Lateral flow analysis signal analysis method using signal expression pattern during reagent reaction, and lateral flow analysis device using same

Abstract

An embodiment of the present invention provides a lateral flow analysis method for calculating a final signal magnitude of a lateral flow analysis device comprising at least one processor, the method comprising the steps of: acquiring time-series data by measuring a reagent reaction signal of a test line and / or a control line when a reaction occurs between a reagent and an injected sample; acquiring reagent reaction signal characteristic information of the test line and / or the control line on the basis of the time-series data; compensating a signal magnitude at a reagent reaction end time point of the test line by using the reagent reaction signal characteristic information; and calculating the concentration of an analyte on the basis of the compensated signal magnitude.

Description

Lateral flow analysis signal analysis method using signal expression patterns during reagent reactions and lateral flow analysis device using the same

[0001] The present invention relates to a lateral flow analysis device and a lateral flow analysis method for analyzing signal patterns that appear during the reaction process between a reagent and a sample.

[0002] A lateral flow assay (LFA) is a simple device that detects analytes present in fluid samples, such as pregnancy test kits, coronavirus self-test kits, or cartridges. This testing method has the advantages of being easy to use, providing rapid results, and being inexpensive.

[0003] When a sample to be tested is injected into the cartridge for lateral flow testing, the sample moves along the strip due to capillary action and reacts with the reagent components of the reagent pad to form an analyte complex. This analyte complex then undergoes an additional binding reaction with the reagent already applied to the test line located within the reagent reaction section to generate a signal. Furthermore, the reagent reaction required to determine the validity of the test takes place at the control line; the control line signal allows for the determination of whether the sample reaction is normal or the level of background signal specific to each sample.

[0004] The signal generated in this way is detected visually or using a separate analysis device, but when high sensitivity or quantitative analysis is required, fluorescent materials and analysis devices capable of measuring them are mainly used.

[0005] Finally, the analysis device measures the generated signal intensity and calculates the biomarker concentration by comparing it with a preset reference value. At this stage, the biomarker concentration proportional to the signal intensity is determined, and through this, a biomarker quantitative test is performed by quantifying the final concentration of the biomarker in the sample.

[0006] However, the above method had a problem in that it failed to meet the precision (CV, Coefficient of Variation) guideline, which is a necessary condition for quantitative analysis, because interference occurred due to differences in sample viscosity, non-uniformity of the cartridge dry reagent elution amount, and non-uniformity of the cartridge membrane micropore structure as it analyzed the signal at the end of the reagent reaction.

[0007] The present disclosure is conceived in response to the aforementioned background technology and aims to provide a lateral flow analysis signal method for analyzing signal expression patterns during a reagent reaction and a lateral flow analysis apparatus using the same.

[0008] According to an embodiment of the present invention, a method for calculating the final signal magnitude of a lateral flow analysis device comprising at least one processor may include the steps of: obtaining time series data by measuring at least one reagent reaction signal among a test line and a control line; obtaining reagent reaction signal characteristic information among at least one of the test line and the control line based on the time series data; compensating the signal magnitude at the time of termination of the reagent reaction of the test line using the reagent reaction signal characteristic information; and calculating the concentration of an analyte based on the compensated signal magnitude.

[0009] In addition, the reagent reaction signal characteristic information may include at least one of the following: the growth rate or decrease rate of the time series data, information on the maximum or minimum value of the time series data, and information on the time point at which the signal of the test line or control line is observed relative to the background signal among the time series information of the test line or control line.

[0010] In addition, the step of compensating for the signal magnitude at the end of the reagent reaction of the test line using the reagent reaction signal characteristic information may include the step of acquiring standard time series data information of the test cartridge.

[0011] In addition, the above standard time series data information may include standard reagent reaction signal characteristic information per manufacturing lot of the inspection cartridge inserted into the lateral flow analysis device.

[0012] Additionally, the step of acquiring standard time-series data information of the inspection cartridge may include the step of acquiring standard time-series data information of the lateral flow analysis device through information stored in a barcode or QR code provided on the inspection cartridge.

[0013] In addition, standard time-series data information of the above inspection cartridge may be stored in the inspection cartridge, barcode or QR code, memory of the analysis device, or server.

[0014] Additionally, the step of compensating the signal magnitude at the time of termination of the reagent reaction of the test line using the reagent reaction signal characteristic information may include the step of acquiring standard time series data information of the test cartridge and comparing the standard time series data information with at least one time series data information among the test line and the control line to calculate the signal magnitude at the time of termination of the reagent reaction of the test line.

[0015] Additionally, the method may further include a step of determining whether the concentration of the analyte calculated based on the above-mentioned compensated signal magnitude is above a threshold value, and determining positive if a concentration above the threshold value is detected, and negative if it is below that value.

[0016] The above-mentioned reagent reaction may further include a test cartridge in which the above-mentioned reagent reaction occurs, and the test cartridge may include a reagent reaction part coated with a label comprising at least one of a fluorescent substance (Fluorophore) and a colorimetric particle.

[0017] In addition, according to an embodiment of the present invention, a lateral flow analysis device comprising at least one processor may include a lateral flow analysis device wherein the processor measures at least one reagent reaction signal among a test line and a control line to obtain time series data, obtains reagent reaction signal characteristic information among at least one test line and a control line based on the time series data, compensates the signal magnitude at the time of termination of the reagent reaction of the test line using the reagent reaction signal characteristic information, and calculates the concentration of an analyte based on the compensated signal magnitude.

[0018] In addition, the reagent reaction signal characteristic information may include at least one of the following: the growth rate or decrease rate of the time series data, information on the maximum or minimum value of the time series data, and information on the time point at which the signal of the test line or control line is observed relative to the background signal.

[0019] In addition, the processor can acquire standard time-series data information of the test cartridge and compensate for the signal magnitude at the end of the reagent reaction of the test line using the reagent reaction signal characteristic information.

[0020] In addition, the above standard time series data information may include standard reagent reaction signal characteristic information per manufacturing lot of the inspection cartridge inserted into the lateral flow analysis device.

[0021] In addition, the processor can obtain standard time-series data information of the lateral flow analysis device through information stored in a barcode or QR code provided in the inspection cartridge.

[0022] In addition, standard time-series data information of the above-mentioned inspection cartridge can be stored in an analysis device or server.

[0023] In addition, the processor can acquire standard time series data information of the test cartridge and compare the standard time series data information with at least one time series data information of the test line and the control line to calculate the signal magnitude at the time of termination of the reagent reaction of the test line.

[0024] In addition, the processor can determine whether the concentration of the analyte calculated based on the compensated signal magnitude is above a threshold value, and determine whether it is positive if a concentration above the threshold value is detected, and negative if it is below that value.

[0025] Additionally, the device may further include a test cartridge in which the above-mentioned reagent reaction occurs, and the test cartridge may include a reagent reaction section coated with a label comprising at least one of a fluorescent substance (Fluorophore) and a colorimetric particle.

[0026] According to an embodiment of the present invention, the accuracy and reliability of a lateral flow analysis device can be improved by utilizing time-series information based on signal expression patterns over time during a reagent reaction.

[0027] In addition, rapid analysis of various samples is possible, which can significantly increase applicability in the diagnostic field. In particular, the analysis method according to the present invention can achieve a coefficient of variation (CV) of 10% or less in quantitative analysis, so it can be effectively used in research and products requiring high precision.

[0028] FIG. 1 is a schematic diagram showing the configuration of a lateral flow analysis device according to one embodiment of the present invention.

[0029] FIG. 2 is a conceptual diagram showing the operation of a lateral flow analysis device according to one embodiment of the present invention.

[0030] FIG. 3 is a flowchart showing the operation of a lateral flow analysis device according to an embodiment of the present invention.

[0031] Figure 4 is a diagram showing time series data of a reagent reaction signal according to an embodiment of the present invention.

[0032] FIG. 5 is a diagram showing time series data of a reagent reaction signal compensated according to an embodiment of the present invention.

[0033] Specific structural or functional descriptions regarding embodiments according to the concept of the present invention disclosed herein are provided merely for the purpose of explaining embodiments according to the concept of the present invention, and embodiments according to the concept of the present invention may be implemented in various forms and are not limited to the embodiments described herein.

[0034] Embodiments according to the concept of the present invention may be subject to various modifications and may take various forms; therefore, embodiments are illustrated in the drawings and described in detail in this specification. However, this is not intended to limit the embodiments according to the concept of the present invention to specific disclosed forms, and includes all modifications, equivalents, or substitutions that fall within the spirit and scope of the present invention.

[0035] Terms such as "first" or "second" may be used to describe various components, but said components should not be limited by said terms. For the sole purpose of distinguishing one component from another, for example, without departing from the scope of rights according to the concept of the present invention, the first component may be named the second component, and similarly, the second component may be named the first component.

[0036] The terms used herein are used merely to describe specific embodiments and are not intended to limit the invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as “comprising” or “having” are intended to indicate the existence of the described features, numbers, steps, actions, components, parts, or combinations thereof, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0037] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this specification.

[0038] Additionally, the term “and / or” as used herein should be understood to refer to and include all possible combinations of one or more of the enumerated related items. Furthermore, the term “or” is intended to mean an implied “or” rather than an exclusive “or.” That is, unless otherwise specified or clear from the context, “X uses A or B” may apply to cases where X uses A; X uses B; or X uses both A and B. Additionally, “at least one selected from A and B” may refer to (1) A, (2) at least one of A, (3) B, (4) at least one of B, (5) at least one of A and at least one of B, (6) at least one of A and B, (7) at least one of B and A, and (8) all of A and B.

[0039] In terms used in this specification, singular expressions should be understood to include plural expressions unless the context clearly indicates otherwise, and terms such as “includes” should be understood to mean that the described features, number, steps, actions, components, parts, or combinations thereof exist, and not to exclude the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0040] Before providing a detailed description of the drawings, it is to clarify that the classification of components in this specification is merely based on the primary function each component is responsible for. That is, two or more components described below may be combined into a single component, or a single component may be divided into two or more components based on more subdivided functions. Furthermore, each component described below may additionally perform some or all of the functions of other components in addition to its own primary function, and it goes without saying that some of the primary functions of each component may be exclusively performed by other components.

[0041] Furthermore, in performing the method or operation method, each process constituting the method may occur differently from the specified order unless a specific order is clearly indicated in the context. That is, each process may occur in the same order as specified, may be performed substantially simultaneously, or may be performed in the reverse order.

[0042] Hereinafter, the present invention will be described in detail by explaining preferred embodiments of the present invention with reference to the attached drawings.

[0043]

[0044] 1. Lateral Flow Analysis Device and Configuration

[0045]

[0046] FIG. 1 is a schematic diagram showing the configuration of a lateral flow analysis device according to an embodiment of the present invention.

[0047] Referring to FIG. 1, a lateral flow analysis device (100) according to an embodiment of the present invention may include an analysis device and may separately provide an inspection cartridge (101) that can be inserted into the analysis device.

[0048] According to an embodiment of the present invention, a reagent reaction may occur by a sample injected into a test cartridge (101). Additionally, when a test cartridge (101) is inserted into an analysis device (100), the device may include a light-emitting unit (110) that supports generating a signal by irradiating light to a reagent reaction unit (1011); a light-receiving unit (120) that detects a signal by detecting light that has changed due to the reaction between the reagent and the sample in the reagent reaction unit; at least one processor (130) that analyzes the signal received from the light-receiving unit and analyzes the components or state of the sample; and a communication unit (160) that transmits information derived from the processor (130) to a user terminal or server. Additionally, the memory (150) may store user information using the lateral flow analysis device, unique terminal information of the lateral flow analysis device, and various data obtained from the lateral flow analysis device.

[0049] Meanwhile, according to an embodiment, the analysis device and the test cartridge may also be provided as an integrated unit.

[0050] FIG. 2 is a conceptual diagram showing the operation of a lateral flow analysis device (100) according to an embodiment of the present invention.

[0051] Referring to FIG. 2, a lateral flow analysis device (100) according to an embodiment of the present invention may include an analysis device (100) and an inspection cartridge (101).

[0052] According to an embodiment of the present invention, the test cartridge (101) can be inserted into the analysis device through a test cartridge insertion part provided in the analysis device (100).

[0053] The inspection cartridge (101) may include a sample pad that performs sample absorption and filtering, a conjugation pad where the label and the analyte are combined, a porous membrane that detects the analyte in the test line and control line, and an absorption pad that absorbs the remaining sample after inspection.

[0054] According to an embodiment of the present invention, a sample may refer to a sample collected for analysis, that is, a specimen expected to contain an analyte.

[0055] In addition, the labeling agent may include a substance that generates an optical signal to confirm the presence of the analyte.

[0056] In addition, the analyte may include a target substance to be detected and measured (e.g., a specific antigen, protein, etc.).

[0057] In addition, the reagent may include a substance that reacts with the analyte in the sample to help the label generate a signal.

[0058]

[0059] 1.1 Inspection Cartridge

[0060] Referring to FIG. 2, the inspection cartridge (101) may include a housing that forms the exterior of the inspection cartridge.

[0061] According to an embodiment of the present invention, the housing of the inspection cartridge may include a sample insertion part in which a sample can be injected into a sample pad and absorbed into the cartridge, and at least one light irradiation part in which the reaction of the sample to light emitted through the analysis device can be observed.

[0062] The above-mentioned at least one light irradiation part may include a form in which a portion of the housing of the inspection cartridge is open, corresponding to a reagent reaction part where the reagent and the sample react.

[0063] Using the light irradiation unit described above, the user can observe the reaction between the sample and the reagent with the naked eye or using an analysis device. Additionally, the analysis device may be able to perform lateral flow analysis by acquiring light that is reflected or generated as light irradiated through the light irradiation unit reacts with the porous membrane.

[0064] Meanwhile, according to one embodiment, the light irradiation part may be implemented as at least one hole.

[0065]

[0066] 1.2 Analysis Device

[0067] According to an embodiment of the present invention, the analysis device may include an insert formed to receive a cartridge (101) in part or in whole into the analysis device.

[0068] The reagent reaction portion (1011) formed in the test cartridge (101) must be inserted into the interior of the analysis device, and a part of the cartridge (101) may be formed protruding without being inserted into the interior of the analysis device.

[0069] When a test cartridge (101) is inserted into the above analysis device, the reagent reaction part (1011) of the test cartridge (101) and the light-emitting part (110) that irradiates light can be spaced apart by a certain distance.

[0070] The light-emitting unit (110) is configured to irradiate light and can irradiate light of a predetermined wavelength toward the reagent reaction unit (1011) of the received inspection cartridge (101).

[0071] The light emitted from the light-emitting part (110) can be reflected or transmitted to the reagent reaction part (1011) of the cartridge (101).

[0072] In one embodiment, the light-emitting part (110) may use an LED light-emitting part (110). Here, the LED light-emitting part (110) may be determined according to the type of fluorescent material that generates a signal.

[0073] In the present invention, a light receiving unit (120) may be further included to receive signal light formed by light irradiated from a light emitting unit (110) passing through or irradiating a reagent reaction unit (1011) of an inspection cartridge (101).

[0074] According to an embodiment, in the present invention, the light receiving unit (120) may be configured to face the light emitting unit (110). Specifically, they may be formed spaced apart by a predetermined distance with the inspection cartridge (101) in between.

[0075] More specifically, the light-emitting part (110) and the light-receiving part (120) can be formed side by side in one direction so that the light emitted from the light-emitting part (110) can be directly received by transmitting or irradiating the inspection cartridge (101) to form a signal light.

[0076] Meanwhile, as various embodiments are provided, the analysis device and inspection cartridge of the present invention are not limited to the shape described above, and should be interpreted to include all forms of an analysis device capable of receiving signal light through a light receiving part, which is formed by light emitted from at least one light source provided in the light-emitting part being transmitted or irradiated to the reagent reaction part (1011) of the inspection cartridge.

[0077] Additionally, at least one test line (1102) and a control line (1103) of the strip may be located in the reagent reaction section (1011), and the at least one test line is a part where a final signal is generated by the reaction of an analyte in the sample with a reagent in the strip.

[0078]

[0079] 2. Signal analysis method of a lateral flow analysis device

[0080] FIG. 3 is a flowchart illustrating a signal analysis method of a lateral flow analysis device according to an embodiment of the present invention.

[0081] Referring to FIG. 3, in a method for calculating the final signal magnitude of a lateral flow analysis device comprising at least one processor (130), a sample may be injected into an inspection cartridge (S310).

[0082] According to an embodiment of the present invention, a lateral flow analysis device may include an analysis device and an inspection cartridge, and as previously described, the inspection cartridge contains a reagent necessary for analysis.

[0083] The above reagent may include a substance prepared to react with a sample while moving along a strip to detect an analyte.

[0084] According to an embodiment of the present invention, the sample injected into the test cartridge may include a sample to be analyzed. For example, it may include various embodiments such as blood, urine, saliva, or other biological samples.

[0085] The user can inject a sample into the sample inlet of the test cartridge for testing, and the injected sample can react with the internal reagent. Subsequently, as the reagent and sample react, a signal may be generated on the test line and control line.

[0086]

[0087] 2.1 Acquisition of Time Series Information

[0088] According to an embodiment of the present invention, the lateral flow analysis device can irradiate light onto an inspection cartridge through a light-emitting unit (110) (S320).

[0089] Specifically, the light-emitting unit (110) may include at least one light source. The light-emitting unit (110) is a device that emits light through a light source included in a lateral flow analysis device and can irradiate light onto an inspection cartridge (101).

[0090] Specifically, the analysis device can irradiate light to a specific location on the inspection cartridge through a light-emitting part.

[0091] The above specific location may include a reagent reaction section (1101). The reagent reaction section (1101) may include a test line (1102) and a control line (1103).

[0092] For example, when a sample is injected into a lateral flow analysis device, the analyte in the sample and the reagent applied to the test cartridge pad combine to cause a reaction, and in the above process, a label can combine with the analyte to generate a signal.

[0093] The light-emitting unit (110) can irradiate light at an optimal wavelength and intensity tailored to the characteristics of a label, such as a fluorescent material or colorimetric particles (e.g., gold nanoparticles, latex particles).

[0094] When light is irradiated, the reagent reaction products formed during the reaction (e.g., particles that cause fluorescence or color change) exhibit a reaction in the form of reflection, scattering, or fluorescence emission.

[0095] According to an embodiment of the present invention, light irradiated from a light-emitting unit generates a signal that varies according to the reaction result, and a sensor of a light-receiving unit (120) can collect the light emitted due to the reflection or reagent reaction.

[0096] For example, in the case of an inspection containing a fluorescent material, a fluorescent signal is generated, and a sensor of the light receiving unit (120) can detect this and record the intensity and temporal change of the fluorescence.

[0097] According to an embodiment, the analysis device (100) may detect the degree to which light is reflected or absorbed and read a signal from a color change when the label applied to the reagent reaction part of the test cartridge (101) is a colorimetric particle (gold, latex, etc.).

[0098] According to an embodiment of the present invention, the lateral flow analysis device (100) can measure at least one of the test line and control line reagent reaction signals when a reaction occurs between the injected sample and the reagent (S330).

[0099] That is, according to the embodiment, the processor of the analysis device may also measure the reagent reaction signal of each of the test line and the control line when a reaction occurs between the injected sample and the reagent (S330-1).

[0100] Specifically, the lateral flow analysis device can store the time-series reagent reaction signal detected through the light receiver as time-series data.

[0101] As previously explained, the reagent reaction signal may be a signal generated from the label by a reagent reaction (the result of the binding of the reagent and the analyte) following sample injection.

[0102] According to an embodiment of the present invention, the processor (130) of the analysis device can convert the signal received from the light receiving unit into time-series data and store it in memory, an external device, or a database of a server.

[0103] According to an embodiment of the present invention, the time series data may refer to data in which the strength of a signal is continuously recorded over time.

[0104] According to an embodiment of the present invention, the time series data is a signal intensity value (signal strength) measured at a specific time, and the signal intensity value may include the reaction intensity between a reagent and an analyte.

[0105] In addition, time series data may include the time elapsed after sample injection.

[0106] The above time may serve as a reference indicating the process of signal generation and change (e.g., the x-axis).

[0107] According to an embodiment of the present invention, the processor (130) of the analysis device can obtain reagent reaction signal characteristic information of at least one of the test line and control line based on the time series data (S340).

[0108] Likewise, according to the embodiment, the processor of the analysis device can acquire reagent reaction signal characteristic information of each of the test line and control line based on the time series data (S340-1).

[0109] According to an embodiment of the present invention, the reagent reaction signal characteristic information may include at least one of the following: an increase or decrease rate of the time series data, information on the maximum or minimum value of the time series data, and information on the time point at which the signal of the test line or control line is observed relative to the background signal among the time series information of the test line or control line.

[0110] In this case, the background signal may refer to a non-specific signal occurring in the strip regardless of the test line or control line.

[0111] Specifically, a light source-sensor pair first measures a background signal while illuminating the strip, and when a sample moves along the strip and a reaction occurs at the test line or control line, the signal at the test line or control line can be observed by comparing it with the background signal.

[0112] For example, the processor of the analysis device can obtain time-series data by measuring the reagent reaction signal of the test line and obtain characteristic information of the reagent reaction signal of the test line based on the time-series data of the test line.

[0113] Likewise, the processor of the analysis device can obtain time-series data by measuring the reagent reaction signal of the control line and obtain characteristic information of the reagent reaction signal of the test line based on the time-series data of the control line.

[0114] Meanwhile, the time series signal according to the embodiment of the present invention does not always mean a continuous signal. The time series signal refers to an arrangement of data that changes over time, and should be interpreted as potentially being continuous or discontinuous.

[0115]

[0116] 2.2 Reagent Reaction Signal Characteristics

[0117] According to an embodiment of the present invention, the signal growth rate among the reagent reaction signal characteristic information may refer to the rate at which the signal increases at an initial point in time.

[0118] The processor of the analysis device can estimate the initiation time of the reagent reaction using the above growth rate and obtain information on the binding rate between the reagent and the analyte.

[0119] A higher increase rate may indicate that the concentration of the analyte in the sample is relatively high or that the reaction occurred rapidly.

[0120] According to an embodiment of the present invention, the signal reduction rate among the reagent reaction signal characteristic information may refer to the rate at which the signal decreases after the reagent reaction has reached a peak.

[0121] The processor of the analysis device can predict the time when the reaction ends through the above reduction rate and obtain information about the reaction duration.

[0122] According to an embodiment of the present invention, the maximum or minimum value of the signal among the reagent reaction signal characteristic information may refer to the time when the reagent reaction reaches its peak through the point in time when the signal reaches its maximum value.

[0123] In the case of the test line, the processor of the analysis device can acquire information on the direct correlation between the maximum value and the analyte concentration and utilize it for future analyte concentration calculations.

[0124] In addition, the minimum value may include information on the time of background signal generation of the reagent reaction.

[0125] The processor of the analysis device will be able to obtain information about the initial moment when the reaction starts by comparing the signal of the test line or control line with the background signal.

[0126] The above time indicates the reaction initiation time, and it is possible to identify when the analyte binds with the reagent and the reaction begins in earnest.

[0127] As described above, the processor (130) can obtain reagent reaction signal characteristic information by measuring the time series signal change from the beginning of the reaction to the end of the reaction for each of the test line and the control line.

[0128] Meanwhile, according to an embodiment, depending on the type of reagent reaction, the graph in which the signal is acquired may also generally include information in the shape of a sigmoidal curve or a bell-shaped curve.

[0129]

[0130] 2.3 Signal Compensation

[0131] According to an embodiment of the present invention, the processor (130) of the analysis device can obtain the test line signal magnitude measured at the time of the end of the reagent reaction (S350).

[0132] In this case, the reagent reaction termination point can be defined as the moment when the reagent reaction signal stabilizes without further fluctuation. The reagent reaction termination point may refer to any one of a preset time, a decrease in signal change, or the point at which the signals of the test and control lines reach equilibrium.

[0133] According to an embodiment of the present invention, the processor (130) of the analysis device can compensate for the signal magnitude at the time of termination of the reagent reaction of the test line using the reagent reaction signal characteristic information (S360).

[0134] First, for signal compensation, the processor (130) of the analysis device according to an embodiment of the present invention can acquire standard time-series signal information of the inspection cartridge.

[0135] The standard time-series signal information of the above-mentioned inspection cartridge may include standard reagent reaction signal characteristic information of the inspection cartridge inserted into the lateral flow analysis device.

[0136] Specifically, the above standard time-series signal information can be obtained through a standard inspection cartridge test performed in advance.

[0137] For example, a standard inspection cartridge test performed in advance may refer to the process of selecting a standard inspection cartridge for each specific manufacturing lot (production batch) of inspection cartridges and performing repetitive tests using it.

[0138] Specifically, during testing, the processor (130) can measure and record time series signals by injecting a sample into a standard test cartridge and recording time series signals generated in the test line and control line at regular time intervals during the reagent reaction process.

[0139] The processor (130) can analyze the acquired time series data to obtain standard reagent reaction signal characteristic information including the signal growth rate, the time of reaching the maximum value, and the time of reaction termination.

[0140] The above standard time-series signal information is set as reference data for the corresponding inspection cartridge manufacturing lot and can be used to compensate for the accuracy of the results by comparing it with the actual signal during subsequent inspections.

[0141] Meanwhile, the above standard time-series signal information may be stored in the barcode or QR code of the inspection cartridge, or in the memory of the analysis device, or in a database of an external device or server connected to the analysis device.

[0142] According to an embodiment, when the inspection cartridge is inserted into the analysis device, the processor of the analysis device can obtain standard time-series information of the inspection cartridge by recognizing the barcode or QR code of the inspection cartridge.

[0143] After acquiring the standard time series signal information, the processor of the analysis device can compensate for the signal magnitude at the end of the reagent reaction of the test line using the standard time series signal information (S360).

[0144] Specifically, the processor (130) can calculate the compensation signal magnitude by comparing the standard time series signal information with at least one of the time series signal information of the control line and the test line.

[0145] According to an embodiment, the processor (130) can compensate for the signal magnitude of the test line using the standard time series signal information, time series data measuring the reagent reaction signal of the test line, and reagent reaction signal characteristic information derived from the time series data.

[0146] Alternatively, the processor (130) can compensate for the signal magnitude of the test line using the standard time series signal information, time series data measuring the reagent reaction signal of the control line, and reagent reaction signal characteristic information derived from the time series data.

[0147] Alternatively, the processor (130) can compensate for the signal magnitude of the test line by comparing the standard time series signal information with the time series data measuring the reagent reaction signal of the control line and the time series data measuring the reagent reaction signal of the test line.

[0148] Hereinafter, according to an embodiment of the present invention, a process for calculating the final signal magnitude by compensating the test line signal value measured at the end-point of the reagent reaction is specifically described.

[0149] A processor (130) according to an embodiment of the present invention can analyze time series signal information of a test line (increase rate, decrease rate, maximum value, minimum value, signal detection time relative to background, signal magnitude, etc.) by comparing it with standard time series signal information.

[0150] According to an embodiment of the present invention, the analysis device can calculate the compensated signal magnitude by multiplying the signal magnitude before compensation by a compensation function.

[0151]

[0152] According to an embodiment of the present invention, is the signal value of the test line before compensation, is the reward function, can mean the signal value of the test line after compensation.

[0153] According to an embodiment of the present invention, in order to reflect the background-relative signal detection time, a compensation function may be determined based on the difference between the background-relative signal detection time of a standard time series signal and the background-relative signal detection time of a test line time series signal.

[0154] For example, if the signal detection time relative to the background of a standard time series signal (Ti standard) is 5 seconds and the signal detection time relative to the background of an actual test line (Ti actual measurement) is 7 seconds, it can be seen that the response started later than the standard. In this case, the compensation function can be expressed as Ti standard / Ti actual measurement.

[0155]

[0156] That is, if the value of Ti standard / Ti actual measurement is less than 1, the signal was detected slowly, so the result can be compensated to the standard boundary by compensating to make the final signal value higher.

[0157] Alternatively, if the value of Ti standard / Ti actual measurement is greater than 1, the signal was detected quickly, so the result can be compensated to the standard boundary by compensating for a further reduction in the final signal value.

[0158] According to an embodiment of the present invention, in order to reflect the growth rate and the decrease rate, a compensation function may be determined based on the difference between the standard time series signal value at a specific time and the time series signal value of the test line.

[0159] Alternatively, a compensation function may be determined based on the growth and decline rates of the standard time series signal and the growth and decline rates of the time series signal of the test line.

[0160] For example, if the growth rate of the standard time series signal (r standard) is 0.8 units / second and the growth rate of the actual measured test line (r actual measurement) is 0.6 units / second, it can be interpreted that the response proceeded more slowly than the standard.

[0161]

[0162] That is, if the value of r_standard / r_measured is greater than 1, the actual signal increase proceeded more slowly than the standard, so the final signal value can be compensated to be higher. Conversely, if the value of r_standard / r_measured is less than 1, the actual signal increase proceeded more quickly than the standard, so the final signal value can be compensated to be lower.

[0163] Similarly, in the case of the reduction rate, the compensation function can be expressed as r-actual / r-standard.

[0164] In addition, to reflect the above maximum and minimum values, the compensation function can be determined based on the difference between the maximum and minimum values ​​of the standard time series signal and the maximum and minimum values ​​of the time series signal of the test line.

[0165] For example, if the standard maximum value (M standard) is 100 units and the actual maximum value (M actual measurement) is 90 units, it may mean that the actual response appeared at a lower intensity than the standard.

[0166] In this case, the compensation function can be expressed as follows.

[0167]

[0168] As shown above, if the ratio of the maximum value is greater than 1, the final signal magnitude is relatively low, so the accuracy of the result can be improved by compensating.

[0169] Likewise, the minimum value corresponds to the background signal and can be used to compensate for noise in the signal. For example, if the standard minimum value is 5 units and the actual minimum value is 3 units, the background signal is lower than the standard, so compensation can be performed using the same compensation function.

[0170] Meanwhile, as the present invention includes various embodiments, it is preferable to obtain a signal value of a test line after compensation that reflects various data included in the reagent reaction signal characteristic information by configuring a compensation function by combining at least one of mathematical formulas 2 to 4.

[0171] In addition, it would also be possible to construct a compensation function using the time series signal of the control line instead of the time series signal of the test line, and to compensate the time series signal of the test line through the constructed compensation function.

[0172] Subsequently, the processor (130) according to the embodiment of the present invention can perform lateral flow analysis by calculating the concentration of the analyte based on the compensated signal magnitude (S370).

[0173] Specifically, the processor (130) can obtain the final analyte concentration by using the correlation between the predefined signal strength and the analyte concentration based on the final signal strength after compensation is completed.

[0174] A processor according to an embodiment of the present invention may determine whether the concentration value of an analyte calculated based on the compensated signal magnitude is greater than or equal to a threshold value, and may determine positive if a concentration greater than or equal to the threshold value is detected, and negative if it is less than or equal to the threshold value.

[0175] Afterward, the processor (130) can store the calculated analyte concentration in memory or a database on a server and provide the results visually to the user.

[0176] Through this, the quantitative concentration of the analyte can be obtained, and if necessary, the results can be output via a screen or a separate device.

[0177]

[0178] 2.4 Time Series Data Compensation Example

[0179] The present invention will be explained in more detail below using an actual time series graph.

[0180] Figure 4 is an example diagram showing time series data before compensation according to an embodiment of the present invention.

[0181] For example, the graph in which the above signal is acquired can generally be acquired in the shape of a sigmoidal curve or a bell-shaped curve.

[0182] Referring to FIG. 4, an example of an S-shaped curve of multiple time series data (41, 42, 43) is shown. In each of the multiple time series data, the signal increases while the sample passes through the test line, and after a certain period of time, the signal reaches a saturation state and then shows a tendency to no longer increase or decrease slightly.

[0183] Each of the above multiple time series data is a signal obtained from the reagent reaction section of a single test cartridge.

[0184] Specifically, one of the multiple time series data (41, 42, 43) represents the reagent reaction signal of the control line, and the remaining time series data represents the reagent reaction signal of at least one test line.

[0185] The above time series data may exhibit significant fluctuations in the signal range depending on reaction conditions or sample conditions, and deviations may exist, particularly in the magnitude and change patterns of the signal.

[0186] Such deviations can occur due to minute differences in the reaction environment, device conditions, or variations in the sample, and these are factors that can reduce the accuracy of the signal.

[0187] Referring to FIG. 4, each of the time series data may include an initial interval (Signal Initiation), a signal rise interval (Signal Rise), and a saturation interval (Signal Plateau).

[0188] The above initial section refers to the time it takes for the sample to pass through the sample pad and move through the porous membrane to reach the test line, and in the above initial section, almost no signal appears and can represent the baseline state on the graph.

[0189] In addition, the signal rise is the phase where the combined analyte and label combine with the substance applied to the test line upon reaching it, at which point a signal begins to be generated.

[0190] In addition, the signal plateau is the region where, once the signal reaches a certain level, the intensity no longer increases and the signal reaches a saturation state. At this point, the graph remains flat, and the height of the saturation point can be determined by the concentration of the analyte in the sample.

[0191] The maximum signal intensity can be proportional to the concentration of the analyte (biomarker) in the sample. The slope of the signal rise section can indicate the rate at which the signal is generated.

[0192] The time it takes for the signal to reach saturation may vary depending on the concentration of the sample and the performance of the analysis device.

[0193] Referring to Figures 2 and 4, the time series data obtained according to the inspection position and the end-point of the reagent reaction are different from each other as the sample moves through the sample pad and the porous membrane until it reaches the test line.

[0194] FIG. 5 is an example diagram showing time series data after compensation according to an embodiment of the present invention.

[0195] Figure 5 is a figure showing test line signals (51, 52, 53) after compensation, showing a state where the deviation of Figure 4 is significantly reduced through the compensation process.

[0196] Referring to FIG. 5, the processor (130) can compensate for the signal magnitude at the end of the reagent reaction of the test line using the reagent reaction signal characteristic information for the time series data (e.g., 41, 43) corresponding to the test line among the plurality of time series data (41, 42, 43) obtained in FIG. 4.

[0197] Through the above compensation, the final signal magnitudes at the end of the reagent reaction are adjusted to be similar to each other, and compared to Figure 4, the range of variation between signals is reduced, so it can be confirmed that the range of variation is reduced.

[0198] The above compensation has the effect of reducing errors that may occur when calculating the final concentration and significantly improving the reliability and accuracy of the analysis.

[0199] As described above, the present invention compensates for the signal value measured at the end of the reaction based on time-series signal information, thereby enabling more accurate calculation of the concentration of the analyte being measured. In contrast, conventional technology calculates results by simply measuring the signal magnitude at the end of the reaction, and thus fails to reflect signal fluctuations caused by changes in reaction time or environmental factors, which may result in reduced reliability.

[0200] Therefore, the present invention can significantly improve the reliability of analyte detection and, in particular, provide the effect of reducing errors caused by environmental variations and increasing the consistency and accuracy of measurements through a compensation process compared with a standard signal.

[0201] Meanwhile, signal compensation according to an embodiment of the present invention may be performed by an analysis device, and it may also be performed through an external device or server communicating with the analysis device.

[0202] A person skilled in the art of the present disclosure will understand that the various exemplary logic blocks, modules, processors (130), means, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented by electronic hardware, various forms of programs or design code (referred to herein as software for convenience), or a combination of all of these.

[0203] The present invention described above can be implemented as computer-readable code on a medium on which a program is recorded. A machine-readable recording medium includes all types of recording devices in which data that can be read by a computer system is stored. Examples of machine-readable media include HDD (Hard Disk Drive), SSD (Solid State Disk), SSD (Silicon Disk Drive), ROM, RAM, CD-ROM, magnetic tape, floppy disk, optical data storage device, etc.

[0204] In one embodiment, the recording medium may be a memory. In one embodiment, the recording medium may be implemented in a distributed form in a networked computer system, etc. Software may be stored and executed in a distributed manner in a computer system, etc. The recording medium may be a non-transitory recording medium. A non-transitory recording medium may refer to a tangible medium that exists regardless of whether data is stored semi-permanently or temporarily.

Claims

1. A method for calculating the final signal magnitude of a lateral flow analysis device comprising at least one processor, A step of acquiring time series data by measuring at least one reagent reaction signal among the test line and the control line; A step of acquiring reagent reaction signal characteristic information of at least one of the test line and control line based on the above time series data; A step of compensating the signal magnitude at the time of termination of the reagent reaction of the test line using the above reagent reaction signal characteristic information and A method comprising the step of calculating the concentration of an analyte based on the above-mentioned compensated signal magnitude, method.

2. In Paragraph 1, The above reagent reaction signal characteristic information is, at least one of the following: the growth rate or decrease rate of the time series data, information on the maximum or minimum value of the time series data, and information on the time point at which the signal of the test line or control line is observed relative to the background signal among the time series information of the test line or control line. method.

3. In Paragraph 1, The step of compensating the signal magnitude at the time of termination of the reagent reaction of the test line using the above-mentioned reagent reaction signal characteristic information is, A step including obtaining standard time-series data information of an inspection cartridge, method.

4. In Paragraph 3, The above standard time series data information includes standard reagent reaction signal characteristic information by manufacturing lot of the inspection cartridge inserted into the above lateral flow analysis device, method.

5. In Paragraph 3, The step of acquiring standard time-series data information of the above-mentioned inspection cartridge is, A step comprising obtaining standard time-series data information of the lateral flow analysis device through information stored in a barcode or QR code provided in an inspection cartridge, method.

6. In Paragraph 3, The standard time-series data information of the above inspection cartridge The above inspection cartridge, barcode or QR code, stored in the memory or server of the analysis device, method.

7. In Paragraph 1, The step of compensating the signal magnitude at the time of termination of the reagent reaction of the test line using the above-mentioned reagent reaction signal characteristic information is, A step of acquiring standard time-series data information of an inspection cartridge; and A method characterized by comparing the above standard time series data information with at least one time series data information among the above test line and the above control line to calculate the signal magnitude at the time of termination of the reagent reaction of the above test line.

8. In Paragraph 1, The method further includes the step of determining whether the concentration of the analyte calculated based on the above-mentioned compensated signal magnitude is above a threshold, and determining positive if a concentration above the threshold is detected, and negative if it is below. method.

9. In Paragraph 1, It further includes a test cartridge in which the above-mentioned reagent reaction occurs, and The above-mentioned test cartridge includes a reagent reaction section coated with a label comprising at least one of a fluorescent substance (Fluorophore) and a colorimetric particle, method.

10. A lateral flow analysis device comprising at least one processor, The above processor is, Time series data is obtained by measuring the reagent reaction signal of at least one of the test line and control line, and Based on the above time series data, reagent reaction signal characteristic information of at least one of the test line and control line is obtained, and Compensating the signal magnitude at the end of the reagent reaction of the test line using the above reagent reaction signal characteristic information, and Calculating the concentration of the analyte based on the above-mentioned compensated signal magnitude, Lateral flow analysis device.

11. In Paragraph 10, The above reagent reaction signal characteristic information is, at least one of the growth rate or decrease rate of the time series data, information on the maximum or minimum value of the time series data, and information on the time point at which the signal of the test line or control line is observed relative to the background signal, Lateral flow analysis device.

12. In Paragraph 10, The above processor is, Acquire standard time-series data information of the inspection cartridge, and Compensating the signal magnitude at the end of the reagent reaction of the test line using the above reagent reaction signal characteristic information, Lateral flow analysis device.

13. In Paragraph 12, The above standard time series data information includes standard reagent reaction signal characteristic information by manufacturing lot of the inspection cartridge inserted into the above lateral flow analysis device, Lateral flow analysis device.

14. In Paragraph 12, The above processor is, Acquiring standard time-series data information of the lateral flow analysis device through information stored in a barcode or QR code provided in an inspection cartridge, Lateral flow analysis device.

15. In Paragraph 12, The standard time-series data information of the above inspection cartridge Stored on an analysis device or server, Lateral flow analysis device.

16. In Paragraph 10, The above processor Acquire standard time-series data information of the inspection cartridge, and Comparing the above standard time series data information with at least one time series data information among the above test line and the above control line to calculate the signal magnitude at the time of termination of the reagent reaction of the above test line, Lateral flow analysis device.

17. In Paragraph 10, The above processor is, Determining whether the concentration of the analyte calculated based on the above-mentioned compensated signal magnitude is above a threshold, and determining positive if a concentration above the threshold is detected, and negative if it is below. Lateral flow analysis device.

18. In Paragraph 10, It further includes a test cartridge in which the above-mentioned reagent reaction occurs, and The above-mentioned test cartridge includes a reagent reaction section coated with a label comprising at least one of a fluorescent substance (Fluorophore) and a colorimetric particle, Lateral flow analysis device.

Images