KR20200132117A - Optical Extracorporeal Diagnostic Device and Diagnostic Method using the Device - Google Patents

Abstract

The present invention, in an optical extracorporeal diagnostic device capable of detecting an antigen-antibody reaction using an immunochromatography, relates to a technique, which ensures the reliability of judgment of a diagnostic kit (analysis strip) by easily correcting the deviation of an optical signal in a region of interest (ROI) of the diagnostic kit (analysis strip) while ensuring that the optical extracorporeal diagnostic device itself checks the operation soundness of a light source for a long time without omission or long passage of time and optical extracorporeal diagnostic device can be checked automatically at all times.

Description

Optical Extracorporeal Diagnostic Device and Diagnostic Method using the Device}

The present invention relates to an optical in vitro diagnostic device for detecting an antigen-antibody reaction by immunochromatography and an in vitro diagnostic method using the same.

The in vitro diagnostic device is used for diagnosis and prognosis of human diseases, determination of health status, disease treatment effect determination, disease prevention, and endocrine diseases, cancer, and infectivity from diagnostic samples (blood, saliva, urine, feces, cells, etc.) collected from the human body. It is a medical device that can test items such as diseases, immune diseases, heart diseases, electrolytes, drugs, pregnancy, and diabetes.

Depending on the field of application, the in vitro diagnosis market can be divided into immunochemical diagnosis, clinical microbiological diagnosis, point of care (POCT), molecular diagnosis, hemostasis diagnosis, self blood glucose measurement, early diagnosis, and blood diagnosis. Among them, the immunochemical diagnostic market occupies the largest share with 40.5% of the total in vitro diagnostic market, and a site where rapid diagnosis and test results can be obtained with a small amount of samples in any region where the examinee is located without pre-treatment for the samples. Diagnostics (POCT) is widely used.

Immunochromatographic analysis, an immunochemical diagnostic technique known as the Rapid Test method, uses antigen-antibody reactions to test various diseases, as well as in various fields such as agriculture, livestock, food, military, and environment. It is developed as a simple method of qualitatively and quantitatively inspecting or analyzing a substance to be analyzed in a relatively short time.

A typical analysis strip used in the immunochromatographic analysis method includes a sample pad (1) for accommodating a liquid sample, as shown in FIG. 1, and a visual signal that can be detected using the naked eye or a sensor (usually, Conjugate pad (2) containing a conjugate obtained by conjugating a label that generates a distinctive colored line to a ligand such as an antigen or antibody (2), an analyte in the sample and/or specific to the conjugate It is composed of a porous membrane pad (4) immobilizing the binding agent (antibody or antigen) that binds to it (3) and a moisture absorption pad (5) that finally receives the liquid sample, and these functional pads are partially overlapped in the order listed above. They are connected in a form and attached to a solid support 6 and arranged continuously.

The principle of immunochromatographic analysis is a method of detecting an analyte contained in the sample while moving a liquid sample in parallel in one direction by the capillary phenomenon of the porous membrane using a very thin porous membrane in the form of a dry solid rather than a liquid. In this parallel shift immunochromatography, an antibody or antigen is attached to a porous membrane in a certain shape, and another antibody or antigen conjugated to a reporter (reporter) material such as gold, a fluorescent material, or a luminescent material is used in an unknown sample. The analyte is captured by immunological action and the result of the capture (binding) is displayed as a color line that can be visually (optically) confirmed. This is called an antigen-antibody reaction. If there is no antigen to be diagnosed (detected) in the sample, the line will not appear. A representative technique for initiating immunochromatographic analysis is US Patent No. 4855240.

Conventionally, in optical in vitro diagnostic devices that detect antigen-antibody reactions using immunochromatography, technologies from various viewpoints have been proposed to increase the reliability and precision of diagnosis, but always check the operational integrity of the optical in vitro diagnostic device itself. There was no point of view technology to ensure the reliability of the diagnosis kit (analysis strip) and the technology of the point of view to ensure the reliability of the diagnosis kit (analysis strip), and furthermore, the operation soundness of the in vitro diagnostic device itself and the diagnosis kit (analysis strip) by a single calibration kit There was no point of view technology to ensure the reliability of judgment at the same time.

First, looking at the operation soundness of the light source of the optical in vitro diagnostic device, it is ideal that optical in vitro diagnostic devices of the same specification should produce the same test results for the same amount of the same specimen, but even if the diagnostic device of the same specification made by the same manufacturer The intensity of the light source is different due to reasons such as the quality of each component constituting the diagnostic device or the assembly state of the component is not uniform, and the optical signal intensity of the analysis strip may be different even for the same specimen. In addition, if the in vitro diagnostic device is used for a long time, the optical signal intensity for the analysis strip may appear different even for the same specimen due to a decrease in durability such as a change in the brightness of a light source (eg, an LED lamp). This problem is a problem of operational soundness caused by defects or deterioration of durability of the optical in vitro diagnostic device, regardless of the sample, reagent, or analysis strip, especially the operational soundness of the light source.It is a problem with the use of a calibration kit periodically. It is necessary to correct the brightness of the light source.

For device calibration of conventional in vitro diagnostic devices, insert a calibration kit supplied from the manufacturer of the in vitro diagnostic device into the channel (or slot) for insertion of the analysis strip whenever it is necessary to perform device calibration (correction of the brightness of the light source). After that, it is common to remove the device calibration kit to empty the channel, and then insert the analysis strip of the in vitro diagnostic device into the empty channel again to analyze.If device calibration is performed in this way, the device calibration kit (calibration kit) The channel into which the device is inserted and the channel into which the analysis strip is inserted are the same (single), and due to intermittent use of the device calibration kit, the recommended use cycle of the device calibration kit may be exceeded or completely forgotten. It becomes impossible to guarantee the operational soundness of the product.

FIG. 2 is a diagram showing a process in which a diagnostic kit and a device calibration kit are used interchangeably in a conventional optical in vitro diagnostic device. As can be seen from Fig. 2, in the conventional optical in vitro diagnostic device, in particular, in order to correct an abnormal light source of the device, a device calibration kit is inserted to perform calibration, and then the device calibration kit is removed and then replaced with a diagnostic kit. It is inserted to diagnose (measure) the specimen. In addition, if the measurement result of the diagnostic kit appears or is suspicious, the diagnostic kit is removed again, and then the device calibration kit is inserted into the channel and the process of calibrating the device is repeated. Existing optical in vitro diagnostic devices In this way, since the device calibration kit and the diagnostic kit are alternately inserted into one slot (measurement channel) and re-measurement is performed, the contamination of the diagnostic sample, an increase in the measurement time, and troublesome work are necessary. Or, there is a fear of oblivion.

Next, another problem that may occur in the related art related to the diagnostic kit (analysis strip) will be described with reference to FIGS. 3 to 8 as follows.

3 is a diagram schematically showing the configuration of an optical case, which is a main part of an optical in vitro diagnostic device for detecting an antigen-antibody reaction, and FIG. 4 is a region of interest of a diagnostic kit inserted into the optical in vitro diagnostic device and used for diagnosis ( Region of interest (ROI) is a diagram showing a typical labeling example (antigen-antibody reaction example), and FIG. 5 is an enlarged view of such a typical labeling example (reaction example).

As can be seen from FIG. 3, the main components of the optical measurement unit of the optical in vitro diagnostic device include a light source unit (LED) that shines light on the surface of the diagnostic kit to maintain a constant brightness, an image input unit (camera) that captures an image on the surface of the diagnostic kit, and external It consists of a blocker that blocks the light source and a stage that puts the diagnostic kit (analysis strip) in a certain position. In general, interest from the image data captured on the surface of the diagnostic kit using the optical case of such an optical in vitro diagnostic device. By image processing and analyzing the area part, the presence or absence of abnormalities due to the qualitative and quantification of the components of the sample (sample) is determined.

The meanings of the control line C and the test line T expressed in the region of interest ROI in FIGS. 3 to 5 described above are as follows. In other words, in an optical in vitro diagnostic device used to detect antigen-antibody reactions by immunochromatography, it is the primary method to ensure (confirm) the operational integrity of the assay strip (whether or not the assay strip itself is defective). -In addition to the test line (T), which is an antibody reaction line, it is common to have the control line (C) appear separately to indicate the operational integrity of the analysis strip itself. The health (negative) of the specimen is determined by the presence or absence of the test line (T), which is the main purpose of diagnosis, and the reliability of the analysis strip is determined by the presence or absence of the control line (C). If the control line C does not appear (the right two cases in FIG. 5), the detection is judged invalid regardless of the presence or absence of the test line T.

On the other hand, if the determination of the presence or absence of the control line C or the presence of the test line T is performed only with the naked eye of the human body, there may be an error, and the optical analysis result can be quantified and displayed. For example, when the difference value (D1) between the optical signal intensity value of the background (control line, the background exposing the test line) and the optical signal intensity value of the control line is less than the predetermined reference value (V1) as a criterion for determining the test invalidity (i.e. If there is no difference because the optical signal intensity of the background and the optical signal intensity of the control line are almost the same), it can be presented as (D1 <V1). In addition, in determining whether the sample is positive or negative by the presence or absence of the test line (T), the difference value (D2) between the background signal intensity value and the signal intensity value of the test line (T) is greater than the predetermined reference value (V2). It may be determined by whether it is small, and these reference values V1 and V2 may be presented differently for each manufacturer of the diagnostic kit.

On the other hand, when testing a specimen using an immunochromatographic analysis strip in the field, anomalies may occur in the expression of the optical signal intensity of the background and the optical signal intensity of the test line (T).For example, representative abnormalities are as follows.

A) If the moisture absorption pad lacks the power to maintain the development component, it is a phenomenon in which the development component from the moisture absorption pad flows backward.

B) Within the specified incubation time (10 to 15 minutes), the developing component is not absorbed by the moisture absorption pad, and a positive signal appearing on the detection unit due to the excess liquid sample remaining on the chromatograph medium is spread to the surrounding (background) or , Since the colored labeling material is not sufficiently recovered, it spreads to the background and the value of the optical reflection intensity of the background decreases (Korean Patent Publication No. 10-2016-0124905).

During diagnostic measurement, the development component is moved by the capillary phenomenon through the porous membrane pad and is received in the shape of the test line and is expressed as a test line.Therefore, if the signal strength of the test line is strong (that is, if it appears clearly), there is no difficulty in determining and it is not a problem. However, if the strength of the test line T is weak (that is, if it is faint), an error may occur to judge it as positive.

6 shows a case that may appear as a result of an in vitro diagnostic test using the same sample sample (specimen), and photographs an example in which the above-mentioned abnormal phenomenon occurs.

In other words, it is possible to visually confirm that the diagnostic kit A (analysis strip) on the left is more reddish over the entire background (background) of the ROI, compared to the diagnostic kit (analysis strip) on the right, The background signal is weakened (darkened) because the colored material is not sufficiently recovered. This is the case when the antigen-antibody reaction color line of the sample expressed according to the antigen-antibody reaction of the assay strip flows backward without being trapped only in the test line (T), or the colored material is not sufficiently recovered, causing noise to occur. In this case, the optical reflection intensity of the background (background) is affected, resulting in a change in the brightness difference between the background (background) and the test line (T). Eventually, the color development line (test line) expressed according to the antigen-antibody reaction It means to be able to influence the judgment of the significance (positive, negative) of optical reflectivity. Therefore, in the case of the A diagnostic kit (analysis strip) on the left, it should be determined as positive normally. If such an abnormality occurs in the analysis strip, an error that is determined as negative may occur.

FIG. 7 is a diagram illustrating a diagnostic kit (analysis strip) photographed and quantitatively image processing (analysis) of the signal intensity of the optical signal of the region of interest. As can be seen from Fig. 7, the signal of the background (background), which is the background of the two signals (control line, test line), is white and the optical signal strength is high (although it is bright), but the two lines are colored and darker than the background (dark). In addition, the signal strength of the control line C is lower than the signal strength of the test line T (it is darker), and the drop width of the signal strength on the graph is larger.

FIG. 8 is a graph in which the optical signal (optical reflection intensity) of the ROI of the two analysis strips A and B shown in FIG. 6 was quantitatively analyzed by the same method as in FIG. 7, and the lower blue is the analysis strip. The optical signal intensity curve of A, and the upper orange color is the optical signal intensity curve of analysis strip B. Overall, since the signal strength curve of analysis strip A (blue) is located below the signal strength curve of analysis strip B (in red), the signal strength of analysis strip A is lower than that of analysis strip B (darker). Can be seen. This is consistent with the fact that in the two analysis strips (A, B) of FIG. 6, the A diagnostic kit has more red spread over the entire ROI (the whole background) than the B diagnostic kit. .

Table 1 below is a table in which the magnitude of the optical signal intensity of FIG. 8 is summarized numerically.

Same sample (same amount) Analysis strip A
(blue) Analysis strip B
(Scarlet) Difference Control line (C) signal strength 4240(a) 4600(b) 350(b-a) Test line (T) signal strength 500(c) 700(d) 200(d-c)

As can be seen from Table 1 above, the difference value (ba) of the optical signal intensity of the control line (C) between the analysis strips A and B is 350 (4600-4240 = 350), and the optical signal intensity of the test line (T) The difference value (dc) was 200 (700-500=200). Even though the same amount of the same specimen was diagnosed with the same optical diagnostic device, the difference in the optical signal intensity of the control line (C) and the optical signal intensity of the test line (T) or the difference value appears according to the different analysis strips. You can see that you can.

Since the same amount of the same specimen was diagnosed with the same optical diagnostic device, it is ideal that this difference should not appear or the difference should be as small as possible, but in reality, this deviation appears due to material deviation, manufacturing error, measurement error, etc. Therefore, it is necessary to establish a meaningful criterion for interpretation of the allowable range of such deviations. If no meaningful criterion for interpretation of the allowable range of such differences is provided, and only with the naked eye, as in the case of Fig. 6, in relation to the possibility of change in the optical signal intensity of the background (possibility of noise), The presence or absence of the antigen to be detected (confirmed) (determining whether the test line is positive or negative depending on whether or not the test line is expressed) may be difficult or misjudgment may occur.

Therefore, even in the case of testing the same amount of the same specimen in the optical in vitro diagnostic device, the optical signal intensity of the background in consideration of the variability that the optical signal intensity of the region of interest may vary for each diagnostic kit (analysis strip) (possible background noise), It is necessary to provide a criterion for each deviation tolerance of the optical signal strength of the control line and the optical signal strength of the test line. In addition, taking into account the possibility of occurrence of anomalies that exceed the allowable range, it is possible to correctly judge the significance of the test line (T) appearing under such background noise conditions even when such anomalies (noise) of background intensity appear. There must be a means to do so.

(Patent Document 001) U.S. Patent No. 4855240 (1980. Announcement) (Patent Document 002) Korean Patent Publication No. 10-2016-0124905 (2016. Announcement)

Therefore, the present invention is an optical in vitro diagnostic device that detects antigen-antibody reactions using immunochromatography, and the calibration kit used to ensure the integrity of the light source of the optical in vitro diagnostic device itself is used for a long period of time. By making it possible to use it at all times without omission, it provides Auto Calibration where the calibration of the device is always automatically performed when using an optical in vitro diagnostic device, and optical signals in the ROI of the diagnostic kit (analysis strip) A single correction that can ensure the reliability of judgment of the diagnostic kit (analysis strip) by easily correcting the deviation of the diagnostic kit (analysis strip), and further guarantee the operational soundness of the light source of the above-described in vitro diagnostic device and the judgment reliability of the diagnostic kit (analysis strip). Its purpose is to provide a reference kit.

The object of the present invention as described above, according to one feature of the present invention,

(a) N optical objects (P1, P2,..,Pi,..,Pj,..,Pn) (n=N) are radially equally spaced so that they can be placed in a radial, grid, or linear shape, respectively. , A stage provided with N mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) at equal intervals in a grid or at equal intervals in a straight line;

(b) driving means for positioning the stage to a predetermined position by linear or curved movement;

(c) a light source for irradiating light toward an upper surface of the subject Pi placed on the mounting seat Si positioned at a predetermined position by the driving means;

(d) a camera for photographing an upper surface of the subject Pi placed on the mounting seat Si to which the light source is irradiated;

(e) a housing for accommodating the stage, a driving means, a light source, and a camera therein;

(f) a display panel for displaying the result of immunochromatographic analysis of the subject;

(g) a hardware interface for controlling each operation of a stage, a driving means, a light source and a camera accommodated in the housing; And

(h) a user interface for controlling the operation of the hardware interface;

It is made including, where,

The optical object Pi placed on any one (Si) of the mounting seats S1 to Sn is a device calibration kit for automatically correcting the brightness of the light source, and another of the mounting seats S1 to Sn The object (Pj) placed on the other (Sj) is a reference kit to correct the optical reflection intensity of the background of the diagnostic kit (analysis strip), and the object placed on the seat other than Si and Sj Is made by an optical in vitro diagnostic device, which is a diagnostic kit (analysis strip).

In addition, the object of the present invention as described above, according to another feature of the present invention,

The predetermined position is made by an optical in vitro diagnostic device, characterized in that a portion including the ROI of the subject Pi placed on the mounting seat Si is a photo zone photographed by the camera.

In addition, the object of the present invention as described above, according to another feature of the present invention,

The driving means for positioning the stage to a predetermined position by linear or curved movement is a step motor that rotates the stage by a predetermined rotation angle in the forward or reverse direction, or a linear motor that moves the stage by a predetermined distance in a linear direction, a rack-pinion mechanism, or a screw bar. It is made by an optical in vitro diagnostic device, characterized in that the mouth.

In addition, the object of the present invention as described above, according to another feature of the present invention,

This is achieved by mounting a single reference calibration kit (Calibration-Reference Kit) that performs both the function of correcting the intensity of the light source of the device and the function of correcting the optical reflection intensity of the background of the analysis strip on one of the mounting seats of the stage. .

In addition, the object of the present invention as described above, according to another feature of the present invention,

Disc-shaped stage and disc-shaped stage equipped with N radial mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) so that multiple analysis strips can be placed radially. Step motor for rotating a predetermined rotation angle in the forward and reverse direction, a light source that irradiates light toward any one of the mounting seats of the disc-shaped stage positioned at a predetermined position, a camera that photographs the mounting seat to which this light source is irradiated, and these disc-shaped A housing that houses the stage, step motor, light source, and camera inside, a display panel to display the results of immunochromatography analysis of the subject, a hardware interface that controls each operation of the stage, step motor, light source and camera housed in the housing, And an optical in vitro diagnostic device including a user interface for controlling the operation of the hardware interface,

A first step of mounting a calibration kit for correcting the operational integrity of the light source of the optical in vitro diagnostic device on any one of the plurality of radial mounting seats of the disc-shaped stage;

A second step of mounting a reference kit for correcting the optical reflection intensity of the background of the analysis strip on another mounting seat Sj among the radial mounting seats of the disc-shaped stage;

A third step of placing a diagnostic kit (analysis strip) on a mounting seat other than Si and Sj;

A fourth step of determining a reference position (zero position) of the disc-shaped stage on which the third step has been completed;

A fifth step of correcting the optical reflection intensity of the device by rotating the disk-shaped stage so that the portion including the ROI of the device calibration kit is located in the photo zone photographed by the camera and then performing device calibration operation;

A sixth step of rotating the disc-shaped stage so that the reference kit is positioned in a photo zone photographed by a camera, and then measuring and storing a reference correction value for correcting the optical reflection intensity of the background of the analysis strip; And

For each diagnostic kit (analysis strip) placed on each mounting seat of the disk-shaped stage, the optical reflection intensity value of the test line (T) obtained by moving one by one to the photo zone and photographing the surface thereof and the reference correction stored by the sixth step process The 7th step of comparing the values and determining the significance (positive, negative) of the specimen on each diagnostic kit (analysis strip) according to the preset comparison criteria

It is made by an optical in vitro diagnostic method comprising a.

In addition, the object of the present invention as described above, according to another feature of the present invention,

Disc-shaped stage and disc-shaped stage equipped with N radial mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) so that multiple analysis strips can be placed radially. Step motor for rotating a predetermined rotation angle in the forward and reverse direction, a light source that irradiates light toward any one of the mounting seats of the disk-shaped stage positioned at the predetermined position, a camera that photographs the mounting seat to which the light source is irradiated, these A disk-shaped stage, a housing that houses a step motor, a light source, and a camera inside, a display panel to display the results of immunochromatographic analysis of a subject, a hardware interface that controls each operation of the stage, step motor, light source and camera contained in the housing. , With respect to the optical in vitro diagnostic device comprising a user interface for controlling the operation of the hardware interface,

A single kit (reference correction kit) is mounted on any one of the radial mounting seats (Si) of the disk-shaped stage, which serves as a function to correct the intensity of the light source of the device and to correct the optical reflection intensity of the background of the analysis strip. A first step and;

A second step of placing a diagnostic kit (analysis strip) on a mounting seat other than the Si;

A third step of determining a reference position (zero position) of the disc-shaped stage on which the second step has been completed;

The disc-shaped stage is rotated to the position of the photo zone where the device calibration kit is photographed by the camera to perform device calibration operation, and the reference calibration value for optical reflection intensity calibration of the analysis strip background obtained by photographing the surface of the device calibration kit is used. A fourth step of storing; And

For each diagnostic kit (analysis strip) placed on each mounting seat of the disc-shaped stage, the optical reflection intensity value of the test line (T) obtained by photographing the surface after moving one by one to the photo zone and the reference correction stored by the above four-step process The fifth step of comparing the values and determining the significance (positive or negative) of the specimen on each diagnostic kit (analysis strip) according to the previously set comparison criteria

It is made by an optical in vitro diagnostic method including

The present invention provides an optical in vitro diagnostic device for detecting an antigen-antibody reaction using an immunochromatography method, in which a plurality of diagnostic channels on a stage on which a diagnostic kit can be placed are provided, and at least any one of them With respect to the channel, it is possible to automatically check the operation soundness of the light source of the optical in vitro diagnostic device itself, not intermittently, to ensure that it is optically checked regardless of the occurrence of background noise in the ROI of the diagnostic kit (analysis strip). By correcting the deviation of the signal, it is possible to reduce the error in determining the significance of the test line.

According to the present invention, it is possible to ensure the operational soundness of the light source of the optical in vitro diagnostic device itself and the reliability of the determination of the diagnostic kit (analysis strip), and further secure the operational soundness of the light source of the in vitro diagnostic device and the determination reliability of the diagnostic kit (analysis strip) at the same time. Since it can be configured with a single calibration reference kit that can be configured, it is possible to obtain an optical in vitro diagnostic device that is simple to use and easy to use.

In addition, the present invention has the effect of greatly reducing the measurement time in the field test (POCT) by varying the size and shape of the stage and increasing the number of measurement (diagnosis) channels.

1 is a block diagram of a typical assay strip used in immunochromatographic analysis.
FIG. 2 is a diagram showing a process in which a diagnostic kit and a correction kit are used interchangeably in a conventional optical in vitro diagnostic device.
3 is a diagram schematically showing the configuration of a conventional optical in vitro diagnostic device for detecting an antigen-antibody reaction.
FIG. 4 is a diagram showing an example of a typical mark that may be inserted into an optical in vitro diagnostic device and appear in a region of interest (ROI) of a diagnostic kit used for diagnosis.
5 is an enlarged view of an example of a typical marker of a region of interest (ROI).
6 illustrates an abnormal case that may appear as a result of an in vitro diagnostic test using the same sample sample (specimen).
FIG. 7 is a diagram illustrating a diagnostic kit (analysis strip) photographed and quantitatively image processing (analysis) of the signal intensity of the optical signal of the region of interest.
FIG. 8 is a graph for quantitatively analyzing the optical signal (optical reflection intensity) of the ROI region in the two analysis strips A and B shown in FIG. 6 in the same manner as in FIG. 7.
9 shows a process of simultaneously automatically performing device calibration and specimen measurement by inserting a device calibration kit and a diagnostic kit into the stage at the same time by providing a plurality of specimen measurement channels (multi-channels) on one stage according to the present invention. It is a drawing shown.
10 is a flowchart showing a process of performing device calibration (light source intensity calibration) of the optical diagnostic device.
11 is juxtaposed so that the configuration of a background correction reference kit for correcting the optical intensity of the background of the analysis strip according to the present invention can be seen in contrast with the conventional analysis strips A and B shown in FIG. 6. This is a picture taken.
FIG. 12 is a control line of two analysis strips (A, B) based on the optical reflection intensity of the background of the background correction reference kit shown in the photograph in FIG. 11 according to the present invention in the region of interest ( C) is a graph showing the difference in optical reflection intensity of the test line (T).
13 is a view showing an example of the shape of a multi-channel for specimen testing provided on one stage according to the present invention in a disk shape (A) and a grid shape (B).
14 is a reference calibration kit (CRK) and a plurality of analysis kits (test kits) (TK) mounted on the top surfaces of the disc-shaped stage (A) and the grid-shaped stage (B) according to the present invention. One, a diagram showing the configuration of two embodiments of the present invention.
15 is a block diagram showing the overall configuration of an optical in vitro diagnostic device according to the present invention as blocks for each function.

9 is a diagram showing a process of simultaneously performing device calibration and measurement of a diagnostic kit.

As can be seen from this drawing, in the optical in vitro diagnostic device according to the present invention, a calibration kit (calibration kit) and a diagnostic kit set with a predetermined device calibration value (calibration value) are inserted into the stage at the same time, and then this calibration kit (calibration) Kit) to the calibration position (calibration position) and first perform calibration (calibration). The process or principle of device calibration using a calibration kit (light source brightness calibration) is performed by a program set in advance by the user's user interface operation as in the case of a conventional optical in vitro diagnostic device. As follows. That is, a calibration kit with a predetermined correction value for correcting the brightness of the light source is inserted into the stage (S1), moved to the photo zone (optical case), and the measured signal intensity taken is extracted (S3), and the extracted value and Compare the set correction value (S4), and if the measured signal intensity is less than the set correction value, increase the backlight value to increase the amount of light of the device (S5).Re-shoot with the increased light intensity to measure the signal strength. , Repeat the process of comparing the measured signal strength value and the device correction value to store the backlight value when the desired measured value is reached, and the device calibration is completed. In other words, the measurement is completed when the device calibration value is reached. If the optical signal strength (background signal strength value) of the extracted ROI as a result of comparison (S4) is the same as the set signal strength value or the difference is within the allowable range, the measured background signal strength value at that time is the background signal of the device. Save as intensity value and finish calibration.

The difference from the prior art of device calibration (calibration) according to the present invention is that after the device calibration kit (calibration kit) and the diagnostic kit are respectively inserted into the stage at the same time, the calibration kit is first moved to the device calibration position, so that the aforementioned device calibration ( This is the point that calibration) always comes first. As described above, in the optical in vitro diagnostic device according to the present invention, the device is constantly calibrated without fear of not using the calibration kit for a long time or omitting its use. Auto calibration is performed in which the brightness of the light source is always automatically adjusted each time it is used.

After such instrument calibration is completed, the calibration kit (calibration kit) is not removed from the stage, but the diagnostic kits placed on the other mounting seats of the stage are moved to a position where the optical reflection intensity of the diagnostic kit is measured one by one and measured (ROI). The measurement for each diagnostic kit is completed by photographing a region including the region and measuring the background (background), optical reflection intensity values of the control line and the test line in the ROI region for the photographed image. After the measurement is completed, the diagnostic kits are removed from the stage of the measurement completed to complete the diagnosis, or, although not shown, other diagnostic kit sets are then mounted and the diagnostic kit measurement as previously described for the new set of diagnostic kits is repeated. .

As described above, device calibration (calibration) is essential and prerequisite for each diagnosis of diagnostic kits, so that device correction for abnormality in light source intensity can be automatically performed, as described later in the present invention. As the diagnostic channel according to is provided as a plurality of multi-channels in a radial or grid type on a disk-shaped or rectangular stage (Fig. 13 Fig. 14), only a conventional single channel is provided, so that the calibration kit (calibration kit) and the diagnosis kit must be replaced. This is because the problem that must be used has been solved.

FIG. 11 is a view in contrast to the conventional analysis strips A and B shown in FIG. 6 so that the configuration of a background correction reference kit for correcting the optical intensity of the background of the analysis strip according to the present invention can be seen. This is a photograph taken, and FIG. 12 is a control of two analysis strips (A, B) based on the optical reflection intensity of the background of the background correction reference kit shown in FIG. 10 according to the present invention in the region of interest. It is a graph showing the difference in optical reflection intensity of the line (C) and the test line (T).

Unlike a diagnostic kit in which a reagent or sample is impregnated, the reference kit for background correction according to the present invention is a non-reactive surface having a fixed optical reflectance value (absolute value) at all times or a separate control. You can make a reference kit by roning only reagents that only output the line. This is a measure that is expected to vary in background intensity for each measurement because the reagent used in the diagnostic kit has a different chemical composition for each antigen to be detected. In the Reference Kit, the meaning of the control line only has the meaning of providing a comparative position for analysis.

Table 2 below is a table summarizing the magnitude of the optical signal intensity of FIG. 11 in numerical terms.

Same sample (same amount) Analysis strip A
(blue) Analysis strip B
(Scarlet) Difference Control line (C) signal strength 4240(a) 4600(b) 350(b-a) Test line (T) signal strength 500(c) 700(d) 200(d-c) Corrected control line signal strength 5350(e) 5400(f) 50(f-e) Calibration test line strength 1900(g) 2000(h) 100(h-g)

As can be seen in Table 2 above, the optical reflection intensity value of the background has a fixed value (absolute value) (e.g. 8500) at a predetermined brightness, and the control line also has a fixed optical reflection intensity value (absolute value) (e.g. 5700). For reference kits, relative optical reflection intensity values for control line (C) and test line (T) of diagnostic kits A and B based on the measured value of optical reflection intensity of the background (backlight) Looking at the difference, in the case of the correction control line, the difference value (fe) of the signal intensity is 50 (5400-5250 = 50), and the difference value (hg) of the optical signal intensity of the calibration test line (T) is 100 (2000). -1900=100). This is less than the difference values 350 (ba) and 200 (dc) of each signal intensity in diagnostic kits A and B in which the optical signal intensity value of the background (backlight) is fluctuated by noise, so it is controlled when background compensation is performed. In the case of the line, the difference value was improved from 350 to 50, and it can be seen that the difference value of the test line (T), which is actually important when diagnosing positive or negative, improved from 200 to 100. Here, the quantitative value of the difference is the quantitative value = REF background signal intensity-the minimum value of the test line signal intensity.

Therefore, it is shown that the problem of increasing the intensity of the background signal on the chromatographic strip (the problem that is darkened by the occurrence of noise) can be improved through background compensation, and in the end, it is judged more than before in determining the significance of the test line signal value. Can increase your trust.

On the other hand, in the above-described device calibration kit (calibration kit) described with reference to FIG. 9, the optical signal intensity value of the background measured by the calibration kit and finally stored as a correction value is as it is, and the reference kit described with reference to FIGS. 11 and 12 above. Since it can be used as the background signal intensity value of (Reference Kit), the present invention does not separately adopt the above-described device calibration kit (calibration kit) and reference kit, but a single reference correction that functions as both of them. It is also possible to configure it as a Kit (Calibration-Reference Kit). In this case, the basic operation is to insert one Calibration-Reference Kit and a plurality of diagnostic kits at the same time, go through the process of finding the origin for the motor, and then install the Calibration-Reference Kit in the photo zone. (This photo zone is preferably an optical case in which camera lamps, etc. are optimized and placed in a predetermined hatch in order to reduce measurement noise such as interference caused by external light blocking or reflected light.) Move to a location and calibrate the device as a calibration kit. After finishing the test as a reference kit, save the measured values. Subsequently, each diagnostic kit is moved one by one to the photo zone to measure the optical signal intensity of the diagnostic kit, and the test line intensity of the diagnostic kit based on the stored background intensity value of the previously measured calibration-reference kit. The acceptable range is determined through comparison with the measured value, and a positive or negative judgment result is derived.

13 is a view showing an example of the shape of a sample test multi-channel provided on one stage (S) according to the present invention in a disk shape (A) and a grid shape (B), and FIG. 14 is a disk shape according to the present invention. Two embodiments of the present invention in which a single reference calibration kit (CRK) and a plurality of analysis kits (test kits) (TK) are mounted on the top surfaces of the stage (A) and the grid-shaped stage (B). It is a diagram showing a configuration diagram. As shown in FIG. 14(B), when the test kit mounting seats are provided on a grid-like stage at equal horizontal and vertical intervals, two origin sensors and two motors may be provided to move the stage in the X-Y axis on a plane. The measurement method proceeds to the correction position by the motor, rotates to the position of the diagnostic kit, or moves the X, Y axis to measure, and moves to the next diagnostic kit to continue the measurement. This process proceeds as many times as the number of diagnostic samples.

15 is a block diagram showing the configuration of an optical in vitro diagnostic device according to the present invention as blocks for each function. However, if the technical idea of achieving the two characteristics according to the present invention, which is the light source correction of the device and the reference correction of the background of the diagnostic kit, is the same, the configuration of the hardware interface or the user interface may be configured in various forms other than the illustrated block diagram. It should be understood as possible.

1: specimen pad 2: conjugate pad
3: binder 4: porous membrane pad
5: moisture absorption pad 6: support
C: Control line T: Test line
CK: Calibration Kit
RK: Background correction kit (Reference Kit)
CRK: Calibration reference kit TK: Diagnosis kit

Claims (6)

(a) N optical objects (P1, P2,..,Pi,..,Pj,..,Pn) (n=N) are radially equally spaced so that they can be placed in a radial, grid, or linear shape, respectively. , A stage provided with N mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) at equal intervals in a grid or at equal intervals in a straight line;
(b) driving means for positioning the stage to a predetermined position by linear or curved movement;
(c) a light source for irradiating light toward an upper surface of the subject Pi placed on the mounting seat Si positioned at a predetermined position by the driving means;
(d) a camera for photographing the top surface of the subject Pi placed on the mounting seat Si to which the light source is irradiated;
(e) a housing for accommodating the stage, a driving means, a light source, and a camera therein;
(f) a display panel for displaying the result of immunochromatographic analysis of the subject;
(g) a hardware interface for controlling each operation of a stage, a driving means, a light source and a camera accommodated in the housing; And
(h) a user interface for controlling the operation of the hardware interface;
It is made including, where,
The optical object Pi placed on any one (Si) of the mounting seats S1 to Sn is a device calibration kit for automatically correcting the brightness of the light source, and another of the mounting seats S1 to Sn The object (Pj) placed on the other (Sj) is a reference kit to correct the optical reflection intensity of the background of the diagnostic kit (analysis strip), and the object placed on the seat other than Si and Sj Is an optical in vitro diagnostic device, characterized in that it is a diagnostic kit (analysis strip) In claim 1,
The predetermined position is an optical in vitro diagnostic device, characterized in that the portion including the ROI of the subject Pi placed on the mounting seat Si is a photo zone photographed by the camera In claim 1 or 2,
The driving means for positioning the stage to a predetermined position by linear or curved movement is a step motor that rotates the stage by a predetermined rotation angle in the forward or reverse direction, or a linear motor that moves the stage by a predetermined distance in a linear direction, a rack-pinion mechanism, or a screw bar. Optical in vitro diagnostic device, characterized in that In claim 1 or 2,
A single reference calibration kit (Calibration-Reference Kit) is mounted on one of the mounting seats of the stage, which also functions to correct the intensity of the light source of the device and the function of correcting the optical reflection intensity of the background of the analysis strip. Optical in vitro diagnostic device. Disc-shaped stage and disc-shaped stage equipped with N radial mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) so that multiple analysis strips can be placed radially. Step motor for rotating a predetermined rotation angle in the forward and reverse direction, a light source that irradiates light toward any one of the mounting seats of the disc-shaped stage positioned at a predetermined position, a camera that photographs the mounting seat to which this light source is irradiated, and these disc-shaped A housing that houses the stage, step motor, light source, and camera inside, a display panel to display the results of immunochromatography analysis of the subject, a hardware interface that controls each operation of the stage, step motor, light source and camera housed in the housing, And an optical in vitro diagnostic device including a user interface for controlling the operation of the hardware interface,
A first step of mounting a calibration kit for correcting the operational integrity of the light source of the optical in vitro diagnostic device on any one of the plurality of radial mounting seats of the disc-shaped stage;
A second step of mounting a reference kit for correcting the optical reflection intensity of the background of the analysis strip on another mounting seat Sj among the radial mounting seats of the disc-shaped stage;
A third step of placing a diagnostic kit (analysis strip) on a mounting seat other than Si and Sj;
A fourth step of determining a reference position (origin position) of the disc-shaped stage on which the third step has been completed;
A fifth step of correcting the optical reflection intensity of the device by rotating the disk-shaped stage so that the portion including the ROI of the device calibration kit is located in the photo zone photographed by the camera and then performing device calibration operation;
A sixth step of rotating the disc-shaped stage so that the reference kit is positioned in a photo zone photographed by a camera, and then measuring and storing a reference correction value for correcting the optical reflection intensity of the background of the analysis strip; And
For each diagnostic kit (analysis strip) placed on each mounting seat of the disk-shaped stage, the optical reflection intensity value of the test line (T) obtained by moving one by one to the photo zone and photographing the surface thereof and the reference correction stored by the sixth step process The 7th step of comparing the values and determining the significance (positive, negative) of the sample on each diagnostic kit (analysis strip) according to the preset comparison criteria
Optical in vitro diagnostic method comprising a Disc-shaped stage and disc-shaped stage equipped with N radial mounting seats (S1, S2,..,Si,..,Sj,..,Sn) (n=N) so that multiple analysis strips can be placed radially. Step motor for rotating a predetermined rotation angle in the forward and reverse direction, a light source that irradiates light toward any one of the mounting seats of the disk-shaped stage positioned at the predetermined position, a camera that photographs the mounting seat to which the light source is irradiated, these A disk-shaped stage, a housing that houses a step motor, a light source, and a camera inside, a display panel to display the results of immunochromatographic analysis of a subject, a hardware interface that controls each operation of the stage, step motor, light source and camera contained in the housing. , With respect to the optical in vitro diagnostic device comprising a user interface for controlling the operation of the hardware interface,
A single kit (reference correction kit) is mounted on any one of the radial mounting seats (Si) of the disk-shaped stage, which serves as a function to correct the intensity of the light source of the device and to correct the optical reflection intensity of the background of the analysis strip. A first step and;
A second step of placing a diagnostic kit (analysis strip) on a mounting seat other than the Si;
A third step of determining a reference position (zero position) of the disc-shaped stage on which the second step has been completed;
The disc-shaped stage is rotated to the position of the photo zone where the device calibration kit is photographed by the camera to perform device calibration operation, and the reference calibration value for optical reflection intensity calibration of the analysis strip background obtained by photographing the surface of the device calibration kit is used. A fourth step of storing; And
For each diagnostic kit (analysis strip) placed on each mounting seat of the disc-shaped stage, the optical reflection intensity value of the test line (T) obtained by photographing the surface after moving one by one to the photo zone and the reference correction stored by the above four-step process The fifth step of comparing the values and determining the significance (positive or negative) of the specimen on each diagnostic kit (analysis strip) according to the previously set comparison criteria
Optical in vitro diagnostic method comprising a

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