conditioning manifold further comprises a valve at the inlet of the conditioning reagent, which is located upstream of the first liquid mixer, and the first liquid mixer, located upstream of the first titrant inlet and the second titrant inlet. 7. The automated titration system of claim 1 or 2, wherein the system further comprises a conditioning agent source in fluid communication with the conditioning agent pump and the conditioning manifold for pumping the conditioning agent from the conditioning agent source into the conditioning manifold for mixing with the sample stream. 8. The automated titration system of claim 7, wherein the conditioning agent source comprises a pH buffer, a reaction catalyst, a chemical indicator, a sequestrant, a surfactant, a conductivity modifying salt, an ion pair reagent, or a biobased chemical. 9. The automated titration system of claim 8, wherein the conditioning agent source contains potassium iodide, sulfuric acid, acetic acid, starch indicator, or ammonium molybdate. 10. The automated titration system of claim 9, wherein the conditioning agent pump further comprises a first conditioning agent pump in fluid communication with the first conditioning agent source and the conditioning manifold to pump the first conditioning agent and the second conditioning agent source, and a second conditioning agent pump in fluid communication with the conditioning manifold to pump the second conditioning agent, wherein the first conditioning agent is a metal iodide and the second conditioning agent is an indicator. 11. The automated titration system of claim 8, wherein the controller is communicatively coupled to the conditioning agent pump and configured to control the conditioning agent pump to set the flow rate of the conditioning agent introduced into the sample stream. 12. An automated titration system according to claim 1 or 2, wherein the first titrant inlet and the second titrant inlet are at the same point in the reactor manifold. 13. The automated titration system of claim 1 or 2, wherein the sample stream flows from the sample source, through the sample pump, through the sample stream inlet to the reactor manifold, through the reactor manifold, and into the detector. 14. A method for quantitative determination of the concentration of the first target analyte and the concentration of the second target analyte in the sample stream, performed by the automated titration system according to claim 1, including: continuously flowing and continuously updated sample flow into the analyzer containing the reactor manifold and multiwave detector; quantifying the concentration of the first target analyte by continuously adding the first titrant to the analyzer and setting the change in the concentration of the first titrant by changing the concentration of the first titrant by increasing or decreasing the flow rate of the first titrant; And detecting a first titration endpoint for a reaction between a first target analyte in the sample stream and a first titrant in a given concentration range of the first target analyte; quantifying the concentration of the second target analyte by continuously adding the second titrant to the analyzer and setting the change in the concentration of the second titrant by changing the concentration of the second titrant by increasing or decreasing the flow rate of the second titrant within a predetermined range; And detecting a second titration endpoint for a reaction between a second target analyte in the sample stream and a second titrant over a given concentration range of the second target analyte. 15. The method of claim 14, further comprising: detecting the first endpoint of the titration using a multi-wavelength detector that is at a distance from the first titrant addition point, and calculating the concentration of the first titrant using the distance between the detector and the first titrant addition point, the first titrant flow rate, and the system volume, and detecting a second titration endpoint using a multi-wavelength detector that is at a distance from the second titrant addition point, and calculating the concentration of the second titrant using the distance between the detector and the second titrant addition point, the second titrant flow rate, and the system volume.

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