WO2019216460A1 - Diagnostic kit having grid-segmented transparent substrate, and optical diagnostic apparatus using same - Google Patents

Abstract

A diagnostic kit having a grid-segmented transparent substrate capable of improving the detection sensitivity of the diagnostic kit, and an optical diagnostic apparatus using same are disclosed. The diagnostic kit, as a diagnostic kit using an immunochromatography technique, comprises a sample pad, a coupling pad, a detection pad, and an absorption pad connected in the described order from one side to the other side on one surface of a light-transmissive film base material, and a striped opaque pattern is formed on the film base material in correspondence to a space part-shaped test area in the detection pad.

Description

Diagnostic kit with grid-division transparent substrate and optical diagnostic device using same

Embodiments of the present invention relate to a diagnostic kit having a grid-division transparent substrate capable of improving the detection sensitivity of the diagnostic kit and an optical diagnostic apparatus using the same.

Diagnostic kits are developed using lateral flow tests or immunochromatography techniques for membrane materials such as paper and fibers, and are used as in vitro diagnostic drugs for point of care tests (POCTs), not for laboratory use. On-site inspection refers to a test that can be used for diagnosis and treatment by quickly performing a test sample such as centrifugal separation without a pretreatment process or through a simple pretreatment near the subject. Diagnostic kits are sometimes called rapid diagnostic kits.

Immunochromatography techniques use insoluble carrier particles bound to ligands that uniquely recognize the substance to be detected, to capture the substance to be detected, transfer it using capillary phenomena in the membrane, and fix the blood to be fixed at a predetermined position in the specimen. It is one of immunological techniques to analyze the presence or absence of a substance to be detected by using insoluble carrier particles that are aggregated at another predetermined position in a test specimen by binding to a capture substance that specifically binds to a detection substance.

In general, testing of the diagnostic result of the rapid diagnosis kit is performed by physical detection of the detection result such as the concentration and mass of the antibody captured in the capture line or the test line after the sample moves through the detection pad or the membrane. By acquiring an optical signal or an electrical signal converted from the image and analyzing the signal.

Existing rapid diagnosis kits that apply optical detection methods, rather than visual detection, do not analyze capture substances or antibodies in all areas of the test line, but rather virtual rectangular areas of a specific size for the area to which the optical beam is irradiated. Inspection, diagnosis and reading of hollow or window areas are performed.

On the other hand, in the conventional rapid diagnostic kit, the rectangular hollow is ideally uniformly distributed in the area of the trapping material or the antibody in the horizontal and vertical hollow areas of a constant size, and has a uniform distribution and speed in a homogeneous state. Accurate inspection, diagnostics and readings are possible assuming passing and evenly integrated in the hollow area. However, in reality, there are many variations of kit manufacturing, and the state of the sample itself is not completely homogeneous, and thus, the existing rapid diagnosis kits often show uneven and irregular test results.

As such, it is very difficult to detect the microscopic changes in the overall aspect of the hollow by examining the overall state of the entire hollow, which occupies a relatively large area, even if there is no special irregularity in the existing quick diagnosis kit.

Therefore, the present invention can solve the problem of detection reliability caused by mechanical error of the membrane, manufacturing deviation of the square pattern, and the like, and irregularity of the detection signal due to such error or deviation in the existing diagnostic kit using the rectangular hollow area. To provide a diagnostic kit having a grid-division transparent substrate and an optical diagnostic apparatus using the same. That is, an object of the present invention is to provide a diagnostic kit having a grid-dividing transparent substrate that can improve the reliability and stability of the device by changing the two-dimensional rectangular hollow pattern into a one-dimensional grid, and an optical diagnostic apparatus using the same.

Another object of the present invention is to improve the accuracy of the diagnosis even when the concentration of the detection target of the sample for diagnosis is low, the absolute amount at the beginning of the disease, or the concentration is reduced due to dilution by the reaction solution, grid The present invention provides a diagnostic kit having a split transparent substrate and a method of manufacturing the same.

It is another object of the present invention to accurately and precisely diagnose a diagnosis result in a quantitative diagnosis, to accurately capture a small state change between a plurality of samples in a state having various variants, and to effectively derive a quantitative result. The present invention provides a diagnostic kit having a grid-divided transparent substrate, a method of manufacturing the diagnostic kit, an optical diagnostic apparatus using the diagnostic kit, and an optical diagnostic method.

In order to solve the above technical problem, a diagnostic kit according to an aspect of the present invention is a diagnostic kit using an immunochromatography technique, and a sample pad and a bonding pad connected to one side to another side on one surface of a light-transmitting film substrate ( a conjugate pad, a detection pad, and an absorbent pad, wherein a stripe-shaped opaque pattern is disposed on the film substrate to correspond to a test area having a shape of a space in the detection pad. .

In one embodiment, a direction in which each line pattern extends in the opaque pattern may be perpendicular to a direction in which the coupling pad and the detection pad are connected to each other, or a direction in which the detection pad and the absorption pad are connected and extended. .

In an exemplary embodiment, each line pattern in the opaque pattern may be tilted at a specific angle of 45 ° or less with a direction in which the coupling pad and the detection pad are connected and extend, or in a direction in which the detection pad and the absorption pad are connected and extend. It may extend to correspond to the picture direction.

In an embodiment, the width of the first line pattern and the distance between the second line pattern adjacent to the first line pattern may be the same in the opaque pattern.

In one embodiment, the width of each line pattern and the distance between adjacent line patterns in the opaque pattern may be the same.

In one embodiment, the opaque pattern may be disposed on the one surface of the film substrate, on the other surface that is opposite to the one surface, or may be disposed between the one surface and the other surface.

In one embodiment, the opaque pattern may be buried so that the surface is exposed on the one surface or the other surface of the film substrate.

In one embodiment, the diagnostic kit may further include a transmissive protective film covering the detection pad and the test area.

In one embodiment, the diagnostic kit may further include a case for housing a pad assembly consisting of the film substrate, the sample pad, the bonding pad, the detection pad, and the absorbent pad. The case may include a sample inlet corresponding to the sample pad and an opening positioned to correspond to the test area, and the opening may expose the test area and the control area on the detection pad to the outside.

According to another aspect of the present invention, there is provided a method of manufacturing a diagnostic kit, the method including: arranging stripe-shaped opaque line patterns on a portion of a light-transmitting film substrate; Attaching a detection pad on one surface of the transparent film substrate; Attaching a coupling pad to one side of the detection pad; Attaching an absorption pad to the other side of the detection pad; And coupling a sample pad to one side of the coupling pad opposite to the side where the detection pad is located, wherein a direction in which each of the opaque line patterns extends is connected to the coupling pad and the detection pad. It extends or is perpendicular to the direction in which the detection pad and the absorption pad are connected and extend, or in the opaque pattern, each line pattern is the direction in which the coupling pad and the detection pad are connected and extend, or the detection pad and the absorption pad. The pads are connected to each other and extend in correspondence with the direction inclined at a specific angle of 45 ° or less.

In order to solve the above technical problem, an optical diagnostic apparatus according to another aspect of the present invention includes an optical diagnostic apparatus using a diagnostic kit, the light emitting device emitting light to a signal detection unit of a test area of the diagnostic kit; A light receiving element that detects a change in the amount of light between the stripe-shaped line patterns of the signal detection unit by the incident light when the incident light of the single wavelength from the light emitting element is focused on the signal detection unit of the diagnostic kit; An actuator coupled to the light receiving element to control focusing of the light receiving element; And a driving unit which moves a relative position between the light emitting element, the light receiving element, and the diagnostic kit, and is configured to scan in a direction crossing the line patterns of the signal detection unit by the operation of the driving unit.

In one embodiment, the optical diagnostic device is a lens disposed in front of the light emitting device for condensing light to adjust the amount of light of the light emitting device; And a filter attached to the front end of the lens.

In one embodiment, the optical diagnostic apparatus may further include a control unit for controlling the operation of the light emitting device, the light receiving device, the actuator and the driving unit. The control unit can be connected to the other components of the optical diagnostic device via a wired cable or a wireless network.

In one embodiment, the optical diagnostic device may further include an analysis unit connected to the light receiving element and analyzing a signal detected by the light receiving element.

In one embodiment, the analysis unit is a matrix (m *) for the decomposition interval consisting of a column (m) of the direction (x) orthogonal to the crossing direction (y) to the row (n) create a two-dimensional memory array of n matrices, store a voltage V of a signal detected by the light receiving element corresponding to the matrix in A [n] [m], where an opaque section corresponding to the line patterns The base voltage of is set to 0 or a predetermined voltage, the voltage from the first (x [0]) to the last (x [m-1]) of x for the i th (y [i]) of y. A voltage one-dimensional memory array B [n] for storing the sum is generated, and the voltages for the x [0] to x [m-1] for the y [i] are summed to specify a specific memory array B [ j]), and sum the voltages for x [0] to x [m-1] with respect to [0] to [n-1] of y, respectively, to the specific memory array B [j]. Store, award Calculating the surface area (Si) sensitivity (Ii) by dividing for each B [j], and may be adapted to select the maximum value of sensitivity is determined as the effective reference value.

In one embodiment, the assay unit may be configured to determine the maximum and minimum of the standard sample for each antibody and adjust the gain thereof according to the sample reaction or the concentration of the sample.

In one embodiment, the analysis unit may determine the positive of the sample exceeding the threshold value in each sample based on the threshold value based on the correlation between the output signal of the test area and the concentration of the biomarker.

According to the diagnostic kit having a grid-divided transparent substrate of the present invention, a method for manufacturing the diagnostic kit, and an optical diagnostic apparatus using the diagnostic kit, mechanical errors in the membrane (combination pad) or the signal detection unit in the membrane in the diagnostic kit, The detection reliability problem due to the manufacturing deviation of the square pattern and the like, and the problem that the detection signal is irregularly generated due to this error or deviation can be effectively solved. That is, the reliability and stability of the diagnostic kit and the optical diagnostic apparatus using the same can be greatly improved by changing the two-dimensional rectangular hollow pattern into a one-dimensional grid.

According to the present invention, the accuracy and reliability of diagnosis can be ensured even when the concentration of the detection target of the sample for diagnosis is low, the absolute amount is insufficient at the initial stage of the disease, or when the concentration decreases due to dilution by the reaction solution. There are advantages to it.

In addition, according to the present invention, it is possible to accurately and precisely diagnose the diagnosis result in the quantitative diagnosis, and to accurately capture the small state change between the plurality of samples in the state having various variance elements and to effectively derive the quantitative result. There is this.

1 is a front view of a diagnostic kit according to an embodiment of the present invention.

2 is a partial perspective view of the diagnostic kit of FIG.

3 is a partially exploded perspective view for explaining the assembly structure of the diagnostic kit of FIG.

4 to 6 are views for explaining another embodiment of the opaque grid of the diagnostic kit of FIG.

7 is a partially enlarged plan view of the structure of the opaque grid for the signal detection unit of the diagnostic kit of the present embodiment.

8 is a cross-sectional view illustrating a structure in which the diagnostic kit of FIG. 1 is accommodated in a case.

9 is a schematic reduced plan view of the diagnostic kit of FIG. 8.

10 is a view for explaining the principle of operation of the optical diagnostic device using the diagnostic kit of FIG.

11 is a view for explaining the principle of operation of the diagnostic kit having a signal detection unit according to this embodiment.

FIG. 12 is a diagram illustrating a signal waveform detected by the diagnostic kit having the signal detector of FIG. 11.

13 is a view for explaining the principle of operation of the diagnostic kit having a signal detector according to a comparative example.

14 is a perspective view of an optical diagnostic apparatus according to another embodiment of the present invention.

15 is a perspective view of a detection optical system of the optical diagnostic device of FIG. 14.

FIG. 16 is a perspective view from another side of a detection optical system of the optical diagnostic device of FIG. 14.

17 is a view for explaining the principle of operation of the optical diagnostic device of FIG.

18 is a block diagram of a control system of a detection reader according to another embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

In the following description, the term 'opaque' or 'opaque' is not limited to meaning that the material completely blocks light, and indicates that the material has a relatively low light transmittance compared to other areas having the property of light transmission or transparency. Can be.

1 is a front view of a diagnostic kit according to an embodiment of the present invention. 2 is a partial perspective view of the diagnostic kit of FIG.

1 and 2, the diagnostic kit 100 according to the present embodiment includes a substrate 110, a membrane 120, a conjugate pad 130, and an absorbent pad 140. A sample pad 150 and a transparent cover 160.

In more detail, the substrate 110 may be referred to as a base, a base substrate, a transparent substrate, or a transparent film. The substrate 110 may have a length obtained by adding the first length L1, the second length L2, and the third length L3 in the y-direction or the length direction. The length of the substrate 110 may be about 60 mm, but is not limited thereto.

In the present embodiment, an opaque grid 112a is formed on the substrate 110 to form the detector or the signal detector 112. The opaque grid 112a is formed in a straight stripe pattern extending in one direction or y-direction. The signal detector 112 may include an empty space 120e formed without a membrane material in the middle of the membrane 120.

Each line pattern of the opaque grid 112a may have the same width and have the same separation distance as other adjacent line patterns. In addition, the width and distance of each line pattern in the signal detector 112 may be the same. By using this pattern structure, signal analysis can be simplified to greatly increase the analysis speed and performance.

The width of each line pattern in the signal detector 112 may be 80 μm to 120 μm, and the interval between adjacent line patterns may be 80 μm to 120 μm. The width and the interval may be the same, but are not limited thereto. Such width and spacing may have a difference in size depending on the size of a substance to be detected, such as a protein to be detected.

Membrane 120 includes a test line consisting of antibodies capturing the sample and a control line indicating whether the experiment was performed normally. The inspection line corresponds to the test line or the signal detector 112 (see FIGS. 8 and 9). In the present embodiment, the membrane 120 has a space portion 120e in the middle portion thereof in the longitudinal direction. The space portion 120e functions as some component of the signal detector 112 arranged to detect a desired signal using the light transmissivity of the biomarker captured on the membrane 120.

The space portion 120e may correspond to a portion where the membrane is not disposed in the middle portion of the membrane 120. The width L4 of the space part 120e may be about 1 mm. The space part 120e is installed to expose at least a portion of the opaque grid partially disposed on the bottom surface of the substrate 110 to the outside through the membrane 120. The opaque grid may be a printed pattern, but is not limited thereto. The method of forming the opaque grid is not particularly limited as long as it can form an opaque pattern on a portion of the substrate 110. Opaque grid is used interchangeably herein to refer to the same object as a unidirectional grid, opaque pattern, and the like.

On the other hand, depending on the implementation, the space portion 120e may be 1 mm or less in size or spatially not configured according to the optical characteristics of the sample. That is, the length L4 of the space part 120e may be zero. When the space part is not installed, the concentration of the sample may be measured by directly transmitting the membrane 120 with strong laser light. In addition, the membrane 120 may have a single connection structure, and the transparent cover 160 may be omitted.

The membrane 120 may be selected and used according to analytical materials in various conventional reverse osmosis membranes, nanofiltration membranes, ultrafiltration membranes, microfiltration membranes, and the like. For example, NC (Nitrocellulose) membrane or PVDF (Polyvinylidene fluoride) membrane may be used. The membrane 120 is attached or fixed on the substrate 110 by an adhesive 170 or the like, has a second length L2 smaller than the substrate 110 in the y-direction or the longitudinal direction, and may be referred to as a detection pad or the like. Can be.

The binding pad 130 includes a conjugate such as antibody-HRP that can be identified by color change by reacting with the sample. One end of the bonding pad 130 may be in close contact with or attached to one upper end of the membrane 120, and the other end of the bonding pad 130 opposite to the one end may be in close contact or attached to one lower end of the sample pad 150. .

The bond pad 130 may have a length smaller than the membrane 120 in the longitudinal direction. An adhesive or adhesive film may be inserted into the bonding surface where the bonding pad 130 and the membrane 120 contact each other in a smaller size than the bonding surface. Similarly, the adhesive surface 170 or the adhesive film may be inserted in a smaller size than the bonding surface on the bonding surface that the bonding pad 130 and the sample pad 150 contact.

The absorbent pad 140 serves as a reservoir of sample flowing through the membrane 120. The absorbent pad 140 is in close contact with or attached to the upper end of the other side, which is the opposite side of the membrane 120. The absorbent pad 140 may have a length greater than the predetermined third length L3, and may overlap the other side of the membrane 120 by the remaining length except for the third length L3. An adhesive 170 or an adhesive film may be inserted in a smaller size than the bonding surface at the bonding surface where the absorbent pad 140 and the membrane 120 contact each other.

The sample pad 150 is a portion to which a sample to be detected is supplied from the outside. The sample pad 150 may have a state preprocessed by a buffer reagent or the like. The sample pad 150 may be coupled in an overlapping form to one end of the coupling pad 130 in the y-direction. The sample pad 150 may have a first length L1 in the y-direction.

The transparent cover 160 may be disposed to cover the upper portion of the space 120e of the membrane 120 or may cover the entire exposed upper portion of the membrane 120 including the space 120e. The exposed upper portion may correspond to a constant surface of a portion of the membrane 120 positioned between the bond pad 130 and the absorbent pad 140. The transparent cover 160 prevents the sample from being ejected onto the membrane 120 or the space portion 120e and blocks external contaminants from affecting the membrane 120 or the signal detector 112.

3 is a partially exploded perspective view for explaining the assembly structure of the diagnostic kit of FIG.

2 and 3, the diagnostic kit according to the present exemplary embodiment may include a printing structure for making a transparent substrate detector and a stacked structure between components constituting the diagnostic kit.

First, an opaque grid 112a for forming the detector, that is, the signal detector 120, is formed in a portion of the transparent substrate 110. The opaque grid 112a corresponds to the unidirectional grid or straight stripe-shaped line patterns extending straight in the longitudinal direction or the y-direction of the substrate 110.

The unidirectional grid may be disposed on the bottom surface of the substrate 110. In this case, the upper surface opposite to the lower surface of the substrate 110 may be a surface to which the membrane 120 is attached. When the unidirectional grid is disposed on the lower surface of the substrate 110, the grid may be formed on the opposite surface of the test line disposed on the transparent film substrate where the flow of the sample occurs, thereby not affecting the flow of the sample.

Next, the membrane 120 is disposed on the upper surface opposite to the lower surface of the substrate 110. Membrane 120 may be fixed on substrate 110 by adhesive or other adhesion or bonding means. At this time, the space portion 120e of the membrane 120 is disposed to correspond to the opaque grid 112a.

Next, one end portion of the bonding pad 130 is attached to the top of one end of the membrane 120 in the longitudinal direction or the y-direction of the membrane 120, and the sample pad 150 is placed on the other end of the bonding pad 130. Place one end of the). One end of the absorbent pad 140 is disposed on the other end of the membrane 120.

A first adhesive or an adhesive film may be disposed between the substrate 110 and the membrane 120, between the membrane 120 and the bonding pad 130, and between the membrane 120 and the absorption pad 140. Between the second adhesive may be disposed respectively.

The surface shape of the second adhesive is smaller than the junction area between the membrane 120 and the bond pad 130 and smaller than the junction area between the membrane 120 and the absorbent pad 140. This is a flow path at the interface between the components such that the antigen, insoluble carrier particles, or combinations thereof can be moved properly by capillary shape from the sample pad 150 to the absorbent pad 140 through the membrane 120, which is a porous fibrous body. It is flexible to obtain as wide or diverse as possible.

By using the opaque grid of the above-described stripe pattern, in particular, the width of each line pattern of the opaque grid is equally formed, the same spacing between adjacent line patterns is formed, or the width between each line pattern and the adjacent line patterns If the same interval is formed, different signal analysis results are generated according to the inclination of the signal detection unit 112 and the scanning direction of the laser light (see x-direction in FIG. 8) when the diagnostic kit is placed on the optical diagnostic apparatus. It can not only solve the problems of the existing structure effectively but also greatly improve the stability and reliability of the analysis speed and performance.

4 to 6 are views for explaining another embodiment of the opaque grid of the diagnostic kit of FIG. 7 is a partially enlarged plan view of the structure of the opaque grid for the signal detection unit of the diagnostic kit of the present embodiment.

In the diagnostic kit according to the present exemplary embodiment, the signal detector 112 may include various forms in addition to the structure (see FIG. 3) disposed on the lower surface of the substrate 110. Here, the upper surface opposite to the lower surface of the substrate 110 may be a space (120e of FIG. 3) or a surface on which the membrane 120 is disposed.

For example, the opaque grid 112a of the signal detection unit of the diagnostic kit may be formed on the upper surface of the substrate 110 as shown in FIG. 4. The height of the printed structure of the opaque grid 112a can be adjusted according to the amount of antibody to be captured and the optical properties of the absorbance thus detected.

In addition, as shown in FIG. 5, the opaque grid 112a may be embedded in the upper surface of the substrate 110, and one surface thereof may be exposed on the upper surface of the substrate 110 to be flat with the upper surface of the substrate 110. In this case, the opaque grid 112a may be disposed on the upper surface of the substrate 110 while not affecting the flow of the sample. The arrangement structure of the opaque grid 112a may be formed on the lower surface opposite to the upper surface of the substrate 110, depending on the implementation.

In another embodiment, the opaque grid 112a may be installed between the upper and lower surfaces of the substrate 110 and not exposed to the upper and lower surfaces as shown in FIG. 6. That is, the opaque grid 112a may be disposed inside the substrate 110. For example, the substrate 110 may have a laminated structure of a first transparent film and a second transparent film, in which case the opaque grid 112a may be disposed between the first transparent film and the second transparent film. The first transparent film and the second transparent film may be pressed flat on both sides in the form of a single film.

Meanwhile, the opaque grid 112a employed in the present embodiment is not limited to the above-described embodiment, and may include a structure in which the opaque grid is disposed as a separate film on the film substrate. The thickness of the opaque grid 112a protruding from the substrate 110 or installed in conjunction with the substrate 110 may be much smaller than the width, and may be, for example, several tens of micrometers or less.

In the above-described embodiments, as shown in FIG. 7, the opaque grid 112a extends in the longitudinal direction or the y-direction in which each line pattern in the pattern extends from the diagnostic kit, the membrane of the diagnostic kit, and the like. The main feature may be that the width w and the spacing d between adjacent line patterns are the same. In certain embodiments, the aforementioned width w and spacing d may each be equal to each other at 100 μm. Of course, the aforementioned width w, spacing d or both may have other spacings such as 400 μm, 500 μm, 800 μm and the like.

According to the opaque grid of the microstructure, in addition to the effect of improving the analysis speed and analysis performance, there is an advantage that can greatly improve the detection sensitivity by increasing the detection density can be calculated in the same area.

For example, if you have a test line with no grid applied, the particle density is the number of particles in the total area divided by the total area. On the other hand, in the stripe-shaped opaque pattern, that is, the unidirectional grid application structure, the particle density is a value obtained by dividing the number of particles in the divided area divided by the grid by the divided area. It can greatly improve.

8 is a cross-sectional view illustrating a structure in which the diagnostic kit of FIG. 1 is accommodated in a case. 9 is a schematic reduced plan view of the diagnostic kit of FIG. 8.

8 and 9, the diagnostic kit 100A according to the present embodiment includes a pad assembly and a case 190 accommodating the pad assembly.

The pad assembly includes a substrate 110 in the form of a film substrate, a membrane 120 corresponding to the detection pad, a bonding pad 130, an absorbent pad 140, and a sample pad 150. The pad assembly may be in the form of any one of the embodiments described above with reference to FIGS. 1 to 7.

The case 190 may have a shape of a small flat box that is approximately rectangular parallelepiped. Here, the pad assembly may be seated in the case 190 by the concave-convex structure in the case 190. The case 190 is divided into an upper case and a lower case and may be formed to simply receive the pad assembly by combining the upper and lower cases. The upper case and the lower case may have a fitting structure paired with each other.

The opaque grid or line patterns constituting the opaque grid of the signal detection unit disposed on the substrate 110 are light-blocking or non-transparent stripes that are approximately parallel to the flow direction of the fluid or object in the diagnostic kit and are spaced at regular intervals in the width direction. stripe) shape. The flow direction of the fluid may be the same as the direction in which each line pattern of the stripe pattern of the opaque grid extends. The direction in which the fluid flows may be a direction orthogonal to the direction in which the laser light moves (x-direction) when the laser kit Li is irradiated to the diagnostic kit or to cross at or below about 45 ° with the orthogonal direction. have.

The case 190 may include a sample inlet 192 positioned corresponding to the sample pad 150, and an opening 194 exposing a portion of the upper portion of the membrane including the test area. The opening 194 may be installed to expose the test area or test line corresponding to the signal detector 112 and the control area or control line 114 on the membrane 120 detection pad to the outside. The control line 114 is provided with a predetermined antigen and is used to check whether the sample is a proper and meaningful object such as saliva, blood, urine, or the like of a human body.

For reference, in FIG. 9, for convenience of illustration and description, the coupling pad 130 and the absorption pad 140 are slightly visible at both ends thereof in the longitudinal direction of the opening 194, but the present invention is not limited thereto. The coupling pad 130 and the absorbent pad 140 may be disposed to be less exposed to the outside by the opening 194.

10 is a view for explaining the principle of operation of the optical diagnostic device using the diagnostic kit of FIG.

The scanning operation of the optical diagnostic apparatus using the above-described diagnostic kit 100 will be described with reference to FIG. 10. In FIG. 10, the opaque grid 112a of the signal detector 112 is enlarged for convenience of illustration.

The laser diode 241 is disposed on one surface of the diagnostic kit 100 including the opaque grid 112a, and the photodiode 280 is disposed on the other surface of the diagnostic kit 100. When the laser beam Li is irradiated to the signal detecting unit 112 of the diagnostic kit 100 and moves in the scan direction (x-direction), the photodiode 280 surrounds the opaque grid around the signal detecting unit 112. The signal to be analyzed according to the sample concentration can be detected.

An objective lens 244 may be disposed between the laser 241 and the diagnostic kit 100 to focus incident light having a single wavelength onto the transparent substrate. In addition, changes in the amount of light in the transparent portions between the respective grid patterns of the opaque grid 112a may be focused onto the photodiode 280 through the sensor lens 282.

The spacing between the fine pattern of the opaque grid 112a and the objective lens 244 may be focused through a driving unit 284 such as a variable charge motion (VCM) actuator as necessary. The driving unit 284 may be coupled to the housing 283 supporting the photodiode 280 and the sensor lens 282. In addition, the light quantity change in the grid pattern in the signal detector 112 may detect the signal to be analyzed for the entire area of the signal detector 112 by scanning the optical pickup module including the photodiode 280.

Using the diagnostic kit of the above-described embodiment, the sample or sample is moved in the first direction along the y axis, and the opaque grid in the signal detector is arranged to extend in the first direction along the y axis orthogonal to the x axis. Even when extending at an angle to one direction and a predetermined angle, that is, regardless of the manufacturing process or the method of handling the diagnostic kit of the operator, it is possible to perform a substantially stable signal detection, thereby obtaining a fast and reliable analysis analysis signal. can do.

11 is a view for explaining the principle of operation of the diagnostic kit having a signal detection unit according to this embodiment. FIG. 12 is a diagram illustrating a signal waveform detected by the diagnostic kit having the signal detector of FIG. 11.

11 and 12, the diagnostic kit according to the present embodiment includes an opaque grid 112a in the form of a straight line pattern. The opaque grid 112a may be referred to as a unidirectional grid in that it is a set of line patterns extending in one direction. The optical diagnostic apparatus irradiates a laser beam to the signal detection unit of the above-described diagnostic kit and scans the light quantity change in the signal detection unit. The scanning direction Sd1 may be an x-direction which is a direction orthogonal to the y-direction which is an extension direction of the line pattern of the opaque grid 112a (see FIG. 11A).

The laser beam may be used in the form of a pulse, and may exhibit signal variations and differences in the transparent film portion and the printed portion (opaque grid portion). The focused beam spot p1 may be formed on the signal detector 112 of the diagnostic kit by the laser beam. In FIG. 11, four are shown at an arbitrary point for comparison with the size of the fine pattern. However, only one beam spot p1 may be formed near the focal point of the laser beam moving along the scanning direction.

In addition, in this embodiment, by using the opaque grid 112a in the form of a stripe, it is possible to overcome the constraint of the comparison configuration (see FIG. 13) that the x-axis grid and the y-axis grid must vertically intersect to ensure reliability. . That is, in the present embodiment, as shown in Figs. 11A and 11B, by using the signal detection unit 112 having the opaque grid 112a, it is not necessary to arrange the x-axis grid and the y-axis grid. Do not need to cross vertically, and even if a manufacturing error occurs in the opaque grid 112a, the signal detection and analysis can be performed substantially stably.

The manufacturing error may include a case where the extending direction of the line patterns in the opaque grid 112a is inclined at a predetermined angle with the length direction or the y-direction of the diagnostic kit. In addition, the manufacturing error may include a case in which a deviation occurs in the width of each of the line patterns in the opaque grid, and the width of the line pattern and the distance between adjacent grid patterns are different.

In another aspect, the grid pattern in the signal detection unit 112 of the diagnostic kit may be manufactured to be inclined at any angle in the y-direction and the y1-direction as shown in FIG. 11 (b). The internal angles in the y-direction and the y1-direction may be 45 degrees or less. Even in such a case, according to the diagnostic kit according to the present embodiment, analysis speed and analysis performance can be maintained.

That is, when a signal is detected by the diagnostic kit through the optical analysis device, an opaque grid or a diagnostic kit is determined with respect to the scan direction Sd1 of the laser diode due to manufacturing errors, mechanical errors, operator's working patterns or mistakes. Even if it is set to rotate by an angle (see (b) of FIG. 11), as shown in FIG. 12, since the signal waveform s1 of the section corresponding to the opaque grid always appears at a constant magnitude and interval as a reference voltage. Based on this, the signal waveform can be analyzed effectively.

Here, the magnitude of the reference voltage may be set to a desired voltage (voltage, vol.) By the user. Further, the predetermined section of the waveform appearing in the detection signal according to the reference voltage, that is, the section corresponding to the opaque grid always has a constant interval s1 even when the opaque grid rotates. That is, when the unidirectional grid rotates, there is a slight difference in the length of each section in the reference voltage waveform according to the rotation angle with respect to the scan direction Sd1, and the lengths of the sections are substantially the same.

Furthermore, even if the mechanical error of the detector including the light emitting device or the light receiving device occurs, the reference voltage of the signal detection section corresponding to the opaque grid always appears at a constant size and interval, thereby limiting the constraints on the mechanical error of the detector. Can be effectively overcome.

In addition, the line region other than the opaque grid of the signal detector 112 may represent a signal waveform having a voltage level different from the reference voltage as the transmissive region. In particular, the signal waveform or the detection signal s2 in the light transmitting area may show different levels or waveforms depending on the concentration of the sample, the sample, the sample, or the precipitate captured in the light transmitting area. The detection signal s2 may have a predetermined voltage V or a peak to peak as a difference between the minimum voltage and the maximum voltage. As described above, according to the present exemplary embodiment, the diagnostic kit has a quantitative analysis in consideration of the noise of the result in the diagnostic kit having the convenience, high performance, and economical efficiency of the sample in the diagnostic kit using the peak value, and maximizes the user's convenience. There is an advantage that can greatly improve the reliability.

13 is a view for explaining the principle of operation of the diagnostic kit having a signal detector according to a comparative example.

This comparative example focuses on the problems occurring in the diagnostic kit to which the bidirectional grid (square pattern) is applied.

As shown in FIG. 13A, when a manufacturing error occurs in the bidirectional grid (square pattern), the grid extending in the x-axis direction and the grid extending in the y-axis direction may not vertically intersect due to the manufacturing error. This may result in irregularities in the detection signal. In particular, due to manufacturing errors when attaching the bidirectional grid to the diagnostic kit, it is often considered that the bidirectional grid is rotated and attached.

In addition, in the case of the comparative example, the scanning in the x-direction or the y-direction may not be constant due to the mechanical error of the detector. That is, when the y-direction is not arranged to be orthogonally orthogonal to the scan direction Sd1 of the laser beam (see FIG. 13B), the physical detection result such as the concentration and mass of the antibody captured in the test line When acquiring an optical signal or an electrical signal converted therefrom and analyzing the acquired signal, the obtained signal appears different according to the arrangement error of the signal detector, thereby greatly reducing the reliability of the analysis result. .

That is, in the above-described comparative example, the accuracy of the division of the grid boundary line in the signal detected by one beam spot p1 passing through the grid becomes low, making it difficult to analyze the transparent section and the opaque section. This has a problem of inaccurate analysis results when performing optical analysis based on the detection signal.

As described above, in the comparative example, errors in the detection signal due to manufacturing errors, mechanical errors, handling deviations, and the like may cause problems in accuracy and reliability of analysis.

Meanwhile, in another comparative example, the width of the line pattern of the opaque grid may be configured to be smaller than or different from the interval between adjacent line patterns, but in that case, if the scan direction and the pattern direction are not almost exactly aligned, it is still one. In the signal detected by the laser point p1 transmitted through the signal detector 112, the accuracy of the division of the grid boundary is lowered, which makes it difficult to analyze the transparent and opaque sections.

14 is a perspective view of an optical diagnostic apparatus according to another embodiment of the present invention. 15 is a perspective view of a detection optical system of the optical diagnostic device of FIG. 14. FIG. 16 is a perspective view from another side of a detection optical system of the optical diagnostic device of FIG. 14. 17 is a view for explaining the principle of operation of the optical diagnostic device of FIG.

Referring to FIG. 14, the optical diagnostic apparatus 200 according to the present exemplary embodiment includes a base plate 210, a support frame 220, a work table 230, a detection optical system 240, a first motor 250, and a second. The motor 260 and the connection terminal 270 are provided. The detection optical system 240 may include a laser diode, and the photodiode may be disposed below the work table 230 through a connection frame 283 that is a part of the support frame 220. The photodiode may form a light receiving module together with the focusing lens. The detection optical system 240 and the light receiving module may be installed to move simultaneously by a predetermined interval on the x-y plane by the first motor 250 and the second motor 260.

The support frame 220 is installed on the base plate 210 to support the work table 230, the detection optical system 240, the first motor 250, the second motor 260, and the connection terminal 270. The working table 230 may be provided with an uneven part or a protrusion for fixing or supporting the diagnostic kit as a diagnostic kit or a placed part. The first motor 250 and the second motor 260 may correspond to an x-axis motor and a y-axis motor for moving the detection optical system 240 and the light receiving module in the x-y plane. In addition, the connection terminal 270 is a part for electrically connecting the laser diode, the photodiode, the first motor 250 and the second motor 260 to a control system described later. The connection terminal 270 may be omitted when signals and data are processed by a wireless communication module in a wireless communication method.

The detection optical system 240 of the optical diagnostic apparatus 200 may include a laser diode 241, a plurality of mirrors 242 and 245, a filter 243, a collimator lens, and the like, as shown in FIGS. 15 and 16. 244 and housing 246. One side of the housing 246 may be moved back and forth and left and right according to the rotation of the first shaft of the first motor 250 and the second shaft of the second motor 260 on the support frame 220. Coupling portion 247 may be provided to engage with the second shaft.

The laser diode 241 may irradiate a laser beam having a wavelength of 405 nm, 650 nm or 780 nm. The filter 243 is installed in front of the collimator lens 244 to function to adjust the amount of light of the laser beam to a desired level or a predetermined level. The filter 243 may operate to block wavelengths other than certain wavelengths, such as the 405 nm wavelength.

The collimator lens 244 functions to focus the laser beam whose light amount is adjusted through the filter 243 to the signal detector 112. The plurality of mirrors 242 and 245 may be used to change the direction of travel of the laser beam.

In addition, the light receiving module of the optical diagnostic apparatus 200 may include an emission filter 283, a condensing lens 282, and a photodiode 280 as illustrated in FIG. 17. The light receiving module may be disposed below the work table 230 by the connection frame (see 283 of FIG. 14). The emission filter 283 is a filter for observing the wavelength emitted from the sample. The condenser lens 282 condenses the light passing through the diagnostic kit 100 to the photodiode 280.

In addition, the filter 243 is attached to the front end of the collimator lens 244 where the light is focused to adjust the laser light amount to adjust the amount of light to a desired level, and the transmission type diagnostic kit 100 at the spot spot where the collected light is collected. The light transmitted from the test surface of the signal detector 112 may detect a signal through an integrated circuit (PDIC) of a photodiode.

The distance d6 from the reflective surface of the specific mirror 245 installed in the detection optical system 240 to the test surface of the diagnostic kit may be 24.0 mm. At this time, the distance d1 between the photodiode 280 and the condenser lens 282 is 0.9 mm, the thickness d2 of the condenser lens 282 on the optical path is 1.9 mm, and the condenser lens 282 and the emission The distance d3 between the filters 283 is 0.4 mm, the thickness d4 of the emission filter 283 is 0.7 mm, and the distance to the test surface of the emission filter 283 and the transmissive diagnostic kit 100. (d5) may be 2.0 mm. This design dimension can be changed to improve the characteristics of the detection optical system as an example.

Signal detection can be accomplished by measuring the black intensity of light at that wavelength using a laser of a particular wavelength. In this case, the laser may be operated to continuously irradiate light in the form of a pulse, adjust the intensity of the laser beam through the filter 243, and collect the house with the collimator lens 244.

Specifically, since the signal is not transmitted through the opaque part of the grid, the voltage detected by the photodiode maintains the reference voltage state. If there is no material reaction in the transparent part of the grid, the irradiated light is completely transmitted. If any part occurs, only part of the irradiated light is transmitted, and thus, when the transmitted light between the grid divisions is captured by the photodiode, the change in voltage may be checked and quantified to detect the presence of a signal (see FIG. 12).

For example, the absorbance voltage of distilled water is 1.41V, the absorbance voltage for the first mixture of the first concentration (1/40) in which a predetermined material is mixed in distilled water at a first content is 1.82V, and the same material is used in distilled water. Absorption voltage for the second mixture of the second concentration (1/20) mixed with the second content is 2.26 V, and the third mixture of the third concentration (1/10) with the same material mixed with distilled water in the third content Absorption voltage for represents 2.48V. In this embodiment, the sensitivity and characteristics of the detection signal according to the concentration change of the sample can be analyzed precisely, quickly and reliably based on the difference in absorbance voltage according to the concentration.

18 is a block diagram of a control system of an optical diagnostic apparatus according to another embodiment of the present invention.

Referring to FIG. 18, the control system 290 according to the present embodiment includes an input unit 291, an output unit 292, a main control unit (MCU) 293, and a laser diode power supply. (LD Power) 294, an amplifier 295, an analog-to-digital converter (ADC) 296, and a motor driving unit (Moter driver) 297, and the laser of the optical diagnostic apparatus 200 described above with reference to FIG. The diode LD may be connected to the photodiode PD, the first motor 250, and the second motor 260.

The control system 290 may be connected to the display device 298, and the display device 298 may include a touch screen for input / output such as a touch LCD.

The main control unit 293 may operate to extract data of the photodiode at regular intervals by, for example, decomposing the unit reference signal in 4096 steps at 12-bit resolution. In addition, the main control unit 293 sets a frequency for the digital signal through pulse width modulation (PWM) control, and the pulse width or duty cycle can adjust the intensity of the laser diode by adjusting the amplitude of the signal. have. According to such a configuration, the conversion speed can be greatly improved in an analog digital conversion scheme compared to a control unit having 4 or 8 bit resolution.

The main control unit 293 may be referred to as a control unit, a controller, a central processing unit, or the like, and may be implemented as a microprocessor, a microcomputer, or the like.

In addition, the main control unit 293 may store an analysis program for reducing noise and obtaining valid information in a memory, and perform the analysis program through the main control unit 293 connected to the memory.

The analysis program may include a scanning schedule algorithm, a photodiode (PD) detection voltage accumulation and an analysis algorithm.

The scanning schedule algorithm is a first step of driving to autofocus array formation in the y-axis direction, where the y-axis is decomposed into sections larger than 100 to 200 sections; a second step of returning to the y-axis origin; a third step of driving to form an autofocus array in the x-axis direction, wherein the x-axis is decomposed into sections larger than 40 to 80 sections; a fourth step of returning to the x-axis origin; a fifth step of moving in the y-axis direction to start scanning the test line and then moving the microsection in the y-axis direction, wherein the microfocus movement uses the autofocus arrangement formed in the first step; In addition, the sixth step may be continuously applied to complete the scan from the x-axis origin to the end point, and may include a series of sixth steps of returning to the x-axis origin.

The PD detection voltage accumulation and analysis algorithm is a two-dimensional memory array A [n] of a matrix (m * n matrix) for a decomposition section consisting of rows (n) in the y-axis direction and columns (m) in the x-axis direction. a first step of generating [m]; The second step of storing the voltage (V) of the signal detected by the scan and light irradiation photodiode or light receiving element in a specific memory region of the two-dimensional memory array A [n] [m], where the base voltage of the opaque section is 0 or corresponding to a predetermined voltage; Voltage one-dimensional memory array B [n] for storing the voltage summation from the first (x [0]) to the last (x [m-1]) of the x-axis for the i-th (y [i]) of the y-axis Creating a third step; A fourth step of adding up the voltages for x [0] to x [m-1] for y [i] and storing them in a specific one-dimensional memory array B [j]; By repeating the fourth step, a specific one-dimensional memory array B [j] is obtained by summing voltages for x [0] to x [m-1] with respect to [0] to [n-1] of the y-axis. Storing each in a fifth step; A sixth step of calculating the detection sensitivity Ii by dividing by the corresponding area Si for each B [j]; And a seventh step of selecting the maximum value Imax of the detection sensitivity as the effective determination reference value.

Here, the sum of the detection voltages in the above-described transparent period may be calculated by Equation 1 below.

In addition, the respective mountain detection sensitivity may be calculated by the following equation (2).

According to the present embodiment, it is possible to provide a new optical diagnostic apparatus having excellent sensitivity and specificity discrimination performance by evaluating the difference in the photodiode voltage between the transparent section and the opaque section using a diagnostic kit having a grid-divided transparent substrate.

On the other hand, the control system 290 described above may have a form coupled to the base plate or the support frame of the optical diagnostic device described above with reference to FIG. 14, and vice versa. That is, the optical diagnostic apparatus described above with reference to FIG. 14 may be implemented to be integrally coupled to a housing or a case of the control system described with reference to FIG. 18.

Claims (13)

1. As diagnostic kit using immunochromatography technology,

   A sample pad, a conjugate pad, a detection pad, and an absorbent pad, which are connected on one surface of the light-transmitting film substrate in the order described from one side to the other side,

   A diagnostic kit in which a stripe-shaped opaque pattern is disposed on the film substrate to correspond to a test area in the form of a space in the detection pad.
2. The method according to claim 1,

   And a direction in which each line pattern extends in the opaque pattern is perpendicular to a direction in which the coupling pad and the detection pad are connected to each other, or a direction in which the detection pad and the absorption pad are connected and extended.
3. The method according to claim 1,

   Each line pattern in the opaque pattern corresponds to a direction in which the coupling pad and the detection pad are connected and extend or a direction in which the detection pad and the absorption pad are connected and extended and inclined at a specific angle of 45 ° or less. Extended diagnostic kit.
4. The method according to claim 1,

   And a width of the first line pattern in the opaque pattern and a distance between the second line pattern adjacent to the first line pattern is the same.
5. The method according to claim 1,

   A diagnostic kit having the same width as each line pattern in the opaque pattern and an interval between adjacent line patterns.
6. The method according to claim 1,

   The opaque pattern is disposed on the one surface of the film substrate, on the other surface opposite to the one surface, or diagnostic kit disposed between the one surface and the other surface.
7. The method according to claim 6,

   The opaque pattern is a diagnostic kit is embedded so that the surface is exposed on the one surface or the other surface of the film substrate.
8. The method according to claim 1,

   And a translucent protective film covering the detection pad and the test area.
9. The method according to claim 1,

   And a case accommodating a pad assembly including the film substrate, the sample pad, the bonding pad, the detection pad, and the absorption pad.

   The case has a sample inlet positioned corresponding to the sample pad and an opening positioned corresponding to the test region.

   And the opening exposes the test area and the control area on the detection pad to the outside.
10. An optical diagnostic apparatus using a diagnostic kit,

    A light emitting device emitting light to the signal detection unit of the test area of the diagnostic kit;

    A light receiving element that detects a change in the amount of light between the stripe-shaped line patterns of the signal detection unit by the incident light when the incident light of the single wavelength from the light emitting element is focused on the signal detection unit of the diagnostic kit;

    An actuator coupled to the light receiving element to control focusing of the light receiving element; And

    It includes a drive unit for moving the relative position between the light emitting element and the light receiving element, and the diagnostic kit,

    And an optical diagnostic apparatus for scanning in a direction intersecting the line patterns of the signal detection unit by an operation of the driving unit.
11. The method according to claim 10,

    A lens disposed at a front end of the light emitting device to condense light to adjust the amount of light of the light emitting device; And a filter attached to the front end of the lens.
12. The method according to claim 10,

    And a control unit for controlling the operation of the light emitting element, the light receiving element, the actuator and the driving unit.
13. The method according to claim 12,

    The control unit is a two-dimensional matrix (m * n matrix) for a decomposition section consisting of columns (m) in the direction (y) of the crossing direction (y) and the direction (orthogonal to the crossing direction). A memory array is generated, and a voltage V of a signal detected by the light receiving element corresponding to the matrix is stored in a specific memory region A [n] [m], where an opacity interval corresponding to the line patterns is obtained. The low voltage is set to 0 or a predetermined voltage, summing the voltage from the first (x [0]) to the last (x [m-1]) of x for the i th (y [i]) of y; A voltage one-dimensional memory array B [n] for storing is generated, and the voltages for the x [0] to x [m-1] for the y [i] are summed to specify a specific memory array B [j]. ), Summing the voltages for x [0] to x [m-1] with respect to [0] to [n-1] of y and storing them in a specific memory array B [j], respectively. , The detection sensitivity Ii is calculated for each B [j] by dividing by the area Si, and the maximum value of the detection sensitivity is selected as an effective determination reference value.

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