A multi-method urine test kit and reading, recording, and visualization system capable of progressively determining hCG levels in early pregnancy.

Abstract

This provides a means to continuously, concisely, and objectively visualize the trends in measurement results. [Solution] An in vitro diagnostic test kit for determining information on human chorionic gonadotropin contained in the urine of a subject in multiple stages, comprising one or more detectors equipped with a capture member that specifically binds to human chorionic gonadotropin upon contact with a sample, wherein one or more visual indicator parts provided on the detector itself exhibit multiple visual states that can be identified by at least one of position, hue, intensity, or number of appearances upon reaction with urine, and the visual states or combinations thereof are associated with multiple judgment criteria corresponding to human chorionic gonadotropin.

Description

Technical Field

[0001] The invention of the present disclosure belongs to the field of in vitro diagnosis, and relates to an inspection technique for gradually obtaining information on human chorionic gonadotropin (hCG) contained in the urine of a subject and visually displaying and determining the information. Further, the invention of the present disclosure also relates to a reading, recording, and visualization system that images, analyzes, records, and visualizes the determination information obtained by the inspection technique.

Background Art

[0002] Many home pregnancy test drugs are configured to determine whether the hCG in urine exceeds a predetermined threshold value in binary values of positive or negative, and it is not easy to continuously grasp the increasing trend of hCG in the early stage of pregnancy in a home environment. There is an increasing demand for easily confirming trends such as increase, stagnation, or decrease through daily measurements at short intervals, such as immediately after in vitro fertilization or embryo transfer. Conventional general pregnancy test drugs use a threshold of about 25 to 50 mIU / mL and only show positive / negative, so the change in concentration cannot be visually recognized. Especially after IVF (in vitro fertilization) or ET (embryo transfer), it is clinically important that the hCG after implantation establishment increases by 1.5 to 2 times every 24 to 48 hours, and there is a high need to grasp this natural increase pattern on a daily basis. In addition, with the increasing age of pregnant women in recent years, the number of cases where pregnancy does not continue even though implantation is established has increased, and the desire to monitor the unstable period up to the confirmation of the heartbeat around the 6th week of pregnancy at home has become apparent.

[0003] In recent years, attempts have been made to digitally process and display the measurement results of urine hCG, and devices have been proposed to improve the visibility of determination. For example, there is Japanese Patent Application Laid-Open No. 2022-532799, and technologies related to information processing and display of urine tests are known. However, this document does not disclose the easy grasping of the gradual and daily changes of hCG in the early stage of pregnancy at home.

Prior Art Documents

Patent Documents

[0004] [Patent Document 1] Japanese Patent Publication No. 2019-132771 [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] This provides a means to continuously, concisely, and objectively visualize the trends in measurement results. [Means for solving the problem]

[0006] To solve the above problems, for example, the following configuration can be adopted. An in vitro diagnostic test kit for determining information on human chorionic gonadotropin contained in the urine of a subject in multiple stages, comprising one or more detectors equipped with a capture member that specifically binds to human chorionic gonadotropin upon contact with a sample, wherein one or more visual indicator parts provided on the detector itself exhibit multiple visual states that can be identified by at least one of position, hue, intensity, or number of appearances upon reaction with urine, and the visual states or combinations thereof are associated with multiple judgment criteria corresponding to human chorionic gonadotropin.

[0007] A test kit that allows the user to instantly read a stage as an evaluation of the concentration value of human chorionic gonadotropin or the stage of pregnancy progression, without referring to a separate judgment chart, by associating at least one of the position, hue, or number of occurrences of the visual state exhibited by the user with a reference display section permanently printed on the detection body or housing.

[0008] A test kit in which multiple criteria indicators showing different judgment criteria are permanently printed, the criteria indicators include concentration values ​​or graded evaluations showing the progression of pregnancy, and the visual state is configured to appear in accordance with each criterion indicator, and the number of graded indicators can be set to 2 or more and 5 or less.

[0009] A test kit comprising a detector having a lateral flow structure, wherein a plurality of visual indicators are arranged along the direction of urine flow, each of the visual indicators is immobilized with an anti-human chorionic gonadotropin antibody of different sensitivities or affinities, and the test kit performs a grade determination based on the position or number of appearances of the expressed visual state.

[0010] A test kit comprising a plurality of visual indicator units arranged in order from lowest to highest threshold along the flow direction of the sample, and further comprising a test confirmation unit for confirming that the test has been performed correctly, wherein the test confirmation unit is in the final position when viewed from the urine collection side and is located downstream of the visual indicator unit corresponding to the highest judgment criterion.

[0011] A test kit in which the visual indicator portion displays the visual state at multiple positions arranged along the direction of urine flow, each of the multiple visual states exhibits a different hue that is mutually distinguishable, and a grade determination is made based on the combination of hue and position.

[0012] An inspection kit comprising a calibration section near the visual indicator section, which includes a white reference area and a reference color area having known reflective properties.

[0013] A test kit in which the detection substance consists of multiple strips corresponding to different concentration thresholds as judgment criteria, each strip exhibits a single color when it reaches its corresponding criterion, and a graded judgment is made based on the number of colored strips or the highest corresponding criterion among the colored strips.

[0014] For the purpose of an in vitro diagnostic test that determines information on human chorionic gonadotropin contained in the urine of a subject in stages, a system that outputs to the user the time-series trend based on the relationship between past reading data and current reading data, based on the determination result data of a testing device, comprising: an input means for acquiring determination result data; and an output means for storing the determination result data in association with time information and generating a result display showing the trend of increase, stagnation, or decrease in the subject based on a comparison with stored past data.

[0015] The system further comprises: an imaging means for imaging the testing device, the testing device having a visual indicator on its display surface, the visual indicator causing a visual state that can be identified by position, hue, intensity, or number of occurrences in response to a reaction with urine; and an analysis means for extracting at least one of the position, hue, intensity, or number of occurrences of the visual state from the captured image to determine step information.

[0016] In the system, the inspection device is of the lateral flow type and has a structure in which multiple visual indicators are provided along the direction of urine flow, and the analysis means recognizes the presence or absence, location and number of occurrences of the visual state, and determines stage information based on these.

[0017] In the system, the inspection device is of the lateral flow type and has a plurality of visual indicators arranged along the direction of urine flow, each of which a visual state is manifested in response to the reaction with urine, and the analysis means identifies the hue and position of each visual state and determines stage information based on the correspondence between hue and position.

[0018] In the system, the testing device comprises a visual indicator unit consisting of a single reaction point, the visual indicator unit causing a visual state to appear in response to contact with urine, and the analysis means acquires the hue or intensity of the visual state and determines step information.

[0019] In the system, the testing device consists of multiple strips corresponding to different concentration thresholds, each strip is equipped with a visual indicator part, and the visual indicator part causes the visual state to appear in response to the reaction with urine. The analysis means recognizes the presence or absence of the visual state in the multiple strips, the difference in hue or brightness, and the number of strips that have shown the visual state, and determines step information based on the corresponding threshold that is judged to be the largest among those that have shown color, or the number of occurrences.

[0020] In a system, an output means calculates and displays at least one of a change rate, an increase / decrease direction, an estimated doubling time, or a half-life time from a comparison between the past data and the current data.

[0021] In a system, an output means visualizes the time-series data as a graph, and in the graph, displays the subject data, a preset reference band, and a preset representative curve on the same screen. The reference band is composed of an upper limit value and a lower limit value.

[0022] In a system, an analysis means automatically calculates the number of days elapsed after embryo transfer based on the embryo transfer date input by a user, automatically determines a time coordinate on one of preset coordinate axes, and automatically plots the time-series data at a position corresponding to the time coordinate.

[0023] In a system, an output means assigns and displays a qualitative evaluation category based on the stage information.

Advantages of the Invention

[0024] According to the invention of the present disclosure, by a stage determination based on at least one of the position, hue, shading, and number of appearances of the visual index part, the change in urinary hCG in the early stage of pregnancy can be intuitively grasped at home, and the tendency of gradual increase, stagnation, and decrease can be visually confirmed from the results of consecutive measurements. Therefore, it contributes to early progress monitoring, assistance in diagnosis determination, and reduction of psychological burden. Problems, configurations, and effects other than those described above will be clarified by the description of the following embodiments.

Brief Description of the Drawings

[0025] [Figure 1] shows an example of a method (lateral flow, step line) using a linear visual index part in an inspection kit. [Figure 2] shows an example of a method (lateral flow, multi-color display) using an area-type visual index part in an inspection kit. [Figure 3]This shows an example of a test kit that uses a reaction point type visual indicator (non-lateral flow, single point / multicolor change). [Figure 4] This shows an example of a test kit using a monochromatic method with multiple strips (non-lateral flow, multiple strips). [Figure 5] This shows a block diagram of the system. [Figure 6] This shows the system's processing flow (S1-S6). [Figure 7] This shows an example of a user interface for time-series visualization and display of judgment results in the system. [Modes for carrying out the invention]

[0026] The present invention uses a detector (11) equipped with a capture member that specifically binds to human chorionic gonadotropin (hCG) upon contact with the subject's urine, and a visual indicator section (3, 5, or 6) provided on the display surface of the detector displays a visual state that can be identified in response to the urine. The visual state is expressed by at least one of the position, hue, intensity, or number of appearances of the visual indicator section, and a stage determination is made based on a plurality of judgment criteria (concentration value or stage evaluation) associated with hCG. The determination may be made by the user visually reading the result directly, or the stage information may be determined by imaging and data conversion using analytical means. This allows for the gradual and time-series confirmation of hCG dynamics in early pregnancy in a home environment, contributing to early progress tracking, assistance in deciding whether to seek medical attention, and reduction of psychological burden. The test kit (10) of the present invention includes at least the detector (11) and is configured in combination with a housing (12), etc., depending on the embodiment.

[0027] The detection object (11) may be one or more, and the visual indicator part may be one or more. The stage determination may be based on the visual state of a single visual indicator part, or on a combination of the visual states of multiple visual indicator parts or multiple detection objects (e.g., appearance pattern, number of appearances, identification of the maximum corresponding criterion).

[0028] All methods share a common indicator: five representative threshold levels useful for early pregnancy monitoring (e.g., 100, 300, 500, 700, 1000 mIU / mL). The number of levels can be set from 2 to 5 depending on regulations and applications. The configuration may also conform to Japanese domestic administrative guidelines (qualitative or semi-quantitative methods with approximately 2 to 3 levels are appropriate). Furthermore, in line with the clinical practice of IVF / ET, we can illustrate the correspondence with typical post-ET days: 9-11 days: approximately 100 mIU / mL, 11-13 days: approximately 300 mIU / mL, 13-15 days: approximately 500 mIU / mL, 15-17 days: approximately 700 mIU / mL, 17-19 days: approximately 1000 mIU / mL. These correspond to the physiological significance of the period from around the time of gestational sac confirmation to around the time of heartbeat confirmation (roughly late 4th to 6th week of pregnancy).

[0029] The reference display section (8) permanently displays multiple judgment criteria and enables direct reading of the stages through positional or hue correspondence with the visual indicator sections (3, 5, or 6). The reference display section (8) may be permanently printed near at least one of the visual indicator sections of the detector (11) or housing (12). The contents displayed on the reference display section include concentration values ​​or stage evaluations. This allows the user to immediately read the stage (concentration value or stage evaluation indicating the progression of pregnancy) by associating the reference display section with the observed visual state without referring to a separate judgment chart.

[0030] In this specification, the visual indicator area (3, 5, or 6) refers to the reaction / display area itself, which exhibits color or intensity due to an immune response or the like, and is therefore visible. Urine moves through the internal pathway of the detection body by capillary action or the like, and reacts at the visual indicator area formed at a predetermined position, thereby exhibiting a visual state. In this specification, "visual state" means a state that can be identified by at least one of the following: position, hue, intensity, or number of occurrences. Furthermore, "stage information" refers to the identification result obtained by mapping the visual state to hCG concentration values ​​or stage evaluations indicating the progression of pregnancy. As used herein, "combination of visual states" includes patterns of visual state occurrences between multiple visual indicator areas or between multiple detection objects.

[0031] The invention disclosed herein does not require a special reading device and can be operated at low cost. Furthermore, since the number of stages can be adjusted from 2 to 5, it can also conform to the administrative guidelines that "it is appropriate to standardize qualitative or semi-quantitative judgments to about 2 to 3 stages." In addition, if necessary, a high-concentration model with a different specification to accommodate high concentration ranges exceeding 1000 mIU / mL (e.g., 3000, 5000, 10000 mIU / mL, etc.) may be designed.

[0032] The first embodiment of the test kit shown in Figure 1 will be described. The test kit (10) according to this embodiment comprises a detector (11) having a lateral flow structure and a housing (12).

[0033] The detection unit (11) includes a urine collection unit (1) for introducing urine, an absorption unit (2) located inside the housing that holds excess urine at the end of the flow path and drives the flow, multiple visual indicator units (3) arranged linearly along the flow direction, and a test confirmation unit (4) that indicates the success of the test. The visual indicator units (3) are reaction / display areas in which a capture member for hCG is fixed at a predetermined amount and affinity for each line, and a visual state (identifiable by at least one of position, hue, intensity, or number of occurrences) is expressed in response to the reaction with urine. Multiple visual indicator units are arranged sequentially with lower judgment criteria on the upstream side and higher judgment criteria on the downstream side, and the stage is determined by the position or number of occurrences of the expressed visual state. The number of stages can be set to 2 to 5 stages, for example, corresponding to judgment criteria of 100 (T1), 300 (T2), 500 (T3), 700 (T4), and 1000 (T5) mIU / mL. As an example of visibility, the line width can be approximately 0.5 mm, the line spacing approximately 2 mm, and the field of view for judgment can be approximately 6 mm vertically x 15 mm horizontally.

[0034] The housing (12) includes a gripping section (13) to enhance holding during inspection, a window section (14) corresponding to the position of the visual indicator section (3) and the inspection confirmation section (4), and a reference display section (8) for permanently printing multiple judgment criteria (concentration values ​​or grade evaluations). The window section (14) may be an opening (hole) to the display surface, or it may be configured to be visible through a translucent material (transparent or semi-transparent). The window section (14) is positioned to encompass the entire row of visual indicators, and the alignment error between the window and the row of indicators is controlled to approximately ±0.3 mm.

[0035] The user can visually read the levels based on the positional correspondence between the reference display unit (8) and the visual indicator unit (3), or they may determine the levels by capturing images and extracting at least one of the position, hue, intensity, or number of occurrences. Furthermore, in the usage example in Figure 1, it can be seen that in measurement example 1, the visual state corresponding to the judgment criterion of "300 mIU / mL" appears, and in the subsequent measurement example 2, the visual state corresponding to the judgment criterion of "500 mIU / mL" appears. This upward trend in the reference value visually indicates that urinary hCG is on an upward trend due to daily measurements, contributing to early monitoring of the progress, assistance in deciding whether to seek medical attention, and increased user confidence. This method is suitable for daily follow-up after a positive result obtained with conventional qualitative pregnancy tests and is useful for monitoring the progress of early pregnancy (before heartbeat confirmation).

[0036] The urine collection section (1) uses a cellulose-based or glass fiber nonwoven material, and urine is introduced via capillary flow. The absorption section (2) uses superabsorbent cellulose or the like, and the flow is driven by a higher capillary pressure than the urine collection section. The visual indicator section (3) is a reaction / display area to which a predetermined amount of captured anti-hCG antibody is fixed. By capturing the hCG complex bound to the labeled antibody (e.g., gold colloid or stained latex-conjugated antibody) upstream, the label accumulates, and a linear visual pattern appears. The test confirmation section (4) is equipped with a mechanism to non-specifically capture free labels (e.g., anti-species specific antibody) and demonstrates the effectiveness of the flow and reaction.

[0037] To distinguish between multiple stages (e.g., 100, 300, 500, 700, 1000 mIU / mL), the expression thresholds for each visual indicator are adjusted. The main methods involve staggering the amount of captured antibody immobilized, employing different antibody affinity (Kd) values ​​for each line, and optimizing geometric parameters such as line width and line length. As a result, at low concentrations, expression occurs sequentially from the upstream side, and as the concentration increases, the stages become clearer in both the number of appearances and the furthest reached position.

[0038] The determination may be made by the user visually reading the relationship between the reference display unit (8) and the visual indicator unit, or by capturing an image, converting it into data, and determining the step information using an analysis means.

[0039] The second embodiment of the test kit, shown in Figure 2, is described below. The test kit (10) according to this embodiment, like the first embodiment, comprises a detection body (11) and a housing (12), including a lateral flow structure, and includes a urine collection section (1), an absorption section (2), and a plurality of visual indicator sections (5) arranged along the flow direction. The difference is that the visual indicator sections (5) exhibit mutually different hues at each position, and the visual state is graded by a combination of "hue + position". That is, each visual indicator section exhibits a visual state of a different hue, such as yellow, yellow-green, green, orange, or red, in response to its reaction with urine, and the user makes a determination based on the correspondence between the position (threshold sequence) and hue (stage assigned to each position) of the exhibited visual state. The test confirmation section (4) may be provided at the downstream end. The window section (14) may be an opening (hole), or it may be configured to be visible through a transparent or translucent material. One example of the colors and concentrations is yellow: approximately 100 mIU / mL, yellow-green: approximately 300 mIU / mL, green: approximately 500 mIU / mL, orange: approximately 700 mIU / mL, and red: approximately 1000 mIU / mL. A color chart with the same arrangement is permanently printed on the reference display section to facilitate direct reading.

[0040] Each visual indicator section (5) is equipped with a capture member for the same antigen (hCG), and the color development system is differentiated at each position to obtain mutually distinguishable hues. Examples of color development systems include binding different colored latex particles (e.g., Yellow, Green, Orange, Red) to a labeled antibody, hue switching by enzyme labeling (HRP, ALP, etc.) + substrate system differentiation, and chromaticity adjustment by gold colloid + auxiliary staining. The hue separation (ΔE) is designed to be 8 to 10 or higher in a D65 light source and CIE L*a*b* space, and a color sample with the same sequence is permanently printed on the reference display section (8) to enable direct reading of hue correspondence. Color bleeding and mixing may be suppressed by setting the spacing between indicator sections, surface treatment of the substrate, and optimization of the fluid conditions for label release.

[0041] In this method, the visual indicator unit (5) reacts with urine to display a visual state (primarily hue) at multiple locations. The user can associate the judgment criteria shown on the reference display unit (8) with the hue at each location and directly read the grade visually. Judgment by imaging is also possible; the visual state at each location is extracted from the acquired image, and after conversion to a color space, the grade information is determined by the combination of hue (or color difference) + location. In the usage example in Figure 2, it can be seen that in measurement example 1, a visual state of a hue specific to that location appears at the location corresponding to the judgment criterion of "500 mIU / mL", and in the subsequent measurement example 2, a visual state of the same hue appears at the location corresponding to the judgment criterion of "700 mIU / mL". This upward trend in the reference value visually indicates the upward trend of urinary hCG through the combination of hue and location, contributing to the understanding of short-term trends and assisting in initial judgment. Other components and functions (materials, quality control, etc.) are the same as in Embodiment 1, so their explanation is omitted. This method suppresses subjective differences in line shading due to differences in hue, thereby improving intuitive identification at home.

[0042] The third embodiment of the test kit, shown in Figure 3, is described below. This embodiment is a non-lateral flow type, and the test kit (10) is similar to embodiments 1 and 2 in that it comprises a detector (11) and a housing (12), but differs in that a single visual indicator part (6) provided at the tip of the detector (11) also serves as the urine collection part. The detector (11) includes a urine collection part and a visual indicator part (6), and an absorbent part (2) located inside the housing that holds excess urine at the end of the flow path, and a visual state is expressed at the visual indicator part (6) in response to the reaction with urine. The housing (12) is equipped with a gripping part (13) to improve holding during testing. In this embodiment, there is no reference display part, so the concentration value of human chorionic gonadotropin or the stage evaluation indicating the stage of pregnancy progression can be read by comparing the reference display, which is a separate unit, with the expressed visual state. In other embodiments, a reference display part may be provided on the housing (12).

[0043] The visual indicator section (6) is a reaction / display area in which a capture member for hCG is fixed under predetermined conditions, and a visual state (mainly hue or intensity) is expressed at a single location by reaction with urine. Stage determination is performed by matching a reference display (numerical value or stage evaluation) with the hue or intensity of the expressed visual state. As a supplement, the number of occurrences (presence or absence of the visual state: 0 / 1) may be used as an indicator.Specific examples of obtaining a stepwise hue change with a single visual indicator section (6) include: (i) a ratio measurement type in which two or more different colored labels coexist with different effective affinity and fixed density, and the color mixing ratio transitions with changes in the binding ratio as the concentration increases; (ii) a sequential color development type in which an oxidoreductase label and a two-stage substrate are designed at the same point, and the hue shifts stepwise by adjusting the substrate supply amount, reaction time, and catalyst density; and (iii) a multilayer sequential exposure type in which the lower layer color is exposed as the upper layer color develops and becomes transparent, and the apparent hue changes stepwise. Visibility between stages is ensured by optimizing the mixing ratio, immobilization amount, and reaction time so that the ΔE on the CIE L*a*b*(D65) scale is 8-10 or higher. The number of stages can be set to 2-5, and can correspond to standards such as 100, 300, 500, 700, and 1000 mIU / mL, for example.

[0044] The determination may be made by visually comparing the displayed visual state with a separate reference display and reading it directly, or by capturing an image, digitizing it, and extracting hue / intensity (and the number of occurrences if necessary) from the image to determine the stage information. Other components and functions (materials, quality control, etc.) are the same as in Embodiment 1, so their description is omitted.

[0045] Figure 4 describes a test kit as a fourth embodiment. The test kit (10) according to this embodiment is a non-lateral flow type and is composed of multiple detectors (11), each having a urine collection section and a visual indicator section (6), a gripping section (13), and a reference display section (8). Each detector (11) is associated with a different judgment criterion (e.g., 100, 300, 500, 700, 1000 mIU / mL), and the visual indicator section (6) at the tip displays a visual state as a single color or the presence or absence of shades depending on the reaction with urine. Since a housing (12) is not used, a window section (14) is not required, but the gripping section (13) formed on the body of each detector ensures holding during the urine collection operation. A hydrophilic porous substrate (cellulose-based, glass fiber, hydrophilic polymer nonwoven, etc.) is suitably used for the urine collection section and visual indicator section (6), and a hydrophobic thermoplastic resin (PP, PE, ABS, etc.) with excellent moisture resistance, mechanical strength, and moldability is used for the gripping section (13) to provide a non-slip texture. The other configurations and functions are the same as in Embodiment 1 unless otherwise specified.

[0046] The visual indicator area (6) of each detector (11) is a reaction / display area in which a capture member for hCG is fixed under predetermined conditions, and a visual state (presence or absence of a single color or predetermined intensity) is expressed at a single location upon reaction with urine. Stage determination is performed based on at least one of the following: the number of detectors that exhibit the expressed visual state, or the identification of the highest corresponding determination criterion among the detectors that exhibit the expressed visual state. The corresponding determination criterion (concentration value or stage evaluation indicating the stage of pregnancy progression) is permanently printed on the criterion display area (8) of each detector, and the user can directly read it by associating it with the presence or absence of the visual state.

[0047] The user applies multiple detection bodies (11) to the same urine simultaneously or sequentially, and checks the presence or absence (or intensity) of the visual state at each tip after a predetermined time (e.g., 3 to 10 minutes). When data is collected by imaging, the presence or absence of the visual state, the number of occurrences, and the optical density, if necessary, are extracted to determine the stage information. Other matters such as quality control, stage design, and non-specific suppression are the same as in Embodiment 1, so they are omitted from this explanation.

[0048] As shown with reference to Figures 5 to 7, the present invention may include a reading, recording, and visualization system for continuously handling judgment information obtained from an inspection kit (10). The system includes an imaging means (21) for imaging the display surface of an inspection tool, an input means (24) for acquiring judgment result data by imaging or manual input, an analysis means (22) for determining stage information by extracting at least one of the position, hue, intensity, or number of occurrences of the visual state from the image or judgment result, a time-series data storage (27) for storing the stage information and time information in association, an output means (23) for displaying the trend of increase, stagnation, or decrease, the rate of change, the estimated doubling time, or the half-life time based on a comparison with past data, and a terminal / application (26) for visualizing a reference band (25) and a representative curve superimposed on a graph. These functions are executed sequentially in each step S1 to S6 of the processing flow shown in Figure 6.

[0049] In S1 (imaging / input), the input means (24) accepts at least one of the following: image input by the imaging means (21) and manual input by the user directly selecting a step value. The imaging means (21) preferably uses the rear camera of a smartphone or the like, and a resolution of 8 megapixels or higher is desirable. The shooting distance should be 20 to 40 cm, the illumination 400 to 800 lux as a guideline, the flash should be off, and reflections should be avoided under white diffuse lighting. Furthermore, when using manual input (direct selection of step values), the process does not go through S2 (calibration / normalization), S3 (index extraction), and the judgment node D1, which presuppose the processing of the captured image, nor does it require the analysis process of S4 (step determination). The step information obtained in S1 is used directly to proceed to S5 (save, compare, calculate).

[0050] In S2 (calibration / normalization), the analysis means (22) performs exposure correction, white balance adjustment, geometric correction (trapezoidal correction, resizing), and noise reduction on the acquired image. In the embodiments 1 to 4 described above, a calibration unit may be included as needed. If the inspection kit (10) has a calibration unit near the visual indicator unit, the white reference area and the reference color area with known reflectivity characteristics included in the calibration unit are detected and used for normalization of the color space and automatic setting of the color difference threshold. If there is no calibration unit, normalization is performed based on standard white estimation, gray card reference, or pre-learned parameters within the application. After S2, the validity of the measurement is determined at the judgment node D1 in Figure 6, and if it is valid, the process transitions to S3.

[0051] In S3 (Indicator Extraction), for lateral flow types (Figure 1: line type, Figure 2: multi-color area type), visual indicators are detected from the display surface, and (i) for line types, the presence or absence, location, and number of occurrences of the visual state are recognized, and (ii) for multi-color area types, the hue and location of the visual state at each position are identified. For non-lateral flow types (Figure 3: single point, Figure 4: multiple strips), (iii) the hue or intensity of the visual state is extracted for the single point (the number of occurrences is an indicator of 0 / 1), and (iv) for multiple strips, the presence or absence of the visual state for each strip, the difference in hue or lightness, and the number of occurrences of strips that exhibit the visual state are recognized.

[0052] In S4 (stage determination), the stage value may be determined (i) based on the correspondence between the judgment criteria (density value or stage evaluation) shown in the reference display unit (8) and the visual state (position, hue, intensity, number of occurrences), or (ii) in the analysis by the terminal / application (26), the reference display unit (8) may be taken into consideration, but the determination may also be based on internal criteria (hue threshold or ΔE, position threshold, number of occurrence threshold, etc.) that are set and stored in advance within the terminal / application (26). For example, if a reference display unit is not provided as in Embodiment 3, the visual state (hue or intensity) is extracted from the captured image and the stage is determined in light of the internal criteria. If necessary, the number of occurrences within a short time (number or presence of expression positions) is used as an auxiliary indicator, and variability is reduced by robust estimation such as outlier removal and moving median.

[0053] In S5 (save, compare, and calculate), the input means (24) times-stamps the stage information and records it in the time-series data storage (27), and the analysis means (22) calculates the direction of increase or decrease, the rate of change, and the estimated doubling time or halving time from the stage information (C1, C2) at two consecutive points in time and the observation interval Δt. The estimated doubling time td is td = Δt × ln2 / ln(C2 / C1) Given by, during the descent, the half-life t1 / 2 t1 / 2 = Δt × ln2 / ln(C1 / C2) This formula is given by quantifying the rate of increase (doubling) or decrease (halving) from discrete step measurements as a time indicator, based on an exponential growth model. This allows for comparison of trends between cases even when measurement intervals differ, and objectively supports the assessment of the progress in early pregnancy (e.g., using a doubling time of 24-48 hours as a guideline). If the step values ​​are discrete, they are mapped to representative concentrations (isometric centers) for calculation.

[0054] In S6 (Visualization Output), the output device (23) displays a time-series graph on the terminal / app (26), overlaying the upper and lower limits of a pre-set reference band (25B) and a pre-set representative curve (25C) onto the subject data (25A). The vertical axis is displayed in mIU / mL units, rounded to the nearest whole number. To improve visibility of low concentration ranges, it is possible to switch to a logarithmic scale. The latest estimated concentration or abstract evaluation is highlighted as a heading, and the status of increase, stagnation, or decrease, the rate of change, td, or t1 / 2 are also indicated. If the user enters the embryo transfer date, the number of days elapsed since embryo transfer is automatically calculated, and the data is automatically plotted on the corresponding time coordinate. Qualitative evaluation categories based on stage information (e.g., "increasing trend," "requires follow-up observation," etc.) may also be added and displayed.

[0055] In the user interface example (Figure 7), headings such as "Pregnancy (Positive)" and "710 mIU / mL" are displayed, along with the "Relationship between hCG and days elapsed since embryo transfer (reference band)," which shows not only the subject data (25A) but also the reference band (25B) and representative curve (25C) superimposed, illustrating a display format that also includes the percentage change from the most recent measurement (e.g., +56%).

[0056] If the analysis means (22) detects image quality issues (blurring, overexposure / underexposure), failure to detect the visual indicator, or non-functioning of the inspection confirmation unit (4) (in the line type), it will not save the image as invalid and will instead display a message from the output means (23) prompting re-imaging or re-execution. [Explanation of Symbols]

[0057] 10: Test kit 11: Detected object 12: Cabinet 13: Grip part 14: Window section 1: Urine collection area 2: Absorbent part 3: Visual indicator section (line type) 4: Inspection and Verification Department 5: Visual indicator section (area type, multiple colors) 6: Visual indicator area (single reaction point / strip tip) 8: Reference display section 21: Imaging means 22: Analysis means 23: Output means 24: Input method 25A: Subject data 25B: Reference bandwidth 25C: Representative curve 26: Devices / Apps 27: Time-series data storage

Claims

1. An in vitro diagnostic test kit that determines the concentration level of human chorionic gonadotropin in the urine of a subject or a staged evaluation indicating the progression of pregnancy, The detector includes a capture member that comes into contact with the sample and specifically binds to human chorionic gonadotropins, The detection body has a lateral flow structure, with multiple visual indicators arranged along the direction of urine flow, each of which is immobilized with an anti-human chorionic gonadotropin antibody of different sensitivities or affinities, and the multiple visual indicators on the detection body exhibit a visual state that can be identified by position or number upon reaction with urine, and this visual state is associated with multiple criteria corresponding to human chorionic gonadotropins. By associating the location or number of occurrences of the visual state exhibited by the user with a reference display permanently printed on the detector or housing, the concentration value of human chorionic gonadotropin or the stage of pregnancy progression can be immediately read without referring to a separate judgment chart. The multiple visual indicators are arranged in descending order of their concentration thresholds as criteria for determining human chorionic gonadotropin, from lowest to highest, and are configured to sequentially display the visual states from upstream to downstream as the urinary human chorionic gonadotropin concentration increases. A test kit further comprising a test confirmation unit for confirming that the test has been performed correctly, wherein the test confirmation unit is located at the final position when viewed from the urine collection side, and is positioned downstream of the visual indicator unit corresponding to the highest concentration threshold, and is characterized in that a stage determination is made based on the position or number of occurrences of the expressed visual state.

2. A test kit according to claim 1, wherein the reference display section permanently prints reference displays indicating a plurality of different judgment criteria, the reference displays include concentration values ​​or grade evaluations indicating the stage of pregnancy progression, the visual state is expressed in accordance with each reference display, and the number of grades of the reference displays can be set to 2 or more and 5 or less.

3. A test kit according to claim 1, wherein the visual indicator portion exhibits the visual state at a plurality of positions arranged along the direction of urine flow, each of the plurality of visual states exhibits a different hue that is mutually distinguishable, a stage determination is made based on the combination of hue and position, and the different hues are exhibited by a color development system differentiated for each position, and the color development system includes at least one of different colored latex particles, enzyme labeling and substrate system differentiation, or gold colloid and auxiliary staining.

4. An inspection kit according to claim 1, comprising a calibration section near the visual indicator section, which includes a white reference area and a reference color area having known reflective properties.

Images